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Biophysical properties of HCV evolve over course of infection
Hepatitis C virus (HCV) particles are of lowest density and most infectious early in the course of infection, based on findings from a study of chimeric mice.
Over time, however, viral density became more heterogeneous and infectivity fell, reported Ursula Andreo, PhD, of Rockefeller University, New York, with her coinvestigators. A diet of 10% sucrose, which in rats induces hepatic secretion of very-low-density lipoprotein (VLDL), caused HCV particles to become slightly lower density and more infectious in the mice, the researchers reported. Although the shift was “minor,” it “correlated with a trend toward enhanced triglyceride and cholesterol levels in the same fractions,” they wrote. They recommended studying high-fat diets to determine whether altering the VLDL secretion pathway affects the biophysical properties of HCV. “A high-fat diet might have a more significant impact on the lipoprotein profile in this humanized mouse model,” they wrote in Cellular and Molecular Gastroenterology and Hepatology (2017 Jul;4[3]:405-17).
Because HCV tends to associate with lipoproteins, it shows a range of buoyant densities in the blood of infected patients. The “entry, replication, and assembly [of the virion] are linked closely to host lipid and lipoprotein metabolism,” wrote Dr. Andreo and her colleagues.
They created an in vivo model to study the buoyant density and infectivity of HCV particles, as well as their interaction with lipoproteins, by grafting human hepatocytes into the livers of immunodeficient mice that were homozygous recessive for fumarylacetoacetate hydrolase. Next, they infected 13 of these chimeric mice with J6-JFH1, an HCV strain that can establish long-term infections in mice that have human liver grafts (Proc Natl Acad Sci USA. 2006;103[10]:3805-9). The human liver xenograft reconstituted the FAH gene, restoring triglycerides to normal levels in the chimeric mice and creating a suitable “humanlike” model of lipoprotein metabolism, the investigators wrote.
Density fractionation of infectious mouse serum revealed higher infectivity in the low-density fractions soon after infection, which also has been observed in a human liver chimeric mouse model of severe combined immunodeficiency disease, they added. In the HCV model, the human liver grafts were conserved 5 weeks after infection, and the mice had a lower proportion of lighter, infectious HCV particles.
The researchers lacked sufficient material to directly study the composition of virions or detect viral proteins in the various density fractions. However, they determined that apolipoprotein C1 was the lightest fraction and that apolipoprotein E was mainly found in the five lightest fractions. Both these apolipoproteins are “essential factors of HCV infectivity,” and neither redistributed over time, they said. They suggested using immunoelectron microscopy or mass spectrometry to study the nature and infectivity of viral particles further.
In humans, ingesting a high-fat milkshake increases detectable HCV RNA in the VLDL fraction, the researchers noted. In rodents, a sucrose diet also has been found to increase VLDL lipidation and secretion, so they gave five of the infected chimeric mice drinking water containing 10% sucrose. After 5 weeks, these mice had increased infectivity and higher levels of triglycerides and cholesterol, but the effect was small and disappeared after the sucrose was withdrawn.
HCV “circulates as a population of particles of light, as well as dense, buoyant densities, and both are infectious,” the researchers concluded. “Changes in diet, as well as conditions such as fasting and feeding, affect the distribution of HCV buoyant density gradients.”
Funders included the National Institutes of Health and the American Association for the Study of Liver Diseases. The investigators disclosed no conflicts.
A hallmark of HCV infection is the association of virus particles with lipoproteins. The HCV virion (lipo-viro particle, LVP) is composed of nucleocapsid and envelope glycoproteins associated with very-low- and low-density lipoproteins, cholesterol, and apolipoproteins. The lipid components determine the size, density, hepatotropism, and infectivity of LVPs and play a role in cell entry, morphogenesis, release, and viral escape mechanisms. LVPs undergo dynamic changes during infection, and dietary triglycerides induce alterations in their biophysical properties and infectivity.
Dr. Andreo and colleagues used humanized Fah–/– mice to analyze the evolution of HCV particles during infection. As previously reported, two viral populations of different densities were detected in mice sera, with higher infectivity observed for the low-density population. The proportions and infectivity of these populations varied during infection, reflecting changes in biochemical features of the virus. Sucrose diet influenced the properties of virus particles; these properties’ changes correlated with a redistribution of triglycerides and cholesterol among lipoproteins.
Changes in biochemical features of the virus during infection represent a fascinating aspect of the structural heterogeneity, which influences HCV infectivity and evolution of the disease. Further studies in experimental models that reproduce the lipoprotein-dependent morphogenesis and release of virus particles, maturation, and intravascular remodeling of HCV-associated lipoproteins would help to develop novel lipid-targeting inhibitors to improve existing therapies.
Agata Budkowska, PhD, is scientific advisor for the department of international affairs at the Institut Pasteur, Paris. She has no conflicts of interest.
A hallmark of HCV infection is the association of virus particles with lipoproteins. The HCV virion (lipo-viro particle, LVP) is composed of nucleocapsid and envelope glycoproteins associated with very-low- and low-density lipoproteins, cholesterol, and apolipoproteins. The lipid components determine the size, density, hepatotropism, and infectivity of LVPs and play a role in cell entry, morphogenesis, release, and viral escape mechanisms. LVPs undergo dynamic changes during infection, and dietary triglycerides induce alterations in their biophysical properties and infectivity.
Dr. Andreo and colleagues used humanized Fah–/– mice to analyze the evolution of HCV particles during infection. As previously reported, two viral populations of different densities were detected in mice sera, with higher infectivity observed for the low-density population. The proportions and infectivity of these populations varied during infection, reflecting changes in biochemical features of the virus. Sucrose diet influenced the properties of virus particles; these properties’ changes correlated with a redistribution of triglycerides and cholesterol among lipoproteins.
Changes in biochemical features of the virus during infection represent a fascinating aspect of the structural heterogeneity, which influences HCV infectivity and evolution of the disease. Further studies in experimental models that reproduce the lipoprotein-dependent morphogenesis and release of virus particles, maturation, and intravascular remodeling of HCV-associated lipoproteins would help to develop novel lipid-targeting inhibitors to improve existing therapies.
Agata Budkowska, PhD, is scientific advisor for the department of international affairs at the Institut Pasteur, Paris. She has no conflicts of interest.
A hallmark of HCV infection is the association of virus particles with lipoproteins. The HCV virion (lipo-viro particle, LVP) is composed of nucleocapsid and envelope glycoproteins associated with very-low- and low-density lipoproteins, cholesterol, and apolipoproteins. The lipid components determine the size, density, hepatotropism, and infectivity of LVPs and play a role in cell entry, morphogenesis, release, and viral escape mechanisms. LVPs undergo dynamic changes during infection, and dietary triglycerides induce alterations in their biophysical properties and infectivity.
Dr. Andreo and colleagues used humanized Fah–/– mice to analyze the evolution of HCV particles during infection. As previously reported, two viral populations of different densities were detected in mice sera, with higher infectivity observed for the low-density population. The proportions and infectivity of these populations varied during infection, reflecting changes in biochemical features of the virus. Sucrose diet influenced the properties of virus particles; these properties’ changes correlated with a redistribution of triglycerides and cholesterol among lipoproteins.
Changes in biochemical features of the virus during infection represent a fascinating aspect of the structural heterogeneity, which influences HCV infectivity and evolution of the disease. Further studies in experimental models that reproduce the lipoprotein-dependent morphogenesis and release of virus particles, maturation, and intravascular remodeling of HCV-associated lipoproteins would help to develop novel lipid-targeting inhibitors to improve existing therapies.
Agata Budkowska, PhD, is scientific advisor for the department of international affairs at the Institut Pasteur, Paris. She has no conflicts of interest.
Hepatitis C virus (HCV) particles are of lowest density and most infectious early in the course of infection, based on findings from a study of chimeric mice.
Over time, however, viral density became more heterogeneous and infectivity fell, reported Ursula Andreo, PhD, of Rockefeller University, New York, with her coinvestigators. A diet of 10% sucrose, which in rats induces hepatic secretion of very-low-density lipoprotein (VLDL), caused HCV particles to become slightly lower density and more infectious in the mice, the researchers reported. Although the shift was “minor,” it “correlated with a trend toward enhanced triglyceride and cholesterol levels in the same fractions,” they wrote. They recommended studying high-fat diets to determine whether altering the VLDL secretion pathway affects the biophysical properties of HCV. “A high-fat diet might have a more significant impact on the lipoprotein profile in this humanized mouse model,” they wrote in Cellular and Molecular Gastroenterology and Hepatology (2017 Jul;4[3]:405-17).
Because HCV tends to associate with lipoproteins, it shows a range of buoyant densities in the blood of infected patients. The “entry, replication, and assembly [of the virion] are linked closely to host lipid and lipoprotein metabolism,” wrote Dr. Andreo and her colleagues.
They created an in vivo model to study the buoyant density and infectivity of HCV particles, as well as their interaction with lipoproteins, by grafting human hepatocytes into the livers of immunodeficient mice that were homozygous recessive for fumarylacetoacetate hydrolase. Next, they infected 13 of these chimeric mice with J6-JFH1, an HCV strain that can establish long-term infections in mice that have human liver grafts (Proc Natl Acad Sci USA. 2006;103[10]:3805-9). The human liver xenograft reconstituted the FAH gene, restoring triglycerides to normal levels in the chimeric mice and creating a suitable “humanlike” model of lipoprotein metabolism, the investigators wrote.
Density fractionation of infectious mouse serum revealed higher infectivity in the low-density fractions soon after infection, which also has been observed in a human liver chimeric mouse model of severe combined immunodeficiency disease, they added. In the HCV model, the human liver grafts were conserved 5 weeks after infection, and the mice had a lower proportion of lighter, infectious HCV particles.
The researchers lacked sufficient material to directly study the composition of virions or detect viral proteins in the various density fractions. However, they determined that apolipoprotein C1 was the lightest fraction and that apolipoprotein E was mainly found in the five lightest fractions. Both these apolipoproteins are “essential factors of HCV infectivity,” and neither redistributed over time, they said. They suggested using immunoelectron microscopy or mass spectrometry to study the nature and infectivity of viral particles further.
