Sex Differences in Extrahepatic Outcomes After Antiviral Treatment for Hepatitis C.

Abstract

Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.