The prevalence of MASLD (steatotic liver disease associated with metabolic dysfunction) is exploding in most parts of the world, driven by increases in obesity and sedentary lifestyles. MASLD (formerly known as non-alcoholic fatty liver disease) is already the most common liver disease: it affects 30% of adults and between 7% and 14% of children and adolescents, and this prevalence is expected to reach more than 55 %. of adults by 2040. People with MASLD are at increased risk of diabetes, hepatocellular carcinoma, non-liver cancers, chronic kidney disease, age-related muscle loss, and cardiovascular disease.
Previous studies have implicated disruptions of the circadian clock and sleep cycle in the development of MASLD. But the American Academy of Sleep Medicine has recommended that objective measures – rather than subjective ones like sleep questionnaires – be used to prove this hypothetical link between sleep disorders and circadian rhythm, MASLD and MASH. MASH is a more severe form of MASLD, in which the liver suffers damage from inflammation and tissue scarring, caused by abnormal accumulation of fat.
“We show here for the first time with an objective method, 24/7 actigraphy, that the sleep-wake rhythm of patients with MASLD actually differs from that of healthy individuals: those with MASLD have demonstrated significant fragmentation of their nighttime sleep due to frequent awakenings and increased arousal,” said Dr. Sofia Schaeffer, postdoctoral researcher at the University of Basel and the Basel University Center for gastrointestinal and liver diseases, and corresponding author of a new study in Frontiers in network physiology.
Actigraphy involves tracking gross motor activity with a sensor worn on the wrist.
Don’t lose sleep
Between 2019 and 2021, Schaeffer and colleagues recruited 46 adult women and men diagnosed with MASLD, MASH, or MASH with cirrhosis. Eight additional patients with non-MASH-related liver cirrhosis served as comparison, while a second comparison group consisted of 16 age-matched healthy volunteers. Each study participant was equipped with an actigraph, to be worn constantly, which tracked light, physical activity and body temperature.
Participants visited the outpatient clinic at the beginning, midway, and end of the four-week follow-up. At the beginning and end of this period, they underwent a clinical investigation and were questioned by means of sleep questionnaires about their sleeping habits. They also kept a sleep diary.
All MASLD patients were obese and 80% had metabolic syndrome. MASLD patients additionally had significantly higher levels of triglycerides, fasting glucose, and blood insulin than healthy participants, but lower levels of total cholesterol, “bad” LDL cholesterol, and ” good » lower HDL cholesterol.
Sudden awakening
Actigraph measurements revealed no differences between MASLD patients and healthy participants on things like sleep duration or time spent in bed.
Most importantly, actigraphs showed that MASLD patients woke up 55% more often at night and stayed awake 113% longer after first falling asleep, compared to healthy volunteers. MASLD patients also slept more often and longer during the day. Actigraph-measured sleep patterns and quality were also impaired in patients with MASH, MASH with cirrhosis, and non-MASH-related cirrhosis.
Subjectively, patients with MASLD self-reported their disrupted and ineffective sleep as shorter sleep with delayed onset. In their sleep diaries, 32% of MASLD patients reported experiencing sleep disturbances caused by psychological stress, compared to only 6% of healthy participants.
We concluded from our data that sleep fragmentation plays a role in the pathogenesis of human MASLD. It is unknown whether MASLD causes sleep disturbances or vice versa. »
Dr Sofia Schaeffer, postdoctoral researcher, University of Basel
“The underlying mechanism likely involves genetics, environmental factors and activation of immune responses – ultimately driven by obesity and metabolic syndrome. »
Schaeffer and colleagues also attempted to improve participants’ sleep with a single sleep hygiene education session, conducted halfway through the study. Here they learned practical steps to improve their sleep habits. However, results showed that the session did not improve actigraphy or self-reported measures of sleep quality and quantity.
“A single session of sleep hygiene education was not enough to have a lasting impact on circadian rhythm in MASLD patients or healthy controls. Future studies should explore perpetual sleep counseling sessions or interventions such as light therapy in combination with other lifestyle changes to improve sleep. sleep-wake cycle in patients with MASLD,” recommended Dr. Christine Bernsmeier, professor at the University of Basel and lead author of the study.
