Metabolic dysfunction-associated steatotic liver disease (MASLD), previously called non-alcoholic fatty liver disease (NAFLD), has become the most common cause of chronic liver disease, and is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus.1,2 FDA approval of pharmacotherapy has required biopsy resolution of metabolic dysfunction-associated steatohepatitis (MASH) with no worsening of liver fibrosis or improvement ≥1 fibrosis stage with no worsening of steatohepatitis.3 Recently resmetirom has been approved for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis to be used along with diet and exercise.4,5 The current approach is to screen patients with diabetes, metabolic syndrome, or obesity for steatotic liver disease with a fibrosis-4 (FIB-4) score, with or without a follow up vibration controlled transient elastography and controlled attenuation parameter, to predict the level of fibrosis.1 Those with an intermediate or high risk for fibrosis would be referred to a liver specialist.1 However, most patients do not have fibrosis. It is estimated that 30 % to 55 % of patients with type 2 diabetes have MASLD (liver fat>5 %), of which 1/3 develop steatohepatitis (MASH, approximately 12 % to 14 %, i.e., with inflammation and hepatocyte injury [ballooning]), of which 20 % develop fibrosis and liver failure (approximately 4 % of all those with MASLD).1

The American Diabetes Association,6 and the combined American Association of Clinical Endocrinology (AACE) and the American Association for the Study of Liver Disease (AASLD)1 suggested pharmacological therapy for moderately advanced liver fibrosis (Fibrosis stages F2 or F3 out of a possible stage F4). However, principles of endocrinologic management of diabetic complications have always been to prevent rather than reverse complications. In a previous meta-analysis, we showed that therapies used in diabetes and metabolic syndrome reversed liver fat into normal ranges as determined by MRI spectroscopy.7 However, the outcome standard for efficacy of therapy has been the analysis of liver biopsies with improvements in NAFLD activity score, (NAS score, an unweighted biopsy score of steatosis [graded 1 to 3], lobular inflammation [graded 1 to 3], and ballooning [graded 1 and 2]), where MASH is usually considered a composite score ≥ 5. There are multiple articles that evaluated Fib-4 scores with regard to change with therapy in the fibrosis stages, but these studies did not evaluate the relationship of FIB-4 versus pre-fibrotic stages of MASH.8., 9., 10. We therefore assessed data base to review the relationship of FIB-4 and therapy to determine whether FIB-4 can effectively screen and monitor changes in steatohepatitis (MASH) in patients with MASLD. We performed a post hoc assessment from the NIDDK Central Repository for data from the Nonalcoholic Steatohepatitis Research Network (NASH/CRN /PIVENS) database to review the relationship of FIB-4 and therapy of pre-fibrotic MASLD.11