Approach Considerations

No pharmacologic therapy has been proven effective for primary sclerosing cholangitis (PSC). The goals of treatment of PSC are to slow and potentially reverse the disease process, but treatment may ultimately involve managing disease progression and the associated complications. Drug therapy is aimed at treating symptoms and managing complications. Orthotopic liver transplantation (OLT) has been proven successful in treating children with primary sclerosing cholangitis. Liver transplantation is the only therapy that can alter the eventual outcome.

Surgical drainage procedures (eg, portoenterostomy, choledochoenterostomy) are insignificant in the management of PSC. These procedures may provide palliation but do not alter the natural history of the disease because of the consistent involvement of the intrahepatic biliary tree. Surgical drainage procedures are associated with an increased risk of cholangitis postoperatively, and subsequent liver transplantation may become technically more difficult.

Dominant strictures of the extrahepatic biliary tree, most often at the bifurcation of the hepatic ducts, are major problems for patients with PSC. Transhepatic or endoscopic balloon dilatation of strictures has been shown to be useful in children with PSC. Short-term stenting of strictures has also demonstrated clinical improvement of symptomatic strictures.

Surgical, endoscopic, and interventional radiologic procedures to relieve symptomatic dominant strictures have been demonstrated to prolong survival time of the native liver in patients with PSC, but none of these interventions have altered the ultimate rate of progression of PSC to end-stage liver disease.

Bacterial cholangitis, which can occur spontaneously, is more common after endoscopic or surgical manipulation of the biliary tree. Episodes of cholangitis require prompt antibiotic therapy.

Pharmacologic Therapy

Pharmacologic treatment of patients with primary sclerosing cholangitis (PSC) should be directed at managing the following:^[44]

Cirrhosis and portal hypertension
Chronic cholestasis with pruritus and malabsorption
Ductular complications, such as dominant strictures, cholelithiasis, and ascending bacterial cholangitis
Other associated diseases, such as inflammatory bowel disease (IBD) or other autoimmune diseases

Choleretic therapy with ursodeoxycholic acid (UDCA) reportedly improves symptoms and biochemical abnormalities in adult patients with PSC. Some observational and controlled trial data also suggest a reduction in colonic dysplasia rates with UDCA.^[45]Children with PSC experience significant improvements in their liver biochemical indices when treated with UDCA; however, the long-term effect of UDCA on the clinical outcome of PSC has not been determined.^{[46, 47, 48]}

The efficacy of immunosuppressive agents such as glucocorticoids, methotrexate, cyclosporine, and tacrolimus has been studied in adults but has not demonstrated long-term benefit, specifically with regards to histology.^{[49, 50, 51, 52, 53, 54]}The potential therapeutic effect of antibiotics has also been studied in children with primary sclerosing cholangitis. Observational studies using oral vancomycin demonstrated improved symptoms and liver function tests but no consistent improvement in liver histology.^[55]Likewise, adult studies with oral vancomycin or metronidazole have been shown to decrease select liver biochemistries,^[56]but long-term follow-up studies are needed to assess the efficacy of antibiotic therapy.

Liver Transplantation

Orthotopic liver transplantation (OLT) has been proven successful in treating children with primary sclerosing cholangitis (PSC). Data from numerous liver transplantation centers demonstrate excellent long-term patient and graft survival for patients with end-stage primary sclerosing cholangitis.^{[30, 31, 32, 57, 58, 59, 60]}

Actual patient survival rates after OLT for primary sclerosing cholangitis have been shown to be greater than 90% at 1 year and approximately 90% at 5 years. In one study, although children with primary sclerosing cholangitis had patient-survival rates and graft-survival rates equaling those of age-matched children who underwent transplantation for other indications, patients with coexisting IBD demonstrated poorer outcomes. Overall, posttransplant recurrence was noted in 9.8%, and compared with other graft recipients, patients with primary sclerosing cholangitis had higher mean liver enzyme levels 5 years posttransplant.^[29]

Diet

As with other cholestatic disorders, provide fat-soluble vitamin supplementation (vitamins A, D, E, K) and nutritional support to ensure adequate growth. If the patient has steatorrhea, medium-chain triglycerides should be added to the diet. If pancreatic enzyme deficiency is present, oral supplementation is necessary, and calcium supplementation for bone disease may also be needed.

Consultations

Despite progress in early recognition, optimal treatment of patients with primary sclerosing cholangitis remains a challenge and requires a multidisciplinary approach between hepatologists, endoscopists, surgeons, and interventional radiologists. Consultation with a gastroenterologist is necessary, and an endocrinologist may be consulted for management of bone disease.

Medication

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Media Gallery

Fibro-obliterative cholangiopathy. Image courtesy of Dr. Kay Washington.
Endoscopic retrograde cholangiopancreatography performed in a patient with abnormal liver function test results shows multiple intrahepatic bile duct strictures and beading.
Double-contrast barium enema (same patient as in the previous image) shows filiform polyps and an ahaustral colon resulting from ulcerative colitis.
Percutaneous transhepatic cholangiogram shows dilatation, stricturing, and beading of the intrahepatic bile ducts. Note the surgical clips from a previous cholecystectomy.
T-tube cholangiogram shows irregularity of the common bile duct, stricturing, beading, and dilatation of the intrahepatic bile ducts. Note a calculus in the termination of the left hepatic duct (arrow).
Magnetic resonance cholangiopancreatography shows a normal-sized common bile duct, but strictures of both the left and right ducts are noted as well as a dilated proximal left hepatic duct.
Technetium-99m iminodiacetic acid scan shows retention of the radionuclide proximal to strictures in the distribution of the left hepatic duct. Note the lack of filling of the gallbladder because of a previous cholecystectomy. Isotope has entered the small bowel.

of 7

Author

Henry C Lin, MD, MBA Professor, Department of Pediatrics, Division of Gastroenterology, Oregon Health and Science University School of Medicine; Division Head, Division of Gastroenterology, Doernbecher Children’s Hospital

Henry C Lin, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, International Pediatric Transplant Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Oregon Medical Association, Oregon Pediatric Society, Society of Pediatric Liver Transplantation

Disclosure: Received income in an amount equal to or greater than $250 from: Albireo Pharmaceuticals; Mirum Pharmaceuticals<br/>Consultant for: Alexion; Albireo; Mirum.

Coauthor(s)

Hisham Nazer, MBBCh, FRCP, DTM&H Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, University of Jordan Faculty of Medicine, Jordan

Hisham Nazer, MBBCh, FRCP, DTM&H is a member of the following medical societies: American Association for Physician Leadership, Royal College of Paediatrics and Child Health, Royal College of Surgeons in Ireland, Royal Society of Tropical Medicine and Hygiene, Royal College of Physicians and Surgeons of the United Kingdom

Disclosure: Nothing to disclose.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching. for: Abbott Nutritional, Abbvie, speakers' bureau.

Acknowledgements

Robert Baldassano, MD Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.