Transplantation for Sclerosing Cholangitis

Ductal Stricturing/Bacterial Cholangitis

The presence of fibrotic stricturing resulting in impaired bile flow may lead to recurrent episodes of bacterial cholangitis. A “dominant stricture” has been defined as a stenosis with a diameter of 1.5 mm or less in the common bile duct or of 1 mm or less in the hepatic duct system. It is a frequent finding and occurs in 45% to 58% of patients during follow-up cholangiographic studies. Dominant strictures should raise the suspicion of a cholangiocarcinoma (CCA), because this malignant complication presents as a stenotic ductal lesion. Cholangiographic evaluation may identify a dominant stricture amenable to balloon dilation. Before any attempt at endoscopic therapy, brush cytology and/or endoscopic biopsy should be obtained to help exclude a superimposed malignancy. The best therapeutic endoscopic approach for PSC is still a subject of debate, with multiple techniques evaluated, including sphincterotomy, catheter or balloon dilation, and stent placement. Of these, only endoscopic biliary sphincterotomy and balloon dilation with or without stent placement are of value. However, diffuse involvement of the intrahepatic biliary tree not amenable to stenting can lead to recurrent episodes of cholangitis and biliary sepsis. Broad-spectrum antibiotic coverage for gram-negative bacteria and Enterococcus usually leads to improvement, but hepatic abscesses may develop in the face of obliterated bile ducts. Recurrent episodes should prompt referral to a transplant center, even in the absence of complications of end-stage liver disease.

Pruritus

Pruritus is a common complication of cholestatic liver disease. Although dilation of a dominant stricture may lead to improvement or resolution, some patients may complain of pruritus in the absence of jaundice or a dominant stricture. This is likely related to an increase in central opioid receptors. Treatment may range from the simple to the bizarre:

• Antihistamines and topical lotions rarely provide relief, but there is no contraindication.

• Cholestyramine has historically been the treatment of choice.

• UDCA is helpful in a small percentage of patients.

• Rifampin, in a dose of 150 to 300 mg twice a day, can decrease pruritus. If decompensation occurs in a patient using rifampin therapy who has otherwise stable PSC, the patient may have rifampin hepatotoxicity.

• Opiate antagonists, such as naltrexone in a dose of 25 to 50 mg daily to twice a day, can lead to immediate resolution of pruritus.

• Serotonin uptake inhibitors decreased symptoms in one small study.

• Plasmapheresis can lead to transient resolution of symptoms if medical therapy does not lead to improvement. However, plasmapheresis should be used only for patients with severe symptoms, such as soft tissue abscesses related to skin excoriations or suicidal ideation.

• Liver transplantation remains an extreme option; however, the current MELD prioritization system does not give exception points for pruritus unless approved by a regional review board.

Hepatic Osteodystrophy

Hepatic osteodystrophy, a common complication of cholestatic liver disease, can lead to vertebral body compression fractures resulting in severe, immobilizing back pain and atraumatic fractures of the axial skeleton. The incidence of osteoporosis in PSC is between 4% and 10%. The incidence increases with decreasing body mass index, increasing duration of disease, and with age; however, hepatic osteodystrophy does not necessarily correlate with the severity of the liver disease. Bone density should be measured in all patients with PSC being evaluated for a liver transplant. Calcium and vitamin D supplementation, particularly in deficient patients, should be instituted, although evidence that this actually improves bone density in patients with PSC is lacking. The use of antiresorptive agents (such as bisphosphonates or calcitonin) or hormone replacement therapy in postmenopausal or oophorectomized women is also not of proven benefit, although these therapies are frequently used. Debilitating bone disease was once considered an indication for transplantation; however, the worsening of bone density over the course of the first 3 postoperative months, with as many as one third of patients with PSC suffering pathological fractures, has historically led some transplant centers to consider this a contraindication to transplantation.

Inflammatory Bowel Disease

IBD may be diagnosed at any time during the course of PSC. In many cases the diagnosis of IBD precedes that of PSC; however, IBD and PSC are sometimes diagnosed concomitantly. It is now recognized that the onset of IBD can also occur years after the diagnosis of PSC, and de novo IBD may present after liver transplantation. The common association of IBD with PSC often raises management issues before transplantation. The potential for colonic malignancy in patients with ulcerative colitis should result in a screening colonoscopy during the initial evaluation. If colonic dysplasia is present, a practical issue regarding management may be problematic. Although colonic resection in the face of end-stage liver disease may be associated with increased morbidity and even mortality, the issue of delaying resection until a suitable time after the transplant is plagued by the concern that malignancy may be present and, if so, its behavior may be altered by immunosuppression. Each case must be considered individually, with careful assessment of potential risks and benefits. Medical management of the patient with active colitis should be no different from that for any other patient with ulcerative colitis; however, severe cases should be controlled before the patient assumes a position at the top of the list. Attempts to minimize immunosuppressive therapy in a patient at the top of the list to reduce the chance of an opportunistic infection should be carefully weighed against the potential for a disease flare.