Treatment of primary sclerosing cholangitis in children

Abstract

Primary sclerosing cholangitis (PSC) is a rare disease of stricturing and destruction of the biliary tree with a complex genetic and environmental etiology. Most patients have co-occurring inflammatory bowel disease. Children generally present with uncomplicated disease, but undergo a variable progression to end-stage liver disease. Within ten years of diagnosis, 50% of children will develop clinical complications including 30% requiring liver transplantation. Cholangiocarcinoma is a rare but serious complication affecting 1% of children. Ursodeoxycholic acid and oral vancomycin therapy used widely in children as medical therapy, and may be effective in a subset of patients. Gamma glutamyltransferase is a potential surrogate endpoint for disease activity, with improved survival in patients who achieve a normal value. Endoscopic retrograde cholangiopancreatography is a necessary adjunct to medical therapy to evaluate mass lesions or dominant strictures for malignancy, and also to relieve biliary obstruction. Liver transplantation remains the only option for patients who progress to end-stage liver disease. We review special considerations for patients before and after transplant, and in patients with inflammatory bowel disease. There is presently no published treatment algorithm or guideline for the management of children with PSC. We review the evidence for drug efficacy, dosing, duration of therapy, and treatment targets in PSC, and provide a framework for endoscopic and medical management of this complex problem.

Complications of Cryptosporidium infection after pediatric liver transplantation: Diarrhea, rejection, and biliary disease

“…Our efforts were based on publications in pediatric literature suggesting benefit of vancomycin in sclerosing cholangitis. 16,[33][34][35] In light of these findings, we have modified our counseling in the post-transplant setting regarding the risks of Cryptosporidium in our patients. We recommend abstaining from public water parks and freshwater swimming for the first 12 months after transplant.…”

“…This was in concert with UDCA (patients 4 and 5) or following an ineffective UDCA course (patient 3). Our efforts were based on publications in pediatric literature suggesting benefit of vancomycin in sclerosing cholangitis 16,33‐35 . Proposed mechanisms of action for vancomycin efficacy include changes to disease‐related enteral microbial populations and direct effects on the immune system—including increased peripheral regulatory T‐cell populations 35 .…”

Primary Sclerosing Cholangitis (PSC) in Children

“…PSC may present in an IBD patients even after colectomy. Multiple gallbladder abnormalities in the course of primary sclerosing cholangitis including: dilatation (15%), gallstones (25%), cholecystitis, hydrops, polyps (4-6%), carcinoma (2.5-3.5%) are observed more often in patients [2,8,17,22,29,30].…”

“…Liver transplantation is a life-saving procedure with generally good outcomes, however, up to 16% of paediatric patients are affected by recurrent primary sclerosing cholangitis (rPSC) after transplantation. The indications for liver transplantation in PSC are similar to other liver diseases and transplanted with a qualifying MELD/PELD score in a patient with cirrhosis [11,29,51].…”

Geoepidemiologic variation in outcomes of primary sclerosing cholangitis

“…Though a rare disease, PSC is the fifth leading indication for liver transplantation (LT) in the United States and a major indication in other countries[ 1 , 3 - 5 ]. Moreover, no medical therapy has been shown to significantly delay PSC progression; indeed, it has been suggested that PSC treatments are one of the greatest unmet needs in hepatology[ 9 , 10 ].…”