Viral Hepatitis C Associated Neurocognitive Dysfunction in Ireland in the Direct Acting Antiviral (DAA) Era
Citation:
Strahan, Orla, Viral Hepatitis C Associated Neurocognitive Dysfunction in Ireland in the Direct Acting Antiviral (DAA) Era, Trinity College Dublin.School of Psychology, 2020Download Item:
Abstract:
Background & Aims: Neurocognitive dysfunction is common in the setting of cirrhosis and hepatic encephalopathy in individuals infected with the Hepatitis C Virus (HCV). However, neurocognitive dysfunction has also been described in non-cirrhotic, HCVRNA positive individuals. Although the underlying mechanism for HCV-associated neurocognitive dysfunction (HCV-AND) remains unclear, it is thought to be a result of direct viral invasion of brain tissues, or virally induced inflammatory cascades. Abnormalities have been reported in fronto-striatal structures, which are thought to be responsible for difficulties observed in memory, attention and executive functions. However, there is debate regarding the nature and reversibility of HCV-AND. Evidence of HCV-AND improvement has been described following viral eradication using interferon-based therapies, although these studies have produced inconclusive results. To date, no study has investigated the nature and reversibility of HCV-AND in a mono-infected, non-cirrhotic, HCVRNA positive sample using newly available interferon-free therapies (DAAs). Therefore, the aims of this thesis were to determine the profile and nature of HCV-AND (Study 1); to investigate the nature of select extra-hepatic features of HCV-AND (Study 2a); to control for confounding factors common in HCV study samples (Study 2b); and to determine the potential reversibility of HCV-AND following viral eradication using DAAs (Study 3).
Methods: All individuals recruited into these studies had previously abnormal neuropsychological testing performance. For Study 1, HCV-AND was assessed in a sample of 135 mono-infected, non-cirrhotic, HCVRNA positive individuals using a detailed neuropsychological battery. These individuals also completed self-reported questionnaires to assess select extra-hepatic symptoms, forming the basis of Study 2a. Individuals were then randomised into a 6 month intervention where they received DAA treatment (DAA group) or routine care (Control group). Individuals were re-assessed in neuropsychological performance and self-reported extra-hepatic symptoms following their respective intervention (n = 96), which was investigated in Study 3. In addition, Study 2b investigated the potential differences in neuropsychological performance (using a brief cognitive screening test) and mood state between a chronic HCVRNA positive group and a HCVRNA negative group. The HCVRNA positive group were studied as part of a larger research project and for whom screening data were available (n = 709), and the HCVRNA negative group were a specially recruited sample of individuals who, following infection, spontaneously cleared the virus (n = 32).
Results: Study 1 reported that 83% demonstrated difficulties in one or more cognitive domains, including memory (encoding and retrieval but not retention/storage), attention and executive functions, and performance was influenced by factors such as lower education and previous substance abuse. Study 2a reported low mood in 41-64% of the sample, fatigue 73%, and reduced HRQoL 20-33%. These symptoms were independent of disease-related characteristics, however, low mood was found to negatively impact performance on memory tests. Study 2b reported HCVRNA positive individuals were four times more likely to demonstrate impaired neuropsychological performance when compared to HCVRNA negative individuals. In addition, both groups had similarly high levels of mood disturbances, suggesting HCV-AND may be independent of low mood. Study 3 reported significant improvements in measures of memory, attention, executive functions and visuospatial abilities following successful HCV viral eradication using DAAs. In addition, although were some improvements observed in mood, the prevalence of mood issues still remained considerably high.
Conclusion: These results demonstrate the presence of mild, but complex, neurocognitive difficulties among mono-infected, non-cirrhotic, HCVRNA positive individuals. Importantly, these result provide evidence of improvement in HCV-AND following successful viral eradication, extending the benefits of DAAs beyond the liver. Additionally, extra-hepatic symptoms, including low mood, fatigue and HRQoL, are highly prevalent and may further complicate HCV-AND. However, unlike neuropsychological performance, extra-hepatic symptoms persist following viral eradication.
Sponsor
Grant Number
Health Research Board (HRB)
Author's Homepage:
https://tcdlocalportal.tcd.ie/pls/EnterApex/f?p=800:71:0::::P71_USERNAME:STRAHANODescription:
APPROVED
Author: STRAHAN, ORLA
Advisor:
Dockree, PaulCoen, Robert
Publisher:
Trinity College Dublin. School of Psychology. Discipline of PsychologyType of material:
ThesisAvailability:
Full text availableMetadata
Show full item recordLicences: