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Treatment of HCV reduces viral hepatitis-associated liver-related mortality in patients: An ERCHIVES study

Published:March 04, 2020DOI:https://doi.org/10.1016/j.jhep.2020.02.022

      Highlights

      • Treatment of HCV with any regimen was associated with a 75% reduction in liver-related mortality.
      • A sustained virologic response to treatment was associated with a 90% reduction in liver-related mortality.
      • Compared to pegylated interferon/ribavirin, treatment with DAA regimens was associated with reduced liver-related mortality.

      Background & Aims

      Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown.

      Methods

      We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR).

      Results

      Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27–0.30) for Group A; 1.44 (1.38–1.49) for Group B; and 0.06 (0.05–0.06) for Group C; (p <0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05–0.06) for those with SVR vs. 0.78 (0.74–0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09–0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08–0.11) were associated with reduced hazards of liver-related mortality.

      Conclusions

      Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies.

      Lay summary

      Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

      Graphical abstract

      Keywords

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