Prediction of risk for hepatocellular carcinoma by response of serum α-fetoprotein to entecavir therapy

J Gastroenterol Hepatol. 2015 Jul;30(7):1175-82. doi: 10.1111/jgh.12921.

Abstract

Background and aims: Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC.

Methods: All consecutive nucleos(t)ide-naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment.

Results: Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy.

Conclusions: Delayed AFP response to ETV may serve as an indicator of high HCC risk.

Keywords: chronic hepatitis B; entecavir; α-fetoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / etiology
  • Female
  • Forecasting
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / etiology
  • Male
  • Middle Aged
  • Risk
  • Time Factors
  • alpha-Fetoproteins / analysis*

Substances

  • Antiviral Agents
  • Biomarkers, Tumor
  • alpha-Fetoproteins
  • entecavir
  • Guanine