Model for end-stage liver disease (MELD) exception for bacterial cholangitis


Patients with structural biliary disease due to sclerosing cholangitis, Caroli's syndrome, ischemic biliary damage, and other causes carry a high risk of recurrent bacterial cholangitis and septicemia and have a high incidence of morbidity. Because many of these patients have fairly well-preserved hepatic synthetic function, current allocation policy that uses the Model for End-Stage Liver Disease (MELD) score alone may not appropriately prioritize these selected groups of patients to avoid a poor outcome. Given the excellent results of liver transplantation (LT) in patients with chronic cholestatic liver disease and the lack of medical therapies available, exceptional status for some of these patients with severe structural damage of the biliary tree should be provided. Similarly, patients with ischemic biliary injury of the liver allograft under immunosuppression carry an even greater increased risk of morbidity and constitute groups that may benefit from exceptional status for timely LT. However, a precise natural history of these conditions has not yet been well defined.

The most common disease entity leading to structural damage to the biliary tree is primary sclerosing cholangitis (PSC). This disease is progressive, ultimately leading to secondary biliary cirrhosis and progresses to hepatic dysfunction, portal hypertension, and occasionally the development of cholangiocarcinoma. Although the pathogenesis of PSC is unclear, it is commonly associated with inflammatory bowel disease, most commonly as chronic ulcerative colitis. After diagnosis of PSC, the reported median survival is 12 to 15 years.1, 2 Occasionally, a patient with PSC will develop repeat episodes of bacterial cholangitis, although this is unusual (<10%).3 Although death from bacterial cholangitis itself is rare, complications of septicemia have been reported including endocarditis, osteomyelitis, and hepatic abscess formation. These septic complications can greatly affect overall morbidity and mortality in patients with PSC.

In other patients, congential cystic dilatation of the intrahepatic biliary ducts is often associated with congenital hepatic fibrosis. These patients are categorized under the diagnosis of Caroli's syndrome, which in its end stages is manifested by complications of portal hypertension and repeated bouts of bacterial cholangitis, and can be associated with the development of cholangiocarcinoma. Occasionally, patients with secondary sclerosing cholangitis due to surgical mishap involving bile duct injury can also have repeated episodes of bacterial cholangitis. The natural history of these disorders has not been well established in the medical literature.

Finally, there are patients who shortly after LT develop cholestasis, hyperbilirubinemia, an abnormal liver enzyme pattern, and evidence of severe ischemic-type biliary tract injury with the development of biliary sludge, casts, and ectasia. These patients also experience repeated bouts of bacterial cholangitis and can in time develop allograft failure. These findings are commonly associated with hepatic artery thrombosis or biliary ischemia. The exact mechanism of ischemic biliary duct injury is not precisely known, although there are some risk factors that have been identified, including the use of extended criteria grafts and prolonged cold and warm ischemic time. In patients who develop structural biliary disease with recurrent bouts of bacterial cholangitis, the underlying severity of liver disease as manifested by hepatic synthetic function appears to affect both the incidence and severity of septic complications. Liver transplantation remains an excellent treatment for patients with structural biliary disease who have recurrent bouts of bacterial cholangitis.4–9


At this time, there is insufficient objective data to use an evidence-based approach for giving MELD exception guidelines in the setting of structural biliary disease and bacterial cholangitis in both pre- and posttransplant patients.


MELD, Model for End-Stage Liver Disease; LT, liver transplantation; PSC, primary sclerosing cholangitis.


By consensus, our group came to the following conclusions:

  • Patients who have ≥2 culture-proven bacteremias within a 6-month period or who have septic complications of bacterial cholangitis (including either a biliary or hepatic abscess, bacterial meningitis, bacterial endocarditis, bacterial osteomyelitis, fungemia) should be considered as a MELD exceptional case.

  • Bacteremia should be noniatrogenic (unrelated to a procedure such as recent endoscopic retrograde cholangiogram or transhepatic cholangiogram) and should occur in a patient who does not have a biliary tube or stent; in addition, these bacterial cholangitic episodes should occur in patients who have been treated with antibiotic therapy that has failed to suppress these septic episodes.

  • Data needed for exceptional consideration include the following: (1) precise diagnosis of the structural biliary disease, (2) culture evidence of bacteremia, (3) evidence that the patient was on suppressive antibiotic therapy at the time the bacterial cholangitis occur, and (4) evidence that a structural lesion is not correctable (i.e., cholangiographic evidence eliminating a correctable dominant stricture).

Our recommendation is that patients who meet the above criteria should have a calculated MELD score that is based on the serum bilirubin and creatinine concentrations and international normalized ratio, and an additional 8% probability of dying over the next 3 months. If the patient has not been removed from the LT waiting list by way of transplantation, death, or removal for being too sick, the patient should receive an additional 8% probability of dying every 3 months until the patient is transplanted, dies while on the waiting list, or becomes ineligible for transplantation because of being too sick or ineligible on the basis of United Network for Organ Sharing criteria. The data elements defined above should be prospectively collected on all patients with structural biliary disease who are granted exceptions and should be prospectively evaluated by the Organ Procurement Transplantation Network/United Network for Organ Sharing for future assessment and evidence-based decision making.