Diabetes attenuates weight reduction-mediated liver fibrosis regression in persons with morbid obesity

Weight loss by laparoscopic sleeve gastrectomy (LSG) compared to medical weight loss (low-calorie diet: LCD) ameliorates diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate changes in liver pathology 1-year after LSG and their associations with metabolic factors in Japanese participants with severe obesity.

We recruited 27 Japanese participants with severe obesity (BMI > 35 kg/m²) and metabolic disorders who showed inadequate weight loss after at least 6 months of medical treatment. LSG was performed after 4 weeks of LCD. Liver biopsy samples were obtained intraoperatively and at 1-year after surgery. The primary endpoint was the change in liver histopathological scores.

LSG significantly reduced histological scores in hepatic steatosis, hepatocellular ballooning, lobular inflammation, and hepatic fibrosis, together with fasting plasma glucose, hemoglobin A1c, body weight, body mass index, and liver enzymes. Reduction in steatosis was associated with a reduction in glycemic parameters and γ-glutamyl transpeptidase. Reduction in lobular inflammation was associated with reductions in liver enzyme levels and hemoglobin A1c. Changes in hepatic fibrosis were not associated with metabolic or biochemical changes but were related to baseline fibrosis severity and the presence of diabetes. Unexpectedly, weight reduction significantly lowered platelet counts and elevated the fibrosis-4 index.

LSG improves liver histopathology of MASLD in Japanese participants with severe obesity. The comorbidity of diabetes was associated with attenuated improvement in liver fibrosis after LSG, suggesting that glycemic status and diabetes-related factors may be key modifiers of fibrosis reversibility in MASLD.