Hepatic venous pressure gradient in sinusoidal obstruction syndrome: diagnostic value and link with histological lesions.

Background & Aims: Liver sinusoidal obstruction syndrome (SOS) is a well-established complication of myeloablative conditioning regimens used in hematopoietic stem cell transplantation. Hepatic venous pressure gradient (HVPG) >10 mmHg was described as an accurate diagnostic tool for SOS in the 1990s. However, epidemiology and presentation of SOS have dramatically changed.

Evidence for an Association Between Intrahepatic Vascular Changes and the Development of Hepatopulmonary Syndrome.

Background: Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect, defined by an increased alveolar-arterial oxygen gradient, induced by pulmonary vascular dilatations in the context of liver disease. The pathogenesis of HPS is poorly understood. Morphologic changes associated with HPS are unknown.

Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis.

Background & Aims: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis.

Methods: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy.

Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis.

Unlabelled: Microvesicles (MVs) are extracellular vesicles released by cells following activation or apoptosis. Some MV subpopulations augment with cirrhosis severity and contribute to portal hypertension. This study aimed at determining if plasma MV levels can estimate the presence of hepatic venous pressure gradient (HVPG) ≥10 mm Hg and predict mortality in patients with advanced chronic liver disease.

Non-invasive evaluation of portal hypertension using shear-wave elastography: analysis of two algorithms combining liver and spleen stiffness in 191 patients with cirrhosis.

Background: Two algorithms based on sequential measurements of liver and spleen stiffness using two-dimensional shearwave elastography (2D-SWE) have been recently proposed to estimate clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg) in patients with cirrhosis, with excellent diagnostic accuracy.

Aim: To validate externally these algorithms in a large cohort of patients with cirrhosis.

Methods: One hundred and ninety-one patients with stable cirrhosis (Child-Pugh class A 39%, B 29% and C 31%) who underwent liver and spleen stiffness measurements using 2D-SWE at the time of HVPG measurement were included.

A prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis.

Unlabelled: The diagnosis of alcoholic hepatitis (AH) often requires a transjugular liver biopsy (TJLB), a procedure that is not always readily accessible. We analyzed plasma biomarkers to estimate the presence of histological features of AH among patients with clinical suspicion of AH. Using enzyme-linked immunosorbent assay, we tested M65 and M30 (circulating fragments of cytokeratin-18) and their respective fraction carried by microvesicles (MVs), CCL20 and TREM1.

Type I interferon signaling in systemic immune cells from patients with alcoholic cirrhosis and its association with outcome.

Background & Aims: In immune cells, constitutively and acutely produced type I interferons (IFNs) engage autocrine/paracrine signaling pathways to induce IFN-stimulated genes (ISGs). Enhanced activity of IFN signaling pathways can cause excessive inflammation and tissue damage. We aimed to investigate ISG expression in systemic immune cells from patients with decompensated alcoholic cirrhosis, and its association with outcome.

Lack of clinical or haemodynamic rebound after abrupt interruption of beta-blockers in patients with cirrhosis.

Background: Beta-blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta-blockers is based on an animal study and on isolated case reports of variceal bleeding.

Aim: To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta-blockers.

Prospective comparison of spleen and liver stiffness by using shear-wave and transient elastography for detection of portal hypertension in cirrhosis.

Purpose: To prospectively compare the technical success rate and accuracy of shear-wave elastography (SWE) and transient elastography (TE) for the detection of clinically significant portal hypertension (PH) in patients with advanced cirrhosis who are undergoing hepatic vein pressure gradient (HVPG) measurements.

Materials And Methods: The institutional ethics committee approved the study, and written informed consent was obtained. Seventy-nine consecutive patients with cirrhosis who were undergoing SWE and TE at the time of HVPG measurement were studied.

Effect of recombinant Factor VIIa on outcome of acute variceal bleeding: an individual patient based meta-analysis of two controlled trials.

Background & Aims: Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data with special focus on high risk patients.

Methods: The primary outcome measure was the effect of rFVIIa on a composite five day endpoint: failure to control bleeding, 5-day rebleeding or death.

Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial.

Importance: Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown.

Objective: To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.

Plasma fibroblast growth factor 23 concentration is increased and predicts mortality in patients on the liver-transplant waiting list.

