Quantifying a Neglected Burden: Pregnancy-Associated Hepatocellular Carcinoma and Maternal Death in South Africa
Keith Venter, Sanju Sobnach, Urda Kotze, Inae Kim, C. Wendy Spearman, Mark Sonderup, Neliswa Gogela, Dale Creamer, Ayesha Osman, Leann Schoeman, Marc Bernon, Eduard JonasPurpose
Hepatocellular carcinoma (HCC) during pregnancy is rare, with the literature confined to isolated case reports and small series. Women in sub-Saharan Africa (SSA) face disproportionate risk due to chronic hepatitis B virus (HBV) infection acquired perinatally, HCC in noncirrhotic livers at a young age, and fertility rates nearly three times those of Europe. To our knowledge, we report the largest cohort of pregnancy-associated HCC from SSA, drawn from a single South African center, and the first quantitative estimate of regional disparity versus Europe.
Methods
Pregnant women with HCC at Groote Schuur Hospital, Cape Town, over 24 years (2001-2025) were identified from a prospectively maintained registry. A model integrating HCC incidence, age-at-diagnosis, fertility rates, and 1-year mortality compared the probability of pregnancy-associated HCC and maternal death in SSA versus Europe.
Results
Of the 728 registry patients, 192 (26.4%) were female and 10 (5.2%) were pregnant or within 1 year postpartum. The median age was 32.5 (IQR, 28.5-35.3), 70% had chronic HBV infection, and three had cirrhosis. Seven (70%) died, six within 90 days. Two patients survived beyond 10 years following curative resection. Four pregnancies ended in intrauterine fetal demise and five in live births. The modeled probability of pregnancy-associated HCC was 16 per 100,000 women in SSA versus 0.14 per 100,000 in Europe—a 114-fold difference—with a 187-fold greater risk of maternal death.
Conclusion
Pregnancy-associated HCC in SSA is a quantifiable, preventable contributor to maternal mortality—nearly two orders of magnitude greater than in Europe. HBV endemicity, early-onset noncirrhotic HCC, and high fertility rates create a hostile environment for women of reproductive age. HBV-aware liver surveillance in antenatal care, strengthened prevention of mother-to-child transmission programs, and improved maternal mortality data systems are urgently needed.