Alessandro Cucchetti1, Gennaro D'Amico2, Franco Trevisani3, Maria Cristina Morelli4, Alessandro Vitale5, Antonio Daniele Pinna3, Matteo Cescon3. 1. Department of Medical and Surgical Science - DIMEC, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. Electronic address: aleqko@libero.it. 2. Gastroenterology Unit, V Cervello Hospital, Ospedale V. Cervello, Palermo, Italy. 3. Department of Medical and Surgical Science - DIMEC, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. 4. Internal Medicine, S. Orsola - Malpighi Hospital, Bologna, Italy. 5. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
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.
BACKGROUND: The achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infectedpatients 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.