Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study.

Background: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD.

Aim: To evaluate a multifactorial intervention in the treatment of NAFLD.

A systematic review of the quality of liver biopsy specimens.

Characteristics for an optimal liver biopsy specimen were recently defined as 20 to 25 mm long and/or containing more than 11 complete portal tracts (CPTs). A systematic review of percutaneous liver biopsy (PLB) and transjugular liver biopsy (TJLB) series yielded only 32 PLB studies in which these characteristics were evaluated: mean +/- SD length, 17.7 +/- 5.

Spontaneous bacterial peritonitis in cirrhotic patients: Is prophylactic propranolol therapy beneficial?

Background And Aim: It has been suggested that propranolol may have a protective effect on the development of spontaneous bacterial peritonitis by increasing the motility of the bowel and lowering the pressure of the portal vein. The aim of this study is to evaluate the association between the use of propranolol and development of spontaneous bacterial peritonitis in patients with cirrhosis and ascites.

Methods: We retrospectively evaluated 134 patients with cirrhosis and ascites admitted consecutively for a period of 2 years.

The effects of unfractionated heparin, low molecular weight heparin and danaparoid on the thromboelastogram (TEG): an in-vitro comparison of standard and heparinase-modified TEGs with conventional coagulation assays.

To investigate the effects of unfractionated heparin (UFH), low molecular weight heparin (LMWH) and danaparoid (DPD) added to whole blood in vitro on standard and heparinase-modified thromboelastogram (TEG) parameters compared with conventional assays of coagulation. The effects of UFH, LMWH and DPD on standard TEG parameters were compared with the prothrombin time, activated partial thromboplastin time, thrombin time and anti-activated factor X (anti-FXa) activity, at concentrations of these anticoagulants ranging from 0.025 to 1 U/ml.

Liver transplantation for Budd-Chiari syndrome: A European study on 248 patients from 51 centres.

Background/aims: The results of liver transplantation for Budd-Chiari syndrome (BCS) are poorly known and the role and timing of the procedure are still controversial. The aim of this study was to investigate the results of transplantation for BCS, focusing on overall outcome, on prognostic factors and on the impact of the underlying disease.

Methods: An enquiry on 248 patients representing 84% of the patients transplanted for BCS in the European Liver Transplantation Registry between 1988 and 1999.

3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome.

Background: Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation.

Methods: We analysed data from 34,664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after transplantation.

Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.

Background: Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown.

Methods: We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients).

Update on the classification, assessment of prognosis and therapy of Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) occurs as a result of obstruction of hepatic venous outflow at any level from the small hepatic veins to the junction of the inferior vena cava with the right atrium. Diagnosis can be difficult because of the wide spectrum of presentation of the disease and the varying severity of liver damage. The traditional classification of BCS--as fulminant, acute or chronic--is not prognostically useful.

Sustained, spontaneous disappearance of serum HCV-RNA under immunosuppression after liver transplantation for HCV cirrhosis.

Immunosuppression is a main determinant for the increased Hepatitis C Virus (HCV) replication after liver transplantation and the accelerated course of recurrent HCV liver disease. We present two patients both with diabetes, renal dysfunction with proteinuria converted to sirolimus therapy, who cleared serum HCV RNA without antiviral treatment. This is a potentially important observation that should stimulate study into factors that may help viral clearance from blood.

Survival following the development of ascites and/or peripheral oedema in primary biliary cirrhosis: a staged prognostic model.

Objective: Current prognostic models in primary biliary cirrhosis (PBC) have low precision, partly due to the restricted inclusion criteria of some cohorts used for modelling but also because of the prolonged natural course of the disease. It is hypothesized that better precision could be achieved with a staged model, using ascites or peripheral oedema as a new starting-point for prediction.

Material And Methods: The study was based on an established database of 289 consecutive patients, followed between 1977 and 1998.

Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its Lactobacillus mimic.

The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2(212-226) and hsp's is a cross-reactive target. Having found that this same motif is present only in beta-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity.

Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation.

