Patient-reported outcomes assessment in chronic hepatitis C treated with sofosbuvir and ribavirin: The VALENCE study

Published:April 07, 2014DOI:

      Background & Aim

      Interferon (IFN) negatively impacts patients’ well-being and patient-reported outcomes (PROs). Our aim was to assess PROs during treatment with an IFN-free regimen [sofosbuvir (SOF) + ribavirin (RBV)].


      Four PRO questionnaires [Short Form-36 (SF-36), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index: Specific Health Problem (WPAI:SHP)] were administered at baseline, end-of-treatment and post-treatment to 334 HCV genotype 2 and 3 patients (naïve or treatment-experienced) enrolled in the VALENCE study. Of these, 250 genotype 3 patients were treated for 24 weeks while 73 genotype 2 and 11 genotype 3 patients received 12 weeks of treatment.


      Baseline PRO scores were similar between the two arms of the study. Throughout and after treatment, patients receiving 12 or 24 weeks had similar FACIT-F, CLDQ-HCV, SF-36 and WPAI:SHP scores (all p >0.05). Compared to their own baseline scores, patients receiving SOF + RBV experienced modest declines in some aspects of SF-36, CLDQ-HCV, fatigue and WPAI:SHP scores (p = 0.04 to <0.0001). By follow-up week 12, all PRO scores returned to the pre-treatment levels (p >0.05). In patients achieving SVR-12 (regardless of the regimen), significant improvements were noted in general health (p = 0.0004), CLDQ-HCV (p <0.0001), fatigue (p = 0.005), emotional well-being (p <0.0001) and physical component summary score of SF-36 (p = 0.0022). In multivariate analysis, baseline depression, fatigue, insomnia, cirrhosis, and treatment-related adverse events were the most consistent predictors of PRO impairment (all p <0.05).


      PROs are minimally impacted by SOF + RBV regimens. An additional 12 weeks of treatment does not substantially add to the PRO burden.


