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Cognitive function improves after hepatitis C cure

Keith Alcorn
22 October 2021

Curing hepatitis C improves cognitive function, especially in older people already showing signs of cognitive impairment, a Spanish study has found.

Cognitive impairment covers a wide spectrum of problems with memory, concentration, learning, attention span, decision-making ability and difficulties with mental tasks in everyday life. Some people with hepatitis C refer to these problems as ‘brain fog’. Cognitive impairment is more commonly observed in people with cirrhosis. In people with decompensated cirrhosis, it is an early sign of the onset of hepatic encephalopathy.

As cognitive impairment has a significant effect on quality of life, Spanish researchers wanted to find out whether direct-acting antiviral treatment reduced cognitive impairment. Learning that curing hepatitis C can reduce cognitive impairment might also encourage people to overcome their reluctance to start direct-acting antiviral treatment.


decompensated cirrhosis

The later stage of cirrhosis, during which the liver cannot perform some vital functions and complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.


A disease or infection affecting the brain.

The researchers carried out an observational study in randomly selected people with hepatitis C alone attending a viral hepatitis clinic in Madrid between 2015 and 2017.

Cognitive function was assessed prior to treatment, 12 weeks after completion of treatment and 48 weeks after the end of treatment.

The study excluded people co-infected with HIV, people with more advanced hepatocellular carcinoma, recent harmful alcohol consumption, cardiovascular disease or another comorbid condition likely to have an independent effect on cognitive health, or people with a portosystemic shunt.

One hundred and fifty-two out of 912 patients treated for hepatitis C during the study period were recruited (a maximum of three eligible patients per week). One hundred and thirty-five completed the study and achieved viral eradication. Participants had a median age of 57 years and 57% were male. 32.5% had cirrhosis (27% decompensated).

Participants with cirrhosis were significantly more likely to have diabetes (31% vs 6%, p<0.001), higher body mass index (28.5 vs 26, p=0.007) and were more likely to be receiving treatment with beta blockers and diuretic agents as well as hypoglycaemic agents.

The prevalence of alcohol use disorder, substance abuse, anxiety and depression, each of which might affect cognitive function, was low in the study population.

Cognitive function was measured by tests of visuo-motor function, executive function tests to assess planning ability, flexibility and verbal reasoning, and tests of processing speed, memory, attention span and working memory. The researchers also carried out five cognitive tests used to diagnose hepatic encephalopathy.

Cognitive impairment (either HCV-related cognitive impairment in people without cirrhosis or covert hepatic encephalopathy in people with cirrhosis) was defined as being below one standard deviation in more than two cognitive domains.

At study entry, 34% of people with cirrhosis and 14% without cirrhosis had cognitive impairment. At baseline, arterial hypertension significantly increased the risk of cognitive impairment (odds ratio 3.5, 95% CI 1.01-11.4), as did prior hepatic encephalopathy (OR 13.8, 95% CI 0.7-273) and anxiety (OR 1.2, 95% CI 1.1-1.4).

A greater number of years of education was associated with a reduced risk of cognitive impairment (OR 0.80, 95% CI 0.7-0.9).

After eradication of hepatitis C, people with cirrhosis showed significant improvements in measures of motor function, executive function, processing speed, attention and global cognitive function. They also showed improvements in Psychometric Hepatic Encephalopathy Scores.

People with cirrhosis also experienced significant improvements in mood and some measures of health-related quality of life.

However, patients with cirrhosis at baseline still displayed worse cognitive performance than patients without cirrhosis 48 weeks after completing treatment. The researchers did not report on changes in liver function after cure in people with cirrhosis, so it is not possible to judge if differences exist in cognitive function between people with compensated and decompensated cirrhosis.

Patients without cirrhosis showed significant improvement in visuospatial function, executive function, processing speed, attention, working memory and global cognitive function. They also showed improvements in Psychometric Hepatic Encephalopathy Scores.

Improvement in cognitive function was significantly greater in patients with cognitive impairment at baseline, especially those with worse cognitive impairment, and in older patients.

The study authors conclude that curing hepatitis C can improve cognitive function regardless of liver disease stage, with the greatest benefits in older people and those with lower brain reserve.


Ibáñez-Samaniego L, et al. Hepatitis C eradication improves cognitive function in patients with or without cirrhosis: a prospective real-life study. European Journal of Neurology, published online, 11 October 2021.