Vincenza Calvaruso1, Giuseppe Cabibbo1, Irene Cacciola2, Salvatore Petta1, Salvatore Madonia3, Alessandro Bellia4, Fabio Tinè5, Marco Distefano6, Anna Licata7, Lydia Giannitrapani7, Tullio Prestileo8, Giovanni Mazzola9, Maria Antonietta Di Rosolini10, Licia Larocca11, Gaetano Bertino12, Antonio Digiacomo13, Francesco Benanti14, Luigi Guarneri15, Alfonso Averna16, Carmelo Iacobello17, Antonio Magro18, Ignazio Scalisi19, Fabio Cartabellotta20, Francesca Savalli21, Marco Barbara1, Antonio Davì10, Maurizio Russello4, Gaetano Scifo6, Giovanni Squadrito2, Calogero Cammà1, Giovanni Raimondo2, Antonio Craxì1, Vito Di Marco22. 1. Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy. 2. UOC Epatologia Clinica e Biomolecolare and AOUP G Martino, Dipartimento di Medicina Interna e Sperimentale, University of Messina, Messina, Italy. 3. UOC Medicina Interna, AO Villa Sofia-Cervello, Palermo, Italy. 4. UOS Epatologia, ARNAS Garibaldi-Nesima, Catania, Italy. 5. UOC Gastroenterologia, AO Villa Sofia-Cervello, Palermo, Italy. 6. UOC Malattie Infettive, Ospedale Vittorio Emanuele di Siracusa, ASP Siracusa, Siracusa, Italy. 7. UOC Medicina Interna, AOUP Paolo Giaccone, Palermo, Italy. 8. UOC Malattie Infettive, ARNAS Civico-Di Cristina-Benefratelli, Palermo, Italy. 9. UOC Malattie Infettive, Azienda Ospedaliera Universitaria Paolo Giaccone, Palermo, Italy. 10. UOC Malattie Infettive, Ospedale di Modica, ASP Ragusa, Ragusa, Italy. 11. UOC Malattie infettive, AOUP G Rodolico, Catania, Italy. 12. UOC Medicina Interna, AOUP G Rodolico, Catania, Italy. 13. UOC Medicina Interna, Ospedale di Comiso, ASP Ragusa, Ragusa, Italy. 14. UOC Malattie Infettive, ARNAS Garibaldi-Nesima, Catania, Italy. 15. UOC Malattie Infettive, Ospedale di Enna, ASP Enna, Enna, Italy. 16. UOC Malattie Infettive, Ospedale di Caltanissetta, ASP Caltanissetta, Caltanissetta, Italy. 17. UOC Malattie Infettive, AO Cannizzaro, Catania, Italy. 18. UOC Medicina Interna, Ospedale di Agrigento, ASP Agrigento, Agrigento, Italy. 19. UOC Medicina Interna, Ospedale di Mazzara del Vallo, ASP, Trapani, Italy. 20. UOC Medicina Interna, Ospedale Buccheri La Ferla, Palermo, Italy. 21. UOC Malattie Infettive, Ospedale di Trapani, ASP Trapani, Trapani, Italy. 22. Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo, Italy. Electronic address: vito.dimarco@unipa.it.
Abstract
BACKGROUND & AIMS: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. METHODS: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus-associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. RESULTS: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6-24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12-2.82, P = .015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11-7.15, P < .001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89-6.12, P < .001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2-22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P = .07). CONCLUSIONS: In an analysis of data from a large prospective study of patients with hepatitis C virus-associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months.
BACKGROUND & AIMS: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. METHODS: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus-associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. RESULTS: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6-24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12-2.82, P = .015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11-7.15, P < .001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89-6.12, P < .001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2-22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P = .07). CONCLUSIONS: In an analysis of data from a large prospective study of patients with hepatitis C virus-associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months.
Authors: Amit G Singal; Nicole E Rich; Neil Mehta; Andrea D Branch; Anjana Pillai; Maarouf Hoteit; Michael Volk; Mobolaji Odewole; Steven Scaglione; Jennifer Guy; Adnan Said; Jordan J Feld; Binu V John; Catherine Frenette; Parvez Mantry; Amol S Rangnekar; Omobonike Oloruntoba; Michael Leise; Janice H Jou; Kalyan Ram Bhamidimarri; Laura Kulik; George N Ioannou; Annsa Huang; Tram Tran; Hrishikesh Samant; Renumathy Dhanasekaran; Andres Duarte-Rojo; Reena Salgia; Sheila Eswaran; Prasun Jalal; Avegail Flores; Sanjaya K Satapathy; Sofia Kagan; Purva Gopal; Robert Wong; Neehar D Parikh; Caitlin C Murphy Journal: Gastroenterology Date: 2019-07-30 Impact factor: 22.682