In humans, ingesting a high-fat milkshake increases detectable HCV RNA in the VLDL fraction, the researchers noted. In rodents, a sucrose diet also has been found to increase VLDL lipidation and secretion, so they gave five of the infected chimeric mice drinking water containing 10% sucrose. After 5 weeks, these mice had increased infectivity and higher levels of triglycerides and cholesterol, but the effect was small and disappeared after the sucrose was withdrawn.
HCV “circulates as a population of particles of light, as well as dense, buoyant densities, and both are infectious,” the researchers concluded. “Changes in diet, as well as conditions such as fasting and feeding, affect the distribution of HCV buoyant density gradients.”
Funders included the National Institutes of Health and the American Association for the Study of Liver Diseases. The investigators disclosed no conflicts.
Hepatitis C virus (HCV) particles are of lowest density and most infectious early in the course of infection, based on findings from a study of chimeric mice.
Over time, however, viral density became more heterogeneous and infectivity fell, reported Ursula Andreo, PhD, of Rockefeller University, New York, with her coinvestigators. A diet of 10% sucrose, which in rats induces hepatic secretion of very-low-density lipoprotein (VLDL), caused HCV particles to become slightly lower density and more infectious in the mice, the researchers reported. Although the shift was “minor,” it “correlated with a trend toward enhanced triglyceride and cholesterol levels in the same fractions,” they wrote. They recommended studying high-fat diets to determine whether altering the VLDL secretion pathway affects the biophysical properties of HCV. “A high-fat diet might have a more significant impact on the lipoprotein profile in this humanized mouse model,” they wrote in Cellular and Molecular Gastroenterology and Hepatology (2017 Jul;4[3]:405-17).
Because HCV tends to associate with lipoproteins, it shows a range of buoyant densities in the blood of infected patients. The “entry, replication, and assembly [of the virion] are linked closely to host lipid and lipoprotein metabolism,” wrote Dr. Andreo and her colleagues.
They created an in vivo model to study the buoyant density and infectivity of HCV particles, as well as their interaction with lipoproteins, by grafting human hepatocytes into the livers of immunodeficient mice that were homozygous recessive for fumarylacetoacetate hydrolase. Next, they infected 13 of these chimeric mice with J6-JFH1, an HCV strain that can establish long-term infections in mice that have human liver grafts (Proc Natl Acad Sci USA. 2006;103[10]:3805-9). The human liver xenograft reconstituted the FAH gene, restoring triglycerides to normal levels in the chimeric mice and creating a suitable “humanlike” model of lipoprotein metabolism, the investigators wrote.
Density fractionation of infectious mouse serum revealed higher infectivity in the low-density fractions soon after infection, which also has been observed in a human liver chimeric mouse model of severe combined immunodeficiency disease, they added. In the HCV model, the human liver grafts were conserved 5 weeks after infection, and the mice had a lower proportion of lighter, infectious HCV particles.
The researchers lacked sufficient material to directly study the composition of virions or detect viral proteins in the various density fractions. However, they determined that apolipoprotein C1 was the lightest fraction and that apolipoprotein E was mainly found in the five lightest fractions. Both these apolipoproteins are “essential factors of HCV infectivity,” and neither redistributed over time, they said. They suggested using immunoelectron microscopy or mass spectrometry to study the nature and infectivity of viral particles further.
In humans, ingesting a high-fat milkshake increases detectable HCV RNA in the VLDL fraction, the researchers noted. In rodents, a sucrose diet also has been found to increase VLDL lipidation and secretion, so they gave five of the infected chimeric mice drinking water containing 10% sucrose. After 5 weeks, these mice had increased infectivity and higher levels of triglycerides and cholesterol, but the effect was small and disappeared after the sucrose was withdrawn.
HCV “circulates as a population of particles of light, as well as dense, buoyant densities, and both are infectious,” the researchers concluded. “Changes in diet, as well as conditions such as fasting and feeding, affect the distribution of HCV buoyant density gradients.”
Funders included the National Institutes of Health and the American Association for the Study of Liver Diseases. The investigators disclosed no conflicts.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The biophysical properties of the hepatitis C virus evolve during the course of infection and shift with dietary changes.
Major finding: Density fractionation of infectious mouse serum showed higher infectivity in the low-density fractions soon after infection, but heterogeneity subsequently increased while infectivity decreased. A 5-week diet of 10% sucrose produced a minor shift toward infectivity that correlated with redistribution of triglycerides and cholesterol.
Data source: A study of 13 human liver chimeric mice.
Disclosures: Funders included the National Institutes of Health and the American Association for the Study of Liver Diseases. The investigators disclosed no conflicts.
VA shares its best practices to achieve HCV ‘cascade of cure’
The U.S. Department of Veterans Affairs (VA) cares for more patients with hepatitis C virus than any other care provider in the country, and has achieved a rapid and sharp reduction in hepatitis C virus (HCV) infection among veterans over the past 3 years.
The VA has treated more than 92,000 HCV-infected individuals since the advent of oral direct-acting antiviral (DAA) therapy in 2014. The number of veterans with HCV who were eligible for treatment was 168,000 in 2014 and 51,000 in July 2017, according to an article in Annals of Internal Medicine (2017 Sep 26. doi: 10.7326/M17-1073).
Given that success in HCV treatment, with a cure rate that exceeds 90% for those prescribed DAAs, the VA is well positioned to share best practices with other organizations, according to Pamela S. Belperio, PharmD, and her coauthors. The best practices harmonize with the recently outlined national strategy to eliminate hepatitis B and C from the National Academies of Sciences, Engineering, and Medicine.
“The leveraging of health systems data transforms numbers into knowledge” that is used both by individual providers and the VA as a whole, wrote Dr. Belperio, national public health pharmacist in the VA’s public health division, and her coauthors.
Identifying veterans who were infected with HCV is simplified by means of electronic point-of-care reminders that prompt providers to conduct HCV risk assessment and testing. Veterans eligible for testing also receive automated letters that serve as a laboratory order form for HCV testing at a VA laboratory.
Adding HCV birth cohort screening as a performance measure and recommending reflex confirmatory HCV RNA testing for positive antibody tests were additional initiatives that contributed to the 3%-4% annual increase in veterans receiving HCV testing, “substantially higher than in other health care systems,” wrote Dr. Belperio and her colleagues.
To respect regional variations in practice within the VA system, multidisciplinary innovation teams meet in each region to identify opportunities for improving and streamlining HCV testing and treatment, using lean process improvement techniques. Regions also share innovations with each other.
The VA used a multipronged approach to raise awareness about HCV testing and treatment among VA health care providers and veterans. Provider reach has been expanded by extensive use of telemedicine, including real-time video calls between providers and patients or other providers at remote locations. Those telemedicine initiatives allow pharmacists and mental health providers to lend their expertise to physicians and other providers, who are themselves directly caring for HCV-infected individuals.
Patients at more than half of VA facilities receive care from physician assistants, nurse practitioners, and clinical pharmacy specialists, “who have been recognized as delivering the same quality of care and providing more timely access to HCV treatment,” wrote Dr. Belperio and her collaborators. Expanding the use of advanced practice providers allows more targeted use of specialists, and “is an important practice that can be adapted into other health care systems,” they noted.
Non–evidence-based criteria for HCV treatment eligibility remain a major barrier for HCV-infected individuals nationwide, despite VA studies showing “cure rates among veterans with alcohol, substance use, and mental health disorders that are similar to cure rates in those without these conditions,” said Dr. Belperio and her colleagues.
Within the VA, involving alcohol and substance use specialists, mental health providers, case managers, and social workers in the patient’s care team is an approach that can increase adherence and up the chance for a cure among the most vulnerable veterans.
The VA has been able to negotiate reduced pricing for the expensive DAAs, and has continued to receive additional appropriations to fund DAAs and other HCV-related resources. “Financing for HCV treatment and infrastructure resources, coupled with reduced drug prices, has been paramount to the VA’s success in curing HCV infection,” said Dr. Belperio and her colleagues.
However, they added, individual private insurers may not reap the benefits of achieving sweeping HCV cures within their particular patient panel, because patients frequently switch insurers. Still, “consistent leveraging of drug prices and removal of restrictions to HCV treatment among all insurers would help assuage this gap,” they wrote.
Dr. Belperio described the VA’s vision of a “hepatitis C cascade of cure” that occurs when individuals with chronic HCV are identified, linked to care, treated with DAAs, and achieve sustained viral response. The comprehensive strategies employed by the VA have meant that, from 2014 to 2016, the percentage of HCV-infected individuals who have been linked to care and treatment increased from 27% to 59%. Of those treated, SVR rates have risen from 51% to 84% during the same period, said Dr. Belperio and her coauthors.
It will not be easy to extend that success into the nongovernment sector, the article’s authors acknowledged. Still, “the VA recognizes the resources necessary to realize this goal and the innovations that could make it possible, and is poised to extend best practices to other health care organizations and providers delivering HCV care.”
None of the study authors reported conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
The U.S. Department of Veterans Affairs (VA) cares for more patients with hepatitis C virus than any other care provider in the country, and has achieved a rapid and sharp reduction in hepatitis C virus (HCV) infection among veterans over the past 3 years.
The VA has treated more than 92,000 HCV-infected individuals since the advent of oral direct-acting antiviral (DAA) therapy in 2014. The number of veterans with HCV who were eligible for treatment was 168,000 in 2014 and 51,000 in July 2017, according to an article in Annals of Internal Medicine (2017 Sep 26. doi: 10.7326/M17-1073).
Given that success in HCV treatment, with a cure rate that exceeds 90% for those prescribed DAAs, the VA is well positioned to share best practices with other organizations, according to Pamela S. Belperio, PharmD, and her coauthors. The best practices harmonize with the recently outlined national strategy to eliminate hepatitis B and C from the National Academies of Sciences, Engineering, and Medicine.
“The leveraging of health systems data transforms numbers into knowledge” that is used both by individual providers and the VA as a whole, wrote Dr. Belperio, national public health pharmacist in the VA’s public health division, and her coauthors.
