Liver Disease

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

aotto@mdedge.com

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

aotto@mdedge.com

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

aotto@mdedge.com

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

gtwachtman@mdedge.com

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

gtwachtman@mdedge.com

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

gtwachtman@mdedge.com

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

sworcester@mdedge.com

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

sworcester@mdedge.com

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

sworcester@mdedge.com

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

For patients with chronic hepatitis B virus (HBV) infection, up to 10 years of treatment with entecavir was safe and produced a superior rate of sustained virologic response, compared with other HBV nucleoside or nucleotide analogues in a global randomized clinical trial.

Virologic responses were confirmed and maintained in 80% of entecavir patients and 61% of patients who received other therapies, said Jin-Lin Hou, MD, of Southern Medical University in Guangzhou, China, and associates. Regardless of which treatment patients received, a sustained virologic response was associated with a significantly lower rate of liver-related hepatitis B virus (HBV) disease progression and hepatocellular carcinoma. Rates of serious treatment-related adverse events were 0.2% in the entecavir arm and 0.8% in the nonentecavir arm. Moreover, the primary outcome of time-to-adjudicated clinical outcome events “showed that entecavir treatment, compared with nonentecavir, was not associated with an increased risk of malignant neoplasms, including hepatocellular carcinoma, nonhepatocellular carcinoma malignancies, and overall malignancies,” they wrote in Clinical Gastroenterology and Hepatology.

Entecavir is approved for the treatment of adults with chronic HBV infection, and its long-term use has been linked to the regression of hepatic fibrosis and cirrhosis. In treatment-naive patients, genotypic resistance and virologic breakthrough are rare even after up to 5 years of entecavir therapy. Although human studies have not linked this treatment duration with an increased risk of adverse events, murine studies have identified benign and malignant tumors of the brain, lung, and liver in entecavir-treated mice and rats. “With the exception of lung tumors, which were limited to male mice, rodent tumors occurred only at entecavir exposures [that were] significantly higher than those achieved in human beings with standard approved doses,” the researchers wrote.

For the trial, they assigned more than 12,000 patients with chronic HBV infection to receive long-term treatment with entecavir or investigators’ choice of another HBV nucleoside or nucleotide analogue. Patients were from 229 centers in Asia, Europe, and North and South America, and a total of 6,216 received entecavir, while 6,162 received another therapy.

Compared with other HBV nucleoside and nucleotide analogues, long-term treatment with entecavir “provided a high margin of safety” and was not tied to higher rates of liver or nonliver malignancies, the researchers found. The carcinogenicity of entecavir in rodents did not appear to extend to humans. Furthermore, among 5,305 trial participants in China, a sustained virologic response was associated with a clinically and statistically significant reduction in the risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.04-0.22) and hepatocellular carcinoma (HR, 0.03; 95% CI, 0.009-0.113).

The results confirm the appropriateness of long-term entecavir therapy for chronic HBV infection, as recommended by current guidelines, Dr. Hou and associates concluded. However, patients in this trial were relatively young, with a median age of only 39 years. Therefore, the risk of entecavir-associated malignancies in older age cohorts could not be evaluated.

Bristol-Myers Squibb designed the study, performed statistical analyses, and funded the study and manuscript preparation. The Ministry of Science and Technology of China and the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program provided partial support. Dr. Hou disclosed grants and personal fees from Bristol-Myers Squibb, GlaxoSmithKline, and Novartis. Several coinvestigators also disclosed ties to Bristol-Myers Squibb and to several other pharmaceutical companies.

SOURCE: Hou J-L et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi: 10.1016/j.cgh.2019.07.010.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

Currently available fibrosis scoring systems appear to have only a modest predictive ability for development of severe liver disease in the general population, according to authors of a large, retrospective cohort study.

Of five noninvasive scoring systems evaluated, all did have high negative predictive value in the general population, according to authors of the study, which included data on more than 800,000 individuals in Sweden. However, their sensitivities were low, with most of the individuals who developed severe liver disease over a 10-year follow-up period initially classified as being at low risk for advanced fibrosis, according to the study authors, led by Hannes Hagström, MD, PhD, of the division of hepatology, Karolinska University Hospital, Stockholm.

