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HomeJournal of Viral Hepatitisindex/list_12279_1Neuropsychological Effects of Direct-acting Antiviral Treatment for Hepatitis C Virus Subjects

Neuropsychological Effects of Direct-acting Antiviral Treatment for Hepatitis C Virus Subjects

Abstract and Introduction


Direct-acting antivirals (DAAs) have been approved in recent years to treat patients infected by the Hepatitis C virus (HCV). The DAAs treatment is well tolerated and increases sustained virological responses, but there is no consensus about the neuropsychological functioning related to the treatment. This systematic review aims to provide an overview of the recent findings exploring the cognitive effects of DAAs treatment in patients with HCV. After a systematic search on PubMed, Embase, Scopus and LILACS, studies that assessed neuropsychological data related to DAAs treatment were included. We found nine articles, considering the inclusion and exclusion criteria. Three other manuscripts were included after searching for the references listed in the previously mentioned articles. We observed methodological heterogeneity in terms of neuropsychological tests used, cognitive domain explored and the sample characteristic presented between the studies. Studies presented data from HCV subjects monoinfected with or without cirrhosis, advanced liver disease and post-transplant patients; and HCV subjects coinfected with human immunodeficiency virus (HIV). Most results from the 12 studies that explored the effect of DAAs treatment in HCV subjects’ neurocognitive functioning demonstrated cognitive improvement following treatment. In general, HCV and HCV/HIV subjects improved processing speed, verbal fluency and verbal/visual episodic memory. The DAAs treatment is effective for neurocognitive functioning in HCV monoinfected and coinfected subjects, with or without advanced liver disease, since neuropsychological scores increased after treatment. Further studies, however, are needed to confirm these findings.


Chronic Hepatitis C is a disease related to the Hepatitis C virus (HCV), associated with adverse extrahepatic manifestations on the Central Nervous System, with neurological and neuropsychological effects,[1] induction of depression, fatigue, sleep disturbances[2–4] and worse health-related quality of life—HRQoL.[5] These neuropsychiatric and neurocognitive changes have been reported in cases of non-cirrhotic infection,[6] in minimal hepatic encephalopathy[7,8] and in more severe cases of hepatic encephalopathy.

Interferon based-treatment (IFN) for HCV is related to a decrease of neuropsychological functions, such as executive function and attention,[9–11] as well as neuropsychiatric dysfunction involving depression, anxiety, fatigue and deterioration of HRQoL.[12,13] Although there is evidence of the negative effects of IFN treatment on cognition and psychiatric symptoms, the results are controversial, considering other studies that demonstrated cognitive improvement and not worsening of depressive symptoms after IFN treatment.[14,15]

In 2016, the World Health Organization updated the guidelines for screening, care and treatment of individuals with HCV, endorsing the Global Health Sector Strategy on viral hepatitis with direct-acting antivirals (DAAs) treatment.[16] The purpose is to eliminate viral hepatitis as a public health threat by 2030. IFN-free regimens with DAAs, with a short duration of treatment—12 or 24 weeks, and with few side-effects,[17] provide high rates of sustained virologic response (SRV), becoming a gold standard in treating HCV.[18]

The emergence of new DAAs has revolutionized HCV treatment by offering more effective and better-tolerated drugs and allowing cure rates to exceed 90%.[19] DAAs treatment with or without ribavirin has shown high efficacy and is well tolerated in patients with the predominant genotypes, advanced fibrosis stages and human immunodeficiency virus (HIV) co-infection.[20] All-oral DAAs regimens are associated with an improvement in quality of life, functionality,[21–24] depressive symptoms and sleep disorders;[25] but there is no clear effect on cognition.[1] Thus, the objective of this study is to investigate, with a systematic review, the cognitive effects in Hepatitis C subjects treated with DAAs.

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