Identifying veterans who were infected with HCV is simplified by means of electronic point-of-care reminders that prompt providers to conduct HCV risk assessment and testing. Veterans eligible for testing also receive automated letters that serve as a laboratory order form for HCV testing at a VA laboratory.
Adding HCV birth cohort screening as a performance measure and recommending reflex confirmatory HCV RNA testing for positive antibody tests were additional initiatives that contributed to the 3%-4% annual increase in veterans receiving HCV testing, “substantially higher than in other health care systems,” wrote Dr. Belperio and her colleagues.
To respect regional variations in practice within the VA system, multidisciplinary innovation teams meet in each region to identify opportunities for improving and streamlining HCV testing and treatment, using lean process improvement techniques. Regions also share innovations with each other.
The VA used a multipronged approach to raise awareness about HCV testing and treatment among VA health care providers and veterans. Provider reach has been expanded by extensive use of telemedicine, including real-time video calls between providers and patients or other providers at remote locations. Those telemedicine initiatives allow pharmacists and mental health providers to lend their expertise to physicians and other providers, who are themselves directly caring for HCV-infected individuals.
Patients at more than half of VA facilities receive care from physician assistants, nurse practitioners, and clinical pharmacy specialists, “who have been recognized as delivering the same quality of care and providing more timely access to HCV treatment,” wrote Dr. Belperio and her collaborators. Expanding the use of advanced practice providers allows more targeted use of specialists, and “is an important practice that can be adapted into other health care systems,” they noted.
Non–evidence-based criteria for HCV treatment eligibility remain a major barrier for HCV-infected individuals nationwide, despite VA studies showing “cure rates among veterans with alcohol, substance use, and mental health disorders that are similar to cure rates in those without these conditions,” said Dr. Belperio and her colleagues.
Within the VA, involving alcohol and substance use specialists, mental health providers, case managers, and social workers in the patient’s care team is an approach that can increase adherence and up the chance for a cure among the most vulnerable veterans.
The VA has been able to negotiate reduced pricing for the expensive DAAs, and has continued to receive additional appropriations to fund DAAs and other HCV-related resources. “Financing for HCV treatment and infrastructure resources, coupled with reduced drug prices, has been paramount to the VA’s success in curing HCV infection,” said Dr. Belperio and her colleagues.
However, they added, individual private insurers may not reap the benefits of achieving sweeping HCV cures within their particular patient panel, because patients frequently switch insurers. Still, “consistent leveraging of drug prices and removal of restrictions to HCV treatment among all insurers would help assuage this gap,” they wrote.
Dr. Belperio described the VA’s vision of a “hepatitis C cascade of cure” that occurs when individuals with chronic HCV are identified, linked to care, treated with DAAs, and achieve sustained viral response. The comprehensive strategies employed by the VA have meant that, from 2014 to 2016, the percentage of HCV-infected individuals who have been linked to care and treatment increased from 27% to 59%. Of those treated, SVR rates have risen from 51% to 84% during the same period, said Dr. Belperio and her coauthors.
It will not be easy to extend that success into the nongovernment sector, the article’s authors acknowledged. Still, “the VA recognizes the resources necessary to realize this goal and the innovations that could make it possible, and is poised to extend best practices to other health care organizations and providers delivering HCV care.”
None of the study authors reported conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
The U.S. Department of Veterans Affairs (VA) cares for more patients with hepatitis C virus than any other care provider in the country, and has achieved a rapid and sharp reduction in hepatitis C virus (HCV) infection among veterans over the past 3 years.
The VA has treated more than 92,000 HCV-infected individuals since the advent of oral direct-acting antiviral (DAA) therapy in 2014. The number of veterans with HCV who were eligible for treatment was 168,000 in 2014 and 51,000 in July 2017, according to an article in Annals of Internal Medicine (2017 Sep 26. doi: 10.7326/M17-1073).
Given that success in HCV treatment, with a cure rate that exceeds 90% for those prescribed DAAs, the VA is well positioned to share best practices with other organizations, according to Pamela S. Belperio, PharmD, and her coauthors. The best practices harmonize with the recently outlined national strategy to eliminate hepatitis B and C from the National Academies of Sciences, Engineering, and Medicine.
“The leveraging of health systems data transforms numbers into knowledge” that is used both by individual providers and the VA as a whole, wrote Dr. Belperio, national public health pharmacist in the VA’s public health division, and her coauthors.
Identifying veterans who were infected with HCV is simplified by means of electronic point-of-care reminders that prompt providers to conduct HCV risk assessment and testing. Veterans eligible for testing also receive automated letters that serve as a laboratory order form for HCV testing at a VA laboratory.
Adding HCV birth cohort screening as a performance measure and recommending reflex confirmatory HCV RNA testing for positive antibody tests were additional initiatives that contributed to the 3%-4% annual increase in veterans receiving HCV testing, “substantially higher than in other health care systems,” wrote Dr. Belperio and her colleagues.
To respect regional variations in practice within the VA system, multidisciplinary innovation teams meet in each region to identify opportunities for improving and streamlining HCV testing and treatment, using lean process improvement techniques. Regions also share innovations with each other.
The VA used a multipronged approach to raise awareness about HCV testing and treatment among VA health care providers and veterans. Provider reach has been expanded by extensive use of telemedicine, including real-time video calls between providers and patients or other providers at remote locations. Those telemedicine initiatives allow pharmacists and mental health providers to lend their expertise to physicians and other providers, who are themselves directly caring for HCV-infected individuals.
Patients at more than half of VA facilities receive care from physician assistants, nurse practitioners, and clinical pharmacy specialists, “who have been recognized as delivering the same quality of care and providing more timely access to HCV treatment,” wrote Dr. Belperio and her collaborators. Expanding the use of advanced practice providers allows more targeted use of specialists, and “is an important practice that can be adapted into other health care systems,” they noted.
Non–evidence-based criteria for HCV treatment eligibility remain a major barrier for HCV-infected individuals nationwide, despite VA studies showing “cure rates among veterans with alcohol, substance use, and mental health disorders that are similar to cure rates in those without these conditions,” said Dr. Belperio and her colleagues.
Within the VA, involving alcohol and substance use specialists, mental health providers, case managers, and social workers in the patient’s care team is an approach that can increase adherence and up the chance for a cure among the most vulnerable veterans.
The VA has been able to negotiate reduced pricing for the expensive DAAs, and has continued to receive additional appropriations to fund DAAs and other HCV-related resources. “Financing for HCV treatment and infrastructure resources, coupled with reduced drug prices, has been paramount to the VA’s success in curing HCV infection,” said Dr. Belperio and her colleagues.
However, they added, individual private insurers may not reap the benefits of achieving sweeping HCV cures within their particular patient panel, because patients frequently switch insurers. Still, “consistent leveraging of drug prices and removal of restrictions to HCV treatment among all insurers would help assuage this gap,” they wrote.
Dr. Belperio described the VA’s vision of a “hepatitis C cascade of cure” that occurs when individuals with chronic HCV are identified, linked to care, treated with DAAs, and achieve sustained viral response. The comprehensive strategies employed by the VA have meant that, from 2014 to 2016, the percentage of HCV-infected individuals who have been linked to care and treatment increased from 27% to 59%. Of those treated, SVR rates have risen from 51% to 84% during the same period, said Dr. Belperio and her coauthors.
It will not be easy to extend that success into the nongovernment sector, the article’s authors acknowledged. Still, “the VA recognizes the resources necessary to realize this goal and the innovations that could make it possible, and is poised to extend best practices to other health care organizations and providers delivering HCV care.”
None of the study authors reported conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
FROM ANNALS OF INTERNAL MEDICINE
FDA warns of risks of excessive dosing of obeticholic acid
The Food and Drug Administration advised on Sept. 21 that incorrect excessive dosing of the liver disease medicine obeticholic acid (Ocaliva) creates an increased risk of serious liver injury and death. The agency recommends closer monitoring of dosages and following the current label’s recommendations.
Obeticholic acid is used to treat primary biliary cholangitis. Patients taking the drug should first be tested for their baseline liver function so that the effects of the drug can be monitored. The level of liver impairment determines the recommended dosage: Those with moderate to severe impairment should start by taking 5 mg weekly (with a possible increase to 10 mg weekly) instead of the standard 5 mg daily. Those who start at the standard dose and progress to moderate or severe liver impairment can have their dosage reduced or can discontinue the drug altogether.
The Food and Drug Administration advised on Sept. 21 that incorrect excessive dosing of the liver disease medicine obeticholic acid (Ocaliva) creates an increased risk of serious liver injury and death. The agency recommends closer monitoring of dosages and following the current label’s recommendations.
Obeticholic acid is used to treat primary biliary cholangitis. Patients taking the drug should first be tested for their baseline liver function so that the effects of the drug can be monitored. The level of liver impairment determines the recommended dosage: Those with moderate to severe impairment should start by taking 5 mg weekly (with a possible increase to 10 mg weekly) instead of the standard 5 mg daily. Those who start at the standard dose and progress to moderate or severe liver impairment can have their dosage reduced or can discontinue the drug altogether.
The Food and Drug Administration advised on Sept. 21 that incorrect excessive dosing of the liver disease medicine obeticholic acid (Ocaliva) creates an increased risk of serious liver injury and death. The agency recommends closer monitoring of dosages and following the current label’s recommendations.
Obeticholic acid is used to treat primary biliary cholangitis. Patients taking the drug should first be tested for their baseline liver function so that the effects of the drug can be monitored. The level of liver impairment determines the recommended dosage: Those with moderate to severe impairment should start by taking 5 mg weekly (with a possible increase to 10 mg weekly) instead of the standard 5 mg daily. Those who start at the standard dose and progress to moderate or severe liver impairment can have their dosage reduced or can discontinue the drug altogether.
Statin use reduces death and decompensation in cirrhosis patients
Statin use in cirrhosis patients lowers the risk of death, Dr. Ulrich Bang and his associates reported in a retrospective case-cohort analysis.