The scoring systems tended to perform better in patients at higher risk for nonalcoholic fatty liver disease (NAFLD) at baseline, suggesting the best use of the tools is in patients at increased risk or who have liver disease indications, Dr. Hagström and coauthors wrote in a report on the study.

“Although useful in populations with a high prevalence of advanced fibrosis, current scores lack precision for usage in the general population for which the prevalence of advanced fibrosis is much lower,” Dr. Hagström and colleagues said.

The scoring systems were derived from high-risk cohorts with liver diseases, the authors noted, stating that the disease prevalence in any given population will affect the performance of a test that’s intended to diagnose that specific disease.

“New and improved” scoring systems should be developed to more effectively pinpoint patients with NAFLD who are at higher risk of a severe liver event, they added in the report, which appears in Gastroenterology.

The population-based cohort study by Dr. Hagström and colleagues was based on data from 812,073 patients enrolled in the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort between 1985 and 1996. Investigators said they excluded patients under 35 and over 79 years of age, patients with severe liver disease at baseline, and those with a prior diagnosis of alcohol or drug abuse.

Investigators used available data to calculate five scores, including the AST to Platelet Ratio Index (APRI); the body mass index, AST/ALT ratio, and diabetes (BARD) score; the Fibrosis-4 (FIB-4) score; Forns Index; and NAFLD Fibrosis Score (NFS).

At baseline, 0.5%-8.0% of patients were considered to be at high risk for advanced fibrosis, depending on the test used, investigators said. With up to 10 years of follow-up, the proportion of individuals who developed severe liver diseases (cirrhosis, liver failure, hepatocellular carcinoma, liver transplantation, or decompensated liver disease) was 0.3%-0.6%, and with the maximum 27 years of follow-up, the incidence ranged from 1.0% to 1.4%.

There was a “strong association” between baseline risk of fibrosis and development of severe liver diseases; however, the majority of cases occurred in patients deemed low risk at baseline, Dr. Hagström and colleagues noted in their report.

For example, 12.4% of individuals classified as high risk by APRI developed severe liver diseases over 10 years, compared to just 0.4% of the low-risk group, yet out of 723 cases, 502 (69%) occurred in the low-risk patients, the data show.

Hazard ratios did increase with risk level, and at the high-risk level, adjusted hazard ratios ranged from 1.7 (95% confidence interval [CI], 1.1-2.5) for the high-risk BARD patients to 45.9 (95% CI, 36.1-58.3) for the high-risk APRI patients, investigators reported.

Taken together, results of this study demonstrate that the performance of all scores was low in an unselected population, according to investigators.

Of all tests, APRI was least likely to falsely classify patients who never developed severe liver diseases and had an intermediate-risk group of 4%, the lowest of any test, which are findings that may have implications for routine primary care, according to investigators.

“APRI could be the currently best score to exclude a high risk of liver-related events in the near future, and thereby reduce unnecessary testing in a general population,” they said in a discussion of their results.

The study was supported by an independent grant from AstraZeneca. Dr. Hagström reported disclosures related to that company, as well as Novo Nordisk, Gilead Sciences, IQVIA, Intercept, and Bristol Myers-Squibb.

SOURCE: Hagström H et al. Gastroenterology. 2019 Sep 26. doi: 10.1053/j.gastro.2019.09.008.

While initial case reports and series provided preliminarily encouraging results, a larger retrospective study has provided no clear-cut evidence of biochemical response to vedolizumab in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease, investigators report.

A subset of patients in the retrospective analysis did experience a substantial drop in alkaline phosphatase (ALP), according to investigators with the International Primary Sclerosing Cholangitis Study Group.

Overall, however, levels of that cholestasis marker rose by a small but statistically significant amount in this study, which included more than 100 patients with PSC and inflammatory bowel disease (IBD).

Responses were more likely in patients with cirrhosis and in those with elevated ALP at baseline, both of which are indicators of more aggressive disease, according to investigator Kate D. Lynch, MD, PhD, of the University of Oxford (England) and her coauthors.

The rate of liver outcomes was in line with the natural history of the disease, according to Dr. Lynch and coinvestigators, who added that most patients had an endoscopic IBD response, as might be expected based on studies of IBD-only patients treated with vedolizumab.

“Despite the disappointment with lack of a uniform response, further evaluation of vedolizumab as a beneficial treatment in PSC may be warranted in a subset of patients via a stratified randomized clinical trial,” Dr. Lynch and coauthors said in their report, which was published in Clinical Gastroenterology and Hepatology.

Vedolizumab, a monoclonal antibody against integrin alpha4beta7, is effective in Crohn’s disease and ulcerative colitis, according to investigators, who added that the “gut-homing pathway” it targets has also been implicated in the pathophysiology of PSC.

“It is possible that vedolizumab may play a role in reducing lymphocyte infiltration into the liver in patients with PSC and thereby in reducing hepatic and biliary inflammation, authors of the retrospective analysis said.

Their analysis included 102 patients with PSC and IBD at 20 centers in Europe and North America. All patients had received at least three doses of vedolizumab for their IBD, given according to the usual dosing schedule. Most of the patients were male (64 patients, or 62.8%) and about 90% had classical large-duct PSC. About one-fifth had cirrhosis, and the majority (about 65%) had ulcerative colitis. Patients were followed until death, liver transplant, or 56 days after the last vedolizumab dose.

The median ALP increased from 1.53 times the upper limit of normal at baseline to 1.64 times the upper limit of normal by the last follow-up, an increase that was statistically significant (P = .018) but not clinically significant, according to investigators. Likewise, they said, statistically significant increases were seen overall in median alanine transaminase and aspartate aminotransferase levels.

However, 21 patients (20.6%) had a drop in ALP of at least 20% from baseline to last follow-up, and another 39 patients (38.2%) had stable ALP over that period, data show, while the remaining 42 (41.2%) had an increase of 20% or more.

Cirrhosis was associated with a near fivefold odds of a 20% or greater ALP drop from baseline to follow-up (odds ratio, 4.70, 95% confidence interval, 1.61-13.76), according to results of univariate analysis, which investigators said were “reproduced” in multivariate analysis.

While no other variables were so clearly linked to a 20% or greater drop in ALP, Dr. Lynch and colleagues said there was a “trend toward an association” in patients with ALP raised at baseline, and in those who had Crohn’s disease or IBD-unspecified instead of ulcerative colitis.

Endoscopic IBD responses were seen in 42 out of 74 patients (56.8%) for whom those data were available, investigators added.

A total of 22 patients (20.9%) had a liver-related outcome over median follow-up of 561 days; however, that outcome may be “slightly overrepresented” by an incidence of cholangitis in 8.8%, which in and of itself is not necessarily an indicator of advanced liver disease, said Dr. Lynch and coauthors in their report.

“This proportion of liver-related outcomes is consistent with the natural history of PSC and does not by itself indicate that vedolizumab treatment is harmful in PSC,” they said, adding that the findings were similar to a study of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2, in patients with PSC, of whom 20.1% had a PSC-related event and the incidence of cholangitis was 13.2%.

The retrospective study was supported by the Birmingham National Institute for Health Research (NIHR) Biomedical Research Centre in the United Kingdom. Authors of the report provided disclosures related to Takeda, AbbVie, Dr. Falk Pharma, Intercept, MSD, Janssen, Vifor, Gilead, and Novartis, among others.

SOURCE: Lynch KD et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.013.

While initial case reports and series provided preliminarily encouraging results, a larger retrospective study has provided no clear-cut evidence of biochemical response to vedolizumab in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease, investigators report.

A subset of patients in the retrospective analysis did experience a substantial drop in alkaline phosphatase (ALP), according to investigators with the International Primary Sclerosing Cholangitis Study Group.

Overall, however, levels of that cholestasis marker rose by a small but statistically significant amount in this study, which included more than 100 patients with PSC and inflammatory bowel disease (IBD).

Responses were more likely in patients with cirrhosis and in those with elevated ALP at baseline, both of which are indicators of more aggressive disease, according to investigator Kate D. Lynch, MD, PhD, of the University of Oxford (England) and her coauthors.

