Small-duct sclerosing cholangitis associated with Schistosoma mansoni
Authors: Catherine H. McCrann, James L. Boyer
Journal: Hepatology (2010)

A 17-year-old girl presented with a history of elevated alkaline phosphatase and gamma-glutamyl transpeptidase (γGT) levels for several years. She was asymptomatic and did not have jaundice, pruritus, abdominal pain, nausea, vomiting, weight loss, rashes, or diarrhea. Viral hepatitis serologies, autoimmune serologies, and thyroid studies were all normal. γGT, gamma-glutamyl transpeptidase; MRCP, magnetic resonance cholangiopancreatography. She had a past medical history of anxiety, which was treated with Celexa. Otherwise, she was healthy and had no major childhood illnesses or history of substance abuse. She had traveled extensively with her family during her childhood, notably to Northern and Eastern Africa and Southeast Asia. Her physical examination was unremarkable. An abdominal ultrasound examination was performed, and the findings were normal. Magnetic resonance cholangiopancreatography (MRCP) showed mild beading of the intrahepatic ducts consistent with the diagnosis of primary sclerosing cholangitis involving the small ducts. The patient was started on ursodiol (300 mg three times per day), and her alkaline phosphatase and γGT levels promptly normalized. Subsequently, colonoscopy was performed to rule out concomitant inflammatory bowel disease. The mucosa appeared normal on endoscopic examination, but random biopsy samples were taken to rule out quiescent colitis. The pathology specimens revealed schistosoma eggs, and stool studies were positive for Schistosoma mansoni. Percutaneous liver biopsy was then performed to evaluate hepatic involvement. There were portal intravenular granulomas in two triads with a schistosoma egg with otherwise minimal lobular fibrosis There was no evidence of mucopolysaccharide production or hyperplasia of the ductular epithelium (Fig. 1). An endoscopic examination was negative for esophageal varices. She was treated with praziquantel, and ursodiol was continued. One year later, repeat MRCP showed minimal changes with resolution of duct dilation in segment 6. Portal triad demonstrating an intravenular granuloma surrounding a schistosoma egg. Onion-skinning fibrosis impinging on small interlobular ducts can also be noted. The over all histological examination showed minimal portal fibrosis with focal areas of periportal extensions. Schistosomiasis, which is also known as bilharzia, affects more than 207 million people worldwide, with 1 of every 30 people infected with the trematode. Free cercariae penetrate the skin, travel to the pulmonary vessels, and then eventually lodge in the liver; there, they mature, mate, and migrate distally against the venous flow in the portal system. Eggs pass through the intestinal wall into the bowel lumen. Chronic disease results from the ongoing host response to accumulating tissue-trapped eggs. There is a CD4+ T cell response to the egg antigen, and this drives the formation of granulomas around the eggs. When the eggs die in the liver, granulomas involute and leave fibrous plaques. Over a period of years, the accumulation of scar tissue can cause the hepatic vessels to become fibrotic and thereby lead to presinusoidal venous obstruction and portal hypertension. Hepatic function is typically preserved. The characteristic periportal lesion, Symmers' pipestem fibrosis, can be seen on imaging and resected specimens. Bile duct abnormalities associated with schistosomiasis have been described infrequently. Biliary changes in S. mansoni–infected mice were initially reported by Bedi and Isseroff in 1979.1 Bile duct hyperplasia occurs in response to neighboring S. mansoni injury to portal areas, and these changes do not seem to regress despite antiparasitic treatment.2 However, elevations in alkaline phosphatase and γGT levels are common in patients with schistosomiasis, and there is evidence that these perturbations normalize with ursodeoxycholic acid.3 Histological abnormalities of the intrahepatic ducts were originally described in patients by Vianna et al.4; almost all cases demonstrated periductal fibrosis with onion skinning. A schistosomiasis cholangiopathy with abnormal MRCP findings has also been described, and this infection should be included as a cause of ductopenia.5