Growth Differentiation Factor 15 and Histology-Defined Steatohepatitis and Fibrosis in Severe Obesity Undergoing...

Identifying metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis in patients with severe obesity is clinically important but remains challenging. Growth differentiation factor 15 (GDF15) has emerged as a marker of metabolic stress, but its relevance in bariatric surgery patients with histologically confirmed liver disease remains unclear. This study aimed to evaluate the association between preoperative serum GDF15 levels and biopsy-proven MASH and liver fibrosis in patients undergoing bariatric surgery.

We conducted an observational analysis of patients with severe obesity undergoing bariatric surgery, with liver histology evaluated by intraoperative wedge biopsy. Preoperative serum GDF15 levels were measured and categorized into quintiles.

A total of 160 patients were included (48.1% female; mean age 38.2 ± 10.1 years; body mass index [BMI] 41.1 ± 5.6 kg/m²; type 2 diabetes [T2D] 48.8%). Higher GDF15 levels were associated with older age, male sex, greater body weight, BMI, waist circumference, T2D, fasting glucose, glycated hemoglobin (A1C), aspartate aminotransferase, and creatinine. The prevalence of MASH and fibrosis increased across GDF15 quintiles. In multivariable analyses, higher serum GDF15 levels were significantly associated with increased risks of MASH and liver fibrosis across quintiles (p for trend < 0.001). After adjustment for age, sex, BMI, and A1C, the highest GDF15 quintile remained strongly associated with MASH (odds ratio 18.90, 95% confidence interval 4.53-78.81) and fibrosis (odds ratio 10.06, 95% confidence interval 2.80-36.11).

In patients with severe obesity undergoing bariatric surgery, serum GDF15 was independently associated with biopsy-proven MASH and liver fibrosis and may aid noninvasive liver disease risk stratification.