Long-term, Low-Dose Treatment with Pegylated Interferon Alfa-2b (PegIntron) Monotherapy Leads to a Reduction in Fibrosis and Inflammatory Scores in Prior Non-responders

Treatment with current standard antiviral therapy leaves about 50% of chronic hepatitis C patients without sustained viral clearance and therefore with a continued risk of liver disease progression. Some recent data have suggested an anti-fibrotic effect with use of long-term, low-dose interferon treatment.

As reported at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston (November 2-6, 2007), researchers evaluated the efficacy of low-dose pegylated interferon alfa-2b (PegIntron) at 0.5 mcg/kg once-weekly given for 36 months as monotherapy. For comparison, the usual dose of PegIntron in combination with ribavirin is 1.0 mcg/kg/week for 24 (genotypes 2/3) or 48 (genotype 1) weeks.

The study included 182 patients with chronic hepatitis C and significant fibrosis or cirrhosis (Ishak stage 3-6) who were non-responders to prior combination antiviral therapy. These patients were compared to an observational control group of 83 subjects. Liver histology was evaluated at baseline, at 18 months of treatment, and 6 months after the end of treatment.

Results

• In the control group, at 18 months of therapy, there was an increase in fibrosis score from 3.71 to 4.17, which increased to 4.79 at 6 months post-treatment.
  
  
• In the treatment group, fibrosis score decrease from 3.83 at baseline to 2.51 at 18 months, and fell further to 2.05 at 6 months post-treatment.
  
  
• Necroinflammatory scores remained stable in the control group: 7.89 at baseline, 7.56 at month 18, and 7.73 at 6 months post-treatment.
  
  
• In the treatment group, necroinflammatory score decreased from 8.61 at baseline to 5.89 at month 18, but then relapsed to 7.54 at 6 months post-treatment.
  
  
• 61% of patients in the treatment group experienced an HCV viral load decline of > 1 log, and 6% achieved undetectable HCV RNA; however, this was not maintained for any patient upon cessation of therapy.
  
  
• In the treatment group, the drop-out rate was 3% and the dose-reduction rate was 13%.
  
  
• 22 serious adverse events were observed, of which 17 were complications of cirrhosis (6 decompensations, 6 variceal bleeds, and 5 incident cases of hepatocellular carcinoma).
  
  
• There was no significant difference in the rate of these complications between the treatment and control groups.  

Based on these findings, the authors concluded that low-dose therapy with pegylated interferon alfa-2b in patients with HCV and advanced fibrosis or cirrhosis “shows a significant and persistent decrease in fibrosis in comparison to a control group.”

They also observed that, “a significant decrease in the necroinflammatory score is only temporary as long as treatment lasts.” Finally, they stated, “As treatment was well tolerated even for patients with cirrhosis, this treatment could evolve as a salvage therapy for patients with advanced HCV-related liver disease [in whom] standard antiviral therapy has failed.”

Notably, the rate of serious liver complications including decompensation and hepatocellular carcinoma was not lower in the treatment group. These findings -- which agree with results from the HALT-C study of pegylated interferon alfa-2a (Pegasys) maintenance monotherapy presented at the same conference -- suggest that promising surrogate marker data, and even the decrease in fibrosis seen in the present study, may not translate into improved long-term clinical outcomes.

Dept. of Medicine, University Hospital of Tuebingen, Tuebingen, Germany; Medicine, Marienhospital, Stuttgart, Germany.

11/16/07

Reference
S Kaiser, B Lutze, B Sauter, and others. Long-term Low Dose Treatment with Pegylated Interferon alpha 2b leads to a significant Reduction in Fibrosis and Inflammatory Score in Chronic Hepatitis C Nonresponder Patients with Fibrosis or Cirrhosis. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston. November 2-6, 2007. Abstract (poster) 1311.