Objectives: Antiviral therapy leads to HBeAg seroconversion in 10-40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine.
Methods: We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks.
Results: Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN alpha2b. No difference in response was found for those treated with Peg-IFN alpha2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) > 4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those with ALT levels <or= 4 x ULN (53%vs 20%, respectively, p= 0.036).
Conclusions: Peg-IFN alpha2b is effective in approximately one-third of patients who failed to respond to previous treatment with standard IFN or lamivudine. High serum ALT level at baseline of Peg-IFN alpha2b therapy was the best predictor for response in these patients.