[Lysosomal acid lipase deficiency (LAL-D) : Diagnostic and therapeutic options in an underdiagnosed disease]. / Mangel an lysosomaler saurer Lipase (LAL-D) : Diagnostik und aktuelle Therapie einer unterdiagnostizierten Erkrankung.

BACKGROUND AND CLINICAL SETTING: Lysosomal acid lipase deficiency is an autosomal recessive storage disease caused by mutations in the LIPA gene. The accumulation of cholesteryl esters and triglycerides in hepatocytes lead to hepatomegaly with progressive fibrosis and liver cirrhosis. Characteristically, patients have a hepatomegaly combined with high serum levels of cholesterol, LDL-cholesterol and in some cases triglyceride, whereas HDL-cholesterol is decreased. Histologically, hepatocytes show a microvesicular steatosis with typically ballooned Kupffer cells. Even though histological morphology is typical, it is not characteristic. Therefore LAL-D is supposed to be an underdiagnosed disease with a high number of unreported cases misdiagnosed as uncharacteristic fatty liver disease (NASH, NAFLD, cryptogenic liver cirrhosis). Further, there is overlap with other storage diseases, complicating a correct diagnosis. THERAPY: Until recently, different therapeutic options could not prevent development of liver cirrhosis. Patients with Wolman's disease have an especially rapid progression and die within the first six months of life. With the recent development of a new enzyme replacement therapy with sebelipase alfa (Kanuma ®), new therapeutic options with significant improvement of dyslipidemia and reduction of transaminases have become reality. Positive clinical results seem to have the potential to significantly raise life expectancy. CONCLUSION: These new therapeutic options warrant an increase in awareness of LAL-D by clinicians and pathologists. Correct diagnosis of LAL-D is important for effective therapy and long-term survival.

Cholestasis After Pediatric Liver Transplantation-Recurrence of a Progressive Familial Intrahepatic Cholestasis Phenotype as a Rare Differential Diagnosis: A Case Report.

INTRODUCTION: Nonobstructive cholestasis after pediatric liver transplantation is a common diagnostic and therapeutic dilemma. We describe a girl with neonatal cholestasis because of progressive familial intrahepatic cholestasis 2 (PFIC-2) and presence of a homozygous splice site mutation in the ABCB11 gene. Liver transplantation was performed because of end-stage liver disease at the age of 6. Cholestasis with normal gamma-glutamyl transferase (GGT) developed 8 years after liver transplantation. A liver biopsy showed canalicular cholestasis and giant cell hepatitis without evidence of rejection, mimicking PFIC-2. Immunofluorescence staining of normal human liver sections with patient's serum revealed reactivity toward a canalicular epitope, which could be identified as bile salt export pump (BSEP) using BSEP-yellow fluorescent protein (YFP) transfected cells. Our patient developed a recurrence of a PFIC-2 phenotype due to production of antibodies against BSEP (alloimmune BSEP disease [AIBD]). Intensification of immunosuppressive therapy as well as antibody treatment with plasmapheresis and Rituximab were initiated, leading to stabilization of the clinical condition and depletion of anti-BSEP antibodies in serum. However, after 1 year liver transplantation was necessary again because of end-stage liver insufficiency. Afterward, immunomodulatory treatment consisted of tacrolimus, mycophenolate mofetil, prednisone, immunoadsorption, and high-dose immunoglobulin therapy (1 g/kg/d). CONCLUSION: Cholestasis after liver transplantation may indicate an AIBD with a PFIC-2 phenotype. Besides enhancement of immunosuppressive therapy, an antibody depletion with plasmapheresis, immunoadsorption, immunoglobulins, and B-cell depletion represents a therapeutic option.

[Left-Lateral Living Related Liver Donation - The Essen Experience]. / Linkslaterale Leberlebendspende ­ Erfahrungen aus Essen.

Background: The international organ shortage for liver transplantation exists particularly in paediatric transplantation. Therefore left-lateral living related liver donation (LLRLD) plays a major role in this field. The aim of the present study was to analyse all procedures of LLRLD in terms of donor safety from December 2008 to October 2012 at the University Hospital of Essen, Germany. Methods: All procedures of LLRLD from December 2008 to October 2012 at the University Hospital of Essen were included in the present study. All operations were carried out via an open narrowed median longitudinal laparotomy. General donor data were analysed. Complications were recorded and classified in accordance to their relevance. Results: 35 LLRLD were performed between December 2008 and October 2012 at the University Hospital of Essen, Germany. Mean age of the donors was 31.9 (23.4-61.7) years and 60 % were female. Past medical histories of the donors showed no relevant diagnoses. Mean length of the surgical procedure was 180 (± 89) minutes. Survival rate was 100 %. Minor complications were seen in 1 of 35 patients. Laboratory data showed a peak of the transaminases on the first postoperative day which resolved during the further course. Median postoperative hospital stay was 7 (5-11) days. Conclusion: LLRLD can be performed safely for the donors after adequate donor selection. The organ pool for paediatric recipients can be expanded by this procedure at suitable transplant centres.