Durable virological response and functional cure of chronic hepatitis D after long-term peginterferon therapy

Abstract

Background: Hepatitis delta virus (HDV) infection is the most aggressive form of chronic viral hepatitis. Response rates to therapy with 1- to 2-year courses of pegylated interferon alpha (peginterferon) treatment are suboptimal.

Aims: To evaluate the long-term outcomes of patients with chronic hepatitis D after an extended course of peginterferon.

Methods: Patients were followed after completion of trial NCT00023322 and classified based on virological response defined as loss of detectable serum HDV RNA at last follow-up. During extended follow-up, survival and liver-related events were recorded.

Results: All 12 patients who received more than 6 months of peginterferon in the original study were included in this analysis. The cohort was mostly white (83%) and male (92%) and ranged in age from 18 to 58 years (mean = 42.6). Most patients had advanced but compensated liver disease at baseline, a median HBV DNA level of 536 IU per mL and median HDV RNA level of 6.86 log10 genome equivalents per mL. The treatment duration averaged 6.1 years (range 0.8-14.3) with a total follow-up of 8.8 years (range 1.7-17.6). At last follow-up, seven (58%) patients had durable undetectable HDV RNA in serum, and four (33%) cleared HBsAg. Overall, one of seven (14%) responders died or had a liver-related event vs four of five (80%) non-responders.

Conclusions: With further follow-up, an extended course of peginterferon therapy was found to result in sustained clearance of HDV RNA and favourable clinical outcomes in more than half of patients and loss of HBsAg in a third.

Published 2021. This article is a U.S.Government work and is in the public domain in the USA.

Figures

FIGURE 1

Duration of therapy and serological status of all patients. Grey bar: peginterferon treatment duration; Blue bar: HDV RNA positive; Orange bar: HDV RNA negative; Green bar: HBsAg positive; Yellow bar: HBsAg negative; Black star: death; NR: non-responder; R: responder