After applying selection criteria, the investigators identified 5,417 patients with alcoholic cirrhosis from the Danish National Patient Registry based on the International Classification of Diseases, 10th revision, Danish National Prescription Registry based on the Anatomical Therapeutic Chemical, Danish Register of Causes of Death, and the Danish Civil Registration System from 1995 through 2014.
To conduct statistical analysis, the 5,417 were split into two groups – the first being an unmatched cohort. The unmatched cohort, which included all 5,417 patients, was not statistically balanced between statin vs. nonstatin users. Of the 5,417 patients, 744 were selected into a matched cohort using propensity scores (PS). This group was statistically balanced with one patient using statins being compared with two nonstatin users.
The unmatched group of 5,417 patients had 794 members (15%) who had used statins at least twice in a 30-day time period between first reported use and last reported use.
“In the unmatched cohort, we found mortality rates of 96 (86-106) per 1,000 [patient-years] for patients in therapy with statins and 121 (117-125) for the nonstatin patients and a [hazard ratio] of 0.66 (0.59-0.75) for statins vs. no statins,” the researchers wrote.
The PS-matched group’s “mortality rates were 88 (73-105) and 127 (114-142) for statin vs. nonstatin patients, respectively, and the HR was 0.57 (0.45-0.71)” (Aliment Pharmacol Ther. 2017 Oct;46[7]:673-80).
When analyzing decompensation, the rate of decompensation was 135 (114-160) per 1,000 person-years in those who had used statins for treatment. Among patients who had not undergone statin treatment, the rate was 361 (348-375) per 1,000 person-years. These results corresponded to an HR rate of 0.29 in an adjusted analysis. This varied from the PS-matched group, which experienced decompensation rates of 133 (104-170) for statin users and 234 (202-272) for nonstatin users.
In a subcohort analysis of 387 patients suffering from cirrhosis who had received consistent doses of statins, they had a reduced risk of death compared to an unmatched group of 4,975 patients who had not used statins. Patients receiving consistent doses of statins were said to be in a “stable” state. Ultimately, it was found for each 25% increase in stable state statin dosing, the risk of death decreased by 16%.
“The use of statins was associated with a reduced risk of decompensation and death in patients with alcoholic cirrhosis and the association between use of statins and death was more pronounced in patients with cirrhosis compared with noncirrhotic controls,” the investigators noted. “No convincing dose-response association was found but patients with a more constant exposure to statins may benefit more from the treatment.”
One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
Statin use in cirrhosis patients lowers the risk of death, Dr. Ulrich Bang and his associates reported in a retrospective case-cohort analysis.
After applying selection criteria, the investigators identified 5,417 patients with alcoholic cirrhosis from the Danish National Patient Registry based on the International Classification of Diseases, 10th revision, Danish National Prescription Registry based on the Anatomical Therapeutic Chemical, Danish Register of Causes of Death, and the Danish Civil Registration System from 1995 through 2014.
To conduct statistical analysis, the 5,417 were split into two groups – the first being an unmatched cohort. The unmatched cohort, which included all 5,417 patients, was not statistically balanced between statin vs. nonstatin users. Of the 5,417 patients, 744 were selected into a matched cohort using propensity scores (PS). This group was statistically balanced with one patient using statins being compared with two nonstatin users.
The unmatched group of 5,417 patients had 794 members (15%) who had used statins at least twice in a 30-day time period between first reported use and last reported use.
“In the unmatched cohort, we found mortality rates of 96 (86-106) per 1,000 [patient-years] for patients in therapy with statins and 121 (117-125) for the nonstatin patients and a [hazard ratio] of 0.66 (0.59-0.75) for statins vs. no statins,” the researchers wrote.
The PS-matched group’s “mortality rates were 88 (73-105) and 127 (114-142) for statin vs. nonstatin patients, respectively, and the HR was 0.57 (0.45-0.71)” (Aliment Pharmacol Ther. 2017 Oct;46[7]:673-80).
When analyzing decompensation, the rate of decompensation was 135 (114-160) per 1,000 person-years in those who had used statins for treatment. Among patients who had not undergone statin treatment, the rate was 361 (348-375) per 1,000 person-years. These results corresponded to an HR rate of 0.29 in an adjusted analysis. This varied from the PS-matched group, which experienced decompensation rates of 133 (104-170) for statin users and 234 (202-272) for nonstatin users.
In a subcohort analysis of 387 patients suffering from cirrhosis who had received consistent doses of statins, they had a reduced risk of death compared to an unmatched group of 4,975 patients who had not used statins. Patients receiving consistent doses of statins were said to be in a “stable” state. Ultimately, it was found for each 25% increase in stable state statin dosing, the risk of death decreased by 16%.
“The use of statins was associated with a reduced risk of decompensation and death in patients with alcoholic cirrhosis and the association between use of statins and death was more pronounced in patients with cirrhosis compared with noncirrhotic controls,” the investigators noted. “No convincing dose-response association was found but patients with a more constant exposure to statins may benefit more from the treatment.”
One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
Statin use in cirrhosis patients lowers the risk of death, Dr. Ulrich Bang and his associates reported in a retrospective case-cohort analysis.
After applying selection criteria, the investigators identified 5,417 patients with alcoholic cirrhosis from the Danish National Patient Registry based on the International Classification of Diseases, 10th revision, Danish National Prescription Registry based on the Anatomical Therapeutic Chemical, Danish Register of Causes of Death, and the Danish Civil Registration System from 1995 through 2014.
To conduct statistical analysis, the 5,417 were split into two groups – the first being an unmatched cohort. The unmatched cohort, which included all 5,417 patients, was not statistically balanced between statin vs. nonstatin users. Of the 5,417 patients, 744 were selected into a matched cohort using propensity scores (PS). This group was statistically balanced with one patient using statins being compared with two nonstatin users.
The unmatched group of 5,417 patients had 794 members (15%) who had used statins at least twice in a 30-day time period between first reported use and last reported use.
“In the unmatched cohort, we found mortality rates of 96 (86-106) per 1,000 [patient-years] for patients in therapy with statins and 121 (117-125) for the nonstatin patients and a [hazard ratio] of 0.66 (0.59-0.75) for statins vs. no statins,” the researchers wrote.
The PS-matched group’s “mortality rates were 88 (73-105) and 127 (114-142) for statin vs. nonstatin patients, respectively, and the HR was 0.57 (0.45-0.71)” (Aliment Pharmacol Ther. 2017 Oct;46[7]:673-80).
When analyzing decompensation, the rate of decompensation was 135 (114-160) per 1,000 person-years in those who had used statins for treatment. Among patients who had not undergone statin treatment, the rate was 361 (348-375) per 1,000 person-years. These results corresponded to an HR rate of 0.29 in an adjusted analysis. This varied from the PS-matched group, which experienced decompensation rates of 133 (104-170) for statin users and 234 (202-272) for nonstatin users.
In a subcohort analysis of 387 patients suffering from cirrhosis who had received consistent doses of statins, they had a reduced risk of death compared to an unmatched group of 4,975 patients who had not used statins. Patients receiving consistent doses of statins were said to be in a “stable” state. Ultimately, it was found for each 25% increase in stable state statin dosing, the risk of death decreased by 16%.
“The use of statins was associated with a reduced risk of decompensation and death in patients with alcoholic cirrhosis and the association between use of statins and death was more pronounced in patients with cirrhosis compared with noncirrhotic controls,” the investigators noted. “No convincing dose-response association was found but patients with a more constant exposure to statins may benefit more from the treatment.”
One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Key clinical point:
Major finding: As likelihood of stable state increases by 25% with statin dose, death risk decreases by 16%.
Data source: A retrospective case-cohort analysis of information obtained from registrants in the Danish National Patient Registry based on International Classification of Diseases, 10th revision (ICD-10), Danish National Prescription Registry based on the Anatomical Therapeutic Chemical (ATC), Danish Register of Causes of Death, and the Danish Civil Registration System between the years 1995 and 2014.
Disclosures: One coauthor had previously served as an adviser to Ferring Pharmaceuticals and as a speaker for Norgine Danmark. There were no other financial disclosures to report.
Clinical trial: Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis
Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis is an observational study recruiting people with a history of PBC and their family members.
The trial will investigate whether or not there is a genetic factor in the development of PBC. Blood and stool samples will be taken from PBC patients and family members of PBC patients and analyzed. If a genetic component is discovered, it will add to current knowledge of how PBC and other adult chronic cholestatic liver diseases develop, as well as suggest new approaches for prevention, diagnosis, and treatment.
Individuals will be included in the study if they are aged 18-90 years old and have a history of PBC or if they are first-degree relatives of someone with PBC. Patients with PBC who have undergone a liver transplant are not excluded.
The primary outcome measure of the study is the mapping of genes that may make patients susceptible to adult chronic cholestatic liver diseases such as PBC.
The study will be completed in December 2025. About 1,500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis is an observational study recruiting people with a history of PBC and their family members.
The trial will investigate whether or not there is a genetic factor in the development of PBC. Blood and stool samples will be taken from PBC patients and family members of PBC patients and analyzed. If a genetic component is discovered, it will add to current knowledge of how PBC and other adult chronic cholestatic liver diseases develop, as well as suggest new approaches for prevention, diagnosis, and treatment.
Individuals will be included in the study if they are aged 18-90 years old and have a history of PBC or if they are first-degree relatives of someone with PBC. Patients with PBC who have undergone a liver transplant are not excluded.
The primary outcome measure of the study is the mapping of genes that may make patients susceptible to adult chronic cholestatic liver diseases such as PBC.
The study will be completed in December 2025. About 1,500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
Understanding the Genetic Predisposition to the Development of Primary Biliary Cirrhosis is an observational study recruiting people with a history of PBC and their family members.
The trial will investigate whether or not there is a genetic factor in the development of PBC. Blood and stool samples will be taken from PBC patients and family members of PBC patients and analyzed. If a genetic component is discovered, it will add to current knowledge of how PBC and other adult chronic cholestatic liver diseases develop, as well as suggest new approaches for prevention, diagnosis, and treatment.
