Advertisement

A Sustained Virologic Response Reduces Risk of All-Cause Mortality in Patients With Hepatitis C

Published:March 14, 2011DOI:https://doi.org/10.1016/j.cgh.2011.03.004

      Background & Aims

      The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities.

      Methods

      From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009.

      Results

      HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002).

      Conclusions

      An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.

      Keywords

      Abbreviations used in this paper:

      ALT (alanine aminotransferase), AST (aspartate aminotransferase), GT (genotype), HCV (hepatitis C virus), HTN (hypertension), ICD-9 (International Classification of Diseases, 9th revision), PEG-IFN (pegylated interferon alfa), SVR (sustained virologic response), VA (Department of Veterans Affairs)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Singal A.G.
        • Volk M.L.
        • Jensen D.
        • et al.
        A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus.
        Clin Gastroenterol Hepatol. 2010; 8: 280-288
        • Lloyd-Jones D.M.
        • Martin D.O.
        • Larson M.G.
        • et al.
        Accuracy of death certificates for coding coronary heart disease as the cause of death.
        Ann Intern Med. 1998; 129: 1020-1026
        • Mostafa A.
        • Mohamed M.K.
        • Saeed M.
        • et al.
        Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors.
        Gut. 2010; 59: 1135-1140
        • Imazeki F.
        • Yokosuka O.
        • Fukai K.
        • et al.
        Favorable prognosis of chronic hepatitis C after interferon therapy by long-term cohort study.
        Hepatology. 2003; 38: 493-502
        • Yu M.L.
        • Lin S.M.
        • Chuang W.L.
        • et al.
        A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan.
        Antivir Ther. 2006; 11: 985-994
        • Shiratori Y.
        • Ito Y.
        • Yokosuka O.
        • et al.
        Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival.
        Ann Intern Med. 2005; 142: 105-114
        • Fernandez-Rodriguez C.M.
        • Alonso S.
        • Martinez S.M.
        • et al.
        Peginterferon plus ribavirin and sustained virological response in HCV-related cirrhosis: outcomes and factors predicting response.
        Am J Gastroenterol. 2010; 105: 2174-2176
        • Veldt B.J.
        • Heathcote E.J.
        • Wedemeyer H.
        • et al.
        Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis.
        Ann Intern Med. 2007; 147: 677-684
        • Tanaka Y.
        • Kurbanov F.
        • Mano S.
        • et al.
        Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality.
        Gastroenterology. 2006; 130: 703-714
        • Keam S.J.
        • Cvetkovic R.S.
        Peginterferon-alpha-2a (40 kD) plus ribavirin: a review of its use in the management of chronic hepatitis C mono-infection.
        Drugs. 2008; 68: 1273-1317
        • Backus L.I.
        • Boothroyd D.B.
        • Phillips B.R.
        • et al.
        Predictors of response of US veterans to treatment for the hepatitis C virus.
        Hepatology. 2007; 46: 37-47
        • Olshansky S.J.
        • Passaro D.J.
        • Hershow R.C.
        • et al.
        A potential decline in life expectancy in the United States in the 21st century.
        N Engl J Med. 2005; 352: 1138-1145
        • Armstrong G.L.
        • Wasley A.
        • Simard E.P.
        • et al.
        The prevalence of hepatitis C virus infection in the United States, 1999 through 2002.
        Ann Intern Med. 2006; 144: 705-714
        • Mole L.A.
        • Halloran J.P.
        • Backus L.I.
        Numbers for knowledge, knowledge for care.
        Public Health Strategic Health Care Group, Washington, DC2007 (2–3)
        • Butt A.A.
        • Wang X.
        • Moore C.G.
        Effect of hepatitis C virus and its treatment on survival.
        Hepatology. 2009; 50: 387-392
        • Backus L.I.
        • Gavrilov S.
        • Loomis T.P.
        • et al.
        Clinical Case Registries: simultaneous local and national disease registries for population quality management.
        J Am Med Inform Assoc. 2009; 16: 775-783
        • Martinot-Peignoux M.
        • Christianne S.
        • Pierre R.M.
        • et al.
        Assessment of serum HCV RNA at week 12 post-treatment is as relevant as week 24 to predict SVR in patients with chronic hepatitis C treatment with pegylated interferon plus ribavirin.
        Hepatology. 2009; 50: S118
        • Zeuzem S.
        • Heathcote E.J.
        • Shiffman M.L.
        • et al.
        Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon alpha for chronic hepatitis C.
        J Hepatol. 2003; 39: 106-111
        • Cockcroft D.W.
        • Gault M.H.
        Prediction of creatinine clearance from serum creatinine.
        Nephron. 1976; 16: 31-41
        • Dienstag J.L.
        • McHutchison J.G.
        American Gastroenterological Association technical review on the management of hepatitis C.
        Gastroenterology. 2006; 130: 231-264
        • Wright T.L.
        • Yee H.
        VA treatment recommendations for patients with chronic hepatitis C.
        Federal Practitioner. 2003; 20: 1-33
        • Arnold N.
        • Sohn M.
        • Maynard C.
        • et al.
        VIReC technical report 2: VA-NDI mortality data merge project.
        Hines, IL: VA Information Resource Center. 2006;
        • Pai J.K.
        • Pischon T.
        • Ma J.
        • et al.
        Inflammatory markers and the risk of coronary heart disease in men and women.
        N Engl J Med. 2004; 351: 2599-2610
        • Haffner S.M.
        The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease.
        Am J Cardiol. 2006; 97: 3A-11A

      Linked Article