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AASLD 2015: Liver Fibrosis Improves after Successful Treatment for Chronic Hepatitis C


A majority of chronic hepatitis C patients with advanced fibrosis or cirrhosis showed improvement in liver health following treatment, according to study findings presented at the 2015 AASLD Liver Meeting this week in San Francisco. However, the researchers identified few demographic, laboratory, or disease-related factors that could predict who would experience fibrosis regression and who would have worsening liver damage.

Over years or decades chronic hepatitis C virus (HCV) infection can lead to advanced liver disease including cirrhosis, liver cancer, and liver failure requiring a transplant.

Prior studies have shown that treatment with interferon-based therapy for hepatitis C, as well as tenofovir (Viread) for hepatitis B, can lead to some reversal of fibrosis and reduced risk of hepatocellular carcinoma and liver-related death. Direct-acting antiviral agents used in interferon-free regimens can now cure upwards of 90% of people with hepatitis C, but it is not yet known how treatment response will be reflected in long-term clinical outcomes.

Ana Maria Crissien from the Scripps Clinic in La Jolla and colleagues looked at the association between sustained virological response at 12 weeks post-treatment (SVR12) -- recognized as a cure -- and regression of advanced fibrosis or cirrhosis as determined by FibroScan elastography imaging. Long-term follow-up will assess changes in the risk of hepatocellular carcinoma and the need for ongoing liver cancer screening.

Liver biopsy has traditionally been considered the ''gold standard" for determining the extent of liver fibrosis, but clinicians are increasingly using less expensive non-invasive imaging methods and biomarker indexes. Elastography uses shear waves to assess liver elasticity or "stiffness." Higher liver stiffness scores (measured in kiloPascals or kPa) are associated with more advanced liver damage; a score below 6.0 kPa suggests absence of fibrosis while a score above 14.0 kPa indicates cirrhosis.

The researchers conducted a retrospective chart review of data from chronic hepatitis C patients with advanced fibrosis or cirrhosis (according to clinical features, FibroScan, or biopsies) who achieved sustained virological response to treatment. This was followed by prospective FibroScan and clinical assessments at 6-month intervals after SVR.

Of the 224 participants at Scripps who were eligible for the study, the present analysis included 100 patients, of whom 35 had advanced fibrosis and 65 had cirrhosis at baseline. Of the remainder, 110 were still awaiting analysis, 3 declined to participate, and 11 were excluded (1 due to transplantation and 10 due to additional causes of liver disease such as hepatitis B or heavy alcohol use).

About 65% of patients in the present analysis were men, most were white, and the mean age was about 59 years. Most had HCV genotypes 1a or 1b. The most commonly used treatment was the first-generation HCV protease inhibitor telaprevir (Incivek or Incivo) plus pegylated interferon/ribavirin, followed by sofosbuvir (Sovaldi) plus simeprevir (Olysio), pegylated interferon/ribavirin alone, sofosbuvir/ledipasvir (Harvoni), and sofosbuvir plus pegylated interferon/ribavirin; overall, 45% used regimens containing sofosbuvir


  • Among the 35 participants who had advanced fibrosis at baseline, 69% demonstrated improvement by at least one fibrosis stage, 14% remained unchanged, and 17% worsened to cirrhosis.
  • Among the 65 people with cirrhosis at baseline, 55% showed improvement and 45% remained unchanged.
  • Taken together, 60% improved, 34% had no change, and 6% worsened.
  • Median time to improvement was 2.5 years for people with advanced fibrosis and 3.0 years for those with cirrhosis at baseline, indicating that those with less severe liver injury improved faster.
  • The researchers identified few factors that predicted fibrosis improvement or worsening.
  • There were no significant associations with patient sex, age, race/ethnicity, obesity, most medical conditions, or most complications of cirrhosis.
  • However, diabetes and varices (enlarged veins in the stomach or esophagus) were associated with a lower likelihood of fibrosis improvement.
  • Most laboratory tests including albumin and platelet counts showed no association with changes in fibrosis.
  •  Fibrosis improvement was significantly associated with changes in ALT and AST liver enzyme levels and APRI (AST-to-platelet ratio index) scores, but patient numbers were small and the clinical relevance of this is unclear.
  • In a sub-analysis of 6 people with HCV genotype 3 -- which is associated with more aggressive liver disease -- all but 1 (83%) showed regression of fibrosis.
  • Among the 5 people who had developed hepatocellular carcinoma by the end of follow-up, 2 had improved fibrosis, 2 remained unchanged, and 1 worsened.

In summary, this study showed an "overall 60% improvement in subjects with baseline cirrhosis or advanced fibrosis after achieving SVR based on FibroScan," the researchers concluded, suggesting that APRI might be used to predict regression in subjects with advanced fibrosis.



AM Crissien, WB Minteer, JJ Pan, et al. Regression of Advanced Fibrosis or Cirrhosis Measured by Elastography in Patients with Chronic Hepatitis C who Achieve Sustained Virologic Response after Treatment for HCV. AASLD Liver Meeting 2015. San Francisco, November 13-17, 2015. Abstract 108.