Association Between Sustained Virological Response and All-Cause Mortality Among Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis

• Published in: JAMA : the journal of the American Medical Association Vol. 308; no. 24; pp. 2584 - 2593
• Main Authors: van der Meer, Adriaan J, Veldt, Bart J, Feld, Jordan J, Wedemeyer, Heiner, Dufour, Jean-François, Lammert, Frank, Duarte-Rojo, Andres, Heathcote, E. Jenny, Manns, Michael P, Kuske, Lorenz, Zeuzem, Stefan, Hofmann, W. Peter, de Knegt, Robert J, Hansen, Bettina E, Janssen, Harry L. A
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 26.12.2012
• Subjects: Adult; Antiviral Agents - therapeutic use; Biological and medical sciences; Canada - epidemiology; Cause of Death; Epidemiology; Europe - epidemiology; Female; Fibroids; Follow-Up Studies; General aspects; Hepatitis; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - mortality; Hepatitis C, Chronic - virology; Hepatology; Human viral diseases; Humans; Infectious diseases; Interferons - therapeutic use; Liver Cirrhosis - complications; Liver Cirrhosis - virology; Liver Failure - complications; Liver Failure - virology; Male; Medical sciences; Middle Aged; Mortality; Public health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Viral diseases; Viral hepatitis; Viremia; Virology; Canada; Europe; Hepatic fibrosis; Human; Mortality; Hepatic disease; Patient; Epidemiology; Infection; Medicine; Association; Viral disease; Cause; Digestive diseases; Advanced stage; Viral hepatitis C
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2012.144878

CONTEXT Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death. OBJECTIVE To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis. DESIGN, SETTING, AND PATIENTS An international, multicenter, long-term follow-up study from 5 large tertiary care hospitals in Europe and Canada of 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis (Ishak score 4-6). Complete follow-up ranged between January 2010 and October 2011. MAIN OUTCOME MEASURES All-cause mortality. Secondary outcomes were liver failure, HCC, and liver-related mortality or liver transplantation. RESULTS The 530 study patients were followed up for a median (interquartile range [IQR]) of 8.4 (6.4-11.4) years. The baseline median (IQR) age was 48 (42-56) years and 369 patients (70%) were men. The Ishak fibrosis score was 4 in 143 patients (27%), 5 in 101 patients (19%), and 6 in 286 patients (54%). There were 192 patients (36%) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9% [95% CI, 3.3%-14.5%] with SVR and 26.0% [95% CI, 20.2%-28.4%] without SVR; P < .001). In time-dependent multivariate Cox regression analysis, SVR was associated with reduced risk of all-cause mortality (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P < .001) and reduced risk of liver-related mortality or transplantation (HR, 0.06; 95% CI, 0.02-0.19; P < .001), the latter occurring in 3 patients with SVR and 103 without SVR. The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9% (95% CI, 0.0%-4.1%) with SVR and 27.4% (95% CI, 22.0%-32.8%) without SVR (P < .001). There were 7 patients with SVR and 76 without SVR who developed HCC (10-year cumulative incidence rate, 5.1%; 95% CI, 1.3%-8.9%; vs 21.8%; 95% CI, 16.6%-27.0%; P < .001), and 4 patients with SVR and 111 without SVR experienced liver failure (10-year cumulative incidence rate, 2.1%; 95% CI, 0.0%-4.5%; vs 29.9%; 95% CI, 24.3%-35.5%; P < .001). CONCLUSION Among patients with chronic HCV infection and advanced hepatic fibrosis, sustained virological response to interferon-based treatment was associated with lower all-cause mortality.