Etiology of jejunoileal bypass-induced liver dysfunction in rats

Several recent studies suggest that jejunoileal bypass-induced liver disease results from malabsorption of essential nutrients. However, in experimental animals, resection of the defunctionalized bowel substantially reduces bypass-induced liver injury. Such models are often used to support the theory that bacteria in the defunctionalized bowel produce toxic substances which result in liver damage. We used a rat model to first explore the effects of intestinal bypass vs resection on various parameters of liver injury, and subsequently compared these findings to the effect of both bypass and resection on mucosal adaptation in the remaining intact bowel after each procedure. Bypassed animals had lower levels of hepatic cytochrome P-450, glucose-6-phosphatase, pentobarbital hydroxylase, and serum triglycerides than did animals undergoing resection of defunctionalized bowel. Concurrently, resected animals had much greater increases in mucosal weight, DNA content, and protein content in the intact bowel than did bypassed animals. We speculate that the beneficial effects of resection of bypassed bowel on liver function may be a result of increased mucosal hyperplasia in resected animals, rather than elimination of production of toxic substances in the defunctionalized bowel.