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Original Contribution |

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

Adriaan J. van der Meer, MD; Bart J. Veldt, MD, PhD; Jordan J. Feld, MD, PhD; Heiner Wedemeyer, MD, PhD; Jean-François Dufour, MD, PhD; Frank Lammert, MD, PhD; Andres Duarte-Rojo, MD; E. Jenny Heathcote, MD, PhD; Michael P. Manns, MD, PhD; Lorenz Kuske; Stefan Zeuzem, MD, PhD; W. Peter Hofmann, MD, PhD; Robert J. de Knegt, MD, PhD; Bettina E. Hansen, PhD; Harry L. A. Janssen, MD, PhD
JAMA. 2012;308(24):2584-2593. doi:10.1001/jama.2012.144878.
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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.

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Figures

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Figure. Survival Outcomes for All-Cause Mortality, Liver-Related Mortality or Liver Transplantation, Hepatocellular Carcinoma, and Liver Failure in Patients With Chronic Hepatitis C and Advanced Hepatic Fibrosis With and Without Sustained Virological Response (SVR)
Grahic Jump Location

Survival curves for each outcome were constructed using a clock-reset approach; patients who switched from the without SVR to the with SVR group due to successful retreatment during follow-up were censored in the without SVR group at the time of SVR. The time of SVR was then defined as time zero for their further follow-up in the SVR group. Statistical significance between the survival curves in the without and with SVR groups was assessed with univariate Cox proportional hazards regression analyses, including SVR as a time-dependent covariate. The 10-year cumulative occurrence rates for all-cause mortality were 8.9% (95% CI, 3.3%-14.5%) for with SVR and 26.0% (95% CI, 20.2%-28.4%) for without SVR; for liver-related mortality or liver transplantation, 1.9% (95% CI, 0.0%-4.1%) for with SVR and 27.4% (95% CI, 22.0%-32.8%) for without SVR; for hepatocellular carcinoma, 5.1% (95% CI, 1.3%-8.9%) for with SVR and 21.8% (95% CI, 16.6%-27.0%) for without SVR; and for liver failure, 2.1% (95% CI, 0.0%-4.5%) for with SVR and 29.9% (95% CI, 24.3%-35.5%) for without SVR.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

April 10, 2013
Patrick Maisonneuve, DiplEng; Savino Bruno, MD
JAMA. 2013;309(14):1457. doi:10.1001/jama.2013.2726.
April 10, 2013
Adriaan J. van der Meer, MD; Bettina E. Hansen, PhD; Harry L. A. Janssen, MD, PhD
JAMA. 2013;309(14):1457. doi:10.1001/jama.2013.2733.
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