Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation.

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides.

Effects of pharmacological intervention on coagulopathy and organ function in xenoperfused kidneys.

Background: Following pig to primate kidney transplantation, xenogenic activation of the coagulation (XAC) system of the recipient eventually leading to organ dysfunction and disseminated intravascular coagulation (DIC) can be observed.

Methods: Using an ex-vivo perfusion circuit based on low-dose heparin-mediated anticoagulation and exogenous complement inhibition by C1- Inhibitor (C1-Inh), we have analysed XAC following contact of human blood with porcine endothelium. Porcine kidneys (n = 23) were recovered following in situ cold perfusion with histidine-tryptophan-ketoglutarate (HTK) solution and were connected to a perfusion circuit utilizing freshly drawn pooled human AB blood.

Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure.

Background & Aims: Among the potentially helpful indicators of poor prognosis in acute liver failure (ALF) are etiology, encephalopathy grade, blood lactate, and King's College Criteria (KCC). The accuracy of these parameters in predicting transplantation or death shows significant variation in different countries.

Methods: We retrospectively analyzed 102 patients with ALF treated at our institution between 1996 and 2005.

Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous versus systemic-venous graft drainage: impact on glucose regulatory hormones and the growth hormone/insulin-like growth factor-I axis.

Context: Pancreas grafts can be drained through the iliac vein (systemic drainage) or the portal vein.

Objective: We hypothesized that normalization of portal insulin in patients with portal pancreas graft drainage stimulates the GH/IGF-I axis and thereby contributes to glucose control.

Methods: We compared patients after combined kidney and pancreas transplantation with portal drainage (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and nondiabetic controls (n = 8).

[Progress in immunosuppression].

The success of transplantation with good long-term outcome is closely related to the possibilities of iatrogenic immunosuppression. Progress in immunosuppression combines basic scientific research of alloimmunity with practical clinical management of transplanted patients, their underlying diseases, and management of immunosuppressant side effects. Calcineurin inhibitors and steroids form the basis of immunosuppression in liver transplantation.

[Long-term results after liver transplantation].

Liver transplantation has been reported to reach excellent results for selected indications. We analysed the results of liver transplantation in our centre over a period of 23 years, with a total of 2,114 consecutive liver transplants in 1,773 patients (eras I-III 5.5 years each, era IV 6.

Induction of heme oxygenase-1 improves the survival of pancreas grafts by prevention of pancreatitis after transplantation.

Background: Ischemia/reperfusion (I/R) injury after pancreas transplantation might result in graft pancreatitis. The role of heme oxygenase-1 (HO-1) in pancreas transplantation and prevention of graft pancreatitis is unknown.

Method: We studied the impact of HO-1 induction with cobalt protoporphyrin (CoPP) in experimental pancreas transplantation with moderate (6 hr) and prolonged (20 hr) cold ischemic time (CIT).

[Late stage stenoses of bile ducts after iatrogenic bile duct injuries following cholecystectomy].

Introduction: Iatrogenic bile duct injuries represent a severe complication after cholecystectomy. For the attending physician therapy and management of these injuries are a challenge. Inadequate and delayed treatment can lead to stenoses at a late stage, which can necessitate further surgical intervention.

The type of arterial anastomosis influences hepatic hemodynamics and overall survival in liver graft recipients.

Aim: Evaluation of the influence of arterial anastomoses on hepatic hemodynamics and overall survival in liver graft recipients using color Doppler ultrasound.

Method: 224 patients recruited retrospectively were divided into five groups according to arterial anastomoses: (1) common hepatic (CHA)/gastro duodenal, (2) CHA/CHA, (3) aorta/celiac trunc, (4) aorta/aorta, (5) more than one anastomosis. We compared maximum portal [(P)Vmax], systolic [(A)Vmax] and end diastolic [(A)Vmin] arterial velocities, resistance indexes(RI), spleen and liver size between the groups.

The place of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma: report of the European liver transplant registry.

Background: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up.

Material And Methods: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease.

FTY720 improves survival after transient ischemia and reperfusion of the hind limbs.

Background: Ischemia and reperfusion (I/R) damage involves adhesion and transmigration of lymphocytes and neutrophils. FTY720 is an immunosuppressive agent that reduces the number of neutrophils and monocytes in peripheral blood as well as tissue lymphocyte infiltration. This study investigated the effect of FTY720 during hind limb I/R.

Surgical treatment and outcome of iatrogenic bile duct lesions after cholecystectomy and the impact of different clinical classification systems.

Background: Different injury patterns of iatrogenic bile duct lesions after cholecystectomy have prompted the proposal of several different clinical classification systems. The aim of this study was to validate these systems comparatively.

Methods: Results after surgical intervention for iatrogenic bile duct lesions in 74 consecutive patients at a tertiary referral centre were reviewed retrospectively.

Pancreas transplantation with histidine-tryptophan-ketoglutarate (HTK) solution and University of Wisconsin (UW) solution: is there a difference?

