Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis.

Background & Aims: In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites.

Methods: We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders.

Child-Turcotte-Pugh Class is Best at Stratifying Risk in Variceal Hemorrhage: Analysis of a US Multicenter Prospective Study.

Goals/background: Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality.

Study: Prospective 15-center US cohort of patients with cirrhosis presenting with endoscopically proven AVH, all of whom received antibiotics, vapreotide (a somatostain analog) infusion and endoscopic band ligation.

The interpretation of hepatic venous pressure gradient tracings - excellent interobserver agreement unrelated to experience.

Background And Aims: The hepatic venous pressure gradient (HVPG) plays an important role in the diagnosis, prognosis and therapy of patients with cirrhosis and portal hypertension. One barrier to its widespread use is the potential for a low reproducibility. We aimed to evaluate the interobserver agreement in the interpretation of optimally acquired HVPG tracings from patients with cirrhosis and different degrees of portal hypertension.

Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments.

Among the common complication of cirrhosis portal hypertension witnessed a major improvement of prognosis during the past decades. Principally due to the introduction of rational treatments based on new pathophysiological paradigms (concepts of thought) developed in the 1980s. The best example being the use of non-selective beta-blockers and of vasopressin analogs, somatostatin, and its analogs.

Prevention of portal hypertension: from variceal development to clinical decompensation.

Pharmacological treatment of portal hypertension (PH) has been exclusively devoted to gastroesophageal varices-related events at different frameworks, including prophylactic, emergency, or preventive therapy. The goals of treatment are to avoid the first bleeding episode, stop active bleeding, and prevent bleeding recurrence, respectively. The objective of preprimary prophylaxis (PPP) is to avoid variceal development, and therefore it necessarily deals with patients with cirrhosis at earlier stages of the disease.

Novel inflammatory biomarkers of portal pressure in compensated cirrhosis patients.

Unlabelled: The rationale for screening inflammatory serum biomarkers of the hepatic vein pressure gradient (HVPG) is based on the fact that portal hypertension is pathogenically related to liver injury and fibrosis, and that in turn these are associated with the activation of inflammatory pathways. This was a nested cohort study in the setting of a randomized, clinical trial to assess the development of gastroesophageal varices (GEV) (N Engl J Med 2005;353:2254). Patients had cirrhosis and portal hypertension but did not have GEV.

Hepatic venous pressure gradient measurement in pre-primary and primary prophylaxis of variceal hemorrhage.

Pharmacological therapy of portal hypertensión can be accomplished according to different objectives. Among them, pre-primary prophylaxis aims to avoid / delay esophageal varices development while the target of primary prophylaxis is protection against first variceal bleeding. Hepatic venous pressure gradient (HVPG) measurement closely reflects portal pressure in most liver diseases whith predominant sinusoidal network involvement.

Portal hypertension in children: expert pediatric opinion on the report of the Baveno v Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension.

Complications of portal hypertension in children lead to significant morbidity and are a leading indication for consideration of liver transplantation. Approaches to the management of sequelae of portal hypertension are well described for adults and evidence-based approaches have been summarized in numerous meta-analyses and conferences. In contrast, there is a paucity of data to guide the management of complications of portal hypertension in children.

Quantitative histological-hemodynamic correlations in cirrhosis.

Unlabelled: We have previously shown, in a semiquantitative analysis of liver biopsies showing cirrhosis, that thickness of fibrous septa separating cirrhotic nodules and small size of cirrhotic nodules correlated independently with portal pressure (as determined by the hepatic venous pressure gradient; HVPG) and were independent predictors of the presence of clinically significant portal hypertension (PH). This study aimed to confirm these results using quantitative analysis of these biopsies using digital image analysis. Biopsies of 42 patients with cirrhosis and HVPG measurements within 6 months of the biopsy were included in the study.

Intestinal and plasma VEGF levels in cirrhosis: the role of portal pressure.

Increased levels of intestinal VEGF are thought to worsen portal hypertension. The cause of the increase in the level of intestinal VEGF found during cirrhosis is not known. The aim of this study is to demonstrate a relationship between portal pressure (PP) and intestinal/ plasma VEGF levels in different stages of fibrosis/cirrhosis.

Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis.

Unlabelled: Obesity is associated with an aggressive course in chronic viral hepatitis; however, its impact in the development of clinical decompensation (CD) in patients with established cirrhosis is uncertain. We evaluated the role of obesity, in relationship to other recognized predictors, in the development of CD in patients with compensated cirrhosis. The study population, a subset of patients included in a randomized trial of beta-blockers in the prevention of varices in whom data on body mass index (BMI) was available, consisted of 161 patients with compensated cirrhosis.

Reticulon 4B (Nogo-B) is a novel regulator of hepatic fibrosis.

Unlabelled: Nogo-B, also known as Reticulon 4B, plays important roles in vascular injuries. Its function in the liver is not understood. The aim of this study was to characterize Nogo-B in liver fibrosis and cirrhosis.

A distinct nitric oxide and adenosine A1 receptor dependent hepatic artery vasodilatatory response in the CCl-cirrhotic liver.

Unlabelled: Increase of portal venous vascular resistance is counteracted by decrease of hepatic arterial vascular resistance (hepatic arterial buffer response). This process is mediated by adenosine in normal livers. In cirrhosis, hepatic arterial vascular resistance is decreased but the involvement of adenosine in this process is unknown.

Sildenafil has no effect on portal pressure but lowers arterial pressure in patients with compensated cirrhosis.

Background & Aims: The reduction of portal pressure in patients with early compensated cirrhosis may be more responsive to drugs increasing intrahepatic vasodilatation than those reducing portal venous inflow. The phosphodiesterase-5 (PDE-V) inhibitor sildenafil can potentially reduce portal pressure by decreasing intrahepatic resistance, but its systemic vasodilatory effects may be deleterious. The aim of this study was to evaluate the effect of sildenafil on systemic and portal hemodynamics in an open-label pilot study.

Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis.

Background/aims: A total of 213 patients with compensated cirrhosis, portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices. Predictors of the development of hepatocellular carcinoma (HCC), including hepatic venous pressure gradient (HVPG) were analyzed.

Methods: Baseline laboratory tests, ultrasound and HVPG measurements were performed.

Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis.

Background & Aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance.

Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices.

Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition.

The Rho/ROCK pathway is activated in differentiated hepatic stellate cells (HSCs) and is necessary for assembly of actin stress fibers, contractility, and chemotaxis. Despite the importance of this pathway in HSC biology, physiological inhibitors of the Rho/ROCK pathway in HSCs are not known. We demonstrate that adenosine induces loss of actin stress fibers in the LX-2 cell line and primary HSCs in a manner indistinguishable from Rho/ROCK inhibition.

Nitric oxide and vascular remodeling modulate hepatic arterial vascular resistance in the isolated perfused cirrhotic rat liver.

Background/aims: Hepatic arterial resistance is modulated by the hepatic arterioles but the role of NO and vascular remodeling in hepatic arterial resistance in cirrhosis is unknown.

Methods: Cirrhosis was induced by CCl(4) or BDL. Using a bivascular liver perfusion dose-responses curves to methoxamine were obtained from the hepatic artery in absence and presence of L-NMMA.

The role of hepatic arterial flow on portal venous and hepatic venous wedged pressure in the isolated perfused CCl4-cirrhotic liver.

In cirrhosis, hepatic venous pressure gradient is used to measure portal venous and sinusoidal pressures, as well as drug-induced decreases of elevated pressures. The aim of this study was to investigate the influence of hepatic arterial flow (HAF) changes on portal venous perfusion (PVPP) and wedged hepatic venous pressure (WHVP). Normal and CCl4-cirrhotic rats were subjected to a bivascular liver perfusion with continuous measurements of PVPP, WHVP, and hepatic arterial perfusion pressure.

Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis.

Unlabelled: Current guidelines recommend esophagogastroduodenoscopy (EGD) in patients with cirrhosis to screen for gastroesophageal varices (GEV). Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV. There is no agreement regarding a specific platelet count (PLT) that can reliably predict GEV.