手术解剖对新生仔猪肠衰竭相关肝病严重程度无显著影响
肠衰竭PN（PN）支持的婴幼儿大约66%出现肠衰竭相关肝病（IFALD），死亡率高。新生儿肠道手术所致短肠综合征破坏了胆汁酸正常的肠肝循环（EHC），是IFALD的主要致病因素。EHC主要依赖于完整回肠结构。
为了探讨回肠切除术是否能够影响IFALD的严重程度，加拿大阿尔伯塔大学、多伦多儿童医院、多伦多大学对3～5天新生猪仔进行研究。手术分为三组：1、空结肠吻合（JC）组共6只，75%小肠切除，不保留回肠并做空肠结肠吻合术；2、空回肠吻合（JI）组共5只，75%近端小肠切除且行空肠回肠吻合术；3、Sham组共7只，不进行肠切除。
结果发现，术后JC组与JI组胆汁流速显著低于sham组，血浆胆汁酸水平显著高于sham组，而JC组于JI组间无统计学差异，且三组之间总胆红素水平、肝酶水平均无统计学差异。
因此，外科手术所致短肠综合征并不会影响IFALD的严重程度，IFALD可能受其他机制影响，如PN成分及PN所致的肠黏膜免疫受损及菌群紊乱等。
JPEN J Parenter Enteral Nutr. 2017;41(2):268.
Surgical anatomy has no apparent impact on the severity of intestinal failure-associated liver disease in neonatal piglets.
Celeste M. Lavallee, Pamela R. Wizzard, Marihan Lansing, Jason Yap, Benjamin P. Willing, Paul W. Wales, Justine Turner.
University of Alberta, Edmonton, Alberta, Canada; The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
PURPOSE: Intestinal failure-associated liver disease (IFALD) occurs in approximately 66% of infants and children with intestinal failure who are dependent on parenteral nutrition (PN). IFALD continues to be a cause of significant morbidity and mortality for these infants. Neonatal surgical short bowel syndrome (SBS) is the leading cause of IFALD. Neonates with SBS most commonly have resection of the ileum, interrupting the normal enterohepatic circulation (EHC) of bile acids, which is dependent on an intact ileum. The impact of ileal resection in disrupting EHC of bile acids and thus its contribution to IFALD have not been adequately explored. The purpose of this study was to examine the markers of IFALD severity, given SBS of identical gut length with and without remnant ileum. We hypothesized that resection of the ileum would result in more severe IFALD, compared with SBS with remnant ileum.
METHODS: Piglets, 3-5 days old, were allocated to (1) 75% distal intestinal resection without ileum and jejunocolic anastomosis (JC, n = 6), (2) 75% proximal resection with jejunoileal anastomosis (JI, n = 5), or (3) surgical sham without resection (Sham, n = 7). All piglets received 100% PN for 14 days prior to measurement of liver chemistry and bile flow. A group of sow-reared piglets of equivalent age and sex were used for normative reference (REF, n = 6). Blood samples were analyzed for piglets that showed signs of sepsis at any point during the study. Statistical analysis was conducted through 1-way analysis of variance (ANOVA), Student t tests, or Mann-Whitney-Wilcoxon tests depending on data distribution. Data are shown as mean ± standard deviation.
RESULTS: Bile flow was not different between JC and JI (5.9 ± 4.1 vs 5.5 ± 3.0 μg/g liver/10 minutes) but was significantly greater in SBS than Sham piglets (5.7 ± 3.4 vs 1.6 ± 1.5 μg/g liver/10 minutes; P < .001; REF: 6.8-11.4 μg/g liver/10 minutes). Plasma bile acids were greater in Sham than SBS groups (36.8 ± 14.5 vs 13.1 ± 10.4 μmol/L, P < .001), but not different between JC and JI (10.8 ± 6.6 vs 15.9 ± 14.0 μmol/L; REF: 6.9-25.2 μmol/L). Total bilirubin was not different between groups but was elevated to levels consistent with IFALD in 3 JC (50%; 17.4 ± 15.2 μmol/L), 3 JI (60%; 32.2 ± 40.4 μmol/L), and 6 Sham (86%; 22.2 ± 14.7 μmol/L) piglets (REF range: 6-14 μmol/L). While γ-glutamyltranspeptidase was elevated in all piglets, it was not different between groups; alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase were not different between groups. Confirmed sepsis was more prevalent in Sham piglets (4/7) compared with SBS piglets (0/11); septic piglets had lower bile flow (0.9 ± 0.5 vs 5.0 ± 3.4 μg/g liver/10 minutes, P = .03) and higher plasma bile acids (38.4 ± 14.7 vs 17.7 ± 13.1 μmol/L, P = .03) than piglets without confirmed sepsis.
CONCLUSIONS: This study provides evidence that surgical anatomy in SBS does not appear to impact severity of IFALD, contrary to what was expected. It is unclear why Sham piglets had reduced bile flow with increased plasma bile acids, although sepsis may well explain the difference. In brief, these findings suggest that other mechanisms for IFALD are predominant in SBS, including PN compositional factors and the potential impact of PN on host immune responses and microbial communities. Our laboratory is currently investigating these mechanisms leading to IFALD in both SBS and gut-intact piglets.
FINANCIAL SUPPORT: Canadian Liver Foundation.
DOI: 10.1177/0148607116686023