Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients

• Published in: Digestive and liver disease 2018-02, Vol.50 (2), p.156-162
• Main Authors: Cucchetti, Alessandro, D’Amico, Gennaro, Trevisani, Franco, Morelli, Maria Cristina, Vitale, Alessandro, Pinna, Antonio Daniele, Cescon, Matteo
• Format: Article
• Language: English
• Subjects: Competing risk; Direct-acting antivirals; Hepatitis C; Hepatocellular carcinoma; Markov model; Survival benefit; Sustained virological response
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2017.10.004

The achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infected patients will reduce decompensating terminal events. To investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy. A Markov model was built on clinical data of 494 cirrhotic patients and available literature to estimate probabilities of “death before HCC” and of “HCC occurrence” without and with DAA. In comparison to untreated patients, DAA therapy reduced the 20-year mortality before HCC by 21.9% in patients without varices and by 21.5% in those with varices, considering an SVR of 95% and no direct effect on hepatocarcinogenesis. Tumour occurrence increased by 5%–8.2% and the proportion of HCCs diagnosed in compensated stages increased to >98%. If we consider DAA as having “anti-tumoral” effects, the benefit becomes greater, achieving a 20-year survival of 81.5% in patients without varices, and 52.2% in patients with varices. Instead, if we consider DAA as having a “pro-tumoral” effect, then, the increased incidence of HCC nullifies the survival benefits. DAAs drastically reduce the mortality caused by the liver function worsening, increasing the proportion of HCCs diagnosed in compensated stages. Knowledge of the DAA effect on hepatocarcinogenesis remains pivotal.