Beneath the Copper-Pediatric Wilson's Disease Cirrhosis and Hepatocellular Carcinoma: A Case Report with Literature Review.

Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma (HCC) develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease. A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed.

Giant hepatocellular adenoma in a previously obese thirteen-year-old boy.

Hepatocellular adenoma is an uncommon neoplasm, especially in the childhood age group. We describe a previously obese 13-year-old male with a giant hepatocellular adenoma requiring an extensive hepatic resection. The related pediatric tumor literature, diagnosis and clinical management is discussed.

Current concepts in pediatric liver transplantation.

Liver transplantation is the definitive treatment for end-stage liver disease in both children and adults. Advances over the last 2 decades have resulted in excellent patient and graft survival rates in what were previously cases of fatal disorders. These developments have been due to innovations in surgical technique, increased surgical experience, refinements in immunosuppressive regimens, quality improvements in intraoperative anesthetic management, better understanding of the pathophysiology of the liver diseases, and better preoperative and postoperative care. Remarkably, the use of split-liver and living-related liver transplantation surgical techniques has helped mitigate the well-recognized national organ shortage. This review will discuss the major aspects of pediatric liver transplantation as it pertains to indication for transplantation, recipient selection and listing for orthotopic liver transplantation, pre-orthotopic liver transplantation care of children, optimal timing of orthotopic liver transplantation, surgical technical considerations, postoperative care and complications, and patient and graft survival outcomes.

Treatment of adenovirus hepatitis with cidofovir in a pediatric liver transplant recipient.

AdV hepatitis is a rarely reported complication after pediatric liver transplantation that is associated with high rates of morbidity, mortality and graft failure. Successful treatment of AdV relies on early diagnosis of disease by quantitative PCR measurement of adenoviral DNA in blood and histological evidence in tissue biopsy. Pharmacologic treatment largely consists of antiviral therapy with CDV, an acyclic nucleoside phosphonate analog and reduction in immunosuppression. This report describes a case of AdV hepatitis in a pediatric liver transplant recipient successfully treated with a modified, renal sparing dosing of CDV.

Wilson disease: pathogenesis and clinical considerations in diagnosis and treatment.

Nearly a century after Dr. Samuel Alexander Kinnier Wilson composed his doctoral thesis on the pathologic findings of "lenticular degeneration" in the brain associated with cirrhosis of the liver we know that the underlying molecular basis for this autosomal recessive inherited disorder that now bears his name is mutation of a copper transporting ATPase, ATP7B, an intracellular copper transporter mainly expressed in hepatocytes. Loss of ATP7B function is the basis for reduced hepatic biliary copper excretion and reduced incorporation of copper into ceruloplasmin. During the intervening years, there was recognition of the clinical signs, histologic, biochemical features, and mutation analysis of ATP7B that characterize and enable diagnosis of this disorder. These include the presence of signs of liver or neurologic disease and detection of Kayser-Fleischer rings, low ceruloplasmin, elevated urine and hepatic copper, and associated histologic changes in the liver. Medical therapies and liver transplantation can effectively treat patients with this once uniformly fatal disorder. The earlier detection of the disease led to the initiation of treatment to prevent disease progression and reverse pathologic findings if present, and family screening to detect the disorder in first-degree relatives is warranted. Gene therapy and hepatocyte cell transplantation for Wilson disease has only been tested in animal models but represent future areas for study. Despite all the advances we still have to consider the diagnosis of Wilson disease to test patients for this disorder and properly establish the diagnosis before committing to life-long treatment.

Repopulation of rat liver by fetal hepatoblasts and adult hepatocytes transduced ex vivo with lentiviral vectors.

Recent studies have shown that nondividing primary cells, such as hepatocytes, can be efficiently transduced in vitro by human immunodeficiency virus-based lentivirus vectors. Other studies have reported that, under certain conditions, the liver can be repopulated with transplanted hepatocytes. In the present study, we combined these procedures to develop a model system for ex vivo gene therapy by repopulating rat livers with hepatocytes and hepatoblasts transduced with a lentivirus vector expressing a reporter gene, green fluorescent protein (GFP). Long-term GFP expression in vivo (up to 4 months) was achieved when the transgene was driven by the liver-specific albumin enhancer/promoter but was silenced when the cytomegalovirus (CMV) enhancer/promoter was used. Transplanted cells were massively amplified ( approximately 10 cell doublings) under the influence of retrorsine/partial hepatectomy, and both repopulation and continued transgene expression in individual cells were documented by dual expression of a cell transplantation marker, dipeptidyl peptidase IV (DPPIV), and GFP. In this system, maintenance or expansion of the transplanted cells did not depend on expression of the transgene, establishing that positive selection is not required to maintain transgene expression following multiple divisions of transplanted, lentivirus-transduced hepatic cells. In conclusion, fetal hepatoblasts (liver stem/progenitor cells) can serve as efficient vehicles for ex vivo gene therapy and suggest that liver-based genetic disorders that do not shorten hepatocyte longevity or cause liver damage, such as phenylketonuria, hyperbilirubinemias, familial hypercholesterolemia, primary oxalosis, and factor IX deficiency, among others, might be amenable to treatment by this approach.