Long-term Effect of Interferon/Ribavirin on Incidence of Hepatocellular Carcinoma

An estimated one-quarter of people with chronic hepatitis C virus (HCV) will develop advanced liver disease, including cirrhosis and/or hepatocellular carcinoma (HCC) over the course of 10-40 years. But effective treatment may reduce the risk of disease progression.

Researchers in Taiwan conducted a study to assess the efficacy of treatment with conventional interferon plus ribavirin over a follow-up period of 1-5 years. Since HCV was only identified in 1989, and interferon-based combination therapy came several years later, there are few studies of long-term treatment outcomes. The newer, more effective pegylated formulations of interferon (Peg-Intron and Pegasys) were not widely used until the early 2000s.

The study, reported in the June 2006 Journal of Viral Hepatitis, included 132 patients with chronic hepatitis C and liver cirrhosis, who were treated 3 or 5 MU weekly interferon alfa-2b (Intron-A) plus 1000-1200 mg daily ribavirin for 24 or 48 weeks. Follow-up lasted an average of 37 months (range 12-63 months).

Results

• 116 patients completed therapy, and 73 (55%) achieved sustained virological response (SVR).
• Stepwise logistic regression analysis showed that infection with HCV genotypes other than 1b (P < 0.001) and low HCV viral load (P = 0.018) were independent predictors of SVR.
• During the follow-up period, 5 patients with SVR developed HCC, compared to 11 patients who did not achieve a sustained response (P = 0.0178).
• Statistical analysis revealed that age greater than 60 years (P = 0.0034) and infection with genotype 1b HCV (P = 0.0104) were associated with greater risk of HCC.
• In a regression analysis, lack of SVR (OR 3.521; P = 0.036), male sex (OR 6.269; P = 0.011), and older age (OR 3.076; P = 0.049) were significant independent risk factors for HCC.
• There was no difference in HCC incidence rates with regard to transient biochemical response or non-response (i.e., ALT and/or AST normalization) (P = 0.5970).

Conclusion

In conclusion, the authors wrote, “Our results suggest that achieving SVR by interferon alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.”

8/15/06

Reference

C H Hung, C M Lee, S N Lu, and others. Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Journal of Viral Hepatitis 13(6): 409-414. June 2006.