Neuroimaging Findings in Chronic Hepatitis C Virus Infection: Correlation with Neurocognitive and Neuropsychiatric Manifestations

Abstract

Chronic hepatitis C virus (HCV) infection is commonly associated with neurocognitive dysfunction, altered neuropsychological performance and neuropsychiatric symptoms. Quantifiable neuropsychological changes in sustained attention, working memory, executive function, verbal learning and recall are the hallmark of HCV-associated neurocognitive disorder (HCV-AND). This constellation is at variance with the neuropsychological complex that is seen in minimal hepatic encephalopathy, which is typified by an array of alterations in psychomotor speed, selective attention and visuo-constructive function. Noncognitive symptoms, including sleep disturbances, depression, anxiety and fatigue, which are less easily quantifiable, are frequently encountered and can dominate the clinical picture and the clinical course of patients with chronic HCV infection. More recently, an increased vulnerability to Parkinson’s disease among HCV-infected patients has also been reported. The degree to which neurocognitive and neuropsychiatric changes are due to HCV replication within brain tissues or HCV-triggered peripheral immune activation remain to be determined. Without absolute evidence that clearly exonerates or indicts HCV, our understanding of the so-called “HCV brain syndrome”, relies primarily on clinical and neuropsychological assessments, although other comorbidities and substance abuse may impact on neurocognitive function, thus confounding an appropriate recognition. In recent years, a number of functional and structural brain imaging studies have been of help in recognizing possible biological markers of HCV-AND, thus providing a rationale for guiding and justifying antiviral therapy in selected cases. Here, we review clinical, neuroradiological, and therapeutic responses to interferon-based and interferon-free regimens in HCV-related cognitive and neuropsychiatric disorder.

Neurological and psychiatric effects of hepatitis C virus infection

“…Metabolic and neurotransmission alteration: Magnetic resonance spectroscopy allows measurement of the concentration of certain metabolites in specific brain regions. Choline is a metabolite expressed by glial and proliferating cells and is used as a marker of inflammation and of the synthesis and turnover of cell membranes; N-acetyl aspartate is a neuronal metabolite and a marker of neuronal integrity, so its decrease is indicative of neuronal loss or dysfunction; myoinositol is produced only by glial cells and increases with glial proliferation, called gliosis, or with interruption of myelin[ 2 , 16 ].…”

“…In turn, serotonin deficiency can cause an excessive release of inhibitory neurotransmitters leading to depressive symptoms. In fact, serotonergic projections from midbrain nuclei modulate the activities of cortical and subcortical structures involved in behavior, mood and attention regulation[ 16 ].…”

“…The term HCV-associated neurocognitive disorder (HCV-AND) is used to refer to this spectrum of alterations unrelated to advanced liver disease and therefore distinct from potentially reversible complications seen in patients with MHE[ 16 ].…”

“…Cognitive domains related to posterior brain regions, primarily involved in visuospatial and visual perceptual abilities and constructive practice, are rarely involved; conversely these regions are mainly altered in patients with MHE[ 16 ]. Thus, there are some differences from both a pathogenic and a clinical-diagnostic point of view between HCV infected patients and those with hepatic encephalopathy.…”

“…To distinguish between HCV-AND and MHE in terms of cognitive decline, a multimodal approach is required that includes assessment of liver function, brain imaging and extensive neuropsychological tests that assess broad aspects of cognition and not just those related to frontal executive functions[ 16 ].…”