Gastroenterology

Gastroenterology

Volume 125, Issue 4, October 2003, Pages 1227-1234
Gastroenterology

Case report
Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile

Presented in abstract form at the 2002 annual meeting of the American Gastroenterological Association in San Francisco, California (Gastroenterology 2002;122:A645).
https://doi.org/10.1016/S0016-5085(03)01199-5Get rights and content

Abstract

Background & aims: Progressive familial intrahepatic cholestasis (PFIC) is characterized by pruritus, intrahepatic cholestasis, low serum γ-glutamyltransferase levels, and characteristic “Byler bile” on electron microscopy. Many patients require liver transplantation, but partial external biliary diversion (PEBD) has shown therapeutic promise. However, the effect of PEBD on liver morphology and bile composition has not been evaluated. Methods: We reviewed liver biopsy specimens from 3 children with low γ-glutamyltransferase PFIC before and after PEBD. Follow-up liver biopsies were performed 9–60 months after PEBD. Light and electron microscopic features were scored blindly. Biliary bile acid composition was analyzed by gas chromatography—mass spectrometry before and after PEBD in 1 patient and after PEBD in 2 patients. Results: Following PEBD, all patients improved clinically. Preoperative biopsy specimens showed characteristic features of PFIC, including portal fibrosis, chronic inflammation, cholestasis, giant cell transformation, and central venous mural sclerosis. Ultrastructural findings included coarse, granular canalicular Byler bile, effaced canalicular microvilli, and proliferative pericanalicular microfilaments. Following diversion, histology showed almost complete resolution of cholestasis, portal fibrosis, and inflammation with resolution of ultrastructural abnormalities. Biliary bile acids before PEBD consisted predominantly of cholic acid. After PEBD, the proportion of chenodeoxycholic acid increased significantly in 1 patient and was above the PFIC range in a second patient. Conclusions: The resolution of hepatic morphologic abnormalities following PEBD supports PEBD as an effective therapy for PFIC. The improved biliary bile acid composition suggests enhanced bile acid secretion after PEBD, perhaps by induction of alternative canalicular transport proteins.

Section snippets

Patients and methods

We reviewed case histories and liver biopsy specimens from 3 children with PFIC who underwent PEBD. Liver biopsy specimens reviewed in this series were obtained at the time of the diversion procedure and during follow-up. All patients had undergone previous diagnostic liver biopsies several months to years before PEBD. The diagnosis of PFIC was established by the clinical symptoms, liver histology, characteristic bile on electron microscopy, low serum GGT and cholesterol values, and absence of

Results

After PEBD, all 3 patients had improved liver morphology Table 2, Table 3, chemistries, and function (Table 1). The only exception was the prothrombin time in patient 3, which was prolonged because of vitamin K deficiency. In addition, all patients had marked improvement in growth parameters (z-scores) after PEBD (Table 1). No patient experienced fluid or electrolyte difficulties related to biliary drainage, and all stoma problems were temporary and responded to intervention. Table 2 shows the

Discussion

During the past decade, a number of reports have documented a reduction in pruritus and improved growth rate, liver function test results, and serum lipid levels in patients with PFIC after PEBD.2, 13, 14, 15, 16 However, changes in liver histology after this procedure have not to our knowledge been clearly shown. Knowing whether progressive fibrosis is interrupted or reversed by PEBD is essential in assessing the potential long-term benefits of PEBD in PFIC. The 3 patients with PFIC in this

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Supported in part by grant 5 MO1 RR00069 from the General Clinical Research Centers Program, the National Center for Research Resources, the National Institutes of Health, and the Abby Bennett Liver Research Fund.

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