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Depression, anxiety, cognitive performance improve after hepatitis C cure

Keith Alcorn
18 March 2022

Depression, anxiety and cognitive performance each improved significantly in people cured of hepatitis C, Indian researchers report in the Journal of Viral Hepatitis.

Anxiety and depression are frequently reported by people with hepatitis C at all stages of liver disease. Neurocognitive impairment – including slowed mental processing speed and reaction times, reduced attention span and verbal fluency, and impaired memory – may affect up to half of people with hepatitis C. Hepatic encephalopathy, a decline in brain function seen in late-stage liver disease when the liver can no longer remove toxins from the blood, is a more severe form of neurocognitive impairment.

Although anxiety and depression may be direct effects of viral infection, social stigma associated with hepatitis C or with using drugs can also lead to mental health problems in people with hepatitis C. Substance use may also reflect underlying mental health conditions.



A disease or infection affecting the brain.

The Indian state of Punjab provides treatment for hepatitis C and comprehensive health care at 25 decentralised clinics. The Punjab public health treatment model uses a pangenotypic regimen, either sofosbuvir/daclatasvir for people without cirrhosis or sofosbuvir/velpatasvir for people with cirrhosis.

Researchers at Chandigarh University recruited 385 people who started treatment between June 2018 and March 2020, to assess the impact of hepatitis C cure on mental health conditions and neurocognitive functioning.

Study participants were 76% male with a mean age of 39 years. Unsafe injections (59%), surgery (75) and injecting drug use (5%) were the most frequently identified sources of infection. Most of the cohort were literate (82%) and 38% had completed high school. Twenty-one per cent of the study cohort had cirrhosis and 6% had major depressive disorder.

Study participants exhibited substantial cognitive impairment at baseline, regardless of cirrhosis status, when compared to healthy controls or people with non-alcoholic fatty liver disease. On the Stroop test of concentration, attention and processing skills, for example, the median score in healthy controls was 68%, compared to 47% in people with hepatitis C. On the visual memory test, healthy controls scored a median of 6.6, compared to 5.1 in people with hepatitis C.

Substantially inferior scores on tests for cognitive function were also evident in people with hepatitis C when compared to the control group of people with non-alcoholic fatty liver disease, suggesting that impairments in cognitive function are a consequence of viral infection rather than liver disease.

The hepatitis C cure rate was 87% in participants without cirrhosis and 91% in participants with cirrhosis. Just under two-thirds (63%) of participants with cirrhosis received treatment for 24 weeks. The remainder were treated for 12 weeks.

Treatment success was associated with full adherence in participants with cirrhosis.

Study participants were assessed for depression, anxiety and health-related quality of life using validated scoring instruments. They underwent computer-based tests for visual and verbal memory, attention, visual-motor speed, arithmetic and reaction times. All tests were carried out at baseline and 12 weeks after the completion of treatment and the results were compared with healthy controls and a control group of people with non-alcoholic fatty liver disease.

People who were cured of hepatitis C experienced significant improvements in depression, anxiety and cognitive function, whereas those who were not cured experienced no change or deterioration in various measures.

Depression scores fell by 7% on a 40-point scale where 40 is extreme depression and 10 or below reflects normal mood changes. In contrast depression scores rose by 28 points in those who were not cured.

Anxiety scores fell by 15% in people who were cured but rose by 12% in those who were not cured.

But whereas depression and anxiety may reflect individual psychological responses to the outcome of treatment rather than physiological changes as a result of treatment, cognitive changes may occur independent of changes in mood or anxiety.

People who were cured of hepatitis C showed significant improvements in reaction time, visual memory, concentration, attention and processing skills (measured by the Stroop test) and short term and working memory (measured by the digit span test). In contrast, scores on these tests deteriorated in people who were not cured.

The study did not find substantial gender differences in depression, anxiety or neurocognitive test scores, in either cured or uncured participants.

The study authors say the study demonstrates that hepatitis C is associated with cognitive impairment and clearing hepatitis C results in improved cognitive functioning and reduction in depression and anxiety. They say that theirs is the largest prospective cohort study of neurocognitive changes after hepatitis C treatment to date, recruiting almost ten times as many participants as any previous study, and its findings are strengthened by the exclusion of people with a prior history of hepatic encephalopathy.


Kaur H et al. Improvement of chronic HCV-related depression, anxiety and neurocognitive performance in persons achieving SVR12: a real world cohort study. Journal of Viral Hepatitis, published online 10 March 2022.