Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition.
OBJECTIVE
Chronic hepatitis C virus (HCV) infection is associated with altered cerebral metabolism and cognitive dysfunction. We aimed to evaluate the effect of pegylated interferon/ribavirin (PIFN/R) and HCV clearance on cerebral metabolism, and neuropsychological performance.


METHODS
Fifteen non-cirrhotic HCV positive subjects underwent (1)H MR spectroscopy (MRS) before, during, and after treatment with PIFN/R. The metabolites of interest namely, N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), and the control metabolite creatine (Cr), were acquired from 3 different brain regions; left basal ganglia, left frontal cortex, and left dorso-lateral pre-frontal cortex. Coinciding with this, subjects also underwent a battery of neuropsychological tests to evaluate the domains of verbal learning, memory, attention, language, executive functioning, and motor skills. Seven HCV positive controls (not receiving anti-viral therapy) underwent MRS and neuropsychological testing at two time points, 12 weeks apart, to examine for variation in cerebral metabolites over time and the practice effect of repeat neuropsychological testing.


RESULTS
Significant reductions in basal ganglia Cho/Cr (p=0.03) and basal ganglia MI/Cr (p=0.03) were observed in sustained virological responders (SVRs, n=8), but not non-responders/relapsers (NR/R, n=6), indicative of reduced cerebral infection and/or immune activation in those who cleared virus. SVRs demonstrated significant improvements in verbal learning, memory, and visuo-spatial memory. A small but significant improvement in neurocognitive function secondary to the practice effect was seen in both HCV controls and HCV subjects during treatment.


CONCLUSIONS
HCV eradication has a beneficial effect on cerebral metabolism and selective aspects of neurocognitive function and is an important factor when contemplating anti-viral therapy in HCV, especially in those with mild disease.
Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Valerie
V
Byrnes
Anne
A
Miller
Damien
D
Lowry
Erin
E
Hill
Cheryl
C
Weinstein
David
D
Alsop
Robert
R
Lenkinski
Nezam H
NH
Afdhal
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001479:Basal Ganglia / Q000378:metabolism* / Q000821:virology; D002794:Choline / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D003401:Creatine / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007372:Interferons / Q000008:administration & dosage; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009483:Neuropsychological Tests; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D011795:Surveys and Questionnaires
D000998:Antiviral Agents; D001224:Aspartic Acid; D011092:Polyethylene Glycols; D012254:Ribavirin; D007294:Inositol; D007372:Interferons; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline