Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection

Abstract

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

Paradoxical impact of the remnant pancreatic volume and infectious complications on the development of nonalcoholic fatty liver disease after pancreaticoduodenectomy

“…It has been suggested that malnutrition due to pancreatic exocrine insufficiency is a main cause of NAFLD after PD, because supplementation of high-dose pancreatic enzyme improves it. Previously, we hypothesized its mechanism as follows: pancreatic exocrine insufficiency after PD is associated with fat malabsorption, resulting in fatty acid deficiency, which leads to increased conversion of carbohydrates into fat (i.e., increased fat deposition) in the liver [6,7]. In the three patients who developed NAFLD after PD at our institution, daily stool fat excretion was examined 7 RPV remnant pancreatic volume days after cessation of pancreatic enzyme supplementation, revealing that it exceeded markedly the definition of steatorrhea as a daily excretion higher than 5-8 g: 45 g, 52 g and 68 g, respectively [16].…”

“…In 2010, we reported the incidence of NAFLD after PD as 37.0% and revealed that NAFLD after PD was significantly associated with the following three factors: pancreatic adenocarcinoma, resection line, and postoperative diarrhea, suggesting the contribution of malnutrition due to pancreatic exocrine deficiency . We also encountered two patients with PD who later developed NASH confirmed by liver biopsy, in whom treatment of infectious complications and high‐dose pancreatic enzyme supplementation improved liver dysfunction and liver steatosis . The pathogenesis of NAFLD after PD may therefore differ from that of conventional NAFLD.…”

Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

“…Jaundice due to steatohepatitis following pancreatoduodenectomy is a rare occurrence [7, 8, 9, 10, 11]. Our patient progressed rapidly to liver failure and jaundice subsequent to NASH.…”

“…According to previous reports, non-alcoholic fatty liver disease and NASH following pancreatoduodenectomy can be improved by the administration of pancreatic enzymes [10]. After switching the patient's treatment from oral to intravenous zinc, serum zinc levels rose rapidly and ammonia levels declined.…”

“…The presence of secondary kwashiorkor can be indicative of blind loop formation and exocrine pancreatic failure, and is associated with inadequate protein ingestion [4]. It has recently been reported that steatohepatitis occurs in 20–40% of patients who undergo pancreatoduodenectomy [7, 8, 9, 10, 11]. Pancreatoduodenectomy can result in deficiencies of vitamins and trace elements such as zinc, which can lead to fatty liver disease [7, 8, 9, 10, 11].…”