Cytokeratin 18-based modification of the MELD score improves prediction of spontaneous survival after acute liver injury.

Background & Aims: Predicting the probability of patients with acute liver failure (ALF) to recover spontaneously is of major clinical importance. As apoptotic and necrotic cell death are crucial in the pathogenesis of ALF, we determined whether selected cell-death markers predict outcome of patients with ALF and/or discriminate between etiologies.

Methods: In a prospective study (11/2006-06/2009), 68 ALF patients were recruited consecutively.

Detection of biliary stenoses in patients after liver transplantation: is there a different diagnostic accuracy of MRCP depending on the type of biliary anastomosis?

Purpose: Two different forms of biliary anastomosis can be created in patients undergoing liver transplantation: (a) bilio-digestive anastomoses or (b) choledocho-choledochostomy. Aim of this study was to assess the accuracy of MR cholangiopancreatography (MRCP) for the depiction of biliary stenoses in liver transplant patients depending on the type of biliary anastomosis.

Method And Materials: 24 liver transplant patients with clinical suspicion of biliary stenosis were studied (each 12 with bilio-digestive anastomosis/choledocho-choledochostomy).

Apoptosis in immune-mediated liver diseases.

Autoimmune diseases of the liver are chronic inflammatory processes leading to injury of hepatocytes and cholangiocytes. Cell death by apoptosis is a prominent feature in a variety of liver diseases. It is likely that apoptosis is the initial cellular response to liver and biliary injury and may thus initiate several cellular and cytokine cascades.

Apoptosis is associated with CD36/fatty acid translocase upregulation in non-alcoholic steatohepatitis.

Background & Aims: Hepatocyte apoptosis is a key event in non-alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver.

Methods: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.

Assessment of allograft fibrosis by transient elastography and noninvasive biomarker scoring systems in liver transplant patients.

Background: This prospective, monocentric study was designed to assess the efficacy of transient elastography (TE), biochemical tests, and more complex scores in determining fibrosis stage in 157 patients transplanted for hepatitis C virus (HCV) infection or non-HCV-related liver diseases.

Methods And Results: The optimal TE cutoff values for HCV patients and non-HCV patients were 4.7 and 5.

Comparison of different MRCP techniques for the depiction of biliary complications after liver transplantation.

Objective: Biliary strictures after liver transplantation are common. We aimed to compare different magnetic resonance cholangiopancreatography (MRCP) sequences with regard to their diagnostic accuracy in depicting anastomotic stenoses (AST), ischaemic-type biliary lesions (ITBL) and cholelithiasis.

Methods: In patients with clinically suspected biliary obstruction after liver transplantation, MRCP was performed at 1.

Analytical performance characteristics and clinical utility of a novel assay for total hepatitis C virus core antigen quantification.

The detection and quantification of hepatitis C virus (HCV) core antigen in serum or plasma by the use of different assay formats have previously been shown to represent useful markers of viral replication. In the present study, the intrinsic performance characteristics and the potential clinical utility of a novel assay for the quantification of total HCV core antigen were comprehensively assessed by using clinical serum samples and specimens contained in various evaluation panels. The Architect HCV Ag assay showed a specificity of 100%.

Major histocompatibility complex class I-related chains A and B (MIC A/B): a novel role in nonalcoholic steatohepatitis.

Unlabelled: Stress-induced soluble major histocompatibility complex class I-related chains A/B (MIC A/B) are increased in chronic liver diseases and hepatocellular malignancy. We investigated the impact of these molecules on liver injury, apoptosis, and fibrosis in nonalcoholic steatohepatitis (NASH). Blood and liver tissue were obtained from 40 patients with NASH undergoing bariatric surgery for obesity.

Prognostic assessment of three single-nucleotide polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in extrahepatic cholangiocarcinoma.