In HCV cirrhotic patients after liver transplantation, survival and recurrence of HCV appears to be worsening in recent years. Donor age has been suggested as a cause. However, it is not clear if early and/or late mortality is affected and whether donor age is a key factor, as opposed to changes in immunosuppression.

Bleeding ectopic varices--treatment with transjugular intrahepatic porto-systemic shunt (TIPS) and embolisation.

Background/aims: Bleeding ectopic varices due to cirrhosis can be difficult to manage. We report our experience of uncontrolled bleeding from ectopic varices treated with transjugular intrahepatic porto-systemic shunt (TIPS).

Methods: We selected the 21 cirrhotics who underwent TIPS for bleeding ectopic varices from our database: Child-Pugh grade A (2), B (11) and C (8).

Xanthine oxidoreductase is present in bile ducts of normal and cirrhotic liver.

Xanthine oxidoreductase (XOR) is a widely distributed enzyme, involved in the metabolism of purines, which generates superoxide and is thought to be involved in free radical-generated tissue injury. It is present at high concentrations in the liver, from where it may be released during liver injury into the circulation, binding to vascular endothelium and causing vascular dysfunction. The cellular localization of the enzyme, essential to understanding its function, is, however, still debated.

Thromboelastography with citrated blood: comparability with native blood, stability of citrate storage and effect of repeated sampling.

Thromboelastography (TEG) with recalcified citrate blood is used as an alternative to native blood, but there is insufficient data regarding sample reliability and stability over time. Thus, TEG parameters of freshly drawn native blood were compared with those of recalcified citrated blood without celite in 10 healthy subjects, and the effect of repeated sampling over 240-min storage was evaluated. All TEG parameters following citrate storage remained stable between 30 min [clot formation time (k) = 7.

Liver transplantation in cirrhotic patients with small hepatocellular carcinoma: an analysis of pre-operative imaging, explant histology and prognostic histologic indicators.

Background: In recent years, liver transplantation in patients with hepatocellular cancers and cirrhosis has been restricted to those with small cancers (<5 cm for solitary and <3 cm for multifocal HCC with <3 nodules). The selection of patients for liver transplantation is based on pre-operative imaging. The accuracy of imaging correlated with explant histology and the effect of tumour stage has not been evaluated in this selected population.

Disease-specific cross-reactivity between mimicking peptides of heat shock protein of Mycobacterium gordonae and dominant epitope of E2 subunit of pyruvate dehydrogenase is common in Spanish but not British patients with primary biliary cirrhosis.

Previous studies on Spanish patients with Primary Biliary Cirrhosis (PBC) have shown extensive, disease-specific cross-reactivity between the 65-kDa heat shock protein (hsp65) of Mycobacterium gordonae and pyruvate dehydrogenase complex-E2 (PDC-E2), the major target of anti-mitochondrial antibody (AMA). Studies on a British population were unable to substantiate these findings. Having found that there is an excellent and almost unique match between the PDC-E2 autoepitope and a sequence in mycobacterial hsp65s, we tested the corresponding peptides by ELISA for cross-reactivity using sera from 90 PBC patients, 40 Spanish and 50 British, and 84 pathological controls.

A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients.

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir (5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12).

Targeting portal pressure measurements: a critical reappraisal.

Many of the complications of cirrhosis reflect the presence of portal hypertension, which is commonly expressed as the hepatic venous pressure gradient (HVPG). Baseline and repeat measurements of HVPG have been recommended for the management of patients with cirrhosis in the setting of pharmacologic prophylaxis of variceal bleeding and for gaining information about prognosis. However, published studies have demonstrated problems with the interpretation of the data on HVPG monitoring, making its use controversial.

Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis.

Background/aims: Previous studies on patients with primary biliary cirrhosis (PBC) have shown extensive cross-reactivity between the dominant B- and T-cell epitopes of human pyruvate dehydrogenase complex-E2 (PDC-E2), and microbial mimics. Such observations have suggested microbial infection as having a role in the induction of anti-mitochondrial antibodies, through a mechanism of molecular mimicry. However the biological significance of these cross-reactivities is questionable, because PDC-E2 is so highly conserved among various species.