Daytime napping, nighttime sleeping duration, and risk of hepatocellular carcinoma and liver disease-related mortality

Background & Aims: Sleep duration has been linked to metabolic dysfunction and chronic inflammation, which may contribute to the development of liver cancer and chronic liver disease (CLD). However, little is known about the relationship between sleep or napping duration and hepatocellular carcinoma (HCC) risk and CLD mortality. Methods: We followed 295,837 individuals in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. We examined the associations of nighttime sleep duration and daytime napping duration with risk of HCC incidence and CLD mortality. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: A total of 357 incident HCC cases and 578 CLD deaths were identified after a median follow-up time of 15.5 years. After adjusting for confounder factors, we found U-shaped associations of nighttime sleep duration with the incidence of HCC (HR_{<5 vs. 7–8 h} = 2.00, 95% CI: 1.22–3.26 and HR_{≥9 vs. 7–8 h} = 1.63, 95% CI: 1.04–2.65) and CLD mortality (HR_{<5 vs. 7–8 h} = 1.78, 95% CI: 1.18–2.69 and HR_{≥9 vs. 7–8 h} = 1.91, 95% CI: 1.35–2.70). Daytime napping was associated with higher risk of HCC (HR_{≥1 vs. non-nappers} = 1.46, 95% CI: 1.04–2.06) and higher CLD mortality (HR_{≥1 h vs. non-nappers} = 1.54, 95% CI: 1.18–2.01) compared with no napping. Conclusions: We observed U-shaped associations for nighttime sleeping and risk of HCC and CLD mortality. Additionally, longer daytime napping duration was associated with higher risk of HCC and CLD death. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep. Impact and implications: Sleep or napping duration may play a role in the development of liver cancer and chronic liver disease, but little is known about the relationship between them. In addition, abnormal sleep patterns in patients with chronic liver disease may further promote the development of liver disease, creating a vicious cycle. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep, as they can be potentially important factors in the development and progression of liver disease.