Minimal increases of serum alpha-foetoprotein herald HCC detection in Caucasian HBV cirrhotic patients under long-term oral therapy

Liver Int. 2019 Oct;39(10):1964-1974. doi: 10.1111/liv.14197. Epub 2019 Aug 12.

Abstract

Background & aims: In Caucasian patients with compensated cirrhosis caused by hepatitis B virus (HBV), the risk of hepatocellular carcinoma (HCC) developing persist despite long-term nucleos(t)ide analogs (NUC) treatment. In the surveillance of this population with persistently normal transaminases because of NUCs, the added value of serum alpha-foetoprotein (AFP) monitoring is poorly defined.

Methods: Two hundred and fifty-eight Caucasian HCC-free patients with HBV-compensated cirrhosis who started tenofovir or entecavir while having normal serum AFP levels (≤7 ng/mL) at baseline or within the first year of treatment underwent HCC surveillance by semiannual ultrasound evaluation and serum AFP determination.

Results: During 96 (18-120) months of antiviral therapy, 3947 AFP values were collected, median AFP level was 2 ng/mL. Thirty-five patients developed an HCC at an overall 8-year crude cumulative incidence of 14% (annual incidence of 2%). HCC incidence increased in parallel with increasing AFP thresholds: 24%, 36%, 64% and 92% for AFP levels after exceeding 2, 4, 6 and 7 ng/mL for the first-time. Of the 12 patients who experienced an AFP rise > 7 ng/mL, 11 developed an HCC and one had liver metastases of lung cancer. Overall, an AFP > 7 ng/mL had 99.6% specificity, 31.4% sensitivity, 91.7% PPV, 90.2% NPV, LR+ 70.1 and LR- 0.69 for HCC; this excellent specificity was maintained up to 18 months before HCC detection.

Conclusions: In Caucasian patients with HBV-compensated cirrhosis on long-term NUC, an increase in AFP over 7 ng/mL shows excellent specificity, heralding HCC development within 1 year.

Keywords: Alpha-foetoprotein; diagnostic tests; hepatitis B; hepatocellular carcinoma; surveillance.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Guanine / analogs & derivatives
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Italy / epidemiology
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / complications
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Tenofovir
  • Young Adult
  • alpha-Fetoproteins / metabolism*

Substances

  • Antiviral Agents
  • Biomarkers
  • alpha-Fetoproteins
  • entecavir
  • Guanine
  • Tenofovir