A systematic review and meta-analysis appearing in Frontiers in Medicine determined that individuals with sleep-disordered breathing (SDB), encompassing obstructive sleep apnea (OSA), faced 3.62 times the likelihood of developing metabolic dysfunction-associated steatotic liver disease (MASLD) compared to those without SDB or with milder forms. Conducted by investigators at Imam Mohammad Ibn Saud Islamic University in Riyadh, Saudi Arabia, this work shows a strong link between these issues, although the authors state it is “hypothesis-generating.”
MASLD, previously known as nonalcoholic fatty liver disease, affects up to one-third of adults globally. It is characterized by excess liver fat and can progress to metabolic dysfunction–associated steatohepatitis (MASH), leading to cirrhosis or severe liver fibrosis.
The sleep apnea-liver disease connection
OSA shares risk factors with MASLD, such as obesity, insulin resistance, and Type 2 diabetes. Research also suggests a direct link: oxygen drops during sleep may cause oxidative stress, mitochondrial dysfunction, and liver cell activation tied to scarring. Experimental studies have shown that these oxygen fluctuations, measured by indices like the oxygen desaturation index, correlate more closely with liver damage than traditional OSA severity metrics like the apnea-hypopnea index.
The analysis included 22 studies from six databases, ranging from bariatric surgery and sleep clinic cohorts to randomized CPAP trials, with sample sizes from nine to 410 participants. Across eight studies, 75.1% of SDB patients had MASLD or steatosis. In five studies, 13.9% showed liver fibrosis or risk. The evidence on fibrosis was limited; in one biopsy-based cohort, moderate-to-severe OSA was independently linked to nearly 3.5 times the odds of advanced fibrosis.
CPAP’s limited liver impact
Continuous positive airway pressure (CPAP) therapy lowered liver enzyme levels by 7.15 U/L for alanine aminotransferase (ALT) and 3.38 U/L for aspartate aminotransferase. However, randomized trials found no significant reduction in liver fat, MASH, or fibrosis. The authors noted that while CPAP reduces surrogate markers like enzymes, its impact on direct liver outcomes remains unclear.
A six-month trial in patients with biopsy-proven MASLD showed that weight changes correlated more closely with liver fat reduction than CPAP use. This finding aligns with Mendelian randomization studies that failed to establish a causal link between sleep apnea and MASLD. The authors identified short follow-up periods, inconsistent CPAP adherence, and small sample sizes as key limitations in existing studies.
Implications for healthcare
OSA affects an estimated 25 million U.S. adults, while MASH impacts nearly 15 million. The findings raise questions about CPAP’s benefits beyond sleep improvement, echoing a draft report from the Agency for Healthcare Research and Quality, which found insufficient evidence for CPAP’s long-term clinical benefits in OSA patients. This has sparked debate within the sleep medicine industry.
Despite high heterogeneity across studies, the review shows the need for prospective trials to clarify SDB treatment’s impact on liver disease progression. The authors rated the evidence certainty as low to very low for all outcomes. They recommended that clinicians assess liver health in OSA patients, particularly those with obesity, metabolic syndrome, diabetes, raised liver enzymes, or significant nighttime oxygen loss. Conversely, patients with MASLD showing signs of sleep apnea should undergo sleep disorder screening.
