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. 2024 Jun 24;22(1):261.
doi: 10.1186/s12916-024-03440-w.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

Jiahao Song  1   2 , Lieyang Fan  1   2 , Da Shi  3 , Xuefeng Lai  1   2 , Hao Wang  4 , Wei Liu  1   2 , Linling Yu  1   2 , Ruyi Liang  1   2 , Yongfang Zhang  1   2 , Shuhui Wan  1   2 , Yueru Yang  1   2 , Bin Wang  5   6
Affiliations

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study

Jiahao Song et al. BMC Med. .

Abstract

Background: To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer.

Methods: Data of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence.

Results: After a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15-1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15-1.20), 1.20 (1.18-1.22), 1.69 (1.47-1.93), 1.06 (1.06-1.07), 1.08 (1.07-1.09), 1.81 (1.37-2.39), or 0.29 (0.18-0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43-5.48), 4.03 (2.69-6.03), 1.97 (1.40-2.77), 4.69 (2.98-7.37), 2.51 (1.75-3.59), 2.09 (1.51-2.89), or 2.22 (1.55-3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19-1.41).

Conclusions: Unhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Keywords: Joint association; Liver cancer; Liver function biomarker; Prospective cohort study; Sleep.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the study design and workflow. Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; TBIL, total bilirubin; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; TP, total protein; ALB, albumin
Fig. 2
Fig. 2
Risk of incident liver cancer according to sleep and liver function biomarkers (N = 356,894). Abbreviations: HR, hazard ratio; CI, confidence interval; RERI, relative excess risk due to the interaction; AP, attributable proportion due to the interaction; ALT, alanine transaminase; AST, aspartate transaminase; TBIL, total bilirubin; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; TP, total protein; ALB, albumin. Median concentration was used as the cut-off concentration for high or low classification of the liver function biomarker. Models were adjusted for age, sex, ethnicity, BMI, smoking status, alcohol consumption, healthy diet, physical activity, any treatment/medication taken, Townsend deprivation index, family history of cancer, and CRP
See this image and copyright information in PMC

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