Research Article| Volume 74, ISSUE 4, P850-859, April 2021

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

Published:November 24, 2020DOI:


      • We used a case-control paradigm to investigate HCC screening effectiveness in HBV-infected patients.
      • We identified 169 cases who died of HCC, matched to 169 controls who did not die of HCC.
      • HCC screening by ultrasound and/or serum AFP was associated with a significant reduction in HCC-related mortality.

      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.


      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.


      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).


      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.

      Graphical abstract


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