Improvement of Chronic HCV Infection-Related Depression, Anxiety, and Neurocognitive Performance in Persons Achieving SVR-12

A Real-World Cohort Study

Harmanpreet Kaur; Radha K. Dhiman; Anand V. Kulkarni; Madhumita Premkumar; Virendra Singh; Ajay Kumar Duseja; Sandeep Grover; Gagandeep S. Grover; Akash Roy; Nipun Verma; Arka De; Sunil Taneja; Rohit Mehtani; Saurabh Mishra; Harpreet Kaur


J Viral Hepat. 2022;29(5):395-406. 

In This Article

Abstract and Introduction


Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct-acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18–65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD-7]), QoL (SF-36 ver.2) and computer-based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR-12 had mean percentage reduction in BDI (11.3%, p = .000), GAD (8.6%, p = .001) and Stroop test (58.4%, p = .001), with improved NCT (1.7%, p = .001), visual memory (13.7%, p = .001) and digit span (23.8%, p = .002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80–110.50], p = .000), high ALT (OR 1.02 [95% CI 1.00–1.05]), and BDI score (OR 1.73 [95% CI 1.42–3.26] p = .039) predicted cure. SVR-12 was associated with improved visual memory ≥5.5 (AUC-0.708; sensitivity 62.5%, specificity 63%, p = .000) and % correct Stroop test responses >26.6% (AUC-0.918, sensitivity 94.4% specificity 80.4%, p = .000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality-of-life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination.


Patients with chronic hepatitis C virus (HCV) infection report neuropsychological manifestations like fatigue, depression, anxiety and cognitive impairment that is modifiable by treatment with antiviral agents.[1] The cognitive impairment is independent of the stage of liver disease, which suggests that the HCV infection itself may be responsible for some of the cognitive impairment.[2] Imaging studies have suggested evidence of central nervous system (CNS) and systemic inflammation with altered neurotransmission in HCV infection.[3] However, it is unclear whether this is a direct effect of viral replication in the CNS or a result of peripheral factors acting across the blood-brain barrier.[4,5] The HCV genome has been isolated in human microglial cells,[6] and cerebral endothelial cells support a low-level extrahepatic site of HCV replication.[7] The nervous system is an immune-privileged site that may explain the neurocognitive symptoms, depression and associated poor health-related quality of life (HRQoL) in persons living with HCV (PLHCV).[8,9] The presence of depression and cognitive impairment may affect medication adherence in patients on antivirals, although HCV clearance has been demonstrated to improve cognition in a recent meta-analysis.[10] Cognitive impairment has been noted as subtle changes in processing speed or reaction times, memory, performance tests for vigilance, attention, psychomotor speed and verbal fluency in up to 50% of PLHCV.[11] The neurocognitive defects are independent of the presence of hepatic encephalopathy (HE) in patients with cirrhosis. They have been demonstrated in patients without high fibrosis, the absence of HIV coinfection and substance abuse.[12] Therefore, correct estimation of cognitive dysfunction, HRQoL, anxiety and depression is essential before embarking on drug therapy.[13]

Another major knowledge gap is lack of real-world data from public health programmes regarding gender differences in treatment efficacy, as women with HCV report social stigma, present late and lack access to health services.[14] Previous data from India show women tend to present in the 4th and 5th decade, have history of unsafe injections or surgery as risk factors for disease transmission and have an increased level of social stress.[15] These factors compounded with poor social support and put them at risk of developing mood disorders and difficulties in coping with the physical symptoms of chronic hepatitis C (CHC).[16] Women require focus in HCV elimination campaigns, with more holistic medical, social and psychological interventions. Lastly, it is unclear whether the achievement of sustained virological response (SVR) translates into resolution of the HCV-related cognitive and HRQoL impairment equally in patients with and without cirrhosis.[17]

The current prospective study aimed at characterizing the neuropsychological profile of patients with HCV infection treated under public health programmes with a focus on gender differences in cognition, depression and HRQoL and to assess improvement after achievement of virological cure.