Effects of Pancreatic Resection on Liver Fat Content and Amino Acid, Lipid, and Glucose Metabolism: A Prospective 1-Year Follow-up Study

UNLABELLED: Individuals who undergo pancreatic resection are at increased risk of developing hepatic steatosis. Glucagon is a key regulator of hepatic glucose, amino acids, and lipid metabolism, and the change in circulating glucagon is suggested to contribute to the pathogenesis of postoperative steatotic liver disease. Here, we aimed to elucidate hepatic and metabolic changes induced by pancreatic resection. Fifty individuals scheduled to undergo pancreatic surgery were recruited and evaluated by blood samples and a liver biopsy obtained during surgery. One year after surgery, 21 eligible participants (15 following pancreaticoduodenectomy, 6 following total pancreatectomy) met for a follow-up visit, with the remaining being excluded because of recurrent disease, comorbidities, or death. Follow-up MRS indicated increased liver fat in 12 of 19 participants despite a mean numerical decrease in body weight. Five eligible participants underwent a liver biopsy at follow-up, demonstrating increased liver fat content (largest individual increase: 80 percentage points). Circulating glucagon and C-peptide were significantly reduced at follow-up, with no detection of either following total pancreatectomy. No significant changes in fasting plasma glucose or HbA1c were observed, attributed to relevant exogenous insulin supplementation. Amino acids were markedly increased after both pancreaticoduodenectomy and total pancreatectomy, correlating negatively with remnant endocrine pancreatic function. In conclusion, our data suggest that reduced circulating glucagon levels may contribute to the increased liver fat content and hyperaminoacidemia observed after pancreatic resection.

ARTICLE HIGHLIGHTS: Previous studies have demonstrated increased risk of hepatic steatosis in patients following pancreatic resection, which might be linked to decreased pancreatic function. Here, we evaluated liver fat content, circulating pancreatic hormones, amino acids, and more, before and 1 year after either total pancreatectomy or pancreaticoduodenectomy. At 1-year follow-up, we found increased liver fat content in more than half (63%) of the participants, evaluated both by liver histology and magnetic resonance imaging. The participants were characterized by hyperaminoacidemia, which correlated negatively with remnant endocrine pancreatic function. These findings further elucidate the relationship between glucagon, circulating amino acids, and hepatic metabolism.