Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B

Abstract

BackgroundNucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication. ObjectivesTo determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion. Study designWe observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16–15,120)IU/ml. ResultsA continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log10 or 4.25log10 fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A – HBe-positive, genotype A, F3 fibrosis – had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B – HBeAg negative, genotype D, cirrhosis – had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log10 (range 0.01–0.25log10) after 8–24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed. DiscussionWe observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial.