HCV may be implicated in the pathogenesis of neurocognitive impairment (NCI), but its precise contribution in the setting of the HIV infected (HIV+) population is still controversial. HCV-mediated liver injury may itself contribute to NCI. We investigated the effect of HCV infection and liver function (Lf) on neurocognition.
From a prospective, monocenter, observational study conducted from January 2000 to July 2017 on neuropsychological (NP) evaluations, we selected HIV+ patients (pts) with known HCV status: negative serology (HCV-), positive serology (HCV+), viremic (RNA+), aviremic (RNA-). A comprehensive battery of 14 tests on 5 different domains was used to classify HIV-associated neurocognitive disorders (HAND) according to Frascati’s criteria. NPZ8 was used as summary measure of z-scores of NP tests. Fibrosis 4 score (Fib4) was calculated as measure of Lf. Chi-square and K-Wallis tests were used for statistical comparisons. Stepwise backward multivariable logistic regression was employed to investigate predictors of HAND.
Excluding pts with confounding factors for HAND diagnosis, we analyzed 1,305 pts: 953 HCV-, 109 HCV+RNA-, 243 HCV+RNA+. Male 79%, median age 45 yrs (IQR 38-52), median education 13 yrs (IQR 8-13), IDUs 17%, median CD4 nadir 215/mm3 (IQR 98-336) and current 491/mm3 (IQR 285-710), on antiretroviral therapy (ART) 82%, HIV RNA <50 copies/mL 59%. Table 1 depicts HAND prevalence and NPZ8 according to HCV status (1a) and to Fib4 score strata in all pts (1b) and in HCV+RNA+ pts (1c). A higher prevalence of HAND together with lower median NPZ8 scores were found in HCV+ pts (with or without HIV RNA) and with higher Fib4. In HCV+RNA+ pts, frequency of HAND was similar across Fib4 stages. Adjusting for demographics and clinical variables (age, education level, current and nadir CD4 count, HIV-RNA, mode of HIV transmission, years from HIV test, ART, Fib4), HCV+RNA+ was associated to higher risk of HAND [OR 1.51(1.06-2.13), p 0.021]. When excluding the variable age from the model, Fib4 >3.25 had higher risk of HAND [OR 2.04(1.15-3.61), p 0.015].
Our results show that both, HCV co-infection and worse liver function scores were associated with detrimental neurocognitive performance in HIV+ pts. Notably, among pts with actively replicating HCV, NCI was not influenced by liver function scores. Now that curative anti-HCV therapy is available, these findings need further investigation.