Individuals will be included in the study if they are aged 18-90 years old and have a history of PBC or if they are first-degree relatives of someone with PBC. Patients with PBC who have undergone a liver transplant are not excluded.
The primary outcome measure of the study is the mapping of genes that may make patients susceptible to adult chronic cholestatic liver diseases such as PBC.
The study will be completed in December 2025. About 1,500 people are expected to be included in the final analysis.
Find more information at the study page on Clinicaltrials.gov.
Study findings support uncapping MELD score
Uncapping the current Model for End-Stage Liver Disease score may provide a better path toward making sure that patients most in need of a liver transplant get one, results from a large, long-term analysis showed.
Established in 2002, the Model for End-Stage Liver Disease (MELD) scoring system “was arbitrarily capped at 40 based on the presumption that transplanting patients with MELD greater than 40 would be futile,” researchers led by Mitra K. Nadim, MD, reported in the September 2017 issue of the Journal of Hepatology (67[3]:517-25. doi: 10.1016/j.jhep.2017.04.022). “As a result, patients with MELD greater than 40 receive the same priority as patients with MELD of 40, differentiated only by their time on the wait list.”
The mean age of patients was 53 years, and most were white men. The researchers reported that 3.3% of wait-listed patients had a MELD score of 40 or greater at registration, while 7.3% had MELD scores increase to 40 or greater after wait-list registration. In all, 30,369 patients (40.6%) underwent liver transplantation during the study period. Of these, 2,615 (8.6%) had a MELD score of 40 or greater at the time of their procedure. Compared with patients who had a MELD score of 40, those who had a MELD score of greater than 40 had an increased risk of death within 30 days, and the risk increased with rising scores. Specifically, the hazard ratio was 1.4 for those with a MELD score of 40-44, an HR of 2.6 for those with a MELD score of 45-49, and an HR of 5.0 for those with a MELD score of 50 or greater. There were no survival differences between the two groups at 1 and 3 years, but there was a survival benefit associated with liver transplantation as the MELD score increased above 40, the investigators reported.
“The arbitrary capping of the MELD at 40 has resulted in an unforeseen lack of objectivity for patients with MELD [score of greater than] 40 who are unjustifiably disadvantaged in a system designed to prioritize patients most in need,” they concluded. “Uncapping the MELD score is another necessary step in the evolution of liver allocation and patient prioritization.” They added that a significant number of patients with a MELD score of 40 or greater “likely suffer from acute-on-chronic liver failure (ACLF), a recently recognized syndrome characterized by acute liver decompensation, other organ system failures, and high short-term mortality in patients with end-stage liver disease. A capped MELD score fails to capture acute liver decompensation adequately, and data suggest that a model incorporating sudden increases in MELD predicts wait-list mortality better.”
Dr. Nadim and her associates acknowledged certain limitations of the study, including its retrospective design “and that factors relating to a patient’s suitability for transplantation or to a center’s decision to accept or reject a liver allograft, both of which affect graft and patient survival, were not accounted for in the analysis. Despite these limitations, the study results have important implications for improving the current liver allocation policy.”
The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
PRIMARY SOURCE: J Hepatol. 2017;67[3]:517-25. doi: 1016/j.jhep.2017.04.022
Uncapping the current Model for End-Stage Liver Disease score may provide a better path toward making sure that patients most in need of a liver transplant get one, results from a large, long-term analysis showed.
Established in 2002, the Model for End-Stage Liver Disease (MELD) scoring system “was arbitrarily capped at 40 based on the presumption that transplanting patients with MELD greater than 40 would be futile,” researchers led by Mitra K. Nadim, MD, reported in the September 2017 issue of the Journal of Hepatology (67[3]:517-25. doi: 10.1016/j.jhep.2017.04.022). “As a result, patients with MELD greater than 40 receive the same priority as patients with MELD of 40, differentiated only by their time on the wait list.”
The mean age of patients was 53 years, and most were white men. The researchers reported that 3.3% of wait-listed patients had a MELD score of 40 or greater at registration, while 7.3% had MELD scores increase to 40 or greater after wait-list registration. In all, 30,369 patients (40.6%) underwent liver transplantation during the study period. Of these, 2,615 (8.6%) had a MELD score of 40 or greater at the time of their procedure. Compared with patients who had a MELD score of 40, those who had a MELD score of greater than 40 had an increased risk of death within 30 days, and the risk increased with rising scores. Specifically, the hazard ratio was 1.4 for those with a MELD score of 40-44, an HR of 2.6 for those with a MELD score of 45-49, and an HR of 5.0 for those with a MELD score of 50 or greater. There were no survival differences between the two groups at 1 and 3 years, but there was a survival benefit associated with liver transplantation as the MELD score increased above 40, the investigators reported.
“The arbitrary capping of the MELD at 40 has resulted in an unforeseen lack of objectivity for patients with MELD [score of greater than] 40 who are unjustifiably disadvantaged in a system designed to prioritize patients most in need,” they concluded. “Uncapping the MELD score is another necessary step in the evolution of liver allocation and patient prioritization.” They added that a significant number of patients with a MELD score of 40 or greater “likely suffer from acute-on-chronic liver failure (ACLF), a recently recognized syndrome characterized by acute liver decompensation, other organ system failures, and high short-term mortality in patients with end-stage liver disease. A capped MELD score fails to capture acute liver decompensation adequately, and data suggest that a model incorporating sudden increases in MELD predicts wait-list mortality better.”
Dr. Nadim and her associates acknowledged certain limitations of the study, including its retrospective design “and that factors relating to a patient’s suitability for transplantation or to a center’s decision to accept or reject a liver allograft, both of which affect graft and patient survival, were not accounted for in the analysis. Despite these limitations, the study results have important implications for improving the current liver allocation policy.”
The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
PRIMARY SOURCE: J Hepatol. 2017;67[3]:517-25. doi: 1016/j.jhep.2017.04.022
Uncapping the current Model for End-Stage Liver Disease score may provide a better path toward making sure that patients most in need of a liver transplant get one, results from a large, long-term analysis showed.
Established in 2002, the Model for End-Stage Liver Disease (MELD) scoring system “was arbitrarily capped at 40 based on the presumption that transplanting patients with MELD greater than 40 would be futile,” researchers led by Mitra K. Nadim, MD, reported in the September 2017 issue of the Journal of Hepatology (67[3]:517-25. doi: 10.1016/j.jhep.2017.04.022). “As a result, patients with MELD greater than 40 receive the same priority as patients with MELD of 40, differentiated only by their time on the wait list.”
The mean age of patients was 53 years, and most were white men. The researchers reported that 3.3% of wait-listed patients had a MELD score of 40 or greater at registration, while 7.3% had MELD scores increase to 40 or greater after wait-list registration. In all, 30,369 patients (40.6%) underwent liver transplantation during the study period. Of these, 2,615 (8.6%) had a MELD score of 40 or greater at the time of their procedure. Compared with patients who had a MELD score of 40, those who had a MELD score of greater than 40 had an increased risk of death within 30 days, and the risk increased with rising scores. Specifically, the hazard ratio was 1.4 for those with a MELD score of 40-44, an HR of 2.6 for those with a MELD score of 45-49, and an HR of 5.0 for those with a MELD score of 50 or greater. There were no survival differences between the two groups at 1 and 3 years, but there was a survival benefit associated with liver transplantation as the MELD score increased above 40, the investigators reported.
“The arbitrary capping of the MELD at 40 has resulted in an unforeseen lack of objectivity for patients with MELD [score of greater than] 40 who are unjustifiably disadvantaged in a system designed to prioritize patients most in need,” they concluded. “Uncapping the MELD score is another necessary step in the evolution of liver allocation and patient prioritization.” They added that a significant number of patients with a MELD score of 40 or greater “likely suffer from acute-on-chronic liver failure (ACLF), a recently recognized syndrome characterized by acute liver decompensation, other organ system failures, and high short-term mortality in patients with end-stage liver disease. A capped MELD score fails to capture acute liver decompensation adequately, and data suggest that a model incorporating sudden increases in MELD predicts wait-list mortality better.”
Dr. Nadim and her associates acknowledged certain limitations of the study, including its retrospective design “and that factors relating to a patient’s suitability for transplantation or to a center’s decision to accept or reject a liver allograft, both of which affect graft and patient survival, were not accounted for in the analysis. Despite these limitations, the study results have important implications for improving the current liver allocation policy.”
The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
PRIMARY SOURCE: J Hepatol. 2017;67[3]:517-25. doi: 1016/j.jhep.2017.04.022
FROM THE JOURNAL OF HEPATOLOGY
Key clinical point: .
Major finding: Compared with patients who had a MELD score of 40, the increased risk of death within 30 days was 1.4 for those with a MELD score of 40-44.
Study details: A retrospective analysis of 65,776 patients listed for a liver transplant from February 2002 to December 2012.
Disclosures: The study was supported in part by the Health Resources and Services Administration. The researchers reported having no relevant financial disclosures.
Source: Mitra K. Nadim, MD, et al. Inequity in organ allocation for patients awaiting liver transplantation: Rationale for uncapping the model for end-stage liver disease. J Hepatol. 2017;67(3):517-25. doi: 10.1016/j.jhep.2017.04.022.
CREST syndrome and PBC are often associated
Primary biliary cholangitis can be associated with limited cutaneous systemic sclerosis (CREST syndrome), according to a clinical communication to the editor from Amirali Kiyani, MD, and Shannon Ursu, MD.
In their case study, a 56-year-old woman presented to the emergency department with a syncopal episode. The patient’s medical history included primary biliary cholangitis (PBC), breast cancer status post lumpectomy and chemoradiation, gastroesophageal reflux disease, Raynaud’s phenomenon, and multiple episodes of gastrointestinal bleeding. Vital signs were normal at the time of admission.
After examination and testing, the patient was found to have low serum complement levels and elevated C-reactive protein. Anti-Scl 70 antibody, SSA, and SSB antibody were negative, and thyroid-stimulating hormone and antitransglutaminase antibodies were normal. No evidence of heart failure or pulmonary hypertension was seen in a transthoracic echocardiogram, and the patient was diagnosed with limited cutaneous systemic sclerosis.
