Circadian rhythms linked to chronic liver disease risk in a large UK cohort

In 94,006 UK Biobank participants followed for a median 9.8 years, lower wrist-activity circadian rhythm amplitude (lowest quartile) was associated with higher risks of metabolic dysfunction–associated steatotic liver disease, cirrhosis, and hepatocellular carcinoma; MRI data from a 15,106-person subcohort showed higher liver fat and fibroinflammatory scores with lower rhythm amplitude.

This study examined whether circadian rhythms measured by wrist-worn accelerometers were associated with chronic liver disease in the UK Biobank. Researchers analysed 94,006 participants without prior chronic liver disease who provided seven days of accelerometer data and were followed for a median of 9.8 years. Abnormal circadian rhythm was defined as the lowest quartile of relative amplitude, a measure of the difference between most-active and least-active periods. A MRI subcohort of 15,106 participants provided measures of liver fat (PDFF) and fibroinflammatory activity (cT1). Key findings: - Lower relative amplitude (lowest quartile) was associated with higher adjusted hazard ratios: MASLD HR 1.54 (95% CI 1.32–1.78), cirrhosis HR 1.79 (95% CI 1.38–2.32), and hepatocellular carcinoma HR 1.65 (95% CI 1.02–2.76). - The study reported dose–response patterns; relationships with MASLD and cirrhosis were nonlinear, while the association with hepatocellular carcinoma was described as linear. - In the MRI subcohort (15,106 participants), abnormal rhythms were associated with greater liver fat (PDFF difference +0.10; 95% CI 0.07–0.12) and higher cT1 scores (+8.35 ms; 95% CI 6.15–10.56). - Genetic susceptibility modified associations: participants with high polygenic risk and abnormal rhythms had larger reported HRs for MASLD (3.45; 95% CI 2.64–4.41), cirrhosis (5.41; 95% CI 3.09–9.49), and hepatocellular carcinoma (17.06; 95% CI 3.87–75.32). - Circadian measures were derived from seven days of wrist accelerometry; the final cohort excluded poor-quality sensor data and people with pre-existing liver disease. Summary: The analysis found that lower day–night activity amplitude measured by wrist accelerometers was associated with higher risks of fatty liver disease, cirrhosis, and liver cancer over about a decade, and with higher liver fat and fibroinflammation on MRI. The study is observational and cannot establish causality; the authors report that interventional studies are needed to determine whether modifying circadian rhythms changes liver disease risk.