Research Article| Volume 63, ISSUE 2, P337-345, August 2015

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Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir

Published:March 18, 2015DOI:

      Background & Aims

      New interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir + ledipasvir.


      Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir + ledipasvir + ribavirin or sofosbuvir + ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies.


      There were 1005 patients included (stage F0: n = 94; F1: n = 311; F2: n = 301; F3: n = 197; F4: n = 102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0–1 scale p <0.0001). During and post-treatment, HRQL remained lower in patients with advanced fibrosis. After achieving sustained virologic response, significant improvements from baseline in most HRQL domains were observed regardless of fibrosis stage (by 0.024–0.103 on a 0–1 scale; all p >0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to −0.056 in comparison with none-to-mild fibrosis, p <0.05). However, improvement of HRQL and work productivity after viral clearance was not related to the stage of fibrosis (all p >0.05).


      Although advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir + ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis.

      Graphical abstract


      HRQL (health-related quality of life), CLDQ-HCV (Chronic Liver Disease Questionnaire-Hepatitis C Virus), SF-36 (Short Form-36), FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue), WPAI:SHP (Work Productivity and Activity Index:Specific Health Problem), CH-C (chronic hepatitis C), HCV (hepatitis C virus), SOF (sofosbuvir), LDV (ledipasvir), RBV (ribavirin), SVR (sustained virologic response), PF (physical functioning), RP (role physical), BP (bodily pain), GH (general health), VT (vitality), SF (social functioning), RE (role emotional), MH (mental health), PCS (physical component summary), MCS (mental component summary), PWB (physical well-being), EWB (emotional well-being), SWB (social well-being), FWB (functional well-being), FS (fatigue scale), AE (activity/energy scale), EM (emotional scale), WO (worry scale), SY (systemic scale), WI (work productivity impairment), AI (activity impairment), HU (health utility)


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        • Davis G.L.
        • Roberts W.L.
        The healthcare burden imposed by liver disease in aging Baby Boomers.
        Curr Gastroenterol Rep. 2010; 12: 1-6
        • Holmberg S.D.
        • Spradling P.R.
        • Moorman A.C.
        • Denniston M.M.
        Hepatitis C in the United States.
        N Engl J Med. 2013; : 1859-1861
        • Ansaldi F.
        • Orsi A.
        • Sticchi L.
        • Bruzzone B.
        • Icardi G.
        Hepatitis C virus in the new era: perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy.
        World J Gastroenterol. 2014; 20: 9633-9652
        • Younossi Z.M.
        • Kanwal F.
        • Saab S.
        • Brown K.A.
        • El-Serag H.B.
        • Kim W.R.
        • et al.
        The impact of hepatitis C burden: an evidence-based approach.
        Aliment Pharmacol Ther. 2014; 39: 518-531
        • Verna E.C.
        Hepatitis viruses and liver transplantation: evolving trends in antiviral management.
        Clin Liver Dis. 2014; 18: 575-601
        • Forton D.M.
        • Allsop J.M.
        • Cox I.J.
        • Hamilton G.
        • Wesnes K.
        • Thomas H.C.
        • et al.
        A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection.
        AIDS. 2005; 19: S53-S63
        • Morais-de-Jesus M.
        • Daltro-Oliveira R.
        • Pettersen K.M.
        • Dantas-Duarte A.
        • Amaral L.D.
        • Cavalcanti-Ribeiro P.
        • et al.
        Hepatitis C virus infection as a traumatic experience.
        PLoS One. 2014; 9: e110529
        • Quarantini L.C.
        • Miranda-Scippa A.
        • Rocha M.
        • Bressan R.A.
        Neuropsychological function in patients with chronic hepatitis C.
        Liver Int. 2008; 28: 893-894
        • Batista-Neves S.C.
        • Quarantini L.C.
        • de Almeida A.G.
        • Bressan R.A.
        • Lacerda A.L.
        • de-Oliveira I.R.
        • et al.
        High frequency of unrecognized mental disorders in HCV-infected patients.
        Gen Hosp Psychiatry. 2008; 30: 80-82
        • Byrnes V.
        • Miller A.
        • Lowry D.
        • Hill E.
        • Weinstein C.
        • Alsop D.
        • et al.
        Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition.
        J Hepatol. 2012; 56: 549-556
        • Forton D.M.
        Hepatitis C treatment–clearing the mind.
        J Hepatol. 2012; 56: 513-514
        • Alsop D.
        • Younossi Z.
        • Stepanova M.
        • Afdhal N.
        Cerebral MR spectroscopy and patient-reported mental health outcomes in hepatitis C genotype 1 naïve patients treated with ledipasvir and sofosbuvir.
        Hepatol. 2014; 60: 221A
        • Jacobson I.M.
        • Cacoub P.
        • Dal Maso L.
        • Harrison S.A.
        • Younossi Z.M.
        Manifestations of chronic hepatitis C virus infection beyond the liver.
        Clin Gastroenterol Hepatol. 2010; 8: 1017-1029
        • Spiegel B.M.
        • Younossi Z.M.
        • Hays R.D.
        • Revicki D.
        • Robbins S.
        • Kanwal F.
        Impact of hepatitis C on health related quality of life: a systematic review and quantitative assessment.
        Hepatology. 2005; 41: 790-800
        • Martin L.M.
        • Younossi Z.M.
        Health-related quality of life (HRQL) in chronic liver disease.
        Dig Liver Dis. 2005; 37: 819-820
        • DiBonaventura Md.
        • Wagner J.S.
        • Yuan Y.
        • L’Italien G.
        • Langley P.
        • Ray Kim W.
        The impact of hepatitis C on labor force participation, absenteeism, presenteeism and non-work activities.
        J Med Econ. 2011; 14: 253-261
        • 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
        • Su J.
        • Brook R.A.
        • Kleinman N.L.
        • Corey-Lisle P.
        The impact of hepatitis C virus infection on work absence, productivity, and healthcare benefit costs.
        Hepatology. 2010; 52: 436-442
        • Kallman J.
        • O’Neil M.M.
        • Larive B.
        • Boparai N.
        • Calabrese L.
        • Younossi Z.M.
        Fatigue and health-related quality of life (HRQL) in chronic hepatitis C virus infection.
        Dig Dis Sci. 2007; 52: 2531-2539
        • McHutchison J.G.
        • Ware Jr, J.E.
        • Bayliss M.S.
        • Pianko S.
        • Albrecht J.K.
        • Cort S.
        • et al.
        The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity.
        J Hepatol. 2001; 34: 140-147
        • Younossi Z.
        • Kallman J.
        • Kincaid J.
        The effects of HCV infection and management on health-related quality of life.
        Hepatology. 2007; 45: 806-816
        • Snow K.K.
        • Bonkovsky H.L.
        • Fontana R.J.
        • Kim H.Y.
        • Sterling R.K.
        • Di Bisceglie A.M.
        • et al.
        Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C.
        Aliment Pharmacol Ther. 2010; 31: 719-734
        • Bonkovsky H.L.
        • Snow K.K.
        • Malet P.F.
        • Back-Madruga C.
        • Fontana R.J.
        • Sterling R.K.
        • et al.
        Health-related quality of life in patients with chronic hepatitis C and advanced fibrosis.
        J Hepatol. 2007; 46: 420-431
        • Alberti A.
        Impact of a sustained virological response on the long-term outcome of hepatitis C.
        Liver Int. 2011; 31: 18-22
        • Ware Jr, J.E.
        • Bayliss M.S.
        • Mannocchia M.
        • Davis G.L.
        Health-related quality of life in chronic hepatitis C: impact of disease and treatment response. The Interventional Therapy Group.
        Hepatology. 1999; 30: 550-555
        • 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
        • 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
        • Younossi Z.M.
        • Stepanova M.
        • Nader F.
        • Jacobson I.M.
        • Gane E.
        • Nelson D.
        • et al.
        Patient-reported outcomes in chronic hepatitis C patients with cirrhosis treated with sofosbuvir-containing regimens.
        Hepatology. 2014; 59: 2161-2169
        • Afdhal N.
        • Zeuzem S.
        • Kwo P.
        • Chojkier M.
        • Gitlin N.
        • Puoti M.
        • et al.
        Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
        N Engl J Med. 2014; 370: 1889-1898
        • Afdhal N.
        • Reddy K.R.
        • Nelson D.R.
        • Lawitz E.
        • Gordon S.C.
        • Schiff E.
        • et al.
        Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.
        N Engl J Med. 2014; 370: 1483-1493
        • Kowdley K.V.
        • Gordon S.C.
        • Reddy K.R.
        • Rossaro L.
        • Bernstein D.E.
        • Lawitz E.
        • et al.
        Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.
        N Engl J Med. 2014; 370: 1879-1888
      1. Younossi Z, Stepanova M, Marcellin, Afdhal N, Kowdley K, Zeuzem S, Hunt S. Treatment with interferon and ribavirin-free regimens with ledipasvir and sofosbuvir improves patient-reported outcomes for patients with genotype 1 chronic hepatitis C: results from the ION-1, 2 and 3 clinical trials. (Abstract): AASLD 2014.

        • Ware J.E.
        • Kosinski M.
        Interpreting SF-36 summary health measures: a response.
        Qual Life Res. 2001; 10 (Discussion 415–420): 405-413
        • 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
        • Martin L.
        • Younossi Z.
        Health-related quality of life (HRQOL) in chronic liver disease.
        Dig Liver Dis. 2005; 37: 819-820
        • 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
        • Brazier J.E.
        • Rowen D.
        • Hanmer J.
        Revised SF-6D scoring programmes: a summary of improvements.
        PRO Newsletter. 2008; 40: 14-15
        • Bedossa P.
        • Poynard T.
        An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.
        Hepatology. 1996; 24: 289-293
        • 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
        • 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. 2014; 12: 1349-1359.e13
        • Younossi Z.M.
        • Stepanova M.
        • Zeuzem S.
        • Dusheiko G.
        • Esteban R.
        • Hezode C.
        • et al.
        Patient-reported outcomes assessment in chronic hepatitis C treated with sofosbuvir and ribavirin: The VALENCE study.
        J Hepatol. 2014; 61: 228-234
        • Stepanova M.
        • Nader F.
        • Cure S.
        • Bourhis F.
        • Hunt S.
        • Younossi Z.M.
        Patients’ preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens.
        Aliment Pharmacol Ther. 2014; 40: 676-685