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Isolated steatosis, as part of the spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD), can progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Since individuals with clinically significant fibrosis (stage 2 or higher, 鈮�F2) or advanced fibrosis (stage 3 or higher, 鈮�F3) are at an increased risk of morbidity and mortality, a focus area of clinical research has been MASH with 鈮�F2鈥攐r 鈥渁t risk鈥� MASH.

Investigators from the University of California at San Diego (UCSD) assessed the U.S. prevalence of at-risk MASH specifically among older individuals diagnosed with, and receiving treatment for, type 2 diabetes (T2D) and explored the usefulness of noninvasive testing in screening for and managing MASH.¹

Before their study, however, a precise quantification of at-risk MASH in T2D had not been established. Their prospective study, published in a recent issue of Alimentary Pharmacology and Therapeutics, demonstrated a high prevalence of at-risk MASH in older adults with T2D, 鈥減osing a higher risk for cirrhosis and liver-related mortality in this population,鈥� the authors wrote.¹

Screening for at-risk MASH in T2D

The UCSD research team estimated the prevalence of at-risk MASH in a cohort of 530 adults 鈮�50 years of age with T2D, recruited prospectively from primary care and endocrinology clinics or by other means, such as through local newspapers and social media, in southern California from 2016 to 2023.¹

Participants had a mean age of 64.4 years and a mean body mass index of 31.5 kg/m2. Overall, 63.4% were female; in terms of ethnicity, 41.4% were Hispanic and 36.3% were White. During research visits, participants underwent thorough clinical, physical, and laboratory evaluations, as well as various imaging tests.

Setting the study parameters

At-risk MASH was defined according to 3 noninvasive, liver stiffness-based models: 

• Positive magnetic resonance elastography (MRE) plus fibrosis 4 index (MEFIB) score (MRE >3.3 kPa [kilopascals] plus fibrosis 4 index >1.6) 
• FibroScan aspartate aminotransferase (FAST) score of 鈮�0.67
• Magnetic resonance imaging (MRI) aspartate aminotransferase (MAST) score of 鈮�0.242 

MASLD was defined as MRI-proton density fat fraction (PDFF) of 鈮�5% or controlled attenuation parameter 鈮�288 dB/m (decibels per meter) among individuals who ingested no or little alcohol and did not have any secondary causes of liver disease according to the nomenclature of the American Association for the Study of Liver Diseases. 

Cirrhosis was defined as MRE 鈮�4.67 kPa or vibration-controlled transient elastography (VCTE) 鈮�15 kPa if the MRE measure was not available.

鈥淕iven that the positive predictive value of VCTE remains limited (approximately 55%), having most of our patients also undergo MRE and MRI-PDFF (both of which have super[ior] diagnostic accuracy with higher specificity and positive predictive value) allowed for comprehensive and accurate screening for steatosis and fibrosis in our patients,鈥� the authors noted.¹

High rates of several conditions are observed

Prevalence of MASLD, at-risk MASH, and cirrhosis among older individuals with T2D was 69.6%, 13.6%, and 6.8%, respectively. The prevalence of liver disease among individuals with T2D was significantly higher for those who were also considered obese compared to those who were not obese: MASLD (77.8% versus 58.6%; P<.0001), at-risk MASH (15.9% versus 10.1%; P=.0543), and cirrhosis (9.0% versus 3.5%; P=.0128).

The study confirmed that individuals with T2D and at-risk MASH were at higher risk for advanced fibrosis and cirrhosis compared to those with T2D and no evidence of at-risk MASH: advanced fibrosis (69.4% versus 5.7%; P<.0001), cirrhosis (43.1% versus 1.1%; P<.0001).

Greater burden of liver disease

鈥淭his study provides the seminal estimate of individuals with type 2 diabetes who may be candidates for pharmacologic treatment for MASH-related fibrosis,鈥� senior author Rohit Loomba, MD, MHSc, told 番茄社区app. 鈥淚t also provides a noninvasive way of identifying patients who could benefit from treatment,鈥� he added. 

Besides his teaching duties at UCSD, Dr. Loomba is chief of the Division of Gastroenterology and Hepatology at UCSD Health and the founding director of UCSD鈥檚 MASLD Research Center.

When 番茄社区app asked about what future research on at-risk MASH should entail, Dr. Loomba replied that the current findings need to be validated across multiple biogeographic and ethnically diverse groups with T2D. Researchers, he added, also need to study what the risk of progression would be, how often patients with at-risk MASH need to be followed, and whether progression occurs at a faster rate when considering concurrent T2D.

鈥淥verall, the high burden of undiagnosed liver disease supports the use of noninvasive screening for older diabetic patients,鈥� Dr. Loomba and his colleagues concluded in their report.¹

Published: May 15, 2024