Sjögren’s syndrome and autoimmune thyroiditis are the most common extrahepatic autoimmune disorders associated with PBC, but PBC is associated with CREST syndrome in 1%-6% of cases, according to the literature the investigators reviewed, they said.
“Primary biliary cholangitis is commonly associated with extrahepatic autoimmune disorders such as limited cutaneous systemic sclerosis. … Screening for these autoimmune disorders can prevent further morbidity and keep patients viable candidates for liver transplant,” they concluded.
Find the full clinical communication in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.05.019).
This story was updated on 9/13/2017.
Primary biliary cholangitis can be associated with limited cutaneous systemic sclerosis (CREST syndrome), according to a clinical communication to the editor from Amirali Kiyani, MD, and Shannon Ursu, MD.
In their case study, a 56-year-old woman presented to the emergency department with a syncopal episode. The patient’s medical history included primary biliary cholangitis (PBC), breast cancer status post lumpectomy and chemoradiation, gastroesophageal reflux disease, Raynaud’s phenomenon, and multiple episodes of gastrointestinal bleeding. Vital signs were normal at the time of admission.
After examination and testing, the patient was found to have low serum complement levels and elevated C-reactive protein. Anti-Scl 70 antibody, SSA, and SSB antibody were negative, and thyroid-stimulating hormone and antitransglutaminase antibodies were normal. No evidence of heart failure or pulmonary hypertension was seen in a transthoracic echocardiogram, and the patient was diagnosed with limited cutaneous systemic sclerosis.
Sjögren’s syndrome and autoimmune thyroiditis are the most common extrahepatic autoimmune disorders associated with PBC, but PBC is associated with CREST syndrome in 1%-6% of cases, according to the literature the investigators reviewed, they said.
“Primary biliary cholangitis is commonly associated with extrahepatic autoimmune disorders such as limited cutaneous systemic sclerosis. … Screening for these autoimmune disorders can prevent further morbidity and keep patients viable candidates for liver transplant,” they concluded.
Find the full clinical communication in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.05.019).
This story was updated on 9/13/2017.
Primary biliary cholangitis can be associated with limited cutaneous systemic sclerosis (CREST syndrome), according to a clinical communication to the editor from Amirali Kiyani, MD, and Shannon Ursu, MD.
In their case study, a 56-year-old woman presented to the emergency department with a syncopal episode. The patient’s medical history included primary biliary cholangitis (PBC), breast cancer status post lumpectomy and chemoradiation, gastroesophageal reflux disease, Raynaud’s phenomenon, and multiple episodes of gastrointestinal bleeding. Vital signs were normal at the time of admission.
After examination and testing, the patient was found to have low serum complement levels and elevated C-reactive protein. Anti-Scl 70 antibody, SSA, and SSB antibody were negative, and thyroid-stimulating hormone and antitransglutaminase antibodies were normal. No evidence of heart failure or pulmonary hypertension was seen in a transthoracic echocardiogram, and the patient was diagnosed with limited cutaneous systemic sclerosis.
Sjögren’s syndrome and autoimmune thyroiditis are the most common extrahepatic autoimmune disorders associated with PBC, but PBC is associated with CREST syndrome in 1%-6% of cases, according to the literature the investigators reviewed, they said.
“Primary biliary cholangitis is commonly associated with extrahepatic autoimmune disorders such as limited cutaneous systemic sclerosis. … Screening for these autoimmune disorders can prevent further morbidity and keep patients viable candidates for liver transplant,” they concluded.
Find the full clinical communication in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.05.019).
This story was updated on 9/13/2017.
FROM THE AMERICAN JOURNAL OF MEDICINE
No obvious choice for treating pruritus in PBC patients
While multiple options exist for the treatment of pruritus in patients with primary biliary cholangitis (PBC), none have compelling evidence regarding their long-term efficacy and safety, according to a narrative review of literature by Hirsh D. Trivedi, MD, and associates.
There are four treatments commonly used for treating pruritus in PBC patients: bile acid–binding resins, rifampicin, opioid antagonists, and sertraline. In the cases of bile acid–binding resins, rifampicin, and opioid antagonists, significant side effects and a lack of proof of long-term efficacy prevent the treatments from standing out. Sertraline seems to have no significant side effects, but research is lacking, and further investigation is required.
Several experimental treatments for refractory pruritus also exist: These include phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage, ileal bile acid transporter–inhibitors, methotrexate and colchicine, and fibrates. In extreme cases, liver transplant can also be utilized to reduce pruritus symptoms.
“Our ongoing learning [about] this multifaceted symptom will hopefully lead to the development of more effective therapies and improve the quality of life for patients with primary biliary cholangitis,” the investigators concluded.
Find the full narrative review in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.01.037).
While multiple options exist for the treatment of pruritus in patients with primary biliary cholangitis (PBC), none have compelling evidence regarding their long-term efficacy and safety, according to a narrative review of literature by Hirsh D. Trivedi, MD, and associates.
There are four treatments commonly used for treating pruritus in PBC patients: bile acid–binding resins, rifampicin, opioid antagonists, and sertraline. In the cases of bile acid–binding resins, rifampicin, and opioid antagonists, significant side effects and a lack of proof of long-term efficacy prevent the treatments from standing out. Sertraline seems to have no significant side effects, but research is lacking, and further investigation is required.
Several experimental treatments for refractory pruritus also exist: These include phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage, ileal bile acid transporter–inhibitors, methotrexate and colchicine, and fibrates. In extreme cases, liver transplant can also be utilized to reduce pruritus symptoms.
“Our ongoing learning [about] this multifaceted symptom will hopefully lead to the development of more effective therapies and improve the quality of life for patients with primary biliary cholangitis,” the investigators concluded.
Find the full narrative review in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.01.037).
While multiple options exist for the treatment of pruritus in patients with primary biliary cholangitis (PBC), none have compelling evidence regarding their long-term efficacy and safety, according to a narrative review of literature by Hirsh D. Trivedi, MD, and associates.
There are four treatments commonly used for treating pruritus in PBC patients: bile acid–binding resins, rifampicin, opioid antagonists, and sertraline. In the cases of bile acid–binding resins, rifampicin, and opioid antagonists, significant side effects and a lack of proof of long-term efficacy prevent the treatments from standing out. Sertraline seems to have no significant side effects, but research is lacking, and further investigation is required.
Several experimental treatments for refractory pruritus also exist: These include phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage, ileal bile acid transporter–inhibitors, methotrexate and colchicine, and fibrates. In extreme cases, liver transplant can also be utilized to reduce pruritus symptoms.
“Our ongoing learning [about] this multifaceted symptom will hopefully lead to the development of more effective therapies and improve the quality of life for patients with primary biliary cholangitis,” the investigators concluded.
Find the full narrative review in the American Journal of Medicine (doi: 10.1016/j.amjmed.2017.01.037).
FROM THE AMERICAN JOURNAL OF MEDICINE
Burden of HCV-induced cirrhosis expected to shift from men to women
Prevalence of hepatitis C virus (HCV) complications among women grew at a rate similar to that of men, while mortality among men was nearly double that of women, according to a study conducted through the Veterans Affairs office.
While men still have a higher prevalence of conditions such as cirrhosis, investigators expect to see a shift in the burden of care as women with HCV complications outlive men with similar diagnoses.
“The current and near-term burden in HCV-related cirrhosis was disproportionately attributed to men,” according to Jennifer Kramer, PhD, investigator at the Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston. “However, the trends are expected to change after 2020.”
The retrospective cohort study analyzed 264,409 HCV-infected veterans, 7,162 of whom were women, between January 2000 and December 2013.
Investigators found annual average prevalence change (AAPC) among men and women was 13.1% and 15.2%, respectively, for cirrhosis, while overall mortality was 28.7% for men, compared with 15.5% for women (J Viral Hepat. 2017 Aug 16. doi: 10.1111/jvh.12728).
Dr. Kramer and her fellow investigators also found similar rates among decompensated cirrhosis between 15.6% and 16.9% for women and men, respectively, and hepatocellular cancer, 21% and 25.3%, respectively.
Women included in the cohort were, on average, younger (48 years vs. 53 years), were less likely to use alcohol (33% vs. 45%), and were less likely to have contracted diabetes (30% vs. 39%).
While men’s prevalence growth was equal to women’s, male patients are 1.7 times more likely to be infected with HCV (J Hepatol. 2012 Jun 2 doi: 10.1016/j.jhep.2012.05.018), which is reflected in overall incidence rates of complications.
As expected, overall incidence of cirrhosis was higher in men than in women, with incidence rates for men at 28.2% compared with 20.1% of women.
Similar differences were found in rates of decompensated cirrhosis, 18.6% in men compared with 12.4% in women, and hepatocellular cancer, 5.3% in men compared with 1.5% in women.
Shifting trends in burden of care toward women have investigators worried about current HCV treatment practices for female patients.
“The increasing burden of HCV complications in women is concerning,” the researchers wrote. “Studies show that women are less likely to receive antiviral treatment than men.”
Contrary to this claim, antiviral treatment rates among men and women in this study were almost identical: 23.6% of women and 23.3% of men.
While the difference in treatment is not evident, the low rate of treatment for both men and women is another concern for Dr. Kramer and her colleagues.
“In the U.S., HCV infection remains undiagnosed in over 50% of all persons with HCV disease,” the investigators wrote. “Access to highly affective yet expensive direct acting antiviral treatment remains a challenge.”
Findings from this study may not be a true representation of the U.S. HCV-infected population because patients were veterans, with differences such as a higher rate of alcohol use among women.
The researchers reported no relevant financial disclosures.
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Prevalence of hepatitis C virus (HCV) complications among women grew at a rate similar to that of men, while mortality among men was nearly double that of women, according to a study conducted through the Veterans Affairs office.
While men still have a higher prevalence of conditions such as cirrhosis, investigators expect to see a shift in the burden of care as women with HCV complications outlive men with similar diagnoses.
