Sofosbuvir reduces liver fibrosis in chronic hepatitis C




Antiviral treatment with sofosbuvir reduced liver fibrosis, as measured by three independent noninvasive predictors for liver fibrosis, and liver stiffness, in patients with chronic hepatitis C (CHC), according to new research published in the Digestive and Liver Disease (doi:10.1016/j.dld.2015.09.015).

“Despite the relatively small sample size, the effects on fibrosis parameters are impressive, implying clinically significant fibrosis regression and potential reduction of cirrhosis-associated mortality in successfully treated patients with CHC,” wrote Dr. Sebastian Bernuth of Cirrhosis Center Mainz (CCM), Johannes Gutenberg University Mainz, Germany, and colleagues.

Courtesy US. Dept of Veterans Affairs

CHC is a major cause of liver-associated mortality, and is responsible for approximately 25% of primary hepatocellular carcinomas and 25% of liver cirrhosis. Successful antiviral therapy with a sustained virological response (SVR) can reduce liver-related morbidity and mortality, including a decreased need for transplantation.

In 2014, the first NS5B RNA-polymerase inhibitor, sofosbuvir, was approved for use in conjunction with pegylated interferon-alpha (PEG-IFN) and/or ribavirin to treat hepatitis C infection, and yielded high SVR rates of around 90% after short-term therapy in genotype 1-3-infected patients.In this study, Dr. Benuth and his colleagues evaluated early changes in dynamic fibrosis-related parameters using the enhanced liver fibrosis (ELF) panel, combined with liver stiffness measurement (LSM), along with metabolic alterations in insulin resistance, and lipid and iron metabolism during sofosbuvir-based antiviral therapy.

A total of 32 patients were included in the analysis, and all received treatment with sofosbuvir, 19 in combination with PEG-IFN, 29 in combination with ribavirin, and four in combination with simeprevir.Patients experienced a biochemical and virological response within 4 weeks of starting treatment. At 12 weeks, the SVR was 93.8% and two patients experienced a relapse.There was a significant decrease from baseline to 12-week posttreatment follow-up in ELF (10.00 vs. 9.37; P = .007), and the median of the LSM (measured by Fibroscan) significantly decreased over the whole observation period, from 8 kPa (METAVIR F2) at baseline to 6.8 kPa (METAVIR F0-1) at 12 weeks (P = .016). This suggests a significant regression of liver fibrosis at 12 weeks, compared to baseline.The liver enzymes (ALT, AST, and gamma-GT) rapidly normalized under treatment, and total bilirubin also decreased from the baseline upper normal values (0.91 mg/dL) to 0.74 mg/dL (P = .034).“In conclusion, this is the first study implying significant and clinically relevant reduction in liver fibrosis measures by three independent noninvasive predictors for liver fibrosis assessment and liver stiffness measurement under highly effective antiviral regimens with sofosbuvir,” said the authors.

The study was supported by intramural funding of the University of Mainz (Inneruniversitäre Forschungsförderung Stufe I grant) to Dr. Tim Zimmermann, who has also received consultant/lecture fees and/or travel support from Abbvie, BMS, Gilead, Janssen-Cilag, Merck, and Roche. Dr. Martin F. Sprinzl received research funding from Gilead and lecture fees from Roche. All other authors have no conflicts of interest to declare in terms of this manuscript.

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