[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.

Diagnostic value of diffusion-weighted imaging (DWI) for the assessment of the small bowel in patients with inflammatory bowel disease.

AIM: To evaluate diffusion-weighted imaging (DWI) compared to standard magnetic resonance imaging (sMRI) in the assessment of inflammatory lesions of the small bowel. MATERIALS AND METHODS: Two readers retrospectively analysed MRI images of the small bowel including DWI followed by capsule endoscopy (CE) and ileocolonoscopy (ICS) in 30 consecutive patients with a suspected or established diagnosis of inflammatory bowel disease. Small bowel CE and the combination of CE + ICS were used as the standards of reference. Inflammatory lesions of the small bowel detected at endoscopy were compared with the findings of (1) sMRI alone (MRI without DWI), (2) DWI alone, and (3) sMRI in combination with DWI (sMRI + DWI). The sensitivity, specificity, and accuracy were calculated for all three readouts. The results of the three readouts were compared with each other. RESULTS: Using CE + ICS as the standard of reference, the mean sensitivity and specificity for the detection of inflammatory lesions of the small bowel at sMRI were 55.2% and 99.5%, at DWI 60% and 99%, and at sMRI + DWI 70% and 99%. Interobserver agreement between the two readers was very good (k=0.87-0.95). Two lesions in different patients were only detected at DWI. CONCLUSION: DWI of the small bowel not only allowed for the detection of inflammatory lesions with high accuracy, but also enabled the identification of additional lesions that were not found using sMRI alone.

[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.

Growth abnormalities in children with chronic hepatitis B or C.

Background. It has been suggested that chronic hepatitis B infection leads to growth impairment, but data are inconsistent and underlying factors are not defined. Methods. Children and adolescents with chronic hepatitis B (HBV) or C (HCV) were retrospectively evaluated for growth, weight, antiviral treatment, biochemical signs of liver inflammation, route of infection, and HBV DNA, respectively. Results. In all, 135 children (mean age 6.1 years, 81 male, 54 female) with HBV (n = 78) or HCV (n = 57) were studied. Route of infection was vertical in 50%, parenteral in 11%, and unknown in 39%. ALT levels were above 1.5 times above normal in 30% while 70% had normal/near normal transaminases. 80% were Caucasian, 14% Asian, 1% black, and 4% unknown. Mean baseline height measured in SDS was significantly lower in the study population than in noninfected children (boys -1.2, girls -0.4, P < 0.01). 28 children were below 2 standard deviations of the norm while 5 were above 2 standard deviations. SDS measures in relation to individual factors were as follows: elevated ALT: boys -1.4, females -0.5 (P < 0.01), ALT normal/near normal: boys +0.4, females +0.6; parenteral transmission: boys -3.3, girls -0.9 (P < 0.01), vertical transmission: boys -0.2, females -0.2. Antiviral treatment itself or HBV-DNA load did not reach statistically significant differences. Conclusions. Chronic HBV or HCV may lead to compromised growth which is mostly influenced by liver inflammation. Our data may argue for early antiviral treatment in children with significant ALT elevation.