An Exploration of the Neurological Manifestations of Non-Cirrhotic Chronic Hepatitis C Infection in Ireland in the Direct-Acting Antiviral Era

Abstract

An Exploration of the Neurological Manifestations of Non-Cirrhotic Chronic Hepatitis C Infection in Ireland in the Direct-Acting Antiviral Era. Ferguson, Damien. University of Dublin, Trinity College, School of Medicine. BACKGROUND: The hepatitis C virus (HCV) is a ribonucleic acid (RNA) virus that is estimated to infect 3.9 million people across Europe. Although primarily considered a hepatotropic virus, there is evidence supporting microglial tropism and compartmentalisation within the cerebrospinal fluid. HCV-associated neurocognitive dysfunction, which affects domains such as attention, concentration, and working memory, is well-recognised; however, its pathophysiology remains unclear. Small studies employing advanced neuroimaging techniques suggest the presence of neuroinflammation and structural brain changes. Chronic HCV infection is also linked to numerous systemic complications, and the accumulation of comorbidities over a lifetime is associated with frailty. The prevalence of clinical neurological signs and frailty in chronic HCV infection, however, remains unknown. AIMS: The aims of this thesis are: to determine the prevalence of neurocognitive dysfunction in a non-selected cohort with non-cirrhotic chronic hepatitis C infection (Study 1); to assess the prevalence of neurological signs and frailty in individuals with HCV-AND (Study 2); to examine the cross-sectional brain morphometry features of HCV-AND (Study 3); and to evaluate the longitudinal impact of viral clearance on brain morphometry in HCV-AND (Study 4). METHODS: Unselected, non-cirrhotic, HCV mono-infected persons attending St. James's Hospital were screened for HCV-AND using the Brief Neurocognitive Screen (BNCS). Participants who screened positive were recruited to an in-depth clinical and neuroimaging study, which involved a structured clinical examination, frailty assessments, and volumetric brain magnetic resonance imaging (MRI). Neuroimaging was repeated after HCV eradication using direct-acting anti-viral agents (DAA). RESULTS: A total of 709 individuals were screened (68% men; median age 41), with 47% testing positive for HCV-AND. Independent factors associated with HCV-AND included younger age, fewer years of education, use of prescription benzodiazepines, and neurological comorbidities. In the in-depth study, clinical neurological examination abnormalities were observed in 5-68% of participants, while 19-21% were found to be frail. Cross-sectional neuroimaging showed that individuals with HCV-AND exhibited cortical thinning, volume loss in cortical and subcortical grey matter, and white matter volume loss, compared to healthy controls. Post-DAA treatment, viral eradication did not lead to changes in cortical thickness or grey and white matter volumes. CONCLUSION: Non-cirrhotic, chronic hepatitis C infection is associated with significant neurocognitive dysfunction which is independent of various biopsychosocial factors. Furthermore, it leads to cortical thinning and brain volume loss, effects that do not reverse following successful viral eradication.