The rate of liver outcomes was in line with the natural history of the disease, according to Dr. Lynch and coinvestigators, who added that most patients had an endoscopic IBD response, as might be expected based on studies of IBD-only patients treated with vedolizumab.

“Despite the disappointment with lack of a uniform response, further evaluation of vedolizumab as a beneficial treatment in PSC may be warranted in a subset of patients via a stratified randomized clinical trial,” Dr. Lynch and coauthors said in their report, which was published in Clinical Gastroenterology and Hepatology.

Vedolizumab, a monoclonal antibody against integrin alpha4beta7, is effective in Crohn’s disease and ulcerative colitis, according to investigators, who added that the “gut-homing pathway” it targets has also been implicated in the pathophysiology of PSC.

“It is possible that vedolizumab may play a role in reducing lymphocyte infiltration into the liver in patients with PSC and thereby in reducing hepatic and biliary inflammation, authors of the retrospective analysis said.

Their analysis included 102 patients with PSC and IBD at 20 centers in Europe and North America. All patients had received at least three doses of vedolizumab for their IBD, given according to the usual dosing schedule. Most of the patients were male (64 patients, or 62.8%) and about 90% had classical large-duct PSC. About one-fifth had cirrhosis, and the majority (about 65%) had ulcerative colitis. Patients were followed until death, liver transplant, or 56 days after the last vedolizumab dose.

The median ALP increased from 1.53 times the upper limit of normal at baseline to 1.64 times the upper limit of normal by the last follow-up, an increase that was statistically significant (P = .018) but not clinically significant, according to investigators. Likewise, they said, statistically significant increases were seen overall in median alanine transaminase and aspartate aminotransferase levels.

However, 21 patients (20.6%) had a drop in ALP of at least 20% from baseline to last follow-up, and another 39 patients (38.2%) had stable ALP over that period, data show, while the remaining 42 (41.2%) had an increase of 20% or more.

Cirrhosis was associated with a near fivefold odds of a 20% or greater ALP drop from baseline to follow-up (odds ratio, 4.70, 95% confidence interval, 1.61-13.76), according to results of univariate analysis, which investigators said were “reproduced” in multivariate analysis.

While no other variables were so clearly linked to a 20% or greater drop in ALP, Dr. Lynch and colleagues said there was a “trend toward an association” in patients with ALP raised at baseline, and in those who had Crohn’s disease or IBD-unspecified instead of ulcerative colitis.

Endoscopic IBD responses were seen in 42 out of 74 patients (56.8%) for whom those data were available, investigators added.

A total of 22 patients (20.9%) had a liver-related outcome over median follow-up of 561 days; however, that outcome may be “slightly overrepresented” by an incidence of cholangitis in 8.8%, which in and of itself is not necessarily an indicator of advanced liver disease, said Dr. Lynch and coauthors in their report.

“This proportion of liver-related outcomes is consistent with the natural history of PSC and does not by itself indicate that vedolizumab treatment is harmful in PSC,” they said, adding that the findings were similar to a study of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2, in patients with PSC, of whom 20.1% had a PSC-related event and the incidence of cholangitis was 13.2%.

The retrospective study was supported by the Birmingham National Institute for Health Research (NIHR) Biomedical Research Centre in the United Kingdom. Authors of the report provided disclosures related to Takeda, AbbVie, Dr. Falk Pharma, Intercept, MSD, Janssen, Vifor, Gilead, and Novartis, among others.

SOURCE: Lynch KD et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.013.

While initial case reports and series provided preliminarily encouraging results, a larger retrospective study has provided no clear-cut evidence of biochemical response to vedolizumab in patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease, investigators report.

A subset of patients in the retrospective analysis did experience a substantial drop in alkaline phosphatase (ALP), according to investigators with the International Primary Sclerosing Cholangitis Study Group.

Overall, however, levels of that cholestasis marker rose by a small but statistically significant amount in this study, which included more than 100 patients with PSC and inflammatory bowel disease (IBD).

Responses were more likely in patients with cirrhosis and in those with elevated ALP at baseline, both of which are indicators of more aggressive disease, according to investigator Kate D. Lynch, MD, PhD, of the University of Oxford (England) and her coauthors.

