Abstract

Background: Cross-sectional studies have identified individuals from sub-Saharan Africa with (SSA) chronic hepatitis B (CHB) as a potential risk group for hepatocellular carcinoma (HCC) and advocate enrolment in an HCC surveillance program even in the absence of cirrhosis. However, the incidence of HCC and performance of HCC risk scores in this population are unknown.

Methods: We conducted an international multicenter retrospective cohort study of all consecutive hepatitis B virus (HBV) mono-infected individuals with SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5 and 10 year cumulative incidence of HCC in the overall study population and according to baseline fibrosis grade and HBV DNA levels. We also studied potential other predictors of HCC development using Cox regression. Finally, we assessed the performance of the (m)PAGE-B score for stratifying HCC risk.

Results: We analyzed 1473 individuals; the majority of whom were male (59.7%) with a median age of 38 years (interquartile range [IQR] 29-46) at enrolment. At baseline 12.7% had advanced fibrosis (METAVIR ≥F3 based on biopsy or FibroScan). During a median follow-up of 8 years (IQR 3.9 – 11.4) 34 individuals developed HCC. The 5 and 10 year cumulative incidence of HCC was 1% (95% confidence interval [CI] 0.99 – 1.01) and 2.5% (95% CI 2.39–2.41), with no difference observed across ethnicities (p=0.238). Among individuals without advanced fibrosis at baseline, the 5 and 10 year cumulative incidence of HCC was 0% and 0.7%, compared to 7.1% and 12.1% among individuals with advanced fibrosis (p<0.001). The 5 and 10 year cumulative HCC incidence was 0.7% and 1% for individuals with a baseline HBV DNA <2,000 IU/mL compared to 1.3% and 3.6% among individuals with HBV DNA at baseline > 2,000 IU/mL (p=0.031). In addition to baseline fibrosis grade and HBV DNA levels, univariate analysis revealed that older age (hazard ratio [HR] 1.07, 95% CI 1.04–1.10 p<0.001), male sex (HR 2.59, 95% CI 1.13–5.94 p=0.025), platelet count (HR 0.98, 95% CI 0.97–0.98 p<0.001), and albumin (HR 0.89, 95% CI 0.83–0.94 p<0.001) were significantly associated with HCC development. The 10 year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score (n=771, 52.3% of cohort), compared to 2.9% in the intermediate risk group (n=569, 38.6% of cohort) and 15.9% in the high risk group (n=85, 5.8% of cohort; p<0.001). Similar results were obtained for the modified PAGE-B score.

Conclusion: This unique international multicenter cohort of SSA and AS individuals with CHB shows a limited 5 and 10 year cumulative risk of HCC. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. Based on these findings, the majority of these patients can potentially be excluded from HCC surveillance based on absence of advanced fibrosis and/or low HCC risk scores.