The Natural History and Prognostic Determinants of Untreated Hepatocellular Carcinoma in a Sub-Saharan African Cohort

BACKGROUND: Data on the natural history of untreated hepatocellular carcinoma (HCC) are limited and derive mostly from patients in untreated arms of randomised control trials, conducted in high income countries. In this study, we determined the natural history of untreated HCC and identify predictors of survival in a predominantly SSA cohort of patients managed at Groote Schuur Hospital, Cape Town, South Africa. METHODS: A 35-year retrospective cohort study of 469 patients with untreated HCC managed at Groote Schuur Hospital, Cape Town, South Africa from 1990 to 2025 was conducted. Demographics, clinical features, laboratory data, radiological findings and survival were analysed. Multivariate Cox regression identified independent predictors of mortality. RESULTS: The cohort comprised 347 (74%) men, with a median age of 48 [19–89] years. The majority (380/469, 81.0%) were from South Africa, while the remaining 89 patients originated mostly from other neighbouring SSA countries. Chronic hepatitis B virus (HBV) infection was the leading aetiology (53.3%). Most (96.3%) presented with advanced disease (BCLC stage C or D), with high rates of multifocal tumours (69.1%), portal vein tumour thrombosis (38.8%) and extrahepatic metastases (32.6%). The median overall survival was 36.5 days and the one, six and 12-month survival rates were 59.8%, 14.4% and 7.6% respectively. Independent predictors of mortality included poor performance status, elevated alpha-fetoprotein levels, hypoalbuminemia, higher CTP grade, elevated MELD-Na and advanced BCLC stage. CONCLUSION: Untreated HCC in sub-Saharan Africa is marked by advanced presentation and aggressive disease with rapid clinical deterioration and poor long-term survival. This study highlights the critical need for earlier diagnosis, HBV prevention and the development of accessible, early context-appropriate palliative care interventions in resource-limited settings.