乌鸦传媒

Liver diseases known previously as non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction鈥揳ssociated fatty liver disease (MAFLD) are now referred to as metabolic dysfunction鈥揳ssociated steatotic liver disease (MASLD). MASLD had been studied extensively among overweight or obese patients, but only limited data among lean patients are available.¹

To better understand the diagnosis, pathogenesis, treatment, and prognosis of MASLD among lean patients, researchers in the United States and Peru performed a systematic review by searching PubMed and Google Scholar for papers published in January 2012 through September 2023. The final analysis included 85 studies on NAFLD, MAFLD, or MASLD among patients 18 years of age or older who had a lean body mass index indicated by a cutoff of 25 kg/m² for the general population and 23 kg/m² for Asians based on World Health Organization criteria.¹

鈥淔uture studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease,鈥� the authors wrote in their recently published report. 鈥淲e aim to enhance the understanding of steatotic liver disease in lean populations, contributing to a precise approach in research and clinical settings.鈥�¹

Review highlights

Guidelines

Only one guideline for the diagnosis and management of MASLD in lean patients is available for clinicians.²

Prevalence

The prevalence rate of NAFLD among lean individuals varies widely worldwide鈥攆rom 3.8% to 34.1%. Current research findings show variations in MASLD by sex and age, with older males being the most at risk.¹

Pathogenesis

The pathogenesis of NAFLD involves genetic variants, epigenetic modifications, and adaptative metabolic responses, but the precise mechanisms remain poorly understood.¹

Hypertension, metabolic syndrome, and type-2 diabetes are commonly associated with NAFLD, although prevalence rates vary for these risk factors.¹

Comorbidities 

In an interview with 乌鸦传媒, first author Karina Sato-Espinoza, MD, Research Fellow with the Division of Gastroenterology and Hepatology, Department of Medicine at the Mayo Clinic in Rochester, MN, pointed out, 鈥淟ean patients with MASLD have a higher risk of comorbidities and other risk factors compared to the general lean population. Therefore, it is crucial to monitor this group using non-invasive scoring systems,鈥� she added 鈥渁nd to promptly diagnose complications, such as cirrhosis, which can lead to hepatocellular carcinoma.鈥�

Non-invasive tools

The Fibrosis-4 Index (FIB-4) 鈥渁ppears to be the most ideal score to use鈥� among lean patients for diagnosing steatotic liver disease, the authors noted. FIB-4 has been shown to be superior to the NAFLD fibrosis score (NFS) with respect to diagnostic accuracy and performance in NAFLD, although this finding was observed in only one investigation, the authors wrote.¹

鈥淣onetheless, this finding does hold significance, considering that the only clinical guideline for lean MASLD recommends FIB4 and NFS equally,鈥� the research team wrote. 鈥淭hus, it is imperative that new studies compare these non-invasive tools in patients with MASLD due to the updated guidelines.鈥�¹

MASLD management

Lifestyle modifications in lean patients, including reducing body weight by 3%-5%, have proven helpful in mitigating hepatic steatosis and improving cardiometabolic profiles.³

Identifying adequate treatment remains 鈥渃hallenging,鈥� the authors commented. Pharmacological agents have been shown to be efficacious to some extent in improving metabolic profiles or decreasing hepatic steatosis among lean patients with MASLD.¹

鈥淗owever, longitudinal clinical trials with large study populations are still warranted to identify a promising drug for treating both lean MASLD and [metabolic dysfunction-associated steatohepatitis],鈥� the authors wrote.

鈥淕iven the significant impact of comorbidities on MASLD pathogenesis, personalized assessment and treatment plans are crucial,鈥� Dr. Sato-Espinoza told 乌鸦传媒.

Prognosis

Lean patients with NAFLD have a better metabolic profile and clinical characteristics than overweight or obese patients with NAFLD, but lean patients with NAFLD have a higher mortality rate, mainly from cardiovascular disease mortality or all-cause mortality or a quicker progression to advanced liver disease.¹

Cryptogenic steatotic liver disease

People with no known cause of liver disease and who do not meet MASLD criteria have been diagnosed with cryptogenic steatotic liver disease. This is clinically significant, the authors commented, because some patients previously categorized as having NAFLD are currently reclassified as having cryptogenic steatotic liver disease.¹

鈥淒iscussing this reclassification is important because this new approach does not imply that other causes of steatosis should not be considered, and it also allows for a more in-depth characterization of fibrosis severity using a non-invasive test,鈥� the research team remarked.

Benefits of MASLD nomenclature

鈥淭he new nomenclature for diagnosing patients with fatty liver or liver steatosis, called MASLD, is a positive diagnosis,鈥� Dr. Sato-Espinoza commented. 鈥淯nlike previous negative diagnoses that stigmatized patients, this new approach considers at least 1 of 5 cardiometabolic risk factors.鈥� 

For instance, BMI >25 kg/m² is one of the criteria used; however, waist circumference is more clinically significant in assessing lean patients in that someone might have a normal BMI, but still have increased visceral adipose tissue. The remaining criteria involve assessing blood pressure, glucose, and triglyceride and cholesterol levels, she explained, all of which are closely associated with comorbidities that contribute to an increased risk of liver steatosis. 

鈥淪tandardizing these criteria helps in making a correct diagnosis and generalizing results regarding comorbidities, prognosis, treatments, and non-invasive scores that can be evaluated uniformly across different study groups,鈥� Dr. Sato-Espinoza emphasized. 鈥淭he result of this new information could help us to create new clinical guidelines for lean patients.鈥� 

The authors stressed that metabolic diseases have been important factors in prior research among patients with NAFLD, 鈥渋ndicating that the new concept of MASLD that includes cardiometabolic risk criteria provides a more accurate diagnosis for patients with liver steatosis.鈥�¹

Published: May 15, 2024