Effects of Direct-acting Antiviral Agents on HCV Cognitive Function, and Depression in HCV Related Cirrhosis: A Prospective Clinical Trial

Study Overview
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Brief Summary
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Minimal hepatic encephalopathy (MHE) is an important clinical variant of hepatic encephalopathy (HE), which occurs in up to 60-70% of patients with cirrhosis. The condition comprises a cognitive impairment, observed in patients with cirrhosis who have no clinical evidence of overt hepatic encephalopathy (OHE). It is associated with an increased incidence of road traffic accidents, reduced quality of life and it affects the ability to perform tasks of daily living. Successful treatment of hepatitis C has been reported to be associated with 62-84% reduction in all-cause mortality (deaths), 68-79% reduction in risk of HCC and 90% reduction in risk of liver transplantation. In addition, studies have shown that viral eradication may improve cognition when given interferon based regimens for HCV. With the available of safe, efficacious, all oral regimens for HCV, we plan to prospectively analyse the change in mood, depression and cognitive function in response to DAA therapy, in relation to outcomes of treatment.

Detailed Description
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Investigations will be performed according to the Declaration of Helsinki and approval of the enrolment as well as the usage of patient blood samples for research purpose will be obtained from the institutional ethics committee, and written informed consent will be obtained from all patients.The primary analysis upon which the sample size consideration was based involved the comparison of the SVR subgroup and the subgroup of patients without SVR. For the sample size calculation, we a two-factorial design (time course × SVR) with the use of a two-way analysis of variance (ANOVA) analysis, a significance level of 5% and a statistical power of at least 80% to detect a medium effect size (d = 0.5) and thus to show a significant group difference. Based on this background, the optimal sample size is calculated to be a total of 102 subjects. To consider asymmetric subgroups and to allow for a moderate dropout rate and additional calculations (secondary study objectives), we aim to include a total of at least 150 study participants in each group with 25 healthy volunteers as controls.

Official Title
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Effects of Direct-acting Antiviral Agents on Cognitive Function, and Depression in Chronic Hepatitis C

Conditions
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Depression in Chronic Hepatitis C

Intervention / Treatment
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* Other: Depression and Cognitive Tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years and chronic HCV infection. Group A: Patients with hepatitis C (Non-cirrhotic) [n= 150] Group B: Patients with hepatitis C related compensated-cirrhosis [n= 150] Group C: Healthy volunteers [n= 25] Exclusion Criteria: Current overt hepatic encephalopathy or during the last 1 month TIPS (transjugular intra- hepatic porto-systemic shunt) elective surgery planned within the next 8 weeks unable to give informed consent HIV infection chronic respiratory insufficiency current infection and receiving antibiotics renal failure (serum creatinine ≥ 1.5 mg/l) hepatocellular carcinoma, patient with other neurological disease intake of sedatives, antidepressants, benzodiazepines, or benzodiazepines-antagonists (flumazenil, neuromuscular blocking agents)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>Chronic hepatitis C without Cirrhosis | Other: Depression and Cognitive Tests<br>* Health Related Quality of Life, neurocognitive tests, PHES<br>* Other names: SF36;|
| Chronic hepatitis C with Cirrhosis<br> | Other: Depression and Cognitive Tests<br>* Health Related Quality of Life, neurocognitive tests, PHES<br>* Other names: SF36;|
| Healthy Volunteers<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive performance | Computerized battery (Reaction times, simple and choice, visual memory, Number connection test, and Inhibitory Control Test) | Day 0 | 
| Cognitive performance | Computerized battery (Reaction times, simple and choice, visual memory, Number connection test, and Inhibitory Control Test) | 90 days after treatment completion | 
| Cognitive performance using conventional tests | Psychometric hepatic encephalopathy score (PHES), Indian Version. | Day 0 | 
| Cognitive performance using conventional tests | Psychometric hepatic encephalopathy score (PHES), Indian Version. | 90 days after treatment completion | 
| HRQOL by SF-36 |  | Day 0 | 
| HRQOL by SF-36 |  | 90 days after treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Scale | Beck's Depression Inventory (BDI) Generalized anxiety disorder (GAD 7 score) Psychometric hepatic encephalopathy Score (PHES) Montreal Cognitive assessment Score (MoCA Score) | Day 0 | 
| Depression Scale | Beck's Depression Inventory (BDI) Generalized anxiety disorder (GAD 7 score) Psychometric hepatic encephalopathy Score (PHES) Montreal Cognitive assessment Score (MoCA Score) | 90 days after treatment completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurocognition, Minimal hepatic encephalopathy, Direct antivirals, DAAs, Chronic hepatitis C