Prevalence of sleep disturbances in patients with liver cirrhosis

Latha K 1,Kanmani Karthikeyan 2, Viji Devanand 3, Gokulnathan V 4

1Assistant Professor, 2Associate Professor, 3 Professor & Head, 4 Post Graduate, Department of Physiology,Stanley Medical College, Chennai, Tamil Nadu

Background: Disturbed sleep is frequently reported by patients with cirrhosis attending outpatient clinics, but its prevalence, determinants, and consequences are not well understood. Aim: To prospectively assess the prevalence of disturbed sleepin patients with cirrhosis. Materials and Methods: Consecutive patients with cirrhosis attending the liver clinics between June 2021 and December 2021 were invited to participate. They completed the questionnaire to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness using the Epworth sleepiness scale (ESS). Poor sleep according to the PSQI instrument is defined as PSQI>5. Daytime sleepiness is said to be present for the ESS score>8. The characteristics of sleep in cirrhotic patients were assessed using a sleep questionnaire. The results were compared with those of healthy subjects. The presence of subclinical hepatic encephalopathy and individual’s affective state were also analyzed. Results: The questionnaire indicated an elevated number of cirrhotic patients (80%) who complained of unsatisfactory sleep compared with healthy subjects (10%, P value < 0.01). The sleep disturbance in cirrhosis was not associated with clinical parameters nor with cognitive impairment. Conclusion: Disturbed sleep is highly prevalent in ambulatory cirrhotic patients, and it is independently associated with poor quality of life. Further studies are needed for better understanding of the pathogenesis of poor sleep and its management strategies in this population.
Key words: cirrhosis, Pittsburgh sleep quality index, sleep disturbance
Corresponding Author
Dr. Gokulnathan. V, Post-graduate, Department of Physiology, Stanley Medical College, ChennaI, Tamil Nadu. Contact No:9444743881, E-mail: [email protected]

Cirrhosis and chronic liver disease adversely affect neurocognitive functioning. These neurocognitive difficulties severely restrict the patients functioning and are associated with sleep disturbances.1Sleep disturbances are common in patients with cirrhosis and lead to impaired quality of life. The most common abnormalities are insomnia (difficulty in falling asleep and maintaining sleep, or unrefreshing sleep), excessive daytime sleepiness, and sleep-wake inversion (disturbances of circadian rhythmicity).2 The underlying pathophysiological mechanisms for sleep disturbances in cirrhosis are complex and may include disturbed metabolism of melatonin and glucose, alterations in thermoregulation, and altered ghrelin secretion profiles. Sleep-wake abnormalities are related to the presence of hepatic encephalopathy (HE) and improvement in sleep parameters can be observed when HE is properly managed.3

The PSQI is a 19-item self-rated questionnaire for evaluating subjective sleep quality over the previous month. The 19 questions are combined into 7 clinically-derived component scores, each weighted equally from 0–3. The 7 component scores are added to obtain a global score ranging from 0–21, with higher scores indicating worse sleep quality. The clinical and psychometric properties of the PSQI have been formally evaluated by several research groups.Validity is further supported by similar differences between groups using PSQI or polysomnographic sleep measures. The PSQI has been translated into 48 languages and has been used in a wide range of population-based and clinical studies.4

The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person’s average sleep propensity in daily life (ASP), or their ‘daytime sleepiness’. The questionnaire takes no more than 2 or 3 minutes to answer. It is available in many different languages.5

Aim and Objectives
To assess the subjective sleep quality in cirrhotic liver disease patients using Pittsburgh Sleep Quality Index (PSQI) and assess the “daytime sleepiness” using the Epworth sleepiness scale (ESS).
Materials and Methods
This was a cross sectional study completed in a period of 6 months at Stanley Medical Hospital. Sample size for the study was 80.40 healthy individuals belonging to the control group were selected randomly from general population. 40 subjects belonging to the case group were selected from the Medicine Department of Stanley Government hospital. Data collection was done after obtaining Institutional Ethical Committee clearance. The purpose of the study was explained to the subjects and written informed consent was obtained. The diagnosis of cirrhosis was made based on suggestive clinical features, deranged liver function tests, and evidence of portal hypertension on ultrasonography and endoscopy. Patients diagnosed with cirrhosis of the liver were assessed for subjective sleep quality using Pittsburg Sleep Quality Index (PSQI). Daytime sleepiness among the subjects was assessed using the Epworth sleepiness scale (ESS).
Inclusion criteria
• Patients with cirrhosis or chronic liver disease with no evidence of overt Encephalopathy (Grade 1 as per West Haven Criteria, Class ‘B’ in Child-Pugh Criteria).
• Patients between the age group of 20 years and 60 years
• Individuals of either sex
Exclusion criteria
• Primary neurologic and psychiatric disorders
• Cardiovascular diseases
• Diabetes mellitus
• Chronic renal disease
• Active gastrointestinal bleed
• Alcohol intake within last three months
• Consumption of drugs acting on the CNS
• Visual and hearing impairment
Statistical analysis
The data obtained were analyzed by using Statistical Package for Social Sciences (SPSS) version 20. The categorical variables were expressed in percentage.
Table 1:Age distribution of the study participants
Age (Years) No. of Subjects Percentage
35&Below 16 20.0%
36 – 45 33 41.3%
46 &Above 31 38.8%
Total 80

Graph 1: Age distribution of the study participants

Table 2: Sex distribution of the study participants
Sex No. of Subjects Percentage
Male 69 86.3%
Female 11 13.8%
Total 80

