Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma‐glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP‐common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP‐other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP‐common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP‐other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP‐other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. ( Hepatology Communications 2018;2:515‐528)
Institute of Liver Studies, King's College London, London, UK No relevant funding Richard J. Thompson consults for and is on the speakers' bureau for Albireo and Mirum. He consults for and owns stock in Generation Bio and Rectify Pharma. He consults for Alnylam. Correspondence Richard J. Thompson, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS. Email: [email protected]
Objectives: Elevated hepatic dry copper weight is recognized in adults with autoimmune liver disease (AILD) and chronic cholestasis. We aim to review hepatic dry copper weight in pediatric AILD. Methods: Retrospective review of pediatric AILD managed at our institution from 1999 to 2018, and 104 patients with hepatic dry copper weight assessment were included. Results: Median age at presentation was 13.4 years (interquartile range, IQR, 11.7–14.9), 60% female, 54% autoimmune hepatitis, 42% autoimmune sclerosing cholangitis, and 4% primary sclerosing cholangitis. Histological features of advanced liver fibrosis in 68%. Median hepatic dry copper weight was 51.1 µg/g dry weight (IQR, 28.0–103.8). Elevated hepatic dry copper weight (>50 µg/g dry weight) was present in 51%, and was not associated with AILD subtype ( P = 0.83), age at presentation ( P = 0.68), or advanced fibrosis ( P = 0.53). Liver transplantation (LT) was performed in 10%, who had higher hepatic dry copper weight (148.5 µg/g dry weight [IQR, 39.5–257.3] vs 47.5 [IQR, 27.8–91.5], P = 0.04); however this was not associated with LT on multivariate analysis (hazard ratio 1.002, 95% CI 0.999–1.005, P = 0.23). In 8 (7.7%) patients ATP7B was sequenced and potentially disease causing variants were identified in 2 patients, both who required LT. Conclusions: Elevations in hepatic dry copper weight are common in pediatric AILD. Unlike in adults, it is not associated with AILD subtypes with cholestasis. Higher dry copper weight was detected in patients who required LT. While further work is needed to identify the significance of copper deposition in pediatric AILD, we recommend close monitoring of patients with elevated levels for progressive liver disease.
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