Preventive Effect of High-Dose Digestive Enzyme Management on Development of Nonalcoholic Fatty Liver Disease after Pancreaticoduodenectomy: A Randomized Controlled Clinical Trial.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a complication of pancreaticoduodenectomy (PD). We conducted a randomized clinical trial to determine if high-dose digestive enzymes prevented the development of NAFLD after PD. STUDY DESIGN This parallel-group, non-blinded and multicenter study enrolled patients undergoing elective PD at Shinshu University School of Medicine from June 2011 to April 2017. Patients were randomly assigned to receive normal-dose (Excelase: 3.0 g/day) or high-dose digestive enzyme treatment (Excelase: 3.0 g/day, Pancreatin: 3.0 g/day, Berizym: 3.0 g/day, Toughmac-E: 3.0 g/day) within 1 week after surgery. Because patients in the control group switched interventions upon receiving a diagnosis of NAFLD, intention-to-treat analysis was used. The primary endpoint was incidence of NAFLD within 1 year and the secondary were the incidence of NAFLD at 1, 3, 6, and 12 months and the rate of improvement in NAFLD with high-dose transfer in the control group. The secondary analysis comprised assessment of risk factors for the development of NAFLD. RESULTS 84 patients were randomly assigned (42 per group), of whom 80 were finally analyzed (39 normal-dose, 41 high-dose). The incidence of NAFLD was significantly lower in the high-dose (8/41) compared with the normal-dose (25/39) (P CONCLUSIONS High-dose administration of digestive enzymes significantly reduced the onset of NAFLD after PD compared with normal-dose administration. Registration number: UMIN000005595 ( http://www.umin.ac.jp/ctr/ ).