Background/aims: Cholangiocellular carcinoma (CCA) has a devastating prognosis and markers enabling a precise prediction of the clinical outcome have long remained scarce. Recently, it has been demonstrated that genotype distribution of several single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis can serve as helpful predictive parameters in various carcinomas. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA.

Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific.

Little is known of how the Toll-like receptor (TLR) system can modulate the function of non-parenchymal liver cells (NPC) as a major component of the innate and adaptive immune system of the liver. To investigate the diversification of TLR signalling pathways in NPC, we isolated Kupffer cells (KC) and liver sinusoidal endothelial cells (LSEC) from wild-type C57BL/6 mice and examined their responses to TLR1 to TLR9 agonists. The data show that KC respond to all TLR ligands by producing tumour necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6), to TLR3 and TLR4 ligands only by producing interferon-beta (IFN-beta), to TLR1 and TLR8 ligands by significantly up-regulating major histocompatibility complex (MHC) class II and costimulatory molecules, and to TLR1, -2, -4 and -6 ligands by inducing high levels of T-cell proliferation and IFN-gamma production in the mixed lymphocyte reaction (MLR).

Apoptotic markers indicate nonalcoholic steatohepatitis in polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) characterized by chronic anovulation and hyperandrogenism is highly associated with obesity and insulin resistance (IR), two key features of nonalcoholic steatohepatitis (NASH). NASH often leads to cirrhosis, including portal hypertension, liver failure, and hepatocellular carcinoma as long-term complications. The caspase 3-cleaved fragment of cytokeratin 18 (CK18) emerging from ongoing cell death during apoptosis process has been established as a serum marker for NASH.

Surveillance and screening of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) represents an idiopathic chronic cholestatic liver disease due to inflammatory destruction of the biliary tree. Clinically, the progressive disease leads to biliary cirrhosis in association with cholangiocarcinoma in 6-20% of the patients. Currently, liver transplantation remains the only life-extending treatment option in end-stage disease.

Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae.

Background: Acute hepatitis B virus (HBV) infection is followed by high viral replication rates leading to hepatocyte death and ultimately, in some cases, to acute liver failure (ALF) necessitating liver transplantation. Thus, the objective of treating HBV-induced ALF is to eliminate or significantly suppress HBV replication.

Methods/results: This prospective study (02/2008-02/2009) included 6 patients (1 female and 5 males, median age 35.

Apoptosis in selected liver diseases.

Cell death by apoptosis usually occurs in a regulated, limited fashion. Only selected target cells are deleted in the process of ontogeny, development and regeneration. In contrast, under pathophysiological conditions, apoptosis imposes as a massive, chaotic, non-selective event that may occur for periods or even up to decades.

Is there any association between disturbed gastrointestinal visceromotor and sensory function and impaired quality of life in functional dyspepsia?

BACKGROUND Functional dyspepsia (FD) is now categorized into the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS). However, the role of disturbed gastric emptying and sensory function for the reduction of health-related quality of life (HRQOL) has not yet been studied in EPS and PDS. METHODS A total of 300 refractory FD patients and 450 healthy blood donors (BD) were studied.

Acute liver failure in a metropolitan area in Germany: a retrospective study (2002 - 2008).

Objectives: To determine current etiologies of acute liver failure (ALF) and clinical and laboratory parameters associated with the outcome upon ALF, so as to identify the frequency of present causes of ALF in Germany as well as potential new prognostic parameters.

Patients: 134 adult patients (63 % females / 37 % males) aged 41 +/- 16 years (median: 38 years) with established ALF criteria.

Design And Setting: A retrospective study (1 / 2002 - 4 / 2008) on ALF patients from the Ruhr Area, the largest urban region located in northwestern Germany.

Evaluation of quantitative liver function tests in HIV-positive patients under anti-retroviral therapy.

Background And Aims: Quantitative tests of liver function (QTLF) which are based on the hepatic metabolism or clearance of test substances have been successfully used to predict prognosis of a variety of different liver diseases. Still sufficient data in HIV-patients under anti-retroviral therapy (ART) are lacking. Therefore, the aim of this prospective study was to investigate if and to what extent ART influences a broad panel of quantitative tests of liver function in patients with HIV-infection.

