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October 3 -7, 2019
San Francisco, CA
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Attaining SVR Drives Lower Liver Mortality With Treatment of HCV
  IDWeek, October 2-6, 2019, Washington, DC
Mark Mascolini
Liver mortality in people with HCV infection was significantly lower with versus without HCV therapy, and with direct-acting antiviral (DAA) therapy versus pegylated interferon/ribavirin (PEG/RBV) in a 61,629-person analysis of the US veterans ERCHIVES database [1]. But the main driver of lower liver mortality with treatment appeared to be attaining sustained virologic response (SVR), regardless of regimen type.
ERCHIVES investigators who conducted this study noted that research ties DAA therapy to lower overall mortality and to lower rates of hepatic decompensation, hepatocellular carcinoma, nonliver cancers, diabetes, and cardiovascular disease. But whether lower overall mortality with DAAs reflects a drop in liver-related deaths or lower rates of nonliver disease remains uncertain. To address this question, the ERCHIVES team conducted this study.
ERCHIVES is the Electronically Retrieved Cohort of HCV-Infected Veterans, which includes a contingent of HCV-negative controls. Researchers created and update the cohort by extracting demographic, clinical, lab, and pharmacy data from the Veterans Health Administration Corporate Data Warehouse.
This analysis included ERCHIVES veterans who received one or more courses of HCV therapy, excluding people also infected with HIV or HBV and those with missing lab data. For each treated veteran, the researchers identified an untreated veteran with HCV matched to the treated veteran by age, race, sex, body mass index, FIB-4 (liver fibrosis) score, smoking, diabetes, and coronary artery disease.
The investigators identified causes of death by applying ICD-10 codes to causes listed on death certificates; they categorized each cause of death as liver related or not liver related.
The analysis included 37,197 HCV-treated veterans and 24,432 untreated controls with HCV. Age averaged 57.9 in treated veterans and 55.1 in the untreated group (P < 0.0001). About 96% in both veteran groups were men. Treated and untreated proportions of whites were 56% and 54.5%, blacks 27% and 29%, and Hispanics 3% and 5% (P < 0.0001). The treated group included a lower proportion with alcohol use or dependence (42% versus 45%, P < 0.0001) and a lower proportion of current smokers (52% versus 58%, P < 0.0001).
During the 2002-2016 study period, a significantly lower proportion treated versus untreated for HCV died (9% versus 38%, P < 0.0001) and a lower proportion in the treated group had a liver-related death (2.8% versus 7.9%, P < 0.0001). Among treated veterans, 71.7% attained SVR.
Liver-related death rate came to 0.68 per 100 person-years in the HCV-treated group versus 1.29 per 100 in untreated controls, a highly significant difference (P < 0.0001). Liver-related mortality proved steeply and significantly lower in veterans who attained SVR than in those who did not (0.14 versus 1.40 per 100 person-years, P < 0.0001).
Among HCV-treated veterans, liver-related mortality was significantly lower in those treated with DAAs versus PEG/RBV (0.31 versus 0.76 per 100 person-years, P < 0.0001). Among people treated with PEG/RBV, liver-related mortality proved significantly lower in those who attained SVR than in those who did not (0.13 versus 1.44 per 100 person-years, P < 0.0001). Among people treated with DAAs, liver-related mortality was also lower in the SVR group (0.20 per 100 person-years, P = 0.02 versus PEG/RBV SVR group) than in the non-SVR group (0.81 per 100 person-years, P < 0.0001 versus PEG/RBV SVR group).
Calculating liver-related mortality rate difference between various groups indicated that attaining SVR drove the lower liver death rate in treated versus untreated veterans with HCV:
-- DAA SVR versus PEG/RBV SVR: rate difference 0.07 per 100 person-years
-- DAA versus PEG/RBV: rate difference 0.41 per 100 person-years
-- Treated versus untreated: rate difference 0.61 per 100 person-years
-- SVR versus no SVR: rate difference 1.26 per 100 person-years
The ERCHIVES team concluded that lower liver mortality with HCV treatment "is largely driven by attainment of SVR and is independent of the regimen used when stratified by SVR attainment."
1. Butt AA, Yan P, Aslam S, Lo Re V, Shaikh OS. Reduction in liver-related mortality among HCV infected persons is driven by attainment of SVR independent of the regimen used: results from the ERCHIVES cohort. IDWeek, October 2-6, 2019, Washington, DC. Abstract 2896.