Primary Sclerosing Cholangitis in Children Sunpreet Kaur, MD

Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is a rare disease in pediatric patients, with an incidence of 0.2 cases per 100,000 children 10-20 times less common in children than in adults. Chronic disease characterized by inflammation and scarring of the bile ducts outside and/or inside the liver. Why did my child get PSC? Cause Unknown appears to be genetic, environmental and autoimmune components. As a parent, there is nothing you could have done to prevent PSC in your child.

What are the common symptoms of PSC? When diagnosed, most children with PSC are in early stages of the disease process and don’t exhibit symptoms. However, these are the initial symptoms that may develop: • Fatigue • Intense persistent itching • Pain on right side or middle of abdomen • Jaundice (yellowing of eyes and skin) • Elevated liver blood tests • Hepatomegaly (an enlarged liver) • Splenomegaly (an enlarged spleen)

How is PSC diagnosed? PSC is suspected when liver blood tests are abnormal, especially in a child known to have inflammatory bowel disease (IBD) and or autoimmune hepatitis (AIH). PSC is confirmed when scarring, dilation and irregularity of the bile ducts are observed on imaging tests or liver biopsy.

How does PSC in children differ from adult PSC? PSC is less common in children than in adults. Overlap of autoimmune hepatitis with PSC is more common in children, and children have markers of autoimmune disease more often than adults. Almost half of children have autoimmune hepatitis (AIH) in addition to PSC, compared to only 4% of adults.

How does PSC in children differ from adult PSC? Children rarely have dominant strictures of the common bile duct or cancers of the bile ducts and colon. Overall, children tend to present with milder disease, but as they grow older, their disease and its complications look more and more like adult PSC.

Primary Sclerosing Cholangitis There were three main findings from this study. Nearly half of all patients experience an adverse liver- related event within 10 years of diagnosis. Bilirubin, GGT, and APRI at diagnosis correlate directly with a child’s long-term clinical outcome. There are differences in presentation and outcome between PSC subtypes of PSC–AIH, PSC–IBD, and small duct PSC.

Primary Sclerosing Cholangitis PSC–IBD (compared to PSC without IBD): more likely male markedly lower proportion of Autoimmune Hepatitis (AIH) overlap. PSC–IBD patients had a slower progression to complications.

Primary Sclerosing Cholangitis PSC–AIH overlap: More likely to be female and to have additional non-IBD auto-inflammatory diseases such as celiac disease. Event-free survival was nearly identical in patients with and without AIH.

Primary Sclerosing Cholangitis Patients with small duct PSC (versus large duct PSC) or with PSC–IBD (versus no IBD) generally showed favorable out-comes

What is the treatment for PSC? There is currently no medical cure for PSC. Most therapies are directed at managing symptoms rather than the underlying cause of PSC: Ursodeoxycholic acid (Ursodiol, Urso Forte, UDCA, Actigall) may improve liver enzymes and itching in pediatric PSC Oral vancomycin may improve laboratory tests and clinical symptoms Immunosuppressants (steroids, azathioprine) since patients with PSC and autoimmune hepatitis overlap, and elevated IgG4 may respond to immunosuppression Rifampin, cholestyramine, antihistamines and anti-opiates (naltrexone) are prescribed for itching ERCP (balloon dilatation and/or stent placement for dominant strictures) Endoscopy procedures to prevent bleeding from esophageal varices Liver transplantation.

Who will need a liver transplant? About 15% of children may need a liver transplant for PSC before age 18. There is no reliable way to predict who will have progressive disease.

Future Several promising new drugs for the treatment of PSC are in various stages of development in adults, and may be ready for trials in pediatric PSC patients in the near future. pscpartners.org/clinical-trials/

Questions?