BOB Ped Surg 2023 - Maria Tecos, AAP - Presentation

Short gut syndrome patients face a 25% mortality within two years.

Approximately 25% of short gut syndrome survivors go on to have intestinal transplantation.

Less than 50% of short gut syndrome survivors ever regain enteral autonomy.

TPN is a significant contributor to liver injury in short gut syndrome.

In a murine small bowel resection model without TPN, intestinal loss alone is sufficient to mount oxidative stress that results in liver fibrosis.

In mice, serum evidence of liver injury was found as early as post-operative week two in proximal resection mice and persisted to post-operative week 10.

Liver injury was only found in proximal resection mice, not in distal resection mice.

Liver fibrosis measured by Sirius red staining and collagen 1A1 expression were present at higher levels in proximal resection mice, with distal resection showing liver protection.

Inflammatory markers of oxidative stress (tumor necrosis factor alpha, NADPH oxidase, and glutathione synthetase) were all increased in the proximal resection group compared to sham and distal resection.

The proximal resection group had a compensatory increase in lipocalin 2, an acute phase protein known to increase against oxidative stress.

Removal of the ileum decreased the size of the bile acid pools.

Distal resection resulted in decreased taurolithocholic acid (TLCA), the most toxic, insoluble, hydrophobic bile acid.

Distal resection resulted in increased tauro-ursodeoxycholic acid (TUDCA), the most soluble hydrophilic bile acid.

Proximal resection bile acid profile was the exact opposite of distal resection (increased TLCA, decreased TUDCA).

CYP7A1, the rate limiting step of de novo bile acid synthesis in the liver, was increased in the distal resection group.

TUDCA acts as an endogenous antioxidant and cellular chaperone.

TUDCA supplementation in proximal resection mice resulted in significantly less oxidative stress.

The compensatory increase in lipocalin 2 previously observed in proximal resection was absent with TUDCA supplementation.

Liver fibrosis measured by Sirius red staining was rescued by TUDCA supplementation.

TUDCA supplementation rescued the bile acid profile to a healthier milieu in proximal resection mice.

The liver injury in proximal small bowel resection is likely the result of direct liver exposure to oxidative stress and toxic bile acids via enterohepatic circulation.

Removing the ileum where bile acid absorption occurs shields the liver from inflammation and stimulates healthy new bile acid production.