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

Aliment Pharmacol Ther. 2021 Jul;54(2):176-182. doi: 10.1111/apt.16408. Epub 2021 May 28.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / adverse effects
  • Female
  • Hepatitis B Surface Antigens
  • Hepatitis D, Chronic* / drug therapy
  • Hepatitis Delta Virus / genetics
  • Humans
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • RNA, Viral
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols

Associated data

  • ClinicalTrials.gov/NCT00023322