Abstract

Background/AimsLong-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.MethodsCHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment.Results131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54–62) years with median estimated duration of infection 33-years (IQR 29–38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12–17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p = 0.0001). SVR was independently associated with protection from liver fibrosis progression after adjustment for other variables including baseline ALT (p = 0.011), duration of HCV infection and mode of acquisition.ConclusionHCV eradication is associated with lower rates of liver fibrosis progression. The data support early treatment to prevent long-term liver complications of HCV infection.

Highlights

  • 115 million people are chronically infected with hepatitis C (HCV) worldwide, including 230,000 Australians.[1,2] HCV is associated with complications including liver cirrhosis, liver failure and hepatocellular carcinoma

  • HCV eradication is associated with lower rates of liver fibrosis progression

  • We show that achievement of sustained virological response (SVR) halts liver fibrosis progression

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Summary

Introduction

115 million people are chronically infected with hepatitis C (HCV) worldwide, including 230,000 Australians.[1,2] HCV is associated with complications including liver cirrhosis, liver failure and hepatocellular carcinoma. HCV is the most common indication for liver transplant in high-income countries including Australia. It is assumed that eradicating HCV will prevent these complications. The landscape of HCV treatment has changed dramatically over recent years. Interferonfree combinations of direct acting antiviral (DAA) agents are standard of care, with cure rates approaching 100% and excellent tolerability. The cost associated with the new DAAs is a major barrier to treatment access. It is important to evaluate long-term clinical outcomes, to confirm that viral eradication is associated with predicted clinical benefit

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