Hepatitis C causes neurotoxic ‘brain fog’

HCV linked to impaired cognition, decreased motor function. Patients with chronic hepatitis C frequently report a persistent lassitude, or "brain fog", that seriously impairs their functioning. To this end, Canadian researchers have discovered organic brain abnormalities in these patients that suggest a direct link between cerebral dysfunction and hepatitis C, regardless of disease severity. Additional study results show that almost half of patients with even mildly fibrotic hepatitis C virus (HCV) develop impaired learning ability, and one in six suffer from reduced motor skills. Patients with chronic HCV frequently report fatigue and difficulty with concentration, even in the earliest stages of the disease, first author, told attendees of the 2002 Canadian Digestive Diseases Week meeting, where these findings were presented. Brain fog occurs in patients without cirrhosis. It does not reflect the effects of hepatic encephalopathy in these cases, said by a PhD student in the Departments of Neurology and Gastroenterology, University of Toronto Health Network. Nor is it secondary to an effective disturbance, as one might expect in the chronically ill. Rather, the investigators argue that brain fog in noncirrhotic HCV patients may be the result of a neurotoxic response to the virus itself.

Neurophysiological testing

In the first phase of their study, the Toronto group administered neuropsychological tests to 25 noncirrhotic HCV patients (mean age, 45.04+5.60 years) to assess their memory, concentration and processing speed. The mean Metavir fibrosis score of the group was 1.37 Fibrosis is staged 0-4 with 4 being fibrotic. Patients were pre-screened for comorbid medical, psychiatric and neurological conditions that could influence cognitive performance. None of the patients were currently substance abusers or had a prior history of drug dependence. Scores on the Hopkins Verbal Learning Test revealed impaired learning efficiency in 12 patients (48 percent). Three patients showed additional impairment in psychomotor speed following evaluation with the Trail Making Rest (parts A and B) and the digit symbol coding component of the Wechster Adults Intelligence Scale – Third Edition (WAIS-III). Only one patient showed impairment in psychomotor speed without memory impairment.

On the Beck Depression Inventory, 23 patients (92 percent) scored within the non-depressed range (mean score, (9.43+6.90). Notably, the two patients with scores indicating mild depression showed no learning impairment at all. Not only were neuropsychological scores not related to depressive symptoms, they also bore no relation to patients’ fibrosis scores or liver enzymes levels.

Blood chemistry

In the second phase of the study, the brain chemistry of eight consecutive patients in whom neuropsychological impairment had been detected was assessed by magnetic resonance spectroscopy (MRS). Eight matched controls and four cirrhotic HCV patients were also assessed. MRS measures the concentration of cerebral metabolites that serve as markers of cellular dysfunction and neuronal viability, and is sensitive to pathophysiological changes in the central nervous system associated with hepatic encephalopathy. The typical pattern seen in hepatic encephalopathy is elevated levels if glutamine/glutamate (G1x) and decreased levels of choline and myoinositol. Glutamate had been implicated in epilepsy and stroke, so it would be interesting to find it in HCV patients experiencing neuropsychological impairment. The voxels we obtained revealed abnormalities in both brain metabolites and spatial-motor function. These changes were most prominent in the white matter, and present to a lesser extent in the basal ganglia of subject brains. Indeed, three of the four cirrhotic HCV patients examined by MRS did exhibit a brain metabolite pattern typical of hepatic encephalopathy. However, G1x was also elevated in seven (87.5 percent) of the eight noncirrhotic HCV patients. Notably, two (25 percent) of these patients had elevated levels of choline and none had myoinositol abnormalities. These findings mark the first independent confirmation of an organic cause of extrahepatic symptoms in chronic HCV, first suggested by British researchers last July.