“The current and near-term burden in HCV-related cirrhosis was disproportionately attributed to men,” according to Jennifer Kramer, PhD, investigator at the Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston. “However, the trends are expected to change after 2020.”
The retrospective cohort study analyzed 264,409 HCV-infected veterans, 7,162 of whom were women, between January 2000 and December 2013.
Investigators found annual average prevalence change (AAPC) among men and women was 13.1% and 15.2%, respectively, for cirrhosis, while overall mortality was 28.7% for men, compared with 15.5% for women (J Viral Hepat. 2017 Aug 16. doi: 10.1111/jvh.12728).
Dr. Kramer and her fellow investigators also found similar rates among decompensated cirrhosis between 15.6% and 16.9% for women and men, respectively, and hepatocellular cancer, 21% and 25.3%, respectively.
Women included in the cohort were, on average, younger (48 years vs. 53 years), were less likely to use alcohol (33% vs. 45%), and were less likely to have contracted diabetes (30% vs. 39%).
While men’s prevalence growth was equal to women’s, male patients are 1.7 times more likely to be infected with HCV (J Hepatol. 2012 Jun 2 doi: 10.1016/j.jhep.2012.05.018), which is reflected in overall incidence rates of complications.
As expected, overall incidence of cirrhosis was higher in men than in women, with incidence rates for men at 28.2% compared with 20.1% of women.
Similar differences were found in rates of decompensated cirrhosis, 18.6% in men compared with 12.4% in women, and hepatocellular cancer, 5.3% in men compared with 1.5% in women.
Shifting trends in burden of care toward women have investigators worried about current HCV treatment practices for female patients.
“The increasing burden of HCV complications in women is concerning,” the researchers wrote. “Studies show that women are less likely to receive antiviral treatment than men.”
Contrary to this claim, antiviral treatment rates among men and women in this study were almost identical: 23.6% of women and 23.3% of men.
While the difference in treatment is not evident, the low rate of treatment for both men and women is another concern for Dr. Kramer and her colleagues.
“In the U.S., HCV infection remains undiagnosed in over 50% of all persons with HCV disease,” the investigators wrote. “Access to highly affective yet expensive direct acting antiviral treatment remains a challenge.”
Findings from this study may not be a true representation of the U.S. HCV-infected population because patients were veterans, with differences such as a higher rate of alcohol use among women.
The researchers reported no relevant financial disclosures.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
Prevalence of hepatitis C virus (HCV) complications among women grew at a rate similar to that of men, while mortality among men was nearly double that of women, according to a study conducted through the Veterans Affairs office.
While men still have a higher prevalence of conditions such as cirrhosis, investigators expect to see a shift in the burden of care as women with HCV complications outlive men with similar diagnoses.
“The current and near-term burden in HCV-related cirrhosis was disproportionately attributed to men,” according to Jennifer Kramer, PhD, investigator at the Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston. “However, the trends are expected to change after 2020.”
The retrospective cohort study analyzed 264,409 HCV-infected veterans, 7,162 of whom were women, between January 2000 and December 2013.
Investigators found annual average prevalence change (AAPC) among men and women was 13.1% and 15.2%, respectively, for cirrhosis, while overall mortality was 28.7% for men, compared with 15.5% for women (J Viral Hepat. 2017 Aug 16. doi: 10.1111/jvh.12728).
Dr. Kramer and her fellow investigators also found similar rates among decompensated cirrhosis between 15.6% and 16.9% for women and men, respectively, and hepatocellular cancer, 21% and 25.3%, respectively.
Women included in the cohort were, on average, younger (48 years vs. 53 years), were less likely to use alcohol (33% vs. 45%), and were less likely to have contracted diabetes (30% vs. 39%).
While men’s prevalence growth was equal to women’s, male patients are 1.7 times more likely to be infected with HCV (J Hepatol. 2012 Jun 2 doi: 10.1016/j.jhep.2012.05.018), which is reflected in overall incidence rates of complications.
As expected, overall incidence of cirrhosis was higher in men than in women, with incidence rates for men at 28.2% compared with 20.1% of women.
Similar differences were found in rates of decompensated cirrhosis, 18.6% in men compared with 12.4% in women, and hepatocellular cancer, 5.3% in men compared with 1.5% in women.
Shifting trends in burden of care toward women have investigators worried about current HCV treatment practices for female patients.
“The increasing burden of HCV complications in women is concerning,” the researchers wrote. “Studies show that women are less likely to receive antiviral treatment than men.”
Contrary to this claim, antiviral treatment rates among men and women in this study were almost identical: 23.6% of women and 23.3% of men.
While the difference in treatment is not evident, the low rate of treatment for both men and women is another concern for Dr. Kramer and her colleagues.
“In the U.S., HCV infection remains undiagnosed in over 50% of all persons with HCV disease,” the investigators wrote. “Access to highly affective yet expensive direct acting antiviral treatment remains a challenge.”
Findings from this study may not be a true representation of the U.S. HCV-infected population because patients were veterans, with differences such as a higher rate of alcohol use among women.
The researchers reported no relevant financial disclosures.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c
ezimmerman@frontlinemedcom.com
On Twitter @eaztweets
FROM JOURNAL OF VIRAL HEPATITIS
Key clinical point:
Major finding: Average annual change of cirrhosis prevalence in women was 15.2% for women and 13.1% for men, while total mortality was 15.5% compared with 28.7% for women and men, respectively.
Data source: Retrospective cohort study of 264,409 veterans diagnosed with HCV, from the Veterans Affairs corporate wellness data for January 2000 to December 2013.
Disclosures: The investigators reported no relevant financial disclosures.
Statin use cuts risks in compensated cirrhosis
For patients with compensated cirrhosis, statin therapy was associated with about a 46% decrease in the risk of hepatic decompensation and mortality and with a 27% drop in the risk of portal hypertension and variceal bleeding, according to moderate-quality evidence from a systematic review and meta-analysis of 13 studies.
Low-quality data also suggested that statins might help protect against the progression of noncirrhotic chronic liver disease, said Rebecca G. Kim of the University of California at San Diego and her associates. “Large, pragmatic randomized controlled trials in patients with compensated cirrhosis are required to confirm these observations,” they wrote in the October issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.039).
Prior studies have reported mixed findings on how statin therapy affects chronic liver disease. For their review, Ms. Kim and her associates searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Cochrane Database and Systematic Reviews, Scopus, Web of Science, and PubMed for randomized controlled trials or cohort studies published through March 25, 2017. They identified 10 cohort studies and three randomized controlled trials of adults with fibrosis without cirrhosis, compensated cirrhosis, or decompensated cirrhosis that evaluated statin exposure and reported associations between exposure and outcomes related to cirrhosis. They excluded case-control studies, cross-sectional studies, and studies that focused only on the relationship between statin use and the risk of hepatocellular carcinoma.
The resulting data set included 121,058 patients with chronic liver diseases, of whom 85% had chronic hepatitis C virus infection. A total of 46% of patients were exposed to statins, which appeared to reduce their risk of hepatic decompensation, variceal bleeding, and mortality. Among 87 such patients in five studies, statin use was associated with a 46% decrease in the risk of hepatic decompensation and death, with risk ratios of 0.54 (95% confidence intervals, 0.46-0.62 and 0.47-0.61, respectively). Statin use also was associated with a 27% lower risk of variceal bleeding or progression of portal hypertension, based on an analysis of 110 events in 236 patients from three trials (RR, 0.73; 95% CI, 0.59-0.91). Finally, statin use also was associated with a 58% lower risk of fibrosis progression or cirrhosis in patients with noncirrhotic chronic liver disease, but the 95% CIs for the risk estimate did not reach statistical significance (0.16-1.11).
Source: American Gastroenterological Association
Most studies lacked data on dose and duration of statin exposure, the researchers said. However, four cohort studies reported dose-dependent effects that were most pronounced after more than a year of treatment. “Similarly, several different types of statins were studied, and observed effects were assumed to be class-specific effects,” the reviewers wrote. “However, it is possible that lipophilic and lipophobic statins may have differential efficacy in decreasing fibrosis progression.”
Together, these findings support prior studies suggesting that statin therapy is safe and can potentially reduce the risk of hepatocellular carcinoma in this patient population, they concluded. Statins “may potentially improve patient-relevant outcomes in patients with chronic liver diseases and improve survival without significant additional costs.”
The reviewers acknowledged the American Gastroenterological Association Foundation, a T. Franklin Williams Scholarship Award, the National Institutes of Health, and the National Library of Medicine. They reported having no relevant conflicts of interest.
This story was updated on 9/13/2017.
The main mechanism in the development of cirrhosis in patients with chronic liver disease (CLD) is increased hepatic fibrogenesis. The initial consequence of cirrhosis is portal hypertension, which is the main driver of decompensation (defined as the presence of ascites, variceal hemorrhage, or encephalopathy). 
Statins are widely used for reducing cholesterol levels and cardiovascular risk. However, statins ameliorate endothelial dysfunction and have additional antifibrotic, anti-inflammatory, and antithrombotic properties, all of them of potential benefit in preventing progression of CLD/cirrhosis. In fact, statins have been shown to reduce portal pressure in cirrhosis.
In a meta-analysis of 13 studies, Kim et al. demonstrated that statin use is associated with a 58% lower risk of developing cirrhosis/fibrosis progression in patients with CLD (not statistically significant), while in patients with compensated cirrhosis of any etiology, statin use was associated with a statistically significant 46% lower risk of developing decompensation and death.
Most studies in the meta-analysis were observational/retrospective. Although the authors jointly analyzed three randomized controlled trials, only one of the trials looked at clinical outcomes. This important double-blind, placebo-controlled study in patients with recent variceal hemorrhage showed a significantly lower mortality in patients randomized to simvastatin.
Therefore, although the evidence is not yet sufficient to recommend the widespread use of statins in patients with CLD/cirrhosis, providers should not avoid using statins in patients with CLD/cirrhosis who otherwise need them. In fact, they should actively look for indications that would justify their use.
