PATIENTS AT RISK: IDENTIFYING MASH EARLY
Major medical societies, including the AACE, ADA, AGA, AASLD, and European counterparts, are increasingly emphasizing earlier identification and evaluation. 1,2,3,4,5 “This area of medicine is seeing rapid advances, so it’s very important to diagnose patients so that they can receive effective treatments," says Wajahat Mehal, MD, PhD, DPhil, a gastroenterologist and hepatologist and Director of the Yale Fatty Liver Disease Program, in New Haven. Historically, evaluation has relied on liver enzymes (ALT, AST) to prompt further assessment or referral, typically when values exceed conventional thresholds (ALT: ~45 U/L for women, ~55 U/L for men; AST: ~43 U/L for women, ~48 U/L for men). However, these markers have limited sensitivity, says Bril. Importantly, only a minority of patients with MASLD or MASH present with markedly elevated liver enzymes. “Most people in the ‘normal’ range [AST or ALT values ~30 U/L] already have fatty liver, and by the time they’ve hit 40 in their clinical labs—still in the ‘normal’ range—they probably have inflammation and fibrosis,” says Kenneth
Cusi, MD, Chief of the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida, in Gainesville. Up until now there has been limited clinical action until the labs are 50 or 100 percent higher than that, says Cusi. Emerging data suggest that current "normal" ranges may underestimate risk, says Scott Isaacs, MD, an endocrinologist at Emory University School of Medicine in Georgia and a co-author of the 2025 ADA consensus report on MASLD in people with diabetes. “By the time they see the endocrinologist, they already have cirrhosis that had been silently progressing for decades.” Plus, even at the low end of the spectrum, labs can be misleading. A low AST number can occur late in the progression of the disease, but this can be a sign of liver failure, not of a healthy functioning organ. 1 The status quo approach of relying on liver enzymes without using any other screening methods may be one reason why the prevalence of MASLD and MASH is increasing. These findings highlight the need to reconsider reliance on liver enzymes alone when assessing
Many patients with steatotic liver disease remain undiagnosed, often due to its asymptomatic nature and limitations of traditional screening approaches. “If you saw 20 patients with obesity in the last week, but did not diagnose at least one case of clinically significant fibrosis, it may have been missed,” says Fernando Bril, MD, an endocrinologist and co- author on the recent 2026 AGA Clinical Care Pathway for MASLD. Historically, he says, the absence of approved therapies has contributed to variability in screening and evaluation practices. Because of this, "it's been easy to think, 'Why should I be screening if it won't change my management of the patient?'" says Bril.
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