For the roughly one million people globally living with both HIV and hepatitis C, clearing the hepatitis C virus has long been understood as a liver-saving milestone — but how much residual cancer risk remains, and for how long, has been poorly quantified. This matters enormously for designing rational surveillance schedules that neither over- nor under-screen a vulnerable population.
Drawing on HepCAUSAL, a large multinational cohort collaboration spanning Europe and North America, investigators modeled hepatocellular carcinoma (HCC) risk across six years following direct-acting antiviral (DAA) therapy in 3,824 HIV-HCV coinfected individuals who all had advanced liver fibrosis or cirrhosis. The study population was predominantly male, with a median age of 60. Using a weighted pooled logistic regression approach to simulate universal DAA initiation, the estimated six-year cumulative HCC risk was 2.5%. Crucially, annual HCC probability was not static: it began at approximately 0.81% in the first year post-treatment and declined progressively to just 0.10% by year six, suggesting that residual oncogenic risk, while persistent, diminishes meaningfully over time.
This trajectory has real clinical implications. Current guidelines in many countries recommend indefinite biannual ultrasound surveillance for anyone with cirrhosis regardless of HCV cure status, a resource-intensive protocol whose justification partly depends on how quickly risk truly falls. This dataset, one of the largest specifically in HIV-HCV coinfection with advanced fibrosis, provides granular annual probability estimates that could support risk-stratified surveillance — perhaps more intensive early post-cure and less frequent thereafter. A key limitation is that the cohort was predominantly older European males, limiting generalizability to women, younger patients, or lower-income settings. Additionally, the analysis cannot fully disentangle HIV-specific immunological contributions from fibrosis stage alone. Still, the progressive and sustained risk reduction observed adds meaningful, actionable evidence to an area where data in coinfected populations have historically been sparse.