The rate of liver outcomes was in line with the natural history of the disease, according to Dr. Lynch and coinvestigators, who added that most patients had an endoscopic IBD response, as might be expected based on studies of IBD-only patients treated with vedolizumab.

“Despite the disappointment with lack of a uniform response, further evaluation of vedolizumab as a beneficial treatment in PSC may be warranted in a subset of patients via a stratified randomized clinical trial,” Dr. Lynch and coauthors said in their report, which was published in Clinical Gastroenterology and Hepatology.

Vedolizumab, a monoclonal antibody against integrin alpha4beta7, is effective in Crohn’s disease and ulcerative colitis, according to investigators, who added that the “gut-homing pathway” it targets has also been implicated in the pathophysiology of PSC.

“It is possible that vedolizumab may play a role in reducing lymphocyte infiltration into the liver in patients with PSC and thereby in reducing hepatic and biliary inflammation, authors of the retrospective analysis said.

Their analysis included 102 patients with PSC and IBD at 20 centers in Europe and North America. All patients had received at least three doses of vedolizumab for their IBD, given according to the usual dosing schedule. Most of the patients were male (64 patients, or 62.8%) and about 90% had classical large-duct PSC. About one-fifth had cirrhosis, and the majority (about 65%) had ulcerative colitis. Patients were followed until death, liver transplant, or 56 days after the last vedolizumab dose.

The median ALP increased from 1.53 times the upper limit of normal at baseline to 1.64 times the upper limit of normal by the last follow-up, an increase that was statistically significant (P = .018) but not clinically significant, according to investigators. Likewise, they said, statistically significant increases were seen overall in median alanine transaminase and aspartate aminotransferase levels.

However, 21 patients (20.6%) had a drop in ALP of at least 20% from baseline to last follow-up, and another 39 patients (38.2%) had stable ALP over that period, data show, while the remaining 42 (41.2%) had an increase of 20% or more.

Cirrhosis was associated with a near fivefold odds of a 20% or greater ALP drop from baseline to follow-up (odds ratio, 4.70, 95% confidence interval, 1.61-13.76), according to results of univariate analysis, which investigators said were “reproduced” in multivariate analysis.

While no other variables were so clearly linked to a 20% or greater drop in ALP, Dr. Lynch and colleagues said there was a “trend toward an association” in patients with ALP raised at baseline, and in those who had Crohn’s disease or IBD-unspecified instead of ulcerative colitis.

Endoscopic IBD responses were seen in 42 out of 74 patients (56.8%) for whom those data were available, investigators added.

A total of 22 patients (20.9%) had a liver-related outcome over median follow-up of 561 days; however, that outcome may be “slightly overrepresented” by an incidence of cholangitis in 8.8%, which in and of itself is not necessarily an indicator of advanced liver disease, said Dr. Lynch and coauthors in their report.

“This proportion of liver-related outcomes is consistent with the natural history of PSC and does not by itself indicate that vedolizumab treatment is harmful in PSC,” they said, adding that the findings were similar to a study of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2, in patients with PSC, of whom 20.1% had a PSC-related event and the incidence of cholangitis was 13.2%.

The retrospective study was supported by the Birmingham National Institute for Health Research (NIHR) Biomedical Research Centre in the United Kingdom. Authors of the report provided disclosures related to Takeda, AbbVie, Dr. Falk Pharma, Intercept, MSD, Janssen, Vifor, Gilead, and Novartis, among others.

SOURCE: Lynch KD et al. Clin Gastroenterol Hepatol. 2019 May 14. doi: 10.1016/j.cgh.2019.05.013.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – Treatment of persons who inject drugs, updates in pangenotypic direct-acting antiviral therapy, the benefits of sustained virologic response, and preemptive therapy in donor-positive organ transplantation topped the list of notable hepatitis C–related abstracts this year at the annual meeting of the American Association for the Study of Liver Diseases.

That’s according to Marc Ghany, MD, of the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, who gave a hepatitis C debrief to attendees on the final day of the meeting. Here are some of the meeting highlights as summarized by Dr. Ghany in this well-attended last-day session.
 

Treatment of HCV in people who inject drugs

Emerging data suggest it is feasible to treat hepatitis C virus (HCV) infection in persons who inject drugs (PWIDs); however, overcoming adherence issues remains a challenge, Dr. Ghany told attendees.