Context: In clinical pancreas transplantation the choice of preservation solution may have an impact on graft pancreatitis. Experience with histidine-tryptophan-ketoglutarate (HTK) is still limited whereas University of Wisconsin (UW) solution is currently the preferred perfusate worldwide.

Objective: The aim of this study was to analyze our experience with HTK in pancreas transplantation.

Longer survival of liver transplant recipients with hepatitis virus coinfections.

Hepatitis virus coinfections [HBV plus HCV coinfection (HBV/HCV) or HBV plus HDV coinfection (HBV/HDV)] may progress more rapidly to cirrhosis than hepatitis B or C monoinfections in immunocompetent patients. Only limited information is available on the outcome of coinfected patients after liver transplantation. We studied survival rates of 204 patients with viral hepatitis transplanted at our center between 1972 and 1997.

FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia; impact on long-term survival and T-lymphocyte tissue infiltration.

Background: Organ dysfunction due to ischemia-reperfusion (I/R) injury is a common problem in transplant, liver, trauma, and heart surgery. I/R injury is mediated by upregulated expression of endothelial cell surface adhesion molecules and subsequent adhesion and activation of circulating leukocytes. The purpose of this study was to evaluate the effect of an intraoperative administration of FTY720 in an animal model with controlled bilateral warm kidney ischemia compared to steroids or placebo application.

FTY720 application following isolated warm liver ischemia improves long-term survival and organ protection in a mouse model.

Background: Ischemia-reperfusion-Injury (I/RI) is a common complication in transplant-, liver-, and heart surgery. The I/RI is mediated and aggravated by different types of leukocytes such as lymphocytes, monocytes, and neutrophil granulocytes, with consecutive enlargement of the expression of adhesion molecules. This study shows an organ-protective effect of an intraoperative FTY720 administration following warm liver ischemia (Pringle's maneuver).

Video documented follow-up of liver transplantation in Wilson's disease with predominant neurological manifestation.

Wilson's disease (WD) is a rare autosomal-recessive disorder of copper metabolism with predominantly hepatic and extrapyramidal motor symptoms. Copper chelating therapy has proven to be an effective treatment for WD. Yet, if conservative treatment fails, liver transplantation (LT) often is the only remaining therapeutic option.

Failure of hepatitis B vaccination with conventional HBsAg vaccine in patients with continuous HBIG prophylaxis after liver transplantation.

Hepatitis B vaccination after liver transplantation for hepatitis B-related liver disease has been investigated as an alternative strategy to reinfection prophylaxis with hepatitis B immunoglobulin (HBIG) with conflicting results. In most studies, HBIG treatment was discontinued before vaccination. An outstanding good response was achieved with vaccination under continuous HBIG administration using hepatitis B surface antigen (HBsAg)-based vaccine containing special adjuvants.

HBsAg level at time of liver transplantation determines HBsAg decrease and anti-HBs increase and affects HBV DNA decrease during early immunoglobulin administration.

Background/aims: Administration of hepatitis B immunoglobulin (HBIG) initially after liver transplantation of hepatitis B patients is considered important to prevent reinfection reliably. However, dosing schedules differ considerably between centers. We measured HBsAg, anti-HBs and HBV DNA kinetics to create a rational basis for dosing schemes.

Infiltrates in protocol biopsies from renal allografts.

In renal transplantation, clinical decisions are based primarily on the Banff classification of biopsies. However, the incorporation of 'minor or nonspecific' cellular infiltrates into the Banff classification and their interpretation is uncertain. We analyzed 833 protocol and 306 indicated biopsies to test whether such infiltrates are harmless or whether they have a bearing on outcomes.

The hepatocyte nuclear factor 6 (HNF6) and FOXA2 are key regulators in colorectal liver metastases.

The molecular causes leading to secondary liver malignancies are unknown. Here we report regulation of major hepatic nuclear factors in human colorectal liver metastases and primary colonic cancer. Notably, the genes coding for HNF6, HNF1beta, and C/EBPgamma were selectively regulated in liver metastases.

Physiological incompatibilities of porcine hepatocytes for clinical liver support.

In fulminant hepatic failure, the use of bioartificial liver support (BAL) with porcine hepatocytes is the subject of a current and controversial debate.1 Specifically, the issue of cross-species physiological incompatibilities has not been addressed so far. We therefore investigated the effects of species-specific cytokines in single and cocultures on hepatocyte function.

Liver transplantation for hereditary hemorrhagic telangiectasia: Report of the European liver transplant registry.

Background: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a rare disease characterized by the presence of arteriovenous malformations. Hepatic involvement can lead to life-threatening conditions.

Material And Methods: Forty patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation in the treatment of the hepatic disease form.

FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.

FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.

Characterization and clinical course of hepatobiliary carcinoma in patients with primary sclerosing cholangitis.

Objective: Primary sclerosing cholangitis (PSC) confers a high risk of development of hepatobiliary carcinoma (HBC). The aim of the study was to identify indicators and risk factors for developing HBC in PSC patients.

Material And Methods: Thirty-nine PSC patients with HBC at time of HBC diagnosis were compared with 101 PSC patients without HBC at time of acceptance for liver transplantation.