Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure

Hepatology. 2011 Mar;53(3):774-80. doi: 10.1002/hep.24109. Epub 2011 Feb 3.

Abstract

Spontaneous reactivation of chronic hepatitis B (CHB) is an important cause of acute-on-chronic liver failure (ACLF). Antiviral drugs may help reduce the high morbidity and mortality in such patients, especially in places where liver transplant is not available. The aim was to evaluate the efficacy of tenofovir and to determine the predictors of mortality in patients with spontaneous reactivation of CHB with ACLF. Consecutive patients of ACLF due to spontaneous reactivation of CHB were randomized to receive either tenofovir or placebo. The primary endpoint was survival at 3 months. Of the 90 patients with ACLF of different etiologies, 27 (26%) were due to reactivation of CHB and were enrolled. The median baseline hepatitis B virus (HBV) DNA level was 9 × 10(5) IU/mL. Fourteen patients received tenofovir and 13 placebo. At 3 months the probability of survival was higher in the tenofovir than the placebo group (8/14 [57%] versus 2/13 [15%], respectively; P = 0.03). The cause of death in the 15 patients was progressive liver failure leading to multiorgan failure. Liver transplantation could not be offered due to its nonavailability. In the surviving patients, there was a significant improvement in the Child-Turcotte Pugh (CTP) and model for endstage liver disease (MELD) scores and significant decline in the HBV DNA levels in the tenofovir group, whereas these parameters did not change significantly in the placebo group. More than 2 log reduction in HBV DNA levels at 2 weeks was found to be an independent predictor of survival.

Conclusion: Tenofovir significantly reduces HBV-DNA levels, improves CTP and MELD scores, and reduces mortality in patients with severe spontaneous reactivation of CHB presenting as ACLF. Reduction in HBV-DNA levels at 2 weeks should be a desirable goal and is a good predictor of survival.

Trial registration: ClinicalTrials.gov NCT01074645.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use*
  • DNA, Viral* / analysis
  • Female
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • India / epidemiology
  • Liver Failure, Acute / drug therapy*
  • Liver Failure, Acute / mortality
  • Male
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • Tenofovir
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Tenofovir
  • Adenine

Associated data

  • ClinicalTrials.gov/NCT01074645