Direct antivirals and cognitive impairment in hepatitis C: a clinical-neurophysiologic study

Abstract

Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of "cognitive" significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.

Keywords: Cognitive impairment; Direct antiviral agents; Hepatitis C; Neuropsychology; P300 wave.

Fig. 1

Group values of the P300 latency (average of the Cz, Fz, and Pz electrodes) at T0 in the hepatitis C virus (HCV) and non-alcoholic fatty liver disease (NAFLD) patients, and in healthy subjects (HS). Bars represent standard error of the mean. *p = 0.04 vs NAFLDs

Fig. 2

Group values of the change (T1-T0) in the P300 latency (average of the Cz, Fz, and Pz electrodes) across the 3 subject populations. Abbreviations: see Fig. 1. Bars represent standard error of the mean. *p = 0.03 vs NAFLDs and HCVs

Fig. 3

a, b Typical example of a P300 recording in an HCV patient (#15) prior (a) and after (b) the treatment with direct antiviral agents (T0 and T1). All electrodes were referred to averaged mastoids. Blue wave: averaged potential evoked by the standard stimulus. Red wave: averaged potential evoked by the oddball stimulus in the “active” paradigm. Blue vertical line: stimulus onset. Black vertical line: P300 latency, which shows a detectable shortening at T1. EOG Electro-oculogram