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        • Hajarizadeh B.
        • Grebely J.
        • Dore G.J.
        Epidemiology and natural history of HCV infection.
        Nat Rev Gastroenterol Hepatol. 2013; 10: 553-562
        • Vietri J.
        • Prajapati G.
        • El Khoury A.C.
        The burden of hepatitis C in Europe from the patients’ perspective: a survey in 5 countries.
        BMC Gastroenterol. 2013; 13: 16
        • Younossi Z.M.
        • Stepanova M.
        Hepatitis C virus infection, age, and Hispanic ethnicity increase mortality from liver cancer in the United States.
        Clin Gastroenterol Hepatol. 2010; 8: 718-723
        • Ghany M.G.
        • Strader D.B.
        • Thomas D.L.
        • Seeff L.B.
        American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update.
        Hepatology. 2009; 49: 1335-1374
        • Ghany M.G.
        • Nelson D.R.
        • Strader D.B.
        • Thomas D.L.
        • Seeff L.B.
        An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases.
        Hepatology. 2011; 54: 1433-1444
        • Younossi Z.
        • Kallman J.
        • Kincaid J.
        The effects of HCV infection and management on health-related quality of life.
        Hepatology. 2007; 45: 806-816
        • Brook R.A.
        • Kleinman N.L.
        • Su J.
        • Corey-Lisle P.K.
        • Iloeje U.H.
        Absenteeism and productivity among employees being treated for hepatitis C.
        Am J Manag Care. 2011; 17: 657-664
        • McHutchison J.G.
        • Ware J.E.
        • Bayliss M.S.
        • Pianko S.
        • Albrecht J.K.
        • Cort S.
        • et al.
        The effects of interferon alpha 2-b in combination with ribavirin and health related quality of life and productivity.
        J Hepatol. 2001; 34: 140-147
        • Hassanein T.
        • Cooksley G.
        • Sulkowski M.
        • Smith C.
        • Marinos G.
        • Lai M.Y.
        • et al.
        The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C.
        J Hepatol. 2004; 40: 675-681
        • Younossi Z.M.
        • Singer M.E.
        • Mir H.M.
        • Henry L.
        • Hunt S.
        Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.
        J Hepatol. 2014; 60: 530-537
        • Younossi Z.M.
        • Stepanova M.
        • Henry L.
        • Gane E.
        • Jacobson I.M.
        • Lawitz E.
        • et al.
        Effects of sofosbuvir-based treatment, with and without interferon, on outcome and productivity of patients with chronic hepatitis C.
        Clin Gastroenterol Hepatol. 2013;
        • Younossi Z.M.
        • Stepanova M.
        • Henry L.
        • Gane E.
        • Jacobson I.M.
        • Lawitz E.
        • et al.
        Minimal impact of sofosbuvir and ribavirin on health related quality of life in chronic hepatitis C (CH-C).
        J Hepatol. 2014; 60: 741-747
        • Lawitz E.
        • Mangia A.
        • Wyles D.
        • Rodriguez-Torres M.
        • Hassanein T.
        • Gordon S.C.
        • et al.
        Sofosbuvir for previously untreated chronic hepatitis C infection.
        N Engl J Med. 2013; 368: 1878-1887
        • Zeuzem S.
        • Dusheiko G.
        • Salupere R.
        • Mangia A.
        • Flisiak R.
        • Hyland R.
        • et al.
        Sofosbuvir + ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial.
        Hepatology. 2013; 58: 1085
        • Hays R.D.
        • Morales L.S.
        The RAND-36 measure of health-related quality of life.
        Ann Med. 2001; 33: 350-357
        • Cella D.F.
        • Tulsky D.S.
        • Gray G.
        • Sarafian B.
        • Linn E.
        • Bonomi A.
        • et al.
        The Functional Assessment of Cancer Therapy (FACT) scale: development and validation of the general measure.
        J Clin Oncol. 1993; 11: 570-579
        • Webster K.
        • Odom L.
        • Peterman A.
        • Lent L.
        • Cella D.
        The Functional Assessment of Chronic Illness Therapy (FACIT) measurement system: validation of version 4 of the core questionnaire.
        Qual Life Res. 1999; 8: 604
        • Younossi Z.M.
        • Guyatt G.
        • Kiwi M.
        • Boparai N.
        • King D.
        Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease.
        Gut. 1999; 45: 295-300
        • Reilly M.C.
        • Zbrozek A.S.
        • Dukes E.M.
        The validity and reproducibility of a work productivity and activity impairment instrument.
        PharmacoEconomics. 1993; 4: 353-365
        • Evon D.M.
        • Esserman D.A.
        • Bonner J.E.
        • Rao T.
        • Fried M.W.
        • Golin C.E.
        Adherence to PEG/ribavirin treatment for chronic hepatitis C: prevalence, patterns, and predictors of missed doses and nonpersistence.
        J Viral Hepat. 2013; 20: 536-549
        • Younossi Z.M.
        • Stepanova M.
        • Afendy M.
        • Lam B.P.
        • Mishra A.
        Knowledge about infection is the only predictor of treatment in patients with chronic hepatitis C.
        J Viral Hepat. 2013; 20: 550-555
        • Hézode C.
        • Fontaine H.
        • Dorival C.
        • Larrey D.
        • Zoulim F.
        • Canva V.
        • et al.
        Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890.
        J Hepatol. 2013; 59: 434-441
        • Younossi Z.M.
        • Nader F.H.
        • Bai C.
        • Sjogren R.
        • Ong J.P.
        • Collantes R.
        • et al.
        A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment.
        J Viral Hepat. 2008; 15: 370-378
        • John-Baptiste A.A.
        • Tomlinson G.
        • Hsu P.C.
        • Krajden M.
        • Heathcote E.J.
        • Laporte A.
        • et al.
        Sustained responders have better quality of life and productivity compared with treatment failures long after antiviral therapy for hepatitis C.
        Am J Gastroenterol. 2009; 104: 2439-2448