Abstract
BACKGROUND: Pancreatic exocrine insufficiency due to pancreatic atrophy is considered a major factor in the occurrence of liver fat deposition after pancreaticoduodenectomy (PD). This study aimed to investigate whether liver fat deposition was less frequent in patients who received combination therapy with high-titer pancreatic enzyme and zinc supplementation, considering the severity of remnant pancreatic atrophy between reconstruction methods (pancreaticogastrostomy (PG) vs. pancreaticojejunostomy (PJ)). METHODS: Patients who underwent PD and periodic postoperative computed tomography (CT) were retrospectively reviewed. Remnant pancreatic volume and atrophy, estimated by 3D reconstruction CT, were compared between the PG and PJ groups. Liver fat deposition was defined as a ≥ 0.10 decrease in the liver-to-spleen attenuation ratio from postoperative day 7 to 3, 6, or 12 months. The risk of liver fat deposition was assessed after adjusting for confounders using traditional and Bayesian logistic regression analyses. RESULTS: Sixty-two patients (48 PJ, 14 PG) were analyzed; 13 patients received combination therapy. PG resulted in more severe atrophy than PJ (median maximum atrophy rate 0.37 [interquartile range: 0.24-0.54] vs. 0.23 [0.13-0.34], p = 0.037). Compared with the non-therapy group (n = 49), the combination therapy group (n = 13) had a higher frequency of PG reconstruction (54% vs. 14%, p = 0.006) and greater maximum pancreatic atrophy rate (0.35 [0.25-0.55] vs. 0.23 [0.13-0.34], p = 0.009), yet similar fat deposition rates (31% vs. 47%, p = 0.30). Multivariate analyses suggested that combination therapy modified the effect of pancreatic atrophy on fat deposition (p for interaction = 0.066). Predicted probabilities showed that without therapy, fat deposition increased from 79.0% (95% credible interval: 38.8-96.4%) at an atrophy rate of 0.15 to 92.7% (64.8-99.3%) at 0.45, whereas with therapy, probabilities decreased from 69.7% (20.0-96.5%) to 35.1% (6.0-75.6%). The corresponding odds ratios declined from 0.62 to 0.04 at these levels of atrophy. CONCLUSIONS: Combination therapy with high-titer pancreatic enzyme and zinc supplementation could reduce the risk of liver fat deposition after PD in patients with severe remnant pancreatic atrophy, often associated with PG.