Liver fibrosis improves after successful treatment for hepatitis C

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A majority of people with chronic hepatitis C and advanced fibrosis or cirrhosis showed improvement in liver health following treatment, according to study findings presented last week at the 2015 AASLD Liver Meeting in San Francisco, USA. 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.

Glossary

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

carcinoma

A type of cancer that starts in the cells of the skin or the tissues that cover and line the body cavities and organs. At least 80% of all cancers are carcinomas.

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

regression

Improvement in a tumour. Also, a mathematical model that allows us to measure the degree to which one of more factors influence an outcome.

Ana Maria Crissien of the Scripps Clinic in La Jolla, California, and colleagues looked at the association between sustained virological response at 12 weeks post-treatment (SVR12) – recognised 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 people with chronic hepatitis C and 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 six-month intervals after SVR.

Of the 224 patients at Scripps who were eligible for the study, the present analysis included 100 people, of whom 35 had advanced fibrosis and 65 had cirrhosis at baseline. Of the remainder, 110 were still awaiting analysis, three declined to participate and 11 were excluded (one 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 (Incivo or Incivek) 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 according to FibroScan, 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 oesophagus) 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 six people with HCV genotype 3 – which is associated with more aggressive liver disease – all but one (83%) showed improvement by at least one fibrosis stage. Among the five people who had developed hepatocellular carcinoma by the end of follow-up, two had improved fibrosis, two remained unchanged and one 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 people with advanced fibrosis.

References

Crissien AM 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, abstract 108, 2015.