Achieving viral cure from hepatitis C does not eliminate liver cancer risk — a finding with profound implications for the estimated 57 million people living with chronic HCV globally, millions of whom were infected for decades before modern antivirals became available. This research, conducted in a unique primate cohort, reinforces that sustained virologic response is a treatment milestone, not a cancer-free guarantee.
Eight captive chimpanzees with experimentally induced HCV infections of 25 to 43 years' duration were treated with modern direct-acting antiviral regimens, primarily the NS3/4A and NS5A inhibitor combination glecaprevir/pibrentasvir. Six animals achieved sustained virologic response, confirming that these regimens can eradicate decades-long infection in non-human primates. However, three of the six successfully treated animals subsequently developed hepatocellular carcinoma — and critically, one case arose in the absence of detectable cirrhosis, the condition most commonly assumed to be the prerequisite for post-SVR liver cancer. Two animals experienced virologic failure, with resistance mutations in the NS5A region identified as the likely culprits, mirroring resistance patterns documented in human clinical settings.
This primate model provides longitudinal data that is almost impossible to obtain ethically in human cohorts — animals with known infection dates, controlled exposures, and decades of observation. The emergence of HCC post-SVR, including in a non-cirrhotic liver, challenges the clinical assumption that fibrosis staging alone should dictate surveillance intensity. In human hepatology, guidelines already recommend continued HCC monitoring post-cure for patients with advanced fibrosis, but this finding suggests the threshold for surveillance may need to be reconsidered for anyone with prolonged infection history. The small cohort size (n=8) limits statistical inference, and species differences in hepatic metabolism complicate direct extrapolation. Nevertheless, the biological parallelism is striking, and this study reinforces the mechanistic case that chronic HCV-associated hepatic inflammation may permanently alter oncogenic risk pathways even after the virus is eliminated.