Hemodynamic alterations in liver cirrhosis.

In cirrhotic patients, portal hypertension is often associated with a hyperdynamic circulatory syndrome, with high cardiac output and reduced systemic vascular resistance and arterial pressure. The hyperdynamic circulatory syndrome is due to arterial vasodilation that mainly occurs in the splanchnic circulation, while vascular resistance in the other circulatory districts is normal or increased, accordingly with the degree of portal hypertension, liver impairment and activation of the renin-aldosterone and sympathetic nervous system. The mechanism(s) leading to splanchnic vasodilation is unclear.

Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis.

Background & Aims: Because aldosterone-dependent sodium and water retention contribute to portal hypertension, the safety and effect of an antialdosteronic drug (Kcanrenoate) have been evaluated on the occurrence of de novo appearance of ascites and the development of esophageal varices or the progression of small varices.

Methods: Inclusion criteria were as follows: Child-Pugh A viral pre-ascitic cirrhosis, with either F1 esophageal varices or no varices, but endoscopic and/or ultrasound evidence of portal hypertension. Thirteen Italian Liver Units prospectively enrolled 120 patients randomized to receive double-blind either Kcanrenoate (100 mg/day; 66 patients) or placebo (54 patients).

Uveitis in autoimmune hepatitis: a case report.

In this case report we describe for the first time an association between autoimmune hepatitis (AIH) and uveitis, without any doubts about other possible etiologies, such as HCV, since all the old reports describe the association of AIH with iridocyclitis before tests for HCV-related hepatitis could be available. A 38-year-old businessman with abnormal liver function tests and hyperemia of the bulbar conjunctiva was admitted to the hospital. Six years before admission, the patient presented with persistent fever, arthralgias, conjunctival hyperemia, leukocytosis and increased ESR, referred to acute rheumatic fever.

Thrombopoietin stimulates migration and activates multiple signaling pathways in hepatoblastoma cells.

Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence.

Survival and prognostic factors in patients with hepatocellular carcinoma treated by percutaneous ethanol injection: a 10-year experience.

The treatment of early and intermediate stage hepatocellular carcinoma (HCC) is still debated. Surgical treatments are considered to be the only curative procedures available, and only for a minority of patients. Percutaneous ethanol injection (PEI) is an established technique for the ablation of HCC nodules, and shows survival rates similar to those of resection.

Hemodynamic derangement and cardiac dysfunction in cirrhosis.

Liver cirrhosis is characterized by a long course that lasts between 15 and 20 years. The natural history of this disease depends mainly on the occurrence and progression of single complications which are today more fully understood and therefore more treatable. More specifically, those complications involving hemodynamic mechanisms have been extensively studied in recent years.

Differential requirement of members of the MAPK family for CCL2 expression by hepatic stellate cells.

Hepatic stellate cells (HSC) coordinate the liver wound-healing response through secretion of several cytokines and chemokines, including CCL2 (formerly known as monocyte chemoattractant protein-1). In this study, we evaluated the role of different proteins of the MAPK family (ERK, p38(MAPK), and JNK) in the regulation of CCL2 expression by HSC, as an index of their proinflammatory activity. Several mediators activated all three MAPK, including TNF, IL-1, and PDGF.

The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C.

Background And Aims: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied.

Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis.

Advanced cirrhosis is associated with reduced platelet function and altered renal function and sodium handling. Arachidonic acid (AA) metabolites contribute to platelet aggregation and to maintain the response to diuretics in advanced cirrhosis. In the present study, we tested the effects of a dietary supplementation for 8 weeks with a triacylglycerol (triglyceride) enriched in AA (ARASCO; 4 g/day) or oleic acid (OA) on plasma and membrane fatty acid composition, platelet aggregation and renal prostaglandin (PG) metabolism.

Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.

Hepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B-cell lymphoproliferative disorders (LPDs). The t(14;18) translocation may play a pathogenetic role. Limited data are available regarding the effects of antiviral therapy on rearranged B-cell clones.

Antifibrogenic effects of canrenone, an antialdosteronic drug, on human hepatic stellate cells.

Background & Aims: Several lines of evidence indicate that aldosterone antagonists may exert direct antifibrogenic effects. The aim of this study was to evaluate the possible direct antifibrogenic effects of canrenone, the active metabolite of spironolactone, in activated human hepatic stellate cells.

Methods: The effects of canrenone were assessed on platelet-derived growth factor-induced mitogenic and chemotactic effects and the increased de novo synthesis of different extracellular matrix components induced by transforming growth factor-beta1.

Cell adhesion regulates platelet-derived growth factor-induced MAP kinase and PI-3 kinase activation in stellate cells.

The biologic effects of growth factors are dependent on cell adhesion, and a cross talk occurs between growth factors and adhesion complexes. The aim of the present study was to evaluate the influence of cell adhesion on the major intracellular signaling pathways elicited by platelet-derived growth factor (PDGF) in hepatic stellate cells (HSC). PDGF signaling was investigated in an experimental condition characterized by lack of cell adhesion for different intervals of time.

Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration.

Background/aims: Migration of activated hepatic stellate cells (HSC) is a key event in the progression of liver fibrosis. Little is known about transmembrane proteins involved in HSC motility. Tetraspanins (TM4SF) have been implicated in cell development, differentiation, motility and tumor cell invasion.

Impaired sympathetic regulation of cerebral blood flow in patients with cirrhosis of the liver.

Continuous recording of mean cerebral blood flow velocity (MCBFV) by Doppler ultrasound allows detection of low-frequency (LF) oscillations, which reflect sympathetic activity in the cerebral circulation. To establish whether the sympathetic drive to the cerebral circulation is altered in patients with compensated cirrhosis, and, if so, where alterations take place, LF oscillations of MCBFV, heart rate (RR interval) and systolic arterial pressure (SAP) were analysed in 10 patients with cirrhosis and 10 control subjects during supine rest and on stimulation of carotid baroreceptors using a neck chamber applying sinusoidal suction. Bivariate analysis was used to study the relationship between pairs of oscillations.

Up-regulated expression of fractalkine and its receptor CX3CR1 during liver injury in humans.

Background/aims: Little is known about the role of fractalkine (CX3CL1) in the liver. The aim of this study was to investigate the expression patterns of fractalkine and its receptor CX3CR1 in normal human liver and in conditions of injury.

Methods: Distribution and expression of fractalkine and its receptor were investigated using immunohistochemistry, in situ hybridization, flow cytometry and reverse transcriptase-polymerase chain reaction.

Cardiovascular effects of canrenone in patients with preascitic cirrhosis.

In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (PNE) when on a 150-mmol/d-sodium diet (baseline), after 1 month on canrenone (100 mg/d) plus a 40-mmol/d-sodium diet and after 1 month on canrenone plus a 150-mmol/d-sodium diet.