Impact of direct acting antivirals (DAA) on neurologic disorders in chronic hepatitis C

Neurologic and neuropsychiatric manifestations sometimes provide the first evidence of an unknown HCV infection. These conditions develop with a variable ranging of morbidity, including: "brain fog," fatigue, subtle cognitive and attention impairment, but also with more severe complications or acute presentation, like encephalomyelitis, encephalopathy, stroke and peripheral nerves involvement.

We performed a systematic literature search on PubMed, Cochrane Library and Web of Science databases for articles only in English language, that assessed the relationship between "DAA treatment and neurologic disorders" and after the attainment of SVR in full reports of cases that received the DAA schedule from January 2015 to December 2019. The following terms were used: "chronic Hepatitis C," "HCV," "DAA," "direct-acting antiviral," "SVR," "sustained virologic response," peripheral neuropathy" and "neurologic diseases or disorders."

HCV infection does not only involve the liver, causing cirrhosis and hepatocellular carcinoma (HCC), but also induces extrahepatic manifestations (EHM), mainly due to a complex immune disease, that damage small and medium vessels, called "mixed cryoglobulinemic vasculitis" (MCV). This kind of mechanism generates most of the HCV-induced neurological damages. Since 2015, the availability of direct-acting antiviral (DAA) oral molecules interfering with HCV replication has completely revolutionized therapeutic options and the target population, which now includes patients aged 12 to 80 years and with advanced liver disease. Relevant was the highlighted DAA effectiveness by achievement of a sustained virologic response (SVR) in about 95% of cases, showing a great tolerability.

This favorable effect has arisen in a wide category of patients infected by HCV, including subjects with cirrhosis and complications and/or with EHM, who showed a significant improvement of their symptoms and the disease regression. In this concise review, we examine the clinical outcomes after the introduction of the DAA for the treatment of chronic hepatitis C (CHC), focusing on the neurologic disorders and concluding that there is a strong amelioration of neurologic conditions in several cases, particularly, after attaining the viral eradication with a favorable course in most treated cases.