NEW research suggests that direct-acting antivirals provide long-term protection against hepatocellular carcinoma comparable to interferon-based therapy in patients cured of hepatitis C, while also introducing a practical nomogram to identify individuals who remain at elevated cancer risk years after viral eradication.
With direct-acting antivirals now the standard of care for hepatitis C, concerns have persisted about whether rapid viral clearance alters long-term hepatocellular carcinoma risk. To address this, investigators analysed outcomes in patients achieving sustained virologic response following either interferon-based or DAA therapy and developed a predictive tool for long-term HCC surveillance.
Long-Term Outcomes After Viral Clearance
The study analysed 405 patients treated with either interferon or DAA regimens, using propensity score matching to compare 200 patients who achieved sustained virologic response. Over a median follow-up of 72 months, hepatocellular carcinoma developed in 7% of patients treated with interferon and 15% treated with DAAs.
Despite this numerical difference, cumulative HCC incidence did not differ significantly between groups. Hazard ratio analysis showed no increased long-term HCC risk associated with DAA therapy compared with interferon, supporting the view that DAAs offer equivalent cancer protection following hepatitis C cure.
Building a Predictive Nomogram
To improve post-cure risk stratification, the researchers used Cox regression, LASSO regression, and best subset regression to identify independent predictors of hepatocellular carcinoma. Across models, four variables consistently emerged as key predictors: age, sex, platelet count, and alkaline phosphatase levels.
A nomogram incorporating these factors demonstrated strong predictive performance for 8-year HCC risk, achieving an area under the receiver operating characteristic curve of 0.905. Decision curve analysis indicated meaningful clinical utility, suggesting the tool could support personalised surveillance strategies.
Implications for Post-HCV Care
The findings reinforce that while hepatitis C eradication substantially reduces liver cancer risk, it does not eliminate it entirely. Importantly, the newly developed nomogram offers clinicians a simple, evidence-based approach to identify patients who may benefit from closer long-term monitoring after cure.
The authors conclude that DAAs provide durable protection against hepatocellular carcinoma comparable to interferon therapy, and that risk-adapted screening guided by predictive tools could optimise long-term outcomes for patients cured of hepatitis C.
Reference
Li J et al. Development of a nomogram for predicting the long-term risk of hepatocellular carcinoma after antiviral treatment for hepatitis C. BMC Gastroenterol. 2025;DOI: 10.1186/s12876-025-04412-x.