Graph 2: Sex distribution of the study participants

Mean age of the subjects belonging to study group (cirrhotic patients) is 51 years. Mean age of the subjects belonging to control group (healthy subjects) is 43 years.
The sleep quality of the participants has been presented in table 3. Daytime sleepiness among the participants is presented in table 4. The characteristics of sleep are presented in Table 5. Cirrhotic patients showed a significantly higher prevalence of sleep disturbance than the healthy control group. Most of the cirrhotic patients, 80% complained of unsatisfactory sleep, whereas this complaint was infrequent in the healthy subjects (10%). Unsatisfactory sleep was present for 5 or more years in eight cirrhotic patients.
The comparison of parameters of nighttime sleep between the two groups showed a significantly higher proportion of subjects referring short sleeping time (<6 h/night), difficulties falling asleep (sleep latency >30 minutes) and more frequent nocturnal awakenings in the cirrhotic patients group. In addition, daytime functioning of these patients was affected by higher episodes of undesired sleepiness and more prolonged napping time.
In cirrhosis, unsatisfactory subjective sleep quality was associated with worsening objective parameters of nighttime sleep and daytime functioning. In the healthy control group, the small number of individuals with unsatisfactory sleep precludes meaningful associations.
Table 3: Sleep quality among the groups using PSQI
Healthy subjects (n=40) Cirrhotic patients (n=40) P Value
Good sleep quality(PSQI<5) 36 8 <0.01

Poor sleep quality(PSQI>5) 4 32 <0.01

Table 4: Daytime sleepiness among the groups using ESS
ESS Healthy subjects (n=40) Cirrhotic patients (n=40) P Value
Daytime sleepiness(ESS>8) 35 11 <0.01
No daytime sleepiness(ESS<8) 5 29 <0.01

Table 5: Characteristics of sleep among groups
Healthy subjects (n=40) Cirrhotic patients (n=40)
factory sleep Unsatis-factory sleep Satis-
factory sleep Unsatis-
factory sleep
Number 36 4 8 32
Sleeping time
< 6h/night 5 4 4 23
Sleep latency
>30 min 2 2 3 17
Awakenings (episodes/
night) 0.9±0.1 1 1.7±0.3 4.1±0.6
Daytime naps (minutes/day) 7±2 14±3 19±3 49±8

The results of this study demonstrate that patients with cirrhosis and no evidence of hepatic encephalopathy have poor sleep quality. Nearly one half of patients attending a Liver Clinic complained of unsatisfactory sleep, a frequency slightly greater than that previously reported with quality-of-life questionnaires.6 Analysis of sleep questionnaires in both groups of patients showed a nocturnal sleep characterized by reduced sleeping time and frequent awakenings.7 These results raise the possibility that our findings of disturbed sleep may be nonspecific, reflecting the impact of chronic disease on daily functions.
The majority of patients experienced sleep disturbances for less than 5 years, indicating a direct link between chronic liver illness and sleep disturbances. This causal relationship is also supported by the substantial improvement in the area of sleep that has been observed after liver transplantation.8 In the cirrhotic patients’ group, 15 out of the 32 patients who had poor sleep quality had no history of alcohol consumption. So, the etiology of cirrhosis was not a discriminant factor in this group of alcohol-free patients, which is consistent with recent observations of noncognitive impairments present in all kinds of cirrhosis.9
Circadian disturbances are linked to the development of hepatic encephalopathy. The Rats after portocaval anastomosis are a model of subclinical encephalopathy.10 They showed disruption in their circadian rhythms.11 Thus, it can be hypothesized that sleep disturbance in cirrhosis may be a manifestation of minor forms of encephalopathy. The prevalence of cognitive impairment detected in our patients is in accordance with the study made by Blei and Cordoba et al.12
It was previously postulated that in cirrhosis, alterations of the function of the suprachiasmatic nucleus—the hypothalamic biological clock—may result in an array of circadian abnormalities.13,14 The transitory sleeplessness that occurs with jet lag or shift work is mediated by the desynchronization of the social and internal rhythms.15 Similarly, sleep irregularities, such as sleep disruption, may arise as a result of aging-related failing circadian timekeeping systems.16 Analysis of sleep patterns in cirrhotic patients with sleep disturbance indicated that these subjects had a delayed bedtime, delayed wake-up time, and preference for evening activities as compared with those with normal sleep. A propensity for nighttime activity could indicate a change in circadian function, such as a shift toward later hours as a result of a change in the circadian clock’s output or its afferent/efferent connections. A shift toward later hours in the 24-hour profile of plasma melatonin, which has levels that mirror the output from the circadian clock, was reported in cirrhosis in a prior study.17
Cirrhosis-related sleep disturbances could be linked to the desynchronization of the circadian timekeeping system, according to certain theories. The inversion of sleep patterns seen in people with overt encephalopathy could be the most extreme example of this shift. Cirrhosis-related circadian abnormalities may be caused by a number of factors, including the impact of gut-derived toxins on the brain, decreased sensorial inputs that entrain the circadian clock, such as insufficient light exposure, social isolation, or low levels of activity, as well as retinohypothalamic and endocrine (e.g., melatonin) abnormalities.18
The current study points to a probable link between sleep problems and changes in circadian timekeeping mechanisms. Underlying pathophysiological mechanisms are complex and include disturbed metabolism of melatonin. Because sleep–wake disorders arise when HE is present, HE therapy is the cornerstone of treatment. Recognizing sleep disturbance in cirrhosis and comprehending the underlying pathophysiological causes may lead to treatments that improve patients’ quality of life.
This study assessed only subjective sleep symptoms and lacks polysomnography data.Due to the increased potential for medication toxicity in these disabled patients, further studies are needed to address the potential role of non-drug therapies in this population such as cognitive behavioral therapy, mindfulness, yoga, that have demonstrated usefulness in insomnia disorders.
Acknowledgements: Nil
Conflict of interest: Nil
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