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Background In cirrhosis, portal hypertension is associated with a spectrum of renal dysfunction that has significant implications for morbidity and mortality. Aim To discuss recent progress in the patho-physiological mechanisms and therapeutic options for portal hypertension-related renal dysfunction. Methods A literature search using Pubmed was performed. Results Portal hypertension-related renal dysfunction occurs in the setting of marked neuro-humoral and circulatory derangement. A systemic inflammatory response is a pathogenetic factor in advanced disease. Such physiological changes render the individual vulnerable to further deterioration of renal function. Patients are primed to develop acute kidney injury when exposed to additional 'hits', such as sepsis. Recent progress has been made regarding our understanding of the aetiopathogenesis. However, treatment options once hepatorenal syndrome develops are limited, and prognosis remains poor. Various strategies to prevent acute kidney injury are suggested. Conclusion Prevention of acute kidney injury in high risk patients with cirrhosis and portal hypertension-related renal dysfunction should be a clinical priority. [ABSTRACT FROM AUTHOR]

Background Liver transplantation is potentially a life-saving therapeutic intervention for patients with portopulmonary hypertension and hepatopulmonary syndrome. However, due to limited data, listing criteria for patients with these conditions have not been clearly established. Indeed, this has led some to speculate that transplantation may not be appropriate in cases of moderate-to-severe portopulmonary hypertension and severe hepatopulmonary syndrome. Aim To critically discuss the utility of LT for the treatment of hepatopulmonary syndrome and portopulmonary hypertension. Methods A literature search was conducted in 2012 on PubMed, Ovid Embase, Ovid Medline and Scopus using the following search terms: hepatopulmonary syndrome, portopulmonary hypertension, pulmonary arterial hypertension, liver transplantation. Relevant manuscripts were included in the review. Results Liver transplantation has established itself as an effective treatment for selected patients with hepatopulmonary syndrome and portopulmonary hypertension. A multidisciplinary team approach incorporating focused strategies (both pre- and post-operatively) aimed at improving oxygenation in patients with hepatopulmonary syndrome has led to a dramatic improvement in patient outcomes. Additionally, careful patient selection and the use of targeted pulmonary vascular therapies are successfully being used to treat portopulmonary hypertension and 'bridge' patients to successful liver transplantation. Conclusions Liver transplantation is an effective therapy for patients with hepatopulmonary syndrome and portopulmonary hypertension. However, rigorous screening and early identification of these conditions allied with aggressive pre-operative optimisation of physiology and diligent post-operative care are imperative to ensuring a good outcome. [ABSTRACT FROM AUTHOR]

Background and aims: Increased endothelin (ET)-1 activity may contribute to the complications of cirrhosis and portal hypertension. The aim of this study was to assess the systemic and portal haemodynamic effects of selective ET-A and ET-B receptor antagonism in patients with cirrhosis. Methods: Sixteen patients with cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3)) underwent 24 studies with infusions of: (A) selective ET-A antagonist, BQ- 123 (n = 8), at 1000 and 3000 nmol/min; (B) selective ET-B antagonist, BQ-788 (n = 8), at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind randomised manner. Haemodynamic measurements were performed through pulmonary artery, hepatic venous, and femoral artery catheters. Results: Baseline patient characteristics were well matched. Compared with placebo, BQ-123 decreased mean arterial pressure (MAP -15 (11) mm Hg (-18%); p<0.02) and pulmonary vascular resistance index (PVRI -81 (54) dyn×s×m²/cm5 (-64%); p<0.05), with no effect on hepatic venous pressure gradient (HVPG), cardiac index (Cl), or systemic vascular resistance index (SVRI). Compared with placebo, BQ-788 increased MAP (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn×s×m²/ cm5 (+50%); p<0.05), reduced Cl (-1.0 (0.4) l/min/m² (-29%); p = 0.05) with no effect on HVPG or PVRI. Conclusions: ET-1 contributes to maintenance of systemic and pulmonary haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In this group of patients, the use of selective ET-A and ET-B antagonists for the management of variceal haemorrhage is likely to be limited. [ABSTRACT FROM AUTHOR]

Endothelin (ET)-1 synthesis and receptor expression are increased in the injured liver. To date, there are no studies to examine the role of ET-1 on systemic and portal haemodynamics in patients with cirrhosis. For the first time, researchers have shown that ET-1 contributes to the maintenance of systemic vascular tone in patients with cirrhosis. In addition, the pulmonary effects of ET-A receptor blockade suggest a possible therapeutic role in the portopulmonary hypertension. The aim of the study is to assess the systemic and portal haemodynamic effects of selective ET-A and ET-B receptor antagonism in patients with cirrhosis and to elucidate the possible therapeutic value of selective endothelin receptor antagonism in portal hypertension.