Toll-like receptor activated human and murine hepatic stellate cells are potent regulators of hepatitis C virus replication.

Background/aims: While hepatic stellate cells (HSC) are known to be key mediators of liver fibrosis, only little is known about their functional role in the innate immune system of the liver.

Methods: To address this question, murine HSC were isolated from livers of C57BL/6J mice and human HSC were isolated from liver samples obtained from resections and liver explants. HSC were stimulated with Toll-like receptor (TLR) 1-9 ligands for 20 h.

Combined mycophenolate mofetil and minimal dose calcineurin inhibitor therapy in liver transplant patients: clinical results of a prospective randomized study.

Background: Long-term complications of calcineurin inhibitor (CNI)-based immunosuppression after liver transplantation (LT) have a marked impact on patient morbidity and mortality.

Methods: In this prospective study, LT patients with renal dysfunction were randomized (2:1) to either receive mycophenolate mofetil (MMF) followed by stepwise reduction of CNI with defined minimal CNI trough levels (MMF group) or to continue their maintenance CNI dose (control group).

Results: In the MMF group (n = 60), renal function assessed by serum creatinine improved >10% in 67% of patients, was stable in 32%, and deteriorated >10% in 2% after 12 months compared with baseline values.

Evaluation of organ donor card holders among public officials of a major German city.

Introduction: Each year in Germany, the lack of donor organs results in more than 1000 patients dying while on the transplant waiting list. At the same time, there is an organ donor potential that is not being exploited. The objective of this study was to collect the rate of holders of organ donor cards among public officials in a major German city.

Mycophenolic acid impedes the antigen presenting and lymph node homing capacities of human blood myeloid dendritic cells.

Background: Mycophenolic acid (MPA) is the pharmacologically active compound of the immunosuppressive drug mycophenolate mofetil. Dendritic cells (DC) are the key to initiating and priming the adaptive immune response leading to allograft rejection. We investigated the effects of MPA on human blood myeloid DC (MDC) homeostasis with a particular emphasis on their trafficking properties.

Pregnancy-associated Sweet's syndrome in an acute episode of ulcerative colitis.

A 33-year old pregnant patient (pregnancy week 15) with a past medical history of ulcerative colitis with onset of the disease following the birth of her first child was admitted to the hospital with symptoms of weight loss, pyrexia, leukocytosis and bloody and mucous diarrhoea. Total ileocolonoscopy revealed an acute flare of ulcerative colitis. Within a few days, tender erythematous skin lesions occurred and were histologically proven to be neutrophilic dermatosis.

Renal function and cardiovascular risk profile after conversion from ciclosporin to tacrolimus: prospective study in 80 liver transplant recipients.

Background: Increased risk of cardiovascular and cerebrovascular disease in liver transplant recipients results in particular from the side effects of calcineurin inhibitor-based immunosuppressive therapy. Several studies have demonstrated a more favourable outcome for patients receiving tacrolimus (TAC) as compared with ciclosporin (CS).

Aim: To investigate the effects of conversion from CS to TAC on cardiovascular risk factors and renal function in liver transplant recipients.

Early HBeAg loss during peginterferon alpha-2b therapy predicts HBsAg loss: results of a long-term follow-up study in chronic hepatitis B patients.

Objectives: Treatment with pegylated interferon (PEG-IFN) alpha-2b results in hepatitis B e antigen (HBeAg) loss in 36% of patients at 6 months post treatment. The aim of this study was to determine whether a long-term response to PEG-IFN is dependent on the timing of HBeAg loss.

Methods: A total of 91 patients treated with PEG-IFN alpha-2b alone (100 microg per week) and 81 patients treated with PEG-IFN alpha-2b and lamivudine (100 mg/day) for 52 weeks were enrolled in this study.