Tenofovir disoproxil fumarate reduces hepatocellular carcinoma, decompensation and death in chronic hepatitis B patients with cirrhosis

Aliment Pharmacol Ther. 2019 Nov;50(9):1037-1048. doi: 10.1111/apt.15499. Epub 2019 Sep 16.

Abstract

Background: Lamivudine and entecavir reduce hepatic events and death in chronic hepatitis B (CHB) patients with cirrhosis, but the impact of tenofovir disoproxil fumarate (TDF) is less well studied.

Aim: To investigate the effectiveness of TDF therapy in CHB patients with cirrhosis.

Methods: We studied TDF-treated and untreated CHB patients with cirrhosis from three tertiary centres. TDF cohort included consecutive patients who received TDF for ≥12 months while the untreated cohort were historical controls receiving routine clinical care prior to the availability of anti-viral therapy. The primary outcome was 5-year cumulative probability of hepatocellular carcinoma (HCC) with secondary outcomes being hepatic decompensation and death or liver transplantation (LT).

Results: A total of 1088 (291 untreated and 797 TDF-treated) patients were included in the study. Five-year cumulative probabilities in untreated vs TDF-treated cohorts were 14.9% vs 9.8% for HCC (P = .07), 22.3% vs 5.9% for decompensation (P < .01) and 13.1% vs 1.1% for death or LT (P < .01) respectively. On multivariable Cox regression, TDF treatment was independently associated with reduced risks of HCC (adjusted hazard ratio [aHR] 0.46, P < .01), decompensating events (aHR 0.28, P = .01) and death or LT (aHR 0.06, P < .01). On sensitivity analyses, these risk reductions with TDF treatment were consistently demonstrated regardless of severity of liver disease and prior anti-viral treatment. TDF treatment led to sustained improvements in most validated prognostic scores for predicting HCC, decompensation and death.

Conclusions: Compared to untreated patients, TDF treatment reduces the risks of HCC, hepatic decompensation and death in CHB patients with cirrhosis at 5 years.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / prevention & control*
  • Cohort Studies
  • Female
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / mortality*
  • Hepatitis B, Chronic / pathology
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / mortality
  • Liver Failure / etiology
  • Liver Failure / mortality
  • Liver Failure / pathology
  • Liver Failure / prevention & control*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / prevention & control*
  • Liver Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Tenofovir / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Tenofovir