Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy

Clin Gastroenterol Hepatol. 2017 Jul;15(7):1087-1094.e2. doi: 10.1016/j.cgh.2017.01.032. Epub 2017 Feb 12.

Abstract

Background & aims: Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate.

Methods: We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level.

Results: Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P = .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P = .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P = .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level.

Conclusions: HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. ClinicalTrials.gov registration numbers: NCT00117676 and NCT00116805.

Keywords: Adiponutrin/Patatin-Like Phospholipase-3; HBV; Hepatitis B Virus Infection; Serum Transaminase.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood*
  • Antiviral Agents / administration & dosage*
  • Biopsy
  • Clinical Trials, Phase III as Topic
  • Fatty Liver / pathology
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / pathology*
  • Histocytochemistry
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • Tenofovir / administration & dosage*
  • Young Adult

Substances

  • Antiviral Agents
  • Hepatitis B e Antigens
  • Tenofovir
  • Alanine Transaminase

Associated data

  • ClinicalTrials.gov/NCT00116805
  • ClinicalTrials.gov/NCT00117676