According to one study presented at AASLD by Dhiman and coauthors (Abstract 0165), decentralized care of PWIDs using direct-acting antiviral (DAA) therapy was safe and effective, even in those with cirrhosis. Authors demonstrated an “impressive” rate of sustained virologic response at 12 weeks (SVR12) of 91% by a modified intention-to-treat analysis, Dr. Ghany said; however, treatment interruptions were frequent and reduced the overall SVR rate in the study to 78%.

Other studies at the meeting looked at strategies to improve DAA efficacy in this population of patients at high risk of nonadherence, including use of a digital medicine program (Abstract 1554) and a model of care in which an internist-addiction medicine specialist evaluated opiate-dependent patients for HCV infection in a hepatology clinic (Abstract 1589).

Reinfection remains a focus of research in PWIDs. At this meeting, Janjua and coauthors reported that DAA-treated PWIDs in British Columbia had a threefold higher rate of reinfection versus non-PWIDs; however, there were no detected reinfections among PWIDs who had received uninterrupted opioid agonist therapy. “These data suggested that opioid agonist therapy should be given before and after HCV treatment in persons who inject drugs to prevent the infection,” Dr. Ghany said in his presentation.
 

Updates on pangenotypic DAA therapy

Jonas and coauthors (Abstract 1551) reported on the safety and efficacy of glecaprevir/pibrentasvir for 8 weeks in children with chronic HCV infection enrolled in the ongoing phase 2/3 DORA study. The SVR12 was high, according to Dr. Ghany, at 96% overall, and consistent across age cohorts from 3 to less than 12 years of age.

“In the near future, we should have a safe and effective regimen (approved) for children 3 years or older,” Dr. Ghany said. “I think this will serve us well, as we try to eliminate HCV in children, who number up to 5 million cases worldwide.”

A short course of glecaprevir/pibrentasvir is approved for patients with HCV and compensated cirrhosis, and data to support that was presented last year at The Liver Meeting; however, data were not presented on patients with genotype 3, the most difficult-to-treat genotype, Dr. Ghany said. That gap was filled at this year’s meeting with a report (Abstract LP9) showing SVR12 rates of 98.4% per protocol and 95.2% in intention-to-treat analysis.
 

Relationship of SVR to clinical outcomes

While the impact of sustained virologic response (SVR) on all-cause mortality is clear in patients with HCV, less is known about the effect of SVR on liver-related mortality and other outcomes, Dr. Ghany said. In one study presented here (Abstract 0039), based on analysis of a Veterans Affairs database of patients with chronic HCV infection, SVR was linked to a significant reduction in liver-related mortality, while in another report (Abstract 0037), SVR was associated with significant reductions in acute coronary syndromes, end-stage renal disease, and ischemic stroke.

Similarly, a multinational, propensity score–matched analysis (Abstract 0040) demonstrated that SVR had an impact on 5-year overall survival and liver-related survival in patients with HCV-related hepatocellular carcinoma (HCC). “For HCC patients who are candidates for HCC therapy, consideration should also be given to treating these individuals (with DAA therapy) because of the impact on overall survival,” Dr. Ghany said.
 

Preemptive DAA therapy in organ transplantation

Exciting new data show that preemptive therapy, given for short durations, appears to either prevent or cure HCV infection after organ transplant, said Dr. Ghany.

A retrospective analysis by Wijarnpreecha and colleagues (Abstract 0003) showed that 12 or 24 weeks of direct-acting antiviral (DAA) therapy resulted in an SVR12 for 24 out of 24 HCV-seropositive to HCV-seronegative liver transplants, while Durand and colleagues (Abstract 0042) showed that just 4 weeks of pre- and postexposure DAA prophylaxis resulted in SVR12s for 9 out of 9 HCV donor-positive, recipient-negative kidney transplants. Finally, Feld and coauthors (Abstract 0038) showed that preemptive ezetimibe with DAA therapy for 7 days prevented or rapidly cured infection in an experience that included 16 HCV-positive organ donors and 25 HCV-negative recipients.

