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Hepatitis C Treatment May Improve Liver Fibrosis Even Without a Cure


Experiencing a large decrease in hepatitis C virus (HCV) viral load after starting interferon-based therapy was associated with reduced liver inflammation and lower risk of fibrosis progression, even among patients who did not achieve sustained virological response, researchers reported in the June 12, 2012, advance edition of the American Journal of Gastroenterology.

Over years or decades, chronic HCV infection can lead to severe liver disease including advanced fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Studies have shown that successful treatment that clears the virus -- known as sustained virological response, or SVR -- lowers the risk of disease progression, but less is known about the potential benefits of non-curative therapy among non-responders.

As previously reported, HALT-C was a randomized study evaluating whether extended "maintenance" with pegylated interferon alfa-2a (Pegasys) monotherapy would influence liver disease progression among patients with advanced fibrosis or cirrhosis who did not achieve sustained response to a standard course of pegylated interferon/ribavirin combination therapy (the study was done before the advent of HCV direct-acting antiviral agents).

The primary analysis found that long-term (3.5 years) interferon maintenance monotherapy did not significantly reduce the risk of adverse clinical outcomes including cirrhosis, liver cancer, hepatic decompensation, or death.

In the present analysis, Chihiro Morishima from the University of Washington in Seattle and colleagues assessed whether reduced liver inflammation was associated with clinical benefits among a subset of participants with baseline and follow-up biopsies 1.5 years after they were randomized to receive either pegylated interferon monotherapy or observation with no further treatment.

The researchers looked at relationships between changes in liver inflammation as shown by the Ishak hepatic activity index (HAI), serum alanine aminotransferase (ALT) levels, HCV RNA viral load changes, fibrosis progression, and clinical outcomes after randomization. Histological change was defined as at least a 2-point difference in HAI or Ishak fibrosis score between biopsies.


  • Among 657 patients who received a full course of pegylated interferon/ribavirin before randomization in HALT-C, HCV RNA suppression during the combination therapy period was associated with HAI improvement at 1.5 years.
  • Within this group, significant improvement was seen in both patients randomly assigned to maintenance monotherapy and those who received no further treatment, and occurred even with recurrent viremia.
  • This relationship persisted among 516 patients followed through 3.5 years in both the maintenance monotherapy and no further treatment arms.
  • Among 834 patients with paired biopsies followed for a median of 6 years, significantly fewer clinical events occurred among those with improved HAI scores at year 1.5 compared to those without such improvement, again in both the maintenance monotherapy and control groups.
  • Among patients with Ishak stage F3-F4 fibrosis at baseline, people with improved HAI scores at year 1.5 had less fibrosis progression in both the interferon monotherapy and control groups.

Based on these findings, the study authors concluded, "Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment."



C Morishima, ML Shiffman, JL Dienstag, et al (HALT-C Trial Group). Reduction in Hepatic Inflammation Is Associated With Less Fibrosis Progression and Fewer Clinical Outcomes in Advanced Hepatitis C.American Journal of Gastroenterology57(1). July 2012 (Epub June 12, 2012).