Treatment failure of chronic hepatitis C with new direct antiviral agents


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A Master's thesis.
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Master (thesis) (master)
Treatment failure of chronic hepatitis C with new direct antiviral agents
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Université de Lausanne, Faculté de biologie et médecine
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Introduction. Chronic hepatitis C is an infectious disease of the liver affecting approximately 70 million people worldwide, responsible for elevated morbidity and mortality. In Switzerland, it is a prevalent cause of decompensated cirrhosis, hepatocellular carcinoma and, therefore, liver transplantation. Until 2014, chronic hepatitis C virus (HCV) infection was treated by pegylated interferon- and ribavirin, with unsatisfying sustained virological response (SVR) rates of approximately 40-50% depending on the genotype and the stage of fibrosis. Moreover, these treatments were associated with major side effects. Introduction of so-called direct antiviral agents (DAA) constitutes a major progress in this field. Indeed, these DAA are associated with impressive improvement of SVR rates, currently superior to 95% for all genotypes. Unfortunately, a minority of patients do not achieve viral cure after DAA treatment.
Patients and methods. We conducted an observational retrospective study aiming to characterize all chronically HCV infected patients who experienced a relapse after DAA treatment in the Service of Gastroenterology and Hepatology of the Lausanne University Hospital (CHUV) from January 2015 to February 2018. All adult patients who had experienced virological relapse were included. These were assigned to the relapse group (RG) which was compared to the control group (CG) composed of the patients who had reached SVR within the same period.
Results. A total of 306 patients were included, 22 in the RG and 284 in the CG. Overall SVR rate was 92.8%. The majority of patients were men (68.2% in the RG and 70.1% in the CG). The mean age was 58.7 years in the RG and 55.3 years in the CG. We assessed 20 out of 22 relapser patients for significant mutations in the HCV NS3, NS5A and NS5B coding regions. Significant mutations were identified in all these 20 tested patients. The presence of cirrhosis and increasing age were associated with treatment failure.
Conclusion. We confirm high SVR rates with DAA-based treatment of chronic hepatitis C. However, a small proportion of patients fails on DAAs and requires second-line treatment regimens. A multicentric Swiss retrospective and prospective study is currently being conceived to extend our findings.
direct antiviral agents, hepatitis C, sustained virological response, virological relapse
Create date
07/09/2020 8:55
Last modification date
07/10/2020 5:26
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