“While these data are very encouraging, I think we do need to have long-term follow-up of these patients for graft survival, as well as the effect on wait times,” Dr. Ghany said.

Dr. Ghany reported no disclosures related to his presentation.

BOSTON – For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Andrew D. Bowser/MDedge News

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”
 

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.
 

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A_1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.
 

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.
 

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

The investigators found that 41% of patients achieved a 30% or greater relative reduction in liver fat, as well as reductions in hemoglobin A_1c and lipids, but the treatment was “weight neutral,” Dr. Corey said, adding that no serious adverse events were reported.
 

PF-05221304

This liver-targeted acetyl-CoA carboxylase inhibitor (ACCI) demonstrated robust reduction in liver fat and ALT in a 16-week phase 2a, dose-ranging study in adults with NAFLD, according to Amin and coinvestigators (Abstract 31).

There was a “dramatic” decrease in liver fat in this study, said Dr. Corey, with 90% of treated patients experiencing a 30% or greater decrease. Side effects included a “significant” increase in triglycerides, she added, as well as transient increases in ALT and AST.
 

Selonsertib and emricasan

One agent not meeting study endpoints was selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. While safe and well tolerated, the drug was nevertheless not effective as monotherapy in phase 3 double-blind, placebo-controlled trials including patients with advanced fibrosis due to NASH, investigators said (Abstract 64). Currently, the agent is being evaluated in combination with firsocostat – an ACCI – in a phase 2 study called ATLAS, according to the authors.

Emricasan, an oral pan-caspase inhibitor that suppresses apoptosis, did not improve fibrosis or resolve NASH in a multicenter, double-blind, placebo-controlled randomized trial, and may have even worsened histology, according to Dr. Corey. Investigators said further evaluation of the mechanisms underlying findings could provide insights into the role of necro-apoptosis in NASH pathophysiology (Abstract 61).

Dr. Corey provided disclosures related to BMS, Novo Nordisk, Boehringer Ingelheim, and Gilead.

BOSTON – For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Andrew D. Bowser/MDedge News

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”
 

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.
 

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A_1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.
 

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.
 

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

The investigators found that 41% of patients achieved a 30% or greater relative reduction in liver fat, as well as reductions in hemoglobin A_1c and lipids, but the treatment was “weight neutral,” Dr. Corey said, adding that no serious adverse events were reported.
 

PF-05221304

This liver-targeted acetyl-CoA carboxylase inhibitor (ACCI) demonstrated robust reduction in liver fat and ALT in a 16-week phase 2a, dose-ranging study in adults with NAFLD, according to Amin and coinvestigators (Abstract 31).

There was a “dramatic” decrease in liver fat in this study, said Dr. Corey, with 90% of treated patients experiencing a 30% or greater decrease. Side effects included a “significant” increase in triglycerides, she added, as well as transient increases in ALT and AST.
 

Selonsertib and emricasan

One agent not meeting study endpoints was selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. While safe and well tolerated, the drug was nevertheless not effective as monotherapy in phase 3 double-blind, placebo-controlled trials including patients with advanced fibrosis due to NASH, investigators said (Abstract 64). Currently, the agent is being evaluated in combination with firsocostat – an ACCI – in a phase 2 study called ATLAS, according to the authors.

Emricasan, an oral pan-caspase inhibitor that suppresses apoptosis, did not improve fibrosis or resolve NASH in a multicenter, double-blind, placebo-controlled randomized trial, and may have even worsened histology, according to Dr. Corey. Investigators said further evaluation of the mechanisms underlying findings could provide insights into the role of necro-apoptosis in NASH pathophysiology (Abstract 61).

Dr. Corey provided disclosures related to BMS, Novo Nordisk, Boehringer Ingelheim, and Gilead.

BOSTON – For treatment of nonalcoholic fatty liver disease, cotadutide, licogliflozin, tropifexor, saroglitazar, and PF-05221304 are just a few of the drugs with promising data, Kathleen E. Corey, MD, MPH, said at the annual meeting of the American Association for the Study of Liver Diseases.

Andrew D. Bowser/MDedge News

By contrast, selonsertib and emricasan did not achieve their endpoints in studies described here at the meeting, “but we have a lot to learn from them,” said Dr. Corey, director of the Mass General Fatty Liver Clinic and assistant professor at Harvard Medical School, Boston.

