Viral suppression and cirrhosis regression with tenofovir disoproxil fumarate in Asians with chronic hepatitis B

Dig Dis Sci. 2015 Jan;60(1):260-8. doi: 10.1007/s10620-014-3336-7. Epub 2014 Sep 2.

Abstract

Background: Chronic hepatitis B (CHB) is a major public health concern, particularly in endemic areas like Asia-Pacific. Sustained virologic suppression correlates with regression of histologic fibrosis and cirrhosis.

Aim: This study evaluated efficacy and safety of tenofovir disoproxil fumarate (TDF) in Asian patients through 240 weeks of treatment.

Methods: Post hoc analysis of the Asian subpopulation from two phase 3 clinical studies was performed. Following a 48-week randomized, double-blind evaluation of once-daily TDF versus once-daily adefovir dipivoxil, open-label TDF for up to 240 weeks was evaluated. Patients with both baseline and week 240 liver biopsies were evaluated for histologic changes.

Results: At baseline, 189/641 (29 %) patients randomized were Asian. Sixty-eight percent of Asian patients were male; 50 % were hepatitis B e antigen (HBeAg)-positive. At week 240, similar proportions of Asian (88 %) and non-Asian (87 %) patients demonstrated improvement in liver histology, and 19/22 (86 %) Asian patients with baseline cirrhosis were no longer cirrhotic. By modified intent-to-treat analysis, 74 % of Asian patients and 76 % of non-Asian patients had HBV DNA <400 copies/mL at the end of week 240 (P = 0.602). No differences were seen in HBeAg loss or seroconversion in Asian versus non-Asian patients. No Asian patient experienced hepatitis B surface antigen loss. Safety and tolerability of TDF through week 240, including changes in renal function and in hip/spine bone mineral density (from weeks 192 to 240), were comparable between Asian and non-Asian patients.

Conclusions: Long-term virologic and histologic efficacy and safety of TDF are comparable in Asian and non-Asian CHB patients.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • DNA, Viral / analysis
  • Double-Blind Method
  • Female
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Intention to Treat Analysis
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / immunology
  • Male
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use*
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Risk Factors
  • Tenofovir

Substances

  • DNA, Viral
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • Adenine