Advanced hepatic fibrosis and steatosis are associated with persistent alanine aminotransferase elevation in chronic hepatitis C patients negative for hepatitis C virus RNA during pegylated interferon plus ribavirin therapy

J Infect Dis. 2015 May 1;211(9):1429-36. doi: 10.1093/infdis/jiu630. Epub 2014 Nov 11.

Abstract

Background: Clinical implications of persistent alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon plus ribavirin (peg-IFN/RBV) therapy remain unknown.

Methods: A total of 1113 CHC patients with undetectable HCV RNA during peg-IFN/RBV therapy were enrolled. Baseline characteristics associated with persistent on-treatment ALT elevation (POAE), and its impact on treatment outcomes, were investigated.

Results: Of 1113 CHC patients, 254 (22.8%) had POAE. Among patients with HCV genotype 1 (HCV-1) who had complete early virologic response (EVR) and received 48 weeks of therapy, patients with POAE had a lower rate of sustained virologic response (SVR) than those without POAE (44.1% vs 74.0%; P = .0002). Multivariate analyses showed that body mass index ≥ 27 kg/m(2), ALT level ≥3 times the upper limit of normal, aspartate aminotransferase to platelet ratio index score ≥1.5, hepatic fibrosis ≥F3, and hepatic steatosis ≥S2 were independent factors associated with POAE after viral clearance.

Conclusions: POAE is common in CHC patients during therapy. HCV-1 patients with POAE have a lower SVR rate to 48-week therapy if they achieve complete EVR. Advanced hepatic fibrosis, obesity, and steatosis are factors associated with POAE in these patients.

Keywords: HCV RNA; alanine aminotransferase; chronic hepatitis C; hepatic fibrosis; steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood*
  • Alanine Transaminase / metabolism
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use
  • Drug Therapy, Combination
  • Fatty Liver / enzymology
  • Fatty Liver / pathology*
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / metabolism*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / pathology*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / pathology*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • RNA, Viral / isolation & purification*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Alanine Transaminase
  • peginterferon alfa-2b
  • peginterferon alfa-2a