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      Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C – a real-world study

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      1 , 2 , , 3 , 3 , 4 , 5 , 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 1 , 2 , 14 , 15 , 1 , 16 , 17 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 18 , 11 , 12 , 13
      Clinical and Experimental Hepatology
      Termedia Publishing House
      HCV infection, direct-acting antivirals, drug-drug interactions

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          Abstract

          Aim of the study

          This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy.

          Material and methods

          Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool ( http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used.

          Results

          Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic.

          Conclusions

          Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.

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          Most cited references21

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          Overutilization of proton-pump inhibitors: what the clinician needs to know

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            Hepatitis C virus drug resistance-associated substitutions: State of the art summary.

            Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon-free, all-oral combinations of direct-acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct-acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials.
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              Association of diabetes mellitus and chronic hepatitis C virus infection.

              While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.
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                Author and article information

                Journal
                Clin Exp Hepatol
                Clin Exp Hepatol
                CEH
                Clinical and Experimental Hepatology
                Termedia Publishing House
                2392-1099
                2449-8238
                05 September 2019
                September 2019
                : 5
                : 3
                : 215-223
                Affiliations
                [1 ]Provincial Specialist Hospital. J. Gromkowskiego, Wroclaw, Poland
                [2 ]Department of Infectious Diseases and Hepatology, Wroclaw Medical University, Poland
                [3 ]Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Poland
                [4 ]Hepatology Outpatient Clinic, ID Clinic, Myslowice, Poland
                [5 ]Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, Szczecin, Poland
                [6 ]Department of Infectious Diseases, Voivodeship Hospital and Jan Kochanowski University, Kielce, Poland
                [7 ]Department of Tropical and Infectious Disease and Hepatology, Medical University of Warsaw, Poland
                [8 ]Department of Infectious Diseases, Poznan University of Medical Sciences, Poland
                [9 ]Department of Infectious and Liver Diseases, Medical University of Lodz, Poland
                [10 ]Daily Unit, Hospital of Infectious Diseases in Warsaw, Poland
                [11 ]Department of Infectious Diseases, Liver Diseases and Immune Deficiencies, Wroclaw Medical University, Poland
                [12 ]Department of Infectious Diseases and Hepatology, Medical University of Lublin, Poland
                [13 ]Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
                [14 ]Department of Infectious Diseases and Hepatology, Medical University of Lodz, Poland
                [15 ]Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Poland
                [16 ]2 nd Department of Infectious Diseases, Voivodeship Specialist Hospital, Wroclaw, Poland
                [17 ]Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Krakow, Poland
                [18 ]Department of Adult’s Infectious Diseases, Medical University of Warsaw, Poland
                Author notes
                Address for correspondence Prof. Krzysztof Adam Simon, Department of Infectious Diseases and Hepatology, Wroclaw Medical University, 5 Koszarowa St., 51-149 Wroclaw, Poland. e-mail: krzysimon@ 123456gmail.com
                Article
                37553
                10.5114/ceh.2019.87634
                6781817
                65743137-02a4-47ed-8c84-449fecfc0536
                Copyright: © 2019 Clinical and Experimental Hepatology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                : 21 January 2019
                : 07 March 2019
                Categories
                Original Paper

                hcv infection,direct-acting antivirals,drug-drug interactions

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