Apolipoprotein E‐ε4 deficiency and cognitive function in hepatitis C virus‐infected patients

Abstract

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV-induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV-infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health-related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE-ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE-ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P-value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE-ε4 allele is protective against attention deficit and especially against poor working memory in HCV-infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.

APOE ϵ 4 modifies the relationship between infectious burden and poor cognition

“…Given our limited sample size, the possibility that these isolated positive findings are due to chance cannot be fully excluded. Our findings were, however, consistent with previous studies that have found a protective effect of APOE ϵ 4 against infection 18 – 22 as well as previous studies that suggest beneficial effects of APOE ϵ 4 during childhood development (when infections are particularly common). 44 , 45 …”

“… 17 These results are consistent with observations from multiple studies of patients with chronic hepatitis showing that those with the APOE ϵ 4 genotype appeared to have slower progression of disease and better outcomes. 18 – 22 …”

Hepatitis C virus‐related symptoms, but not quality of life, were improved by treatment with direct‐acting antivirals

“…Serum LDL at the start of DAA treatment is also correlated with changes in CSS. Low‐density lipoprotein may affect HCV‐RNA replication, dietary cholesterol intake is associated with progression of liver disease in patients with HCV infection, and the APOE‐ε4 allele is protective against attention deficit in HCV‐infected individuals . Thus, a full explanation of the relationship between lipids and CSS is still lacking.…”

“…Low-density lipoprotein may affect HCV-RNA replication, 29 dietary cholesterol intake is associated with progression of liver disease in patients with HCV infection, 30 and the APOE-ε4 allele is protective against attention deficit in HCV-infected individuals. 31 Thus, a full explanation of the relationship between lipids and CSS is still lacking. Direct-acting antiviral treatment cleared HCV-RNA in patients, but symptoms and QOL did not fully recover in patients with elevated LDL at baseline.…”

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

“…Intriguingly, there are also genetic factors that play a role in the development of the neurocognitive syndromes and neuropsychiatric symptoms in HCV-infected patients. Available data on the apolipoprotein E (APOE) genotype show that expression of the ε4 allele, an important risk factor for Alzheimer's disease and with ε2 of cerebral amyloid angiopathy [11], results in milder impairment in attention and executive function in HCV-AND [12].…”