Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B

J Hepatol. 2021 Apr;74(4):850-859. doi: 10.1016/j.jhep.2020.11.023. Epub 2020 Nov 24.

Abstract

Background & aims: Patients with chronic hepatitis B (CHB) infection routinely undergo screening for hepatocellular carcinoma (HCC), but the efficacy of screening remains unclear. We aimed to evaluate the impact of screening with ultrasound and/or serum alpha-fetoprotein (AFP) on HCC-related mortality in patients with CHB.

Methods: We performed a matched case-control study of patients with CHB receiving care through the Veterans Affairs (VA) health administration. Cases were patients who died of HCC between 01/01/2004 and 12/31/2017, while controls were patients with CHB who did not die of HCC. Cases were matched to controls by CHB diagnosis date, age, sex, race/ethnicity, cirrhosis, antiviral therapy exposure, hepatitis B e antigen status, and viral load. We identified screening ultrasound and AFPs obtained in the 4 years preceding HCC diagnosis in cases and the equivalent index date in controls. Using conditional logistic regression, we compared cases and controls with respect to receipt of screening. A lower likelihood of screening in cases corresponds to an association between screening and reduced risk of HCC-related mortality.

Results: We identified 169 cases, matched to 169 controls. Fewer cases than controls underwent screening with either screening modality (33.7% vs. 58.6%) or both modalities (19.5% vs. 34.4%). In multivariable conditional logistic regression, screening with either modality was associated with a lower risk of HCC-related mortality (adjusted odds ratio [aOR] 0.21, 95% CI 0.09-0.50), as was screening with both modalities (aOR of 0.13; 95% CI 0.04-0.43).

Conclusions: HCC screening was associated with a substantial reduction in HCC-related mortality in VA patients with CHB.

Lay summary: Patients with hepatitis B infection have a high risk of developing liver cancer. It is therefore recommended that they undergo frequent screening for liver cancer, but whether this leads to a lower risk of dying from liver cancer is not clear. In this study, we show that liver cancer screening is associated with a reduction in the mortality from liver cancer in patients with hepatitis B infection.

Keywords: Alpha-fetoprotein; Hepatitis B; Liver cancer; Surveillance; Ultrasound.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Case-Control Studies
  • Early Detection of Cancer* / methods
  • Early Detection of Cancer* / statistics & numerical data
  • Female
  • Hepatitis B e Antigens / analysis*
  • Hepatitis B, Chronic* / blood
  • Hepatitis B, Chronic* / diagnosis
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / epidemiology
  • Humans
  • Liver / diagnostic imaging
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mortality
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Ultrasonography* / methods
  • Ultrasonography* / statistics & numerical data
  • United States / epidemiology
  • alpha-Fetoproteins / analysis*

Substances

  • AFP protein, human
  • Antiviral Agents
  • Hepatitis B e Antigens
  • alpha-Fetoproteins