Hepatitis C Infection and the Risk of Non-Liver-Related Morbidity and Mortality in HIV-Infected Persons in the Swiss HIV Cohort Study

Abstract

Background: Hepatitis C virus (HCV) infection has been associated with increased non-liver-related morbidity and mortality. However, studies have yielded inconsistent results.
Methods: The incidence of clinical events in human immunodeficiency virus (HIV)–infected HCV-seropositive and incidence density–matched HCV-seronegative participants of the Swiss HIV Cohort Study from August 1994 to December 2014 was studied. We compared (1) HCV-seropositive with HCV-seronegative participants and (2) HCV-viremic with successfully treated nonviremic patients. Poisson regression was used to assess differences between these groups.
Results: We included 2503 HCV-seropositive participants (540 with spontaneous HCV clearance, 1294 untreated HCV RNA positive, 345 treated with sustained virologic response [SVR], 43 during treatment, and 281 treated without SVR), and 2503 HCV-seronegative controls. After a mean follow-up of 8.2 years, we observed (HCV seropositive and HCV seronegative, respectively) 107 and 18 liver events, 41 and 14 kidney events, 230 and 121 osteoporosis/fractures, 82 and 94 diabetes mellitus, 114 and 129 cardiovascular events, 119 and 147 non-AIDS malignancies, 162 and 126 Centers for Disease Control and Prevention HIV category B/C events, 106 and 10 liver-related deaths, and 227 and 218 non-liver-related deaths. Compared with HCV-negative controls, HCV-seropositive participants had an increased risk of liver events (incidence rate ratio [IRR], 6.29 [95% confidence interval {CI}, 3.52–11.22]), liver-related death (IRR, 8.24 [95% CI, 3.61–18.83]), kidney events (IRR, 2.43 [95% CI, 1.11–5.33]), and osteoporosis/fracture (IRR, 1.43 [95% CI, 1.03–2.01]). Among HCV-seropositive individuals, treated participants without SVR vs those with SVR had a higher risk of liver events (IRR, 6.79 [95% CI, 2.33–19.81]), liver-related death (IRR, 3.29 [95% CI, 1.35–8.05]), and diabetes mellitus (IRR, 4.62 [95% CI, 1.53–13.96]). Similar but not statistically significant differences were found between untreated HCV RNA–positive patients and those with SVR.
Conclusions: While HCV exposure was associated with an increased risk of kidney disease and osteoporosis/fracture, this risk did not seem to be dependent of persistent HCV RNA. Successful HCV treatment was associated with a lower incidence of liver disease, liver-related death, and diabetes mellitus, whereas the other conditions studied were less affected.