Progression of liver fibrosis after metabolic bariatric surgery in a MASLD rat model.

Background: Metabolic bariatric surgery (MBS) has been shown to provide significant improvements in metabolic dysfunction-associated steatotic liver disease (MASLD) but its effects on liver fibrosis remain controversial.

Aims: To establish a rodent model of liver fibrosis progression after MBS and to investigate the impact of post-operative diets and different bypass lengths on liver fibrosis progression, weight dynamics, and metabolic effects.

Methods: Male Sprague Dawley rats were subjected to either sham surgery or one anastomosis gastric bypass (OAGB) with moderate or extended biliopancreatic limb lengths, followed by dietary manipulation with a high-fat, high-fructose and high-cholesterol diet (FFC) or standard chow. Histological liver analysis, glucose tolerance tests, and serum parameter evaluations were conducted post-operatively.

Results: Advanced fibrosis was observed in 44.4 % of cases, exclusively in rats on a FFC diet with moderate bypass lengths, despite significant weight reduction and improvements in steatosis and inflammation as assessed by Clinical Research Network (CRN) criteria. Increased oxidative stress and CD206-positive macrophages were prominent in fibrotic livers. Extended bypass or a switch to standard chow was associated with significantly lower fibrosis scores.

Conclusion: Fibrosis progression occurred only in rats after moderate gastric bypass, maintained on the FFC diet, despite weight loss and histological improvement in steatosis and inflammation. Further research is needed to better understand the mechanisms underlying the progression of liver fibrosis after MBS. This model is suitable for such an investigation.