Flink HJ et al. (2006) Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine. Am J Gastroenterol 101: 2523–2529

Sherman M et al. (2006) Peginterferon alfa-2a (40kD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy. Gut 55: 1631–1638

Chronic infection with HBV or HCV can lead to progressive cirrhosis, liver failure, and an increased risk of hepatocellular carcinoma. Before the availability of pegylated interferons (PEG-IFNs), interferon-α, with or without ribavirin, was the preferred first-line treatment for HCV-infected individuals; HBV-infected individuals typically receive first-line therapy with interferon-α and/or lamivudine. A substantial proportion of patients do not respond to (or relapse after) interferon treatment for HBV or HCV, so the efficacy of PEG-IFNs in the re-treatment of these patients has been investigated.

Flink and colleagues' international, multicenter, randomized, controlled trial analyzed data from 76 patients with chronic hepatitis B who had not responded to previous treatment. All patients received 100 µg PEG-IFN-α2b), plus either placebo or 100 µg lamivudine daily, for 52 weeks. The PEG-IFN-α2b dose was reduced to 50 µg after 32 weeks to prevent adverse effects and improve compliance. A response was observed in 13 of 37 patients who previously did not respond to interferon, 5 of 17 patients who previously did not respond to lamivudine and in 4 of 22 patients who previously did not respond to both therapies in combination. The addition of lamivudine to PEG-IFN-α2b did not influence the response to treatment. The best predictor of a response to PEG-IFN-α2b was a baseline serum alanine aminotransferase level >4 times the upper limit of normal; such patients had a significantly improved response rate compared with those whose levels were below this value (53% versus 20%; P = 0.036). The authors estimate that approximately a third of patients with chronic hepatitis B who did not respond to first-line interferon or lamivudine therapy will achieve a sustained virologic response if treated with PEG-IFN-α2b.

Sherman and colleagues conducted a multicenter, open-label study of Canadian patients with chronic hepatitis C who had not responded to (n = 212) or had relapsed after (n = 100) previous interferon-α or interferon-α plus ribavirin treatment. All patients received 180 µg PEG-IFN-α2a weekly plus 400 mg ribavirin twice daily, for 24 weeks (n = 28) or 48 weeks (n = 284). Lack of an early virologic response at 12 weeks accurately predicted the failure of PEG-IFN-α2a therapy. A higher proportion of patients who relapsed after previous interferon treatment achieved an early virologic response, compared with patients who did not respond to previous interferon treatment (84% versus 58%). A sustained virologic response rate of 23% was seen in patients who had not responded to previous interferon treatment and of 41% in patients who had relapsed following previous interferon therapy. Sustained virologic response rates were greater for patients infected with HCV genotypes 2 and 3 (47%) than HCV genotype 1 (24%). This difference might be attributable to the low ribavirin dose used; subsequently, a daily dose of 1.0–1.2 g ribavirin was shown to be the optimal treatment for individuals infected with HCV genotype 1.

Both studies confirm that PEG-IFNs are an effective treatment for patients with chronic hepatitis B or C who have not responded to or relapsed after previous therapies based on interferon-α.