Poor sleep and elevation of liver function biomarkers may be predictive of liver cancer

1. Unhealthy sleep, as well elevations of liver enzymes and decreased levels of albumin and liver functional biomarkers, were significantly associated with increased risk of liver cancer.

Evidence Rating Level: 2 (Good)

Poor sleep quality has been positively associated with cancer risk; however, the association between sleep and liver cancer risk specifically remains unclear. Studies examining routine liver function biomarkers and the risk of incident liver cancer in the general population with large sample sizes are also limited. Such liver function biomarkers include alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), albumin (ALB), alkaline phosphatase (ALP), total bilirubin (TBIL), and total protein (TP). This study thus investigated the separate and joint effects of sleep and liver function biomarkers on liver cancer using data from the UK Biobank, a prospective cohort recruited from 22 centers around the UK. Five sleep traits including sleep duration, morning/evening chronotype, insomnia, snoring, and excessive daytime sleepiness were used to create sleep scores that divide participants into either “healthy sleep” or “unhealthy sleep” categories. A total of 356, 894 participants were included in the study (mean age = 62±9 years, male N (%) = 170,831 (47.87%), mean BMI = 27.40 ± 4.73 kg/m2) and the median follow-up time was 13.1 years. Unhealthy sleep (vs healthy sleep) was associated with a 46% increased risk of liver cancer incidence (multivariable-adjusted hazard ratio (HR) 95% CI = 1.46 (1.15–1.85). Liver cancer risk was also associated with higher levels of ALT, AST, TBIL, GGT, ALP, or TP, and lower levels of ALB (HRs (95% CI): ALT = 1.17 (1.15–1.20), AST = 1.20 (1.18–1.22), TBIL = 1.69 (1.47–1.93), GGT  = 1.06 (1.06–1.07), ALP  = 1.08 (1.07–1.09), TP  = 1.81 (1.37–2.39), ALB  = 0.29 (0.18–0.46)). The highest risk for liver cancer was observed for individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level (HRs 95% CI: ALT = 3.65 (2.43–5.48), AST  = 4.03 (2.69–6.03), TBIL = 1.97 (1.40– 2.77), GGT  = 4.69 (2.98–7.37), ALP  = 2.51 (1.75–3.59), TP  = 2.09 (1.51–2.89), or  ALB  = 2.22 (1.55–3.17). Unhealthy sleep with high TP levels had a significant additive interaction on liver cancer with relative excess risk due to an interaction of 0.80 (0.19–1.41). Overall, the study results suggest that healthy sleep and controlling liver function biomarker levels may reduce the risk of liver cancer. 

Click to read the study in BMC Medicine

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