Sleep apnea linked to higher odds of fatty liver disease, but CPAP benefit limited to liver enzymes

Patients with sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA), had 3.62 times the odds of metabolic dysfunction-associated steatotic liver disease (MASLD) or hepatic steatosis compared with those without SDB or with milder disease, according to a systematic review and meta-analysis published in Frontiers in Medicine.

Continuous positive airway pressure (CPAP) therapy lowered liver enzyme levels, but controlled trials did not show it reduced liver fat or scarring. The authors, from Imam Mohammad Ibn Saud Islamic University in Riyadh, Saudi Arabia, rated the certainty of evidence as low to very low for every outcome.

Why sleep apnea and MASLD overlap

MASLD, formerly called nonalcoholic fatty liver disease, affects up to one-third of adults worldwide, the authors noted. It is characterized by excess fat buildup in the liver and can progress to metabolic dysfunction–associated steatohepatitis (MASH), which leads to cirrhosis or severe liver fibrosis. OSA shares many of its risk factors, including obesity, insulin resistance and Type 2 diabetes.

The link may also be more direct. In experimental research, repeated drops in oxygen during sleep have been tied to oxidative stress, mitochondrial dysfunction and activation of liver cells involved in scarring.

The researchers searched six databases through May 15, 2026, and included 22 studies. These ranged from bariatric surgery and sleep clinic cohorts to randomized CPAP trials, with sample sizes from nine to 410 participants.

What the meta-analysis found on MASLD and fibrosis

Across eight studies, 75.1% of patients with SDB had MASLD or steatosis. Across five studies, 13.9% had liver fibrosis or were at risk for it. Results varied widely from study to study in both analyses.

The 3.62 odds ratio came from five studies that mixed adjusted and unadjusted data, as well as comparisons of sleep apnea presence and severity. The authors described it as “a hypothesis-generating association.”

Evidence on fibrosis was thinner. In one biopsy-based cohort, moderate-to-severe OSA was independently tied to nearly 3.5 times the odds of advanced fibrosis. Measures of nighttime oxygen loss, such as the oxygen desaturation index, tracked more closely with liver damage than the apnea-hypopnea index, the standard gauge of OSA severity.

CPAP lowers liver enzymes, not liver fat

In before-and-after analyses, CPAP was associated with an average drop of 7.15 U/L in alanine aminotransferase (ALT) across seven studies and 3.38 U/L in aspartate aminotransferase across six. Most of those studies were not randomized, and the authors noted that the enzymes are surrogate markers.

Two randomized, controlled analyses did not show significant improvements in steatosis, metabolic dysfunction-associated steatohepatitis (MASH) or fibrosis measures. In one, a six-month trial in patients with biopsy-proven MASLD, therapeutic and subtherapeutic CPAP had similar effects, and weight change tracked more closely with changes in liver fat than CPAP assignment did.

The authors pointed to short follow-up, inconsistent CPAP adherence and small samples as possible explanations. They also cited Mendelian randomization studies that did not establish a causal effect of sleep apnea on MASLD.

What it means for health plans

Both conditions affect large populations. OSA affects an estimated 25 million U.S. adults, according to the American Academy of Sleep Medicine, and MASH affects nearly 15 million, according to FDA figures cited by the American Association for the Study of Liver Diseases.

The findings add to questions about what CPAP delivers beyond sleep. A draft report from the Agency for Healthcare Research and Quality found insufficient evidence that CPAP leads to clinically meaningful long-term benefits in patients with OSA, drawing pushback from the sleep medicine industry, Managed Healthcare Executive® previously reported.

Weight-focused drug options now span both conditions. Zepbound (tirzepatide) is approved for adults with obesity and moderate-to-severe OSA, and Wegovy (semaglutide) received accelerated approval for noncirrhotic MASH with moderate-to-advanced fibrosis, joining Rezdiffra (resmetirom).

Screening recommendations and study limitations

Heterogeneity was high across analyses, and the review did not include subgroup or sensitivity analyses. Liver outcomes were measured by biopsy in some studies and by ultrasound or ALT levels in others, and obesity could not be fully separated from the effects of sleep apnea.

“Pooled point estimates should be viewed as indicative rather than precise,” the authors wrote.

Still, they suggested clinicians consider liver assessment in patients with OSA, particularly those with obesity, metabolic syndrome, diabetes, elevated liver enzymes or significant nighttime oxygen loss. Patients with MASLD who show signs of sleep apnea should be screened for sleep disorders, they added.

“Further high-quality prospective trials are required to assess influence of SDB treatment on steatotic liver disease progression,” the authors concluded.