“This is an exciting time,” Dr. Corey said in a special debriefing oral session held on the final day of the conference. “There are many novel mechanisms of action out there, as well as some known mechanisms of action, with a considerable amount of promise.”
 

Cotadutide (MEDI0382)

Narha and coauthors (Abstract 35) described the effects of cotadutide, a GLP-1/glucagon receptor dual agonist on biomarkers of nonalcoholic steatohepatitis (NASH) at 26 weeks in overweight or obese patients with type 2 diabetes mellitus. In the randomized, phase 2b study, cotadutide produced superior reductions versus liraglutide, the GLP-1 receptor agonist, in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and body weight, which investigators said supported prospective trials of the drug for a potential indication in NASH.

“The adverse events were fairly typical for what we see with the GLP-1s – GI side effects that usually over 8 weeks improve,” Dr. Corey told attendees at the debrief session.
 

Licogliflozin (LIK066)

Interim analysis of a 12-week, randomized, placebo-controlled, phase 2a study showed that this SGLT1/2 inhibitor produced “robust” decreases in ALT and improvements in markers of hepatic and metabolic health in patients with NASH, according to Zhang and coauthors (Abstract L07).

Some 67% of those who received licogliflozin had at least a 30% decrease in their liver fat, while decreases in weight and hemoglobin A_1c were also reported, according to Dr. Corey. “It was associated with diarrhea in about 97%, but this was considered mild, and certainly, we’re seeing good metabolic effects overall,” she said.
 

Tropifexor

Treatment for 12 weeks with this potent FXR agonist resulted in robust, dose-dependent reductions in hepatic fat and serum ALT in patients with fibrotic NASH, according to investigators in a phase 2 randomized, placebo-controlled trial known as FLIGHT-FXR (Abstract L04).

A total of 65% of patients achieved a 30% or greater reduction in liver fat, and decreases in weight and insulin resistance were reported. “Similar to other FXRs, they did have this concerning although potentially manageable increase in low-density lipoprotein (LDL)-cholesterol, and the adverse event of pruritis,” said Dr. Corey.
 

Saroglitazar

Gawrieh and coauthors presented results from EVIDENCES IV, a phase 2, double-blind, randomized, placebo-controlled study of saroglitazar, a novel dual peroxisome proliferator activated receptor (PPAR) alpha/gamma agonist, in patients with NAFLD or NASH (Abstract LO10).

The investigators found that 41% of patients achieved a 30% or greater relative reduction in liver fat, as well as reductions in hemoglobin A_1c and lipids, but the treatment was “weight neutral,” Dr. Corey said, adding that no serious adverse events were reported.
 

PF-05221304

This liver-targeted acetyl-CoA carboxylase inhibitor (ACCI) demonstrated robust reduction in liver fat and ALT in a 16-week phase 2a, dose-ranging study in adults with NAFLD, according to Amin and coinvestigators (Abstract 31).

There was a “dramatic” decrease in liver fat in this study, said Dr. Corey, with 90% of treated patients experiencing a 30% or greater decrease. Side effects included a “significant” increase in triglycerides, she added, as well as transient increases in ALT and AST.
 

Selonsertib and emricasan

One agent not meeting study endpoints was selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor. While safe and well tolerated, the drug was nevertheless not effective as monotherapy in phase 3 double-blind, placebo-controlled trials including patients with advanced fibrosis due to NASH, investigators said (Abstract 64). Currently, the agent is being evaluated in combination with firsocostat – an ACCI – in a phase 2 study called ATLAS, according to the authors.

Emricasan, an oral pan-caspase inhibitor that suppresses apoptosis, did not improve fibrosis or resolve NASH in a multicenter, double-blind, placebo-controlled randomized trial, and may have even worsened histology, according to Dr. Corey. Investigators said further evaluation of the mechanisms underlying findings could provide insights into the role of necro-apoptosis in NASH pathophysiology (Abstract 61).

Dr. Corey provided disclosures related to BMS, Novo Nordisk, Boehringer Ingelheim, and Gilead.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.