New names given nonalcoholic fatty liver diseases fit children: Study
Vast majority of those with NAFLD or NASH meet criteria for MASLD or MASH
Almost every child and adolescent who met diagnostic criteria for forms of nonalcoholic fatty liver disease under their previous names — NAFL, NASH, or NAFLD cirrhosis — were found to meet that form’s criteria under its new nomenclature, meaning they were confirmed to have the disease.
These are the findings of a study into more than 800 pediatric patients in the U.S. participating in the observational TARGET-NASH study (NCT02815891), which was launched by Target RWE in 2016. Target RWE, a real-world clinical data analysis company, previously was known as Target PharmaSolutions.
“This study is the first to investigate the correlation between old and new nomenclature in pediatric patients,” Miriam B. Vos, MD, the study’s senior author and a TARGET-NASH advisory committee member, said in a company press release.
97.5% with NAFLD met MASLD criteria, 99.8% with NASH now have MASH
Specifically, 2.5% of the patients diagnosed with nonalcoholic fatty liver disease (NAFLD; NAFL or nonalcoholic fatty liver is a subtype) did not meet the diagnostic criteria of the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD).
With the more severe form once known as nonalcoholic steatohepatitis (NASH), 0.2% of patients did not fill the criteria for metabolic-associated steatohepatitis (MASH). All of those with cirrhosis, or irreversible liver scarring, associated with NAFLD also were classified as having MASH-related cirrhosis.
“Our findings provide crucial validation for the applicability of the new MASLD/MASH terminology in children and adolescents, ensuring the continued relevance of prior research conducted under the legacy NAFLD framework,” said Vos, who also directs the pediatric program for the Georgia Center for Clinical and Translational Science Alliance at Emory University.
A good concordance was seen between a MASH clinical diagnosis and liver biopsy results, supporting “the use of readily available non-invasive clinical data to diagnose pediatric patients with MASH,” Vos added.
The study, “Concordance of MASLD and NAFLD nomenclature in youth participating in the TARGET-NASH real-world cohort,” was published in Hepatology Communications.
Names changed in 2023 to be more inclusive, reflective of risk factors
Fatty liver disease is marked by the abnormal build-up of fat in the liver, referred to as steatosis. After a nomenclature update in 2023, NAFLD was renamed MASLD, and NASH was renamed MASH.
Over time, the disease form not related to alcohol consumption — traditionally known as NAFLD and now called MASLD — can progress into NASH — now MASH — where fat buildup leads to inflammation, scarring (fibrosis), and cirrhosis.
The nomenclature update aimed to use more inclusive and less stigmatizing terminology, and to restructure definitions to reflect the disease’s association with metabolic risk factors. These include excessive weight or obesity, high blood sugar or type 2 diabetes, high blood pressure, or elevated fats in the blood (triglycerides or cholesterol).
“Previous research findings based on the legacy terminology and definition may not be relevant to the new terminology … unless high concordance can be demonstrated,” the researchers wrote.
To test this, Target RWE and its collaborators at various U.S. institutes turned to data from the ongoing TARGET-NASH observational study that has enrolled more than 6,500 pediatric and adult patients in the U.S. It aims to evaluate the real-world effectiveness and safety of approved medicines or those not included or underrepresented in Phase 3 trials.
Study enrollment was based on the results of a liver biopsy or a clinical assessment (blood and imaging tests). Accordingly, patients were classified as having NAFLD, NASH, or NASH-related cirrhosis by traditional definitions.
Earlier this year, an analysis focusing on adult registry participants showed that the new MALSD/MASH terminology was highly concordant with the older criteria.
Researchers now conducted the same analysis, focusing on 828 children and adolescents (30% girls) enrolled in TARGET-NASH at ages ranging from 4 to 17.
98% of 828 children overweight, 45% had high blood sugar or diabetes
Nearly all (98%) were overweight or obese, while half (50%) had either high triglyceride levels or low levels of high-density lipoprotein cholesterol, known as good cholesterol. Less than half (45%) had high blood sugar or were being treated for type 2 diabetes, and 26% had high blood pressure.
Similar to findings in adults, 99% of the pediatric participants met the new MASLD definition.
Seven patients with NAFLD (2.5%) and one with NASH (0.2%) didn’t meet at least one of the five metabolic criteria, but seven of them had incomplete data at enrollment. Still, two of these children/adolescents met the MASLD or MASH criteria after enrollment.
Notably, all 22 pediatric patients with NAFLD-related cirrhosis met the criteria for MASH-related cirrhosis.
The team also compared MASH diagnosis using clinical assessments, such as blood and imaging tests, or a liver biopsy. Of the 41 biopsy samples available, 37 showed definite, probable, or possible MASH, as assessed by a pathologist. In comparison, 33 of the 37 were classified as MASH based on clinical tests, demonstrating a concordance of 89%.
“The strong concordance between clinical and histological MASH diagnoses presents a valuable opportunity for clinicians to further study MASH in pediatric patients,” said Michael W. Fried, MD, chief medical officer at Target RWE.
“Our findings support the recent consensus recommendations that established the new nomenclature for steatotic liver diseases that better reflects the underlying pathophysiology [effects on the body] of the disease,” Fried added.
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