Elevated gamma glutamyl transferase levels as screening marker of stage 3–4 hepatic fibrosis in youth-onset type 2 diabetes mellitus: a retrospective chart review

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a comorbidity of type 2 diabetes mellitus (T2D) that can lead to metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis. With rising incidence of youth-onset T2D (YOT2D), there is a need for noninvasive screening tools for MASH with fibrosis. Although multiple screening guidelines recommend measuring alanine transaminase (ALT) at YOT2D diagnosis and at regular intervals, ALT has low sensitivity in identifying MASH with fibrosis. The objective of this study is to identify other noninvasive biomarkers in assessing liver fibrosis severity in YOT2D with MASLD. A single-center retrospective chart review was conducted on 51 patients with elevated liver transaminases, liver biopsy from 2010 to 2023, and diagnosis of T2D. Clinical, histopathological, imaging, and biochemical data were extracted from electronic medical records. Hepatic fibrosis prediction scores were calculated. Associations between these factors and stages of fibrosis were examined. 59% of patients had no or stage 1–2 fibrosis and 41% had stage 3–4 fibrosis. Compared to those with no or stage 1–2 fibrosis, patients with stage 3–4 fibrosis were more likely to be male (p = 0.021), had a higher median gamma glutamyl transferase (GGT) (p = 0.026), and higher median liver stiffness on MRE (p = 0.011). For every 10 U/L increase in GGT, the odds of having stage 3–4 fibrosis increased by 20% (odds ratio: 1.20, 95% confidence interval: 1.05, 1.38; p = 0.007), adjusting for age, sex, hemoglobin A1C, and BMI z-score. Using biopsy proven outcomes, we identified a positive association between GGT levels and hepatic fibrosis stages in YOT2D. Pediatric endocrinologists and primary care providers may consider incorporating GGT levels into the screening for MASLD in YOT2D patients with elevated liver enzymes. Not applicable.