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      Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience

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          Abstract

          Objective: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. Material and methods: The impact of established response predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12–16 weeks in accordance with national guidelines. Results: In the NORDynamIC trial, age <40 years or achieving HCV RNA <1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12–16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. Conclusions: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation.

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          Most cited references21

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          Histological grading and staging of chronic hepatitis.

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            Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.

            Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. Randomized, double-blind trial. 99 international centers. 1311 patients with chronic hepatitis C. Peginterferon-alpha2a, 180 microg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
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              Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options.

              Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.).
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                Author and article information

                Journal
                Scand J Gastroenterol
                Scand. J. Gastroenterol
                IGAS
                igas20
                Scandinavian Journal of Gastroenterology
                Informa Healthcare
                0036-5521
                1502-7708
                3 March 2016
                29 September 2015
                : 51
                : 3
                : 337-343
                Affiliations
                [ a ]Department of Infectious Medicine/Virology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Sweden
                [ b ]Clinic of Gastroenterology, Helsinki University Hospital, University of Helsinki , Helsinki, Finland
                [ c ]Department of Clinical Science, University of Bergen , Bergen, Norway
                [ d ]Department of Medicine, Haukeland University Hospital , Bergen, Norway
                [ e ]Department of Infectious Diseases, University of Southern Denmark , Odense, Denmark
                [ f ]Department of Infectious Diseases, Aarhus University , Aarhus, Denmark
                [ g ]Infektion, Skaraborgs Sjukhus Skövde , Skövde, Sweden
                [ h ]Infektionskliniken, Hallands sjukhus , Halmstad, Sweden
                [ i ]Infektionskliniken, Södra Älvsborgs Sjukhus , Borås, Sweden
                [ j ]Infektionskliniken, NÄL , Trollhättan, Sweden
                [ k ]Infektionskliniken, Centralsjukhuset , Karlstad, Sweden
                [ l ]Infektionskliniken, Gävle Sjukhus , Gävle, Sweden
                Author notes
                CONTACT: Martin Lagging, MD, PhD, martin.lagging@ 123456medfak.gu.se , Department of Infectious Diseases/Virology , Guldhedsgatan 10B, SE-413 46 Göteborg, Sweden
                Article
                1087588
                10.3109/00365521.2015.1087588
                4732462
                26418670
                db8b250c-09ff-4906-9dfc-580396295a96
                © 2015 Taylor & Francis

                © 2015 The Author(s). Published by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/Licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 April 2015
                : 20 August 2015
                : 22 August 2015
                Page count
                Pages: 7
                Categories
                Article
                Liver and Biliary Tract

                Gastroenterology & Hepatology
                genotype 2,genotype 3,hepatitis c virus,inosine triphosphate pyrophosphatase,interferon,itpa,ribavirin

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