HCV infection has been associated with increased non-liver-related morbidity and mortality; however studies have yielded inconsistent results.
The incidence of clinical events in four HCV-seropositive groups (untreated spontaneously cleared/detectable HCV-RNA, treated with/without sustained virologic response (SVR)) and matched HCV-seronegative Swiss HIV Cohort Study (SHCS) participants from 08/1994 to 12/2014 were studied. We compared HCV-seropositive to HCV–seronegative patients and aviremic to replicating HCV infection. Poisson regression was used to assess differences across these groups (see footnote in Figure).
We included 2503 HCV-seropositive individuals, 540 with cleared HCV infection, 1294 untreated viremic, 345 treated with SVR, 281 treated without SVR, and 2503 HCV-seronegative controls. After a mean follow-up of 8.2 years, we observed 107/18 (HCV-seropositive/HCV-seronegative) liver events, 41/14 kidney diseases, 230/121 osteoporosis/fracture, 114/129 cardiovascular events, 162/126 HIV CDC B/C events, 106/10 liver-related deaths and 227/218 non-liver-related deaths. Adjusted incidence rate ratios for the HCV-negative and different HCV-seropositive groups are shown in the Figure. Compared to HIV-monoinfected controls, HCV-seropositive groups combined had an increased risk of liver disease (IRR 6.29 [95% CI 3.52-11.22]), liver-related death (8.24 [3.61-18.83]), kidney events (2.43 [1.11-5.33]) and osteoporosis/fracture (1.43 [1.03-2.01]). No evidence for an association with increased risk was found for cardiovascular diseases, HIV CDC B/C events and non-liver-related death. Among HCV-seropositive individuals, those with replicating HCV infection had an increased risk of liver-related events compared to aviremic participants (untreated viremic vs cleared 2.84 [1.36-5.89]; non-SVR vs SVR 6.74 [1.36-5.89]) and liver-related death (untreated viremic vs cleared 2.10 [0.99-4.47]; non-SVR vs SVR 3.36 [1.37-8.21]). Non-liver-related diseases and death did not significantly differ between HCV viremic vs aviremic patients.
While incidence for non-liver-related death and cardiovascular events was not elevated, HCV exposure was associated with an increased risk of kidney disease and osteoporosis. This risk did not seem to be dependent of persistent HCV replication.