Liver Disease and Sleep Disorders - The Association

Introduction

As a significant factor in the disease progression of people with chronic liver disease (CLD), the link between sleep disturbance and CLD is becoming more widely accepted. Reduced health-related quality of life in cirrhotic individuals is independently correlated with sleep disruption. The chance of developing liver cancer may be higher in persons with sleep difficulties. With regard to non-alcoholic fatty liver disease (NAFLD), in particular, liver dysfunction in obstructive sleep apnea (OSA) focuses on the respiratory component in the development of sleep disturbance in CLD. However, it is acknowledged that neurology has a significant influence.

What Are the Sleep Disturbances in Liver Disease Patients?

Sleep disruption is a prevalent occurrence among individuals diagnosed with Chronic Liver Disease (CLD) and cirrhosis. Patients with cirrhosis self-reported experiencing suboptimal sleep quality, as determined by the Pittsburgh Sleep Quality Index (PSQI).

• The Pittsburgh Sleep Quality Index (PSQI) scores were found to be greater in patients exhibiting signs of hepatic encephalopathy (HE).

• Individuals with elevated PSQI scores experienced a lower health-related quality of life. Approximately half of the individuals diagnosed with cirrhosis who do not have hepatic encephalopathy (HE) reported experiencing bad sleep.

• Individuals who have a limited duration of sleep, namely less than six hours per night, exhibit diminished sleep efficiency, prolonged time to fall asleep, heightened latency of rapid eye movement (REM) sleep, decreased duration of REM sleep, frequent awakening during the night, and excessive drowsiness during the day.

• Insomnia was identified in patients with cirrhosis, and its prevalence was found to rise with the severity of the cirrhosis. Additionally, individuals experiencing insomnia also reported greater levels of excessive daytime sleepiness.

• Consequently, it is imperative to conduct screenings for sleep disturbance in patients who are either diagnosed with or exhibit symptoms of Chronic Liver Disease (CLD), namely cirrhosis.

What Are the Treatments for the Disorder?

There has been a limited amount of studies conducted on therapies that explicitly address sleep disturbance in individuals with chronic lung disease (CLD).

• Lactulose is extensively employed for the treatment of hepatic encephalopathy (HE).

• The efficacy of Rifaximin, an antibiotic prescribed for refractory hepatic encephalopathy (HE), has been established in enhancing the duration of rapid eye movement (REM) sleep, without affecting excessive daytime sleepiness (EDS) sleep quality.

• The administration of Hydroxyzine for a brief duration in individuals diagnosed with cirrhosis resulted in enhanced sleep efficiency and a personal assessment of improved sleep quality. The potential correlation between the circadian rhythm of melatonin and sleep disruption in individuals with Chronic Liver Disease (CLD) has not been thoroughly examined in terms of melatonin administration.

• The efficacy of light treatment in rectifying circadian rhythm has been the subject of investigation. However, despite the presence of favorable findings, there is a lack of evidence to establish any significant benefits.

What Connections Exist Between Non-alcoholic Fatty Liver Disease and Sleep Apnea?

Sleep disturbance is observed in individuals with chronic liver disease (CLD), while liver dysfunction is observed in those with obstructive sleep apnea (OSA).

• Obstructive sleep apnea (OSA) is a prevalent respiratory condition with a clinically significant global prevalence.

• The presence of obstructive sleep apnea (OSA) has been found to be significantly correlated with increased levels of transaminases, as well as an increased risk of developing non-alcoholic steatohepatitis (NASH) and liver fibrosis.

• The presence of obstructive sleep apnea (OSA) was found to have a substantial correlation with non-alcoholic fatty liver disease (NAFLD) in obese patients, as evidenced by abnormal liver histology. Conversely, the lack of OSA was linked with normal liver histology, further highlighting the strong link between OSA and NAFLD.

• The accumulation of lipids within hepatocytes. Hepatocyte damage, inflammation, and subsequent fibrosis can be triggered by oxidative stress, proinflammatory cytokines, or mitochondrial malfunction.

• Both nocturnal oxygen saturation and independent risk factors contribute to the development of liver injury, as evidenced by the increase in transaminases, non-alcoholic fatty liver disease (NAFLD), and hepatic fibrosis. Individuals diagnosed with non-alcoholic fatty liver disease (NAFLD) exhibit an elevated apnea-hypopnea index and a decreased mean nocturnal oxygen saturation compared to individuals without NAFLD. These features are considered independent risk factors that contribute to the advancement of hepatic fibrosis.

• The utilization of continuous positive airway pressure (CPAP) therapy demonstrates a potential to impede the advancement of non-alcoholic fatty liver disease (NAFLD) towards liver fibrosis. Hepatic steatosis is a condition that can be reversed, and the use of continuous positive airway pressure (CPAP) does not seem to have a positive effect on the structural alterations in the liver observed in individuals with obstructive sleep apnea (OSA).

• The association between non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) exhibits a notable level of complexity, and the establishment of a causal link between the two conditions remains controversial.

• However, it is evident that the hypoxia associated with OSA does play a role in the emergence of NAFLD and the advancement of NAFLD towards liver fibrosis. Nevertheless, the total reversal of the morphological liver alterations is not achieved by eliminating this hypoxia, indicating the presence of other processes that have yet to be uncovered. The liver enzymes in obstructive sleep apnea (OSA) have proposed the incorporation of basic screening tools, questionnaires for OSA, and liver function tests for non-alcoholic fatty liver disease (NAFLD) as part of the initial evaluation for these patients.

• Additional treatments for obstructive sleep apnea (OSA), such as the mandibular device, also have the objective of mitigating the occurrence of intermittent hypoxia.

Conclusion

Sleep disruption is a prevalent issue in chronic liver disease (CLD) and has been linked to a decrease in overall health-related quality of life. The phenomenon might present itself in diverse manifestations, encompassing delayed initiation of sleep, excessive daytime sleepiness, and diminished subjective perception of sleep quality. The causes of this phenomenon are intricate and multifaceted and still require more elucidation. Various specific disorders can contribute to chronic liver disease (CLD) and have distinct effects on sleep patterns. It has been observed that undergoing liver transplantation does not lead to an improvement in the quality of sleep. At present, there exists a limited range of management strategies that particularly target sleep disruption in individuals with chronic liver disease (CLD). The most compelling body of evidence pertains to the efficacy of proven medications for hepatic encephalopathy (HE), namely lactulose and Rifaximin. However, the administration of continuous positive airway pressure (CPAP) as a treatment for intermittent hypoxia did not lead to a substantial reversal of progressive liver disease in non-alcoholic fatty liver disease (NAFLD).