Do fatigue and quality of life improve after hepatitis C is cured?

Patient-reported outcomes such as fatigue, vitality and mental health improve substantially in the two years following hepatitis C cure for people with cirrhosis, but people with cirrhosis are less likely than others to experience rapid resolution of severe fatigue after successful hepatitis C treatment, according to two studies from the Center for Outcomes Research in Liver Diseases reported last month at the 2018 International Liver Congress in Paris.

Quality of life can be severely impaired in people with chronic hepatitis C, especially in people with cirrhosis. Fatigue, insomnia, problems in physical functioning, depression, anxiety and mood disorders are reported by a substantial proportion of people with hepatitis C.

'Brain fog' – a lack of concentration and confusion – is often described by patients, but the biological mechanism that leads to this problem is not understood.

More severe quality of life problems are caused by hepatic encephalopathy, which develops when the damaged liver begins to lose its capacity to remove ammonia and other toxins from the blood. Poor concentration, insomnia, anxiety, fatigue, slow movement and depression may be present in people with hepatic encephalopathy.

For people living with hepatitis C, improvement in the quality of life after treatment is an important outcome. To measure improvements in quality of life, 786 people with hepatitis C virus and cirrhosis receiving treatment in 12 clinical trials were enrolled in long-term follow-up after being cured of hepatitis C (sustained virologic response, SVR). The study population consisted of 650 people with compensated cirrhosis and 136 people with decompensated cirrhosis.

Participants in the follow-up study were asked to score their physical and mental health using the SF-36 questionnaire every six months for two years (96 weeks).

People with decompensated cirrhosis were significantly more likely to report insomnia at baseline, to have hepatitic encephalopathy and ascites at baseline, but were no more likely to report fatigue, depression, anxiety or diabetes at baseline. When patient-reported outcome scores were calculated as a whole, people with decompensated cirrhosis were more likely to have severe impairment than those with compensated cirrhosis prior to treatment (p < 0.05).

People with decompensated cirrhosis rated their physical health, vitality and activity levels especially low prior to treatment in the SF-36 questionnaire used in this study.

During the follow-up period, significant improvements were reported for 11 out of 20 domains of patient-reported outcomes by people with decompensated cirrhosis. The average improvement in score ranged from 4% to 19% according to the domain. In people with compensated cirrhosis improvement in patient-reported outcomes was more comprehensive (19 out of 20 domains) but of a similar magnitude (2% to 17% improvement in score according to the domain).

Multivariate analysis showed that younger age, lack of diabetes and lack of decompensated cirrhosis were associated with greater improvements in patient-reported outcomes (p < 0.05).

A second analysis, of phase 2 and 3 trials of sofosbuvir-based treatment, reported that fatigue improved in more than half of people cured of hepatitis C in those trials.

The studies included 6113 people who were cured of hepatitis C and who provided fatigue scores before treatment and at the 12-week post-treatment visit.

Thirty-four per cent had compensated cirrhosis and the median APRI score at study entry was 1.2 (indicating significant fibrosis). Nine per cent had co-infection with HIV.

Participants were asked to rate their levels of fatigue 1-5 on a 13-point questionnaire (FACIT-F scale) to assess how fatigue affected their everyday life and the extent of their tiredness. People who scored less than 30 were classified as having severe fatigue. At baseline, 23% had severe fatigue.

By the time of the SVR12 visit, 42% of those with severe fatigue still had severe fatigue, 45% had experienced some improvement and 12% had improved so that they reported minimal or no fatigue.

Fatigue was more likely to improve in younger people, in those without cirrhosis and in those with fewer co-morbidities. Depression, anxiety and insomnia were especially associated with a lack of improvement, as were type 2 diabetes, cirrhosis and co-infection with HIV. People with HIV co-infection were almost 60% less likely to experience an improvement from severe fatigue to minimal or no fatigue compared to those without HIV infection (odds ratio 0.421, 95% CI 0.18-0.98, p = 0.046) and around 63% more likely to experience no improvement from severe fatigue (OR 1.63, 95% CI 1.06-2.5, p = 0.025). People with cirrhosis were approximately 35% less likely to experience rapid recovery from severe fatigue (OR 0.66, 95% CI 0.45-095, p = 0.026).

Longer-term follow-up of people with severe fatigue would be useful so as to give a clearer understanding of the likelihood of improvement beyond the SVR12 visit, the pace of recovery and longer-term risk factors for persistent fatigue after hepatitis C is cured.

The investigators commented that management of fatigue after hepatitis C cure should focus on co-morbidities that contribute to fatigue such as depression, insomnia and type 2 diabetes. The findings also suggest that even in the absence of hepatic encephalopathy, fatigue in people with hepatitis C is a liver-related phenomenon rather than a consequence of viral replication.