A 12-year-old girl presented with a three-week history of jaundice and lethargy, with periumbilical pain every other day. There had been no recent travel or sick contacts. Screening tests revealed platelet level was low (89
K/uL; normal range 150 to 400). Antinuclear Antibody (ANCA) was positive with a homogeneous pattern, and Antinuclear Antibody Titer was elevated (640; normal range <40). Serum copper was normal at 1065
ug/L and ceruloplasmin was normal at 24
-Glutamyl transpeptidase (GGT) level was elevated (139
U/L; reference range from 5 to 36). C-Reactive Protein (CRP) was elevated at 2.80
mg/dL; reference range was from 0.0 to 0.5. PTT was elevated at 48.6
sec; normal range was from 23.3 to 33.8. Prothrombin Time was elevated at 21.0
sec; normal range was from 11.8 to 14.2. INR was increased to 1.9
sec; normal range was from 0.9 to 1.1. Erythrocyte sedimentation rate (ESR) was elevated at 107
mm/hr; bilirubin was elevated at 3.5
mg/dL, and ammonia was elevated at 55
umol/L. Patient underwent an open liver biopsy, which demonstrated the hepatic parenchyma being completely replaced by extensive compartmentalizing fibrosis and regenerative nodules. There was marked bile duct proliferation in the fibrotic areas. The fibrous septae showed a dense inflammatory infiltrate that consisted predominantly of small lymphocytes admixed with plasma cells and neutrophils. There was prominent interface hepatitis at the periphery of the inflamed septae. There was also a component of acute cholangitis showing focal bile duct infiltration and destruction by inflammatory cells, but most of the bile ducts were intact. There was minimal intrahepatocytic cholestasis, but no significant cholestasis was present in the large bile ducts (Figures and ). She underwent colonoscopy and colonic biopsies which demonstrated focal cryptitis, occasional crypt abscesses, and some crypt distortion, mainly in the descending and sigmoid colon, correlating with her serologic marker ANCA, elevated at 640 (Figures and ) consistent with ulcerative colitis. The patient was diagnosed with primary sclerosing cholangitis with inflammatory bowel disease (ulcerative colitis).
Figure 1 Liver and colon biopsies (stained with trichomere): thoracic liver before OLT: (a) onion skin fibrosis and periductular inflammation; (b) cirrhosis nodules surrounded by normal tissue; after OLT with recurrence of PSC (c) periductular fibrosis and inflammation; (more ...)
She underwent an orthotopic liver transplant three months later with postoperative complications consisting of hypertension. She was discharged home on postoperative day ten. Her postoperative medications included Prograf (Tacrolimus), CellCept (Mycophenolate), Prednisone, Actigall (Ursodiol), Magnesium, Septra (Trimethoprim and Sulfamethoxazole), and Valcyte (Valganciclovir). Over the next three years she did well weaning off everything except Prograf and CellCept. On routine labs (three years after transplant) she was found to have an elevated alkaline phosphatase level (204
U/L; normal range from 50 to 136). Her aspartate aminotransferase (AST) was elevated (267
U/L; normal range from 15 to 37). Her alanine aminotransferase (ALT) was elevated (290
U/L; normal range from 30 to 65). Her GGT was also elevated (309
U/L; normal range from 5 to 55). Her sedimentation rate was elevated (25
mm/hr; normal range from 0 to 20). EBV and CMV titers were negative and she had a therapeutic Prograf level of 7.9.
The patient underwent liver biopsy to distinguish between liver rejection or recurrence of primary sclerosing cholangitis. The transplanted liver biopsy demonstrated prominent portal inflammation consisting of large numbers of plasma cells and lymphocytes and rare neutrophils and eosinophils. There was prominent interface inflammation with occasional acidophil bodies near the limiting plate. There was mild to moderate bile ductular proliferation with very prominent lymphocytic infiltration of the bile ducts. Some of the bile ductules showed branching and there was concentric inflammation and “onion skin” fibrosis around bile ductules. Overall, the lobular parenchyma was unremarkable. There was lymphocytic endothelialitis. Trichrome stain demonstrated little periportal fibrosis and no evidence of bridging fibrosis. Iron stain was unremarkable. The biopsy was compatible with recurrent primary sclerosing cholangitis (Figures and ). The lack of eosinophils in the portal infiltrate was more consistent with recurrent disease rather than acute rejection.
She was treated for recurrent primary sclerosing cholangitis. Her immunosuppressant medication remained the same and oral Vancomycin was added to the regimen. She received 500
mg orally three times a day of Vancomycin. During the course of her treatment with oral Vancomycin, liver enzymes (AST, ALT, GGT, ESR, and CRP) returned to normal values (). The patient is currently on Vancomycin and remains well, to date, with normal laboratory values. Her repeat liver biopsy after three years from the recurrence of her primary sclerosing cholangitis showed no evidence of onion skin around the large bile duct and no inflammation of the bile ducts (Figures and ). Comparison of biopsy photos before and after Vancomycin reveals a return to normal liver structure and anatomy ().
Figure 2 Blood liver markers (AST, ALT, GGT, ESR, CRP) returned to normal values after treatment with oral Vancomycin was started in August 2007 (see arrow). To this date, she remains on oral Vancomycin with normal laboratory values (AST: 15–37U/L, (more ...)
Comparative liver biopsy of bile ductules (a) before Vancomycin (recurrent PSC) and (b) after Vancomycin. Resolution of inflammation and cirrhosis is visible.