Sleep-Wake Disturbance Highly Prevalent in Populations With Liver Disease

Sleep-wake disturbance is very common in populations with liver disease, according to a literature review published in The Lancet.

This review aimed to summarize the reciprocal interaction between sleep and liver diseases, including cirrhosis, and investigate potential approaches for therapeutic interventions. In this review, the term sleep-wake disturbance included all types of alterations to normal sleep reported in patients with liver disease.

Sleep-wake disturbance has been epidemiologically linked with obesity and metabolic dysfunction, including nonalcoholic fatty liver disease (NAFLD). Previous experimental studies show the influence of sleep on multiple pathways known to drive hepatic steatosis, inflammation, and fibrogenesis. Due to these findings, sleep-wake disturbance should be considered a significant and potentially modifiable risk factor for the development and progression of NAFLD.

Sleep-wake disturbance is common in patients with alcohol use disorders. It can also increase the severity of underlying alcohol-related liver diseases. However, longitudinal human observational studies evaluating the influence of sleep-wake disturbance on the development and progression of alcohol-related liver diseases are lacking.

There are often overlapping risk factors for both poor sleep and hepatitis C virus (HCV) acquisition. These risk factors include intravenous drug use and premorbid mental health disorders. Sleep-wake disturbance is often a dominant factor in determining health-related quality of life in patients with HCV, which can transpire in the absence of severe underlying liver disease.

Compared with a range of chronic liver disease types, fatigue can be particularly debilitating in patients with primary biliary cholangitis. Fatigue is present in over 50% of primary biliary cholangitis cases. A prominent feature of primary biliary cholangitis is excessive daytime sleepiness, which is closely associated with fatigue.

Sleep-wake disturbance is common in patients with cirrhosis, with approximately 50% to 80% of patients reporting a Pittsburgh Sleep Quality Index score >5. Sleep-wake disturbance appears more common in cirrhosis compared with other long-term health conditions, such as chronic kidney disease and inflammatory bowel disease.

Despite the high frequency of sleep-wake disturbance in cirrhosis, targeted sleep interventions in patients with advanced liver disease remain limited. Previous clinical trials of targeted sleep interventions were noted to be insufficient.

Due to the association between sleep quality and liver disease severity, sleep-wake disturbance is highly prevalent in those awaiting liver transplantation, affecting approximately 50% to 73% of these patients. Sleep appears to improve after liver transplantation. In a prospective study of 201 patients before and after liver transplantation, the frequency of self-reported poor sleep decreased from 50% before transplant to 36% after 6 months, 32% after 12 months, and 23% after 24 months post-transplantation. Further research is needed to evaluate whether targeted sleep intervention in liver transplantation candidates has any influence on perioperative or long-term outcomes.

Overall, sleep-wake disturbance is highly prevalent among individuals with liver disease. Sleep abnormalities are likely to constitute both a cause and effect of underlying liver pathology. Hepatologists should look to identify the clinical effects of poor sleep, and aim to develop management strategies to address sleep-wake disturbance.

Disclosure: One study author declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Marjot T, Ray DW, Williams FR, Tomlinson JW, Armstrong MJ. Sleep and liver disease: a bidirectional relationship. Lancet. Published online July 15, 2021. doi: 10.1016/S2468-1253(21)00169-2