Guadalupe Garcia-Tsao, MD, is professor of medicine at Yale University, chief of digestive diseases at the VA-CT Healthcare System, and director of the clinical core of the Yale Liver Center, New Haven, Conn. She had no conflicts of interest.
The main mechanism in the development of cirrhosis in patients with chronic liver disease (CLD) is increased hepatic fibrogenesis. The initial consequence of cirrhosis is portal hypertension, which is the main driver of decompensation (defined as the presence of ascites, variceal hemorrhage, or encephalopathy).
Statins are widely used for reducing cholesterol levels and cardiovascular risk. However, statins ameliorate endothelial dysfunction and have additional antifibrotic, anti-inflammatory, and antithrombotic properties, all of them of potential benefit in preventing progression of CLD/cirrhosis. In fact, statins have been shown to reduce portal pressure in cirrhosis.
In a meta-analysis of 13 studies, Kim et al. demonstrated that statin use is associated with a 58% lower risk of developing cirrhosis/fibrosis progression in patients with CLD (not statistically significant), while in patients with compensated cirrhosis of any etiology, statin use was associated with a statistically significant 46% lower risk of developing decompensation and death.
Most studies in the meta-analysis were observational/retrospective. Although the authors jointly analyzed three randomized controlled trials, only one of the trials looked at clinical outcomes. This important double-blind, placebo-controlled study in patients with recent variceal hemorrhage showed a significantly lower mortality in patients randomized to simvastatin.
Therefore, although the evidence is not yet sufficient to recommend the widespread use of statins in patients with CLD/cirrhosis, providers should not avoid using statins in patients with CLD/cirrhosis who otherwise need them. In fact, they should actively look for indications that would justify their use.
Guadalupe Garcia-Tsao, MD, is professor of medicine at Yale University, chief of digestive diseases at the VA-CT Healthcare System, and director of the clinical core of the Yale Liver Center, New Haven, Conn. She had no conflicts of interest.
The main mechanism in the development of cirrhosis in patients with chronic liver disease (CLD) is increased hepatic fibrogenesis. The initial consequence of cirrhosis is portal hypertension, which is the main driver of decompensation (defined as the presence of ascites, variceal hemorrhage, or encephalopathy).
Statins are widely used for reducing cholesterol levels and cardiovascular risk. However, statins ameliorate endothelial dysfunction and have additional antifibrotic, anti-inflammatory, and antithrombotic properties, all of them of potential benefit in preventing progression of CLD/cirrhosis. In fact, statins have been shown to reduce portal pressure in cirrhosis.
In a meta-analysis of 13 studies, Kim et al. demonstrated that statin use is associated with a 58% lower risk of developing cirrhosis/fibrosis progression in patients with CLD (not statistically significant), while in patients with compensated cirrhosis of any etiology, statin use was associated with a statistically significant 46% lower risk of developing decompensation and death.
Most studies in the meta-analysis were observational/retrospective. Although the authors jointly analyzed three randomized controlled trials, only one of the trials looked at clinical outcomes. This important double-blind, placebo-controlled study in patients with recent variceal hemorrhage showed a significantly lower mortality in patients randomized to simvastatin.
Therefore, although the evidence is not yet sufficient to recommend the widespread use of statins in patients with CLD/cirrhosis, providers should not avoid using statins in patients with CLD/cirrhosis who otherwise need them. In fact, they should actively look for indications that would justify their use.
Guadalupe Garcia-Tsao, MD, is professor of medicine at Yale University, chief of digestive diseases at the VA-CT Healthcare System, and director of the clinical core of the Yale Liver Center, New Haven, Conn. She had no conflicts of interest.
For patients with compensated cirrhosis, statin therapy was associated with about a 46% decrease in the risk of hepatic decompensation and mortality and with a 27% drop in the risk of portal hypertension and variceal bleeding, according to moderate-quality evidence from a systematic review and meta-analysis of 13 studies.
Low-quality data also suggested that statins might help protect against the progression of noncirrhotic chronic liver disease, said Rebecca G. Kim of the University of California at San Diego and her associates. “Large, pragmatic randomized controlled trials in patients with compensated cirrhosis are required to confirm these observations,” they wrote in the October issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.039).
Prior studies have reported mixed findings on how statin therapy affects chronic liver disease. For their review, Ms. Kim and her associates searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Cochrane Database and Systematic Reviews, Scopus, Web of Science, and PubMed for randomized controlled trials or cohort studies published through March 25, 2017. They identified 10 cohort studies and three randomized controlled trials of adults with fibrosis without cirrhosis, compensated cirrhosis, or decompensated cirrhosis that evaluated statin exposure and reported associations between exposure and outcomes related to cirrhosis. They excluded case-control studies, cross-sectional studies, and studies that focused only on the relationship between statin use and the risk of hepatocellular carcinoma.
The resulting data set included 121,058 patients with chronic liver diseases, of whom 85% had chronic hepatitis C virus infection. A total of 46% of patients were exposed to statins, which appeared to reduce their risk of hepatic decompensation, variceal bleeding, and mortality. Among 87 such patients in five studies, statin use was associated with a 46% decrease in the risk of hepatic decompensation and death, with risk ratios of 0.54 (95% confidence intervals, 0.46-0.62 and 0.47-0.61, respectively). Statin use also was associated with a 27% lower risk of variceal bleeding or progression of portal hypertension, based on an analysis of 110 events in 236 patients from three trials (RR, 0.73; 95% CI, 0.59-0.91). Finally, statin use also was associated with a 58% lower risk of fibrosis progression or cirrhosis in patients with noncirrhotic chronic liver disease, but the 95% CIs for the risk estimate did not reach statistical significance (0.16-1.11).
Source: American Gastroenterological Association
Most studies lacked data on dose and duration of statin exposure, the researchers said. However, four cohort studies reported dose-dependent effects that were most pronounced after more than a year of treatment. “Similarly, several different types of statins were studied, and observed effects were assumed to be class-specific effects,” the reviewers wrote. “However, it is possible that lipophilic and lipophobic statins may have differential efficacy in decreasing fibrosis progression.”
Together, these findings support prior studies suggesting that statin therapy is safe and can potentially reduce the risk of hepatocellular carcinoma in this patient population, they concluded. Statins “may potentially improve patient-relevant outcomes in patients with chronic liver diseases and improve survival without significant additional costs.”
The reviewers acknowledged the American Gastroenterological Association Foundation, a T. Franklin Williams Scholarship Award, the National Institutes of Health, and the National Library of Medicine. They reported having no relevant conflicts of interest.
This story was updated on 9/13/2017.
For patients with compensated cirrhosis, statin therapy was associated with about a 46% decrease in the risk of hepatic decompensation and mortality and with a 27% drop in the risk of portal hypertension and variceal bleeding, according to moderate-quality evidence from a systematic review and meta-analysis of 13 studies.
Low-quality data also suggested that statins might help protect against the progression of noncirrhotic chronic liver disease, said Rebecca G. Kim of the University of California at San Diego and her associates. “Large, pragmatic randomized controlled trials in patients with compensated cirrhosis are required to confirm these observations,” they wrote in the October issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.039).
Prior studies have reported mixed findings on how statin therapy affects chronic liver disease. For their review, Ms. Kim and her associates searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Cochrane Database and Systematic Reviews, Scopus, Web of Science, and PubMed for randomized controlled trials or cohort studies published through March 25, 2017. They identified 10 cohort studies and three randomized controlled trials of adults with fibrosis without cirrhosis, compensated cirrhosis, or decompensated cirrhosis that evaluated statin exposure and reported associations between exposure and outcomes related to cirrhosis. They excluded case-control studies, cross-sectional studies, and studies that focused only on the relationship between statin use and the risk of hepatocellular carcinoma.
The resulting data set included 121,058 patients with chronic liver diseases, of whom 85% had chronic hepatitis C virus infection. A total of 46% of patients were exposed to statins, which appeared to reduce their risk of hepatic decompensation, variceal bleeding, and mortality. Among 87 such patients in five studies, statin use was associated with a 46% decrease in the risk of hepatic decompensation and death, with risk ratios of 0.54 (95% confidence intervals, 0.46-0.62 and 0.47-0.61, respectively). Statin use also was associated with a 27% lower risk of variceal bleeding or progression of portal hypertension, based on an analysis of 110 events in 236 patients from three trials (RR, 0.73; 95% CI, 0.59-0.91). Finally, statin use also was associated with a 58% lower risk of fibrosis progression or cirrhosis in patients with noncirrhotic chronic liver disease, but the 95% CIs for the risk estimate did not reach statistical significance (0.16-1.11).
Source: American Gastroenterological Association
Most studies lacked data on dose and duration of statin exposure, the researchers said. However, four cohort studies reported dose-dependent effects that were most pronounced after more than a year of treatment. “Similarly, several different types of statins were studied, and observed effects were assumed to be class-specific effects,” the reviewers wrote. “However, it is possible that lipophilic and lipophobic statins may have differential efficacy in decreasing fibrosis progression.”
Together, these findings support prior studies suggesting that statin therapy is safe and can potentially reduce the risk of hepatocellular carcinoma in this patient population, they concluded. Statins “may potentially improve patient-relevant outcomes in patients with chronic liver diseases and improve survival without significant additional costs.”
The reviewers acknowledged the American Gastroenterological Association Foundation, a T. Franklin Williams Scholarship Award, the National Institutes of Health, and the National Library of Medicine. They reported having no relevant conflicts of interest.
This story was updated on 9/13/2017.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Statin therapy was associated with a significantly lower risk of hepatic decompensation and death in patients with compensated cirrhosis.
Major finding: Statin therapy was associated with a 46% decrease in the risk of both hepatic decompensation and mortality (risk ratios, 0.54) and with a 27% drop in the risk of portal hypertension and variceal bleeding (RR, 0.73).
Data source: A systematic review and meta-analysis of 10 cohort studies and three randomized controlled trials (121,058 patients).
Disclosures: The reviewers acknowledged the American Gastroenterological Association Foundation, a T. Franklin Williams Scholarship Award, the National Institutes of Health, and the National Library of Medicine. They reported having no relevant conflicts of interest.
