Hepatic failure after injury - a common pathogenesis with sclerosing cholangitis?

Abstract

Objective: Hepatic failure after trauma occurs in about 5 - 10 % of multiple injured patients. Mortality rate remains high and liver dysfunction might deteriorate to complete liver failure and contribute to multi organ failure (MOF). Pathogenesis is multifactorial and distinct mechanisms are unknown.

Methods: To get further knowledge about pathogenesis of posttraumatic liver failure we investigated clinical course, inflammatory mediators, ERCP and histologic findings in 7 patients [6 male, 1 female, mean age 45.7 +/- 12.1 years, mean ISS 38.4 +/- 10.8 pts. (range 25-58 pts.)] that evolved hepatic failure after major trauma. Mortality rate was 14 %.

Results: All patients presented with a prolonged shock period after trauma and severe respiratory failure requiring differentiated ventilatory support and prone positioning. Onset of significant bilirubinemia (> 2.0 mg/dl) was day 3 to 16 days (median 11 days) after trauma. Past medical history did not reveal any underlying liver disease in all patients. Pro-and anti-inflammatory parameters like WBC, Procalcitonin, IL-4, IL-10, IL-11, IL-12, and IL-18 remained close to healthy control values. CRP was elevated but did not correlate with Bilirubin. Transaminases (ALT, AST) remained close to normal values but increased during the further course, whereas alkaline phosphatase (aP) and gamma-glutamyl transpeptidase (gGT) were already significantly elevated even before Bilirubin (gammaGT: 394 +/- 317 U/l; controls: < 56 U/l; aP 557 +/- 311 U/l; controls: < 127 U/l). Although no cholestasis was proven in ultrasound and CT investigations, all patients underwent ERCP and liver biopsy. Here, all patients presented uniform signs of multiple strictures of the intrahepatic bile ducts and sclerosing cholangitis.

Conclusions: Our data provide evidence that sclerosing cholangitis contributes to liver failure after trauma. The pathomorphologic picture can not distinguish between shock liver and sclerosing cholangitis. Ischemia during posttraumatic shock might be an early trigger of hepatic failure, supported by further contributing factors such as catecholamines, parenteral nutrition, and bacterial translocation. As specific therapy for sclerosing cholangitis does not exist yet, prevention of triggers is central to avoid progressive hepatic failure in those patients. Further prospective studies have to prove whether sclerosing cholangitis is commonly involved in the pathogenesis of liver failure after trauma and shock. If so, one might speculate that early therapy with ursodeoxycholic acid might be effective thus reducing incidence and/or severity of hepatic failure in the future.