Recurrent PSC With Active Colitis
A 42-year-old woman underwent liver transplantation 3 years ago for primary sclerosing cholangitis and has a history of ulcerative colitis. She now has pruritus, fatigue, and jaundice. Laboratory tests: alkaline phosphatase 420 U/L, total bilirubin 2.2 mg/dL, ALT 55 U/L, AST 48 U/L, and CA 19-9 45 U/mL. MRCP shows multifocal intrahepatic and anastomotic strictures with mild ductal dilatation. Liver biopsy shows fibro-obliterative bile duct lesions, ductopenia in several portal tracts, and mild portal fibrosis without significant inflammation. Hepatic artery Doppler is normal. Tacrolimus trough is 6 ng/mL. Colonoscopy shows moderate active ulcerative colitis. She asks about retransplantation and whether her colitis matters.
1. What is the differential diagnosis for her biliary strictures, and which features favor recurrent PSC?
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The differential includes recurrent primary sclerosing cholangitis, ischemic cholangiopathy, anastomotic stricture, ductopenic rejection, and cholangiocarcinoma. Features favoring recurrent PSC are the history of PSC, multifocal intrahepatic and anastomotic strictures, fibro-obliterative bile duct lesions, ductopenia, active ulcerative colitis, a normal hepatic artery Doppler, and absence of significant inflammation or C4d. Ischemic cholangiopathy usually follows hepatic artery compromise or prolonged ischemia and often produces casts and necrosis. Anastomotic stricture alone would be focal. Ductopenic rejection usually has more inflammation and may have DSA or C4d. Cholangiocarcinoma must be excluded with brushings, CA 19-9, and imaging. Recurrent PSC remains a diagnosis of exclusion.
2. How would you manage her biliary disease, immunosuppression, and IBD, and what is the role of retransplantation?
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Manage dominant strictures with ERCP and dilation or stenting, with brushings and FISH to exclude malignancy. Ursodeoxycholic acid may improve cholestasis but has not been proven to alter outcomes. Optimize tacrolimus and consider adding mycophenolate, but do not overimmunosuppress. Treat the active ulcerative colitis with mesalamine or biologics; uncontrolled IBD is associated with recurrent PSC and colorectal neoplasia. Retransplantation is an option for progressive graft failure, recurrent cholangitis, or intractable pruritus, but recurrent PSC can recur in the new graft and outcomes are inferior to first transplant. I would not retransplant now with a bilirubin of 2.2 mg/dL and preserved synthetic function; I would optimize the biliary tree and IBD first.
3. What long-term surveillance would you recommend?
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Long-term surveillance should include regular liver tests, CA 19-9, and imaging such as MRCP when strictures progress, with ERCP and brushings for dominant strictures. Colonoscopy with dysplasia surveillance is essential because of PSC-IBD, and the interval should be shortened for active inflammation. Monitor tacrolimus levels, renal function, bone density, and metabolic complications. Screen for cholangiocarcinoma and colorectal cancer, and maintain vaccination and skin cancer surveillance. If liver function declines or recurrent cholangitis becomes frequent, reassess for retransplant. A multidisciplinary team including hepatology, transplant surgery, gastroenterology, and oncology is appropriate.