Factors Related to Sleeping Disorder Due to Pruritus in Patients with Chronic Liver Disease

Abstract

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.

Keywords: FIB-4 index; chronic liver disease; nalfurafine hydrochloride; pruritus; quality of life.

Figure 1.

Flow of the present study. CLD: chronic liver disease

Figure 2.

Correlations of VAS with time of day and seasons. The correlation between the daytime and nighttime VAS values in (a) winter and (b) summer, and between the winter and summer VAS values in (c) daytime and (d) nighttime. Each showed a significant relationship (p<0.001). VAS: visual analogue scale

Figure 3.

The comparison of the VAS values and Kawashima’s pruritus score between seasons. There was no significant difference in the VAS value between winter and summer for (a) daytime or nighttime or between the (c) daytime and (d) nighttime Kawashma’s pruritus scores. VAS: visual analogue scale

Figure 4.

The correlation between the hepatic function or FIB-4 index and visual analogue scale (VAS), and differences regarding pruritus between patients with and without sleep disorder. The albumin-bilirubin score showed a significant relationship with the VAS for summer (a) daytime and (b) nighttime. The FIB-4 index also showed a significant relationship with the VAS for summer (c) daytime and (d) nighttime. Patients with a sleep disorder showed a larger number of pruritus incidents each day (p<0.001) (e). Patients with a sleep disorder showed a greater frequency of longer duration pruritus than those without a disorder (p<0.001) (f).

Figure 5.

Predictive values of visual analogue scale (VAS) for the existence of a sleep disorder and the relationship between Kawashima’s pruritus score and sleep disorder. The predictive values of VAS for the existence of sleep disorder in the (a) daytime were 1.6 [the area under curve (AUC) 0.901, 95% confidence interval (CI) 0.852-0.949], and those in the (b) nighttime were 3.4 (AUC 0.931, 95% CI 0.894-0.968). The predictive value of the FIB-4 index (3.07) was good (AUC 0.748, 95% CI 0.634-0.860) (sensitivity/specificity=0.623/0.800) (c). Patients with a sleep disorder showed a higher Kawashima’s pruritus score in both (d) daytime and (e) nighttime than those without a disorder.