High plasma fibroblast growth factor-23 (FGF23) concentration predicts the risk of death and poor outcomes in patients with chronic kidney disease or chronic heart failure. We checked if FGF23 concentration could be modified in patients with end stage liver disease (ESLD) and predict mortality. We measured plasma FGF23 in 200 patients with ESLD registered on a liver transplant waiting list between January 2005 and October 2008.

Gene- and exon-expression profiling reveals an extensive LPS-induced response in immune cells in patients with cirrhosis.

Background & Aims: Lipopolysaccharide (LPS)-expressing bacteria cause severe inflammation in cirrhotic patients. The global gene response to LPS is unknown in cirrhotic immune cells.

Methods: Gene-expression profiling using Affymetrix Human Exon Array analyzed the expression of 14,851 genes in LPS-stimulated peripheral blood mononuclear cells (PBMCs) from 4 patients with cirrhosis and 4 healthy subjects.

Severe hyponatremia is a better predictor of mortality than MELDNa in patients with cirrhosis and refractory ascites.

Background & Aims: The MELDNa score was developed to improve the prognostic value of the MELD score in cirrhosis and was built for serum sodium concentrations numerically capped between 125 and 140 mmol/L. This model is not validated in a well-defined population of patients with cirrhosis and refractory ascites in whom severe hyponatremia (≤ 125 mmol/L) is frequent. This study assessed the prognostic value of severe hyponatremia and the MELDNa score in these patients.

Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis.

Background & Aims: Circulating membrane-shed microparticles (MPs) participate in regulation of vascular tone. We investigated the cellular origins of MPs in plasma from patients with cirrhosis and assessed the contribution of MPs to arterial vasodilation, a mechanism that contributes to portal hypertension.

Methods: We analyzed MPs from blood samples of 91 patients with cirrhosis and 30 healthy individuals (controls) using flow cytometry; their effects on the vascular response to vasoconstrictors were examined in vitro and in vivo.

Hemodynamics and pharmacokinetics of tezosentan, a dual endothelin receptor antagonist, in patients with cirrhosis.

Purpose: To assess the effect of tezosentan, a parenteral dual ET receptor antagonist, on splanchnic and systemic hemodynamics in patients with cirrhosis. In addition, the safety, pharmacokinetics, and pharmacodynamics of tezosentan were evaluated.

Methods: The population consisted of patients with cirrhosis with clinically significant portal hypertension.

Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89-IgA and IgG-IgA complexes: common mechanisms for distinct diseases.

Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1, were detected in the serum of patients with advanced alcoholic cirrhosis.

Early TIPS with covered stents in high-risk patients with cirrhosis presenting with variceal bleeding: are we ready to dive into the deep end of the pool?

Background & Aims: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients.

Methods: We randomly assigned, within 24h after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 h after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3-5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients).

Changes in autophagic response in patients with chronic hepatitis C virus infection.

Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients.

Detection of bacterial DNA in serum and ascitic fluid of asymptomatic outpatients with cirrhosis and non-neutrocytic ascites.

Background And Aims: Bacterial DNA (bactDNA) has been found in serum and ascitic fluid (AF) of 30-40% of hospitalized patients with cirrhosis and non-neutrocytic ascites, but its prevalence in outpatients is unknown. The aim of this prospective study was to investigate the presence of bactDNA in AF and serum among cirrhotic outpatients with non-neutrocytic ascites.

Methods: Thirty-one consecutive patients with cirrhosis and non-neutrocytic ascites, who underwent therapeutic paracentesis in our outpatient clinic, were enrolled over a 13-week period.

Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study.

Background & Aims: In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. A self control cross-over study was performed.

Glycogen synthase kinase 3 involvement in the excessive proinflammatory response to LPS in patients with decompensated cirrhosis.

Background & Aims: In decompensated cirrhosis, the early innate immune response to the Toll-like receptor 4 (TLR4) agonist, lipopolysaccharides (LPS), is characterized by a hyper-production of pro-inflammatory cytokines and hypo-production of the anti-inflammatory cytokine IL-10. In LPS-stimulated non-cirrhotic immune cells, the constitutively active glycogen synthase kinase (GSK) 3 favors pro- vs. anti-inflammatory cytokines, by acting on gene induction.

Noninvasive assessment of portal hypertension in patients with cirrhosis.

Severe portal hypertension is responsible for complications and death. Although measurement of the hepatic venous pressure gradient is the most accurate method for evaluating the presence and severity of portal hypertension, this technique is considered invasive and is not routinely performed in all centers. Several noninvasive techniques have been proposed to measure portal hypertension.