Impact on QoL and Cognitive Functioning of New Antiviral Therapies in Subjects With Chronic Hepatitis HCV-related

Background HCV-related chronic hepatitis represents the most common cause of chronic liver disease in Italy, with an estimated prevalence of 1-1.1% in the general population, reaching about 15% in subjects over 50 years of age. Chronic HCV infection is the cause of 27% of cases of cirrhosis and 25% of cases of hepatocarcinoma. Persons with chronic hepatitis C present a prevalence of depressive disorders higher than that of the general population (59% vs. 21%). Moreover, there has been repeatedly demonstrated the presence of cognitive deficits, mainly concerning attentive, executive, and verbal comprehension, also in the absence of liver cirrhosis and comorbidities due to the use of substances, and a reduced quality of life. Chronic hepatitis C therapy was based on the combined use of pegylated alpha interferons (PEG-INF) and ribavirin, with SVR (sustained virological response, defined as HCV-RNA undetectable in serum at six months after the end of therapy), normalization of transaminases and improvement of liver histology, altogether in 60% of cases. Recently, new antiviral drugs with direct activity (e.g. antiprotease and antipolymer activity) have been introduced into hepatitis C therapeutic protocols, with the development of PEG-INF-free therapeutic schemes. Unfortunately, because of the excessive cost, in many Countries, including Italy, the access to PEG-INF-free schemas is only for patients with advanced fibrous stages, or who have concomitant extra-hepatic viral diseases HCV-related, or those already transplanted, while others are still expected to be treated with PEG-INF and ribavirin.

There are frequent side effects of antiviral therapy, often of minor magnitude, but sometimes incompatible with the continuation of therapy or life threatening. The most common adverse effects are influenza-like symptoms, occurring in more than half of the patients, especially during the first treatment period, and psychiatric symptoms (depression, anxiety, irritability, insomnia), which occur around the third month of treatment from 12 to 41% of patients. However, in persons with chronic hepatitis C, a high lifetime prevalence of major depressive disorder and panic disorder, and brief recurrent depression have been observed, irrespective of PEG-INF treatment and the use of alcohol and narcotic drugs; such associations between mood and anxiety disorders and chronic hepatitis C may reflect a high prevalence of bipolar disorder, which is more difficult to diagnose using non-dedicated screening tools. Some symptoms before treatment start, such as lack of pleasure or interest, asthenia, loss of appetite, social withdrawal, reduced work function, and hostility, are highly predictive of the onset of depressive disorders during antiviral therapy. Poor cognitive performance prior to antiviral therapy, coupled with the only depressive symptom of sadness, is predictive of more severe depressive disorders during antiviral treatment. However, cognitive deficits found before therapy appear potentially reversible and tend to completely recede when there is a virological response sustained by antiviral therapy. The presence of severe psychopathological symptoms leads to a reduction in posology and high rates of discontinuation of antiviral therapy.

Careful psychiatric and neuropsychological evaluation before, during and after antiviral treatment should therefore be an indispensable part of screening and HCV-related chronic hepatitis therapy. This project represents an innovative psychiatric and neuropsychological screening program for persons with chronic hepatitis C, eligible for antiviral therapy. This program aims:

• to determine which psychopathological symptoms and cognitive deficits are more frequent in persons with chronic hepatitis C;
• to verify the impact of antiviral therapy on persons' reported quality of life, and on the onset, aggravation, maintenance of psychopathological symptoms and/or cognitive deficits;
• to determine which psychopathological and neuropsychological symptoms are predictive to high compliance and the effectiveness of antiviral therapy;
• to verify the existence of specific psychopathological and neuropsychological patterns in persons with chronic hepatitis C before, during and after antiviral therapy;
• to produce a standard procedure for psychiatric and neuropsychological screening in patients with HCV-related chronic hepatitis.

Early identification of subjects at risk of psychiatric and cognitive disorders during antiviral therapy will effectively treat individuals at risk of discontinuing the antiviral therapy itself, improving the quality of the treatment and the effectiveness of the treatments.