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

Abstract

Background: 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.

Aims: To investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Competing risk; Direct-acting antivirals; Hepatitis C; Hepatocellular carcinoma; Markov model; Survival benefit; Sustained virological response.