| Autor: |
Rosato V; Liver Unit, Ospedale Evangelico Betania, 80147 Napoli, Italy., Nevola R; Liver Unit, Ospedale Evangelico Betania, 80147 Napoli, Italy., Dallio M; Hepatogastroenterology Division, Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', 80131 Naples, Italy., Di Micco P; AFO Medica, P.O. Santa Maria delle Grazie, ASL Napoli 2 Nord, 80076 Pozzuoli, Italy., Spinetti A; Division of Infectious and Tropical Diseases, Department of Clinical and Experimental Sciences, University of Brescia and ASST Spedali Civili, 25123 Brescia, Italy., Zeneli L; Division of Infectious and Tropical Diseases, Department of Clinical and Experimental Sciences, University of Brescia and ASST Spedali Civili, 25123 Brescia, Italy., Ciancio A; Gastro-Hepatoloy Unit, Department of Medical Sciences, University of Turin, 10126 Torino, Italy., Milella M; Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, 70121 Bari, Italy., Colombatto P; Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy., D'Adamo G; Umberto I Hospital, UOC General Medicine, 20122 Nocera, Italy., Rosselli Del Turco E; Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero, Universitaria di Bologna, 40138 Bologna, Italy., Gallo P; Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy., Falcomatà A; Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy., De Nicola S; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy., Pugliese N; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy., D'Ambrosio R; Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy., Soria A; Clinic of Infectious Diseases, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy., Colella E; Clinic of Infectious Diseases, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy., Federico A; Hepatogastroenterology Division, Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', 80131 Naples, Italy., Brunetto M; Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy., Vespasiani-Gentilucci U; Clinical Medicine and Hepatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy.; Research Unit of Clinical Medicine and Hepatology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, 00128 Roma, Italy., Aghemo A; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy.; Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy., Lampertico P; Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.; CRC 'A. M. and A. Migliavacca' Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, 20126 Milan, Italy., Izzi A; Infectious Diseases, Azienda Ospedaliera D. Cotugno, 80131 Naples, Italy., Mastrocinque D; Liver Unit, Ospedale Evangelico Betania, 80147 Napoli, Italy., Claar E; Liver Unit, Ospedale Evangelico Betania, 80147 Napoli, Italy. |
| Abstrakt: |
Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results : A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions : In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit. |
