System In Cirrhosis Research Articles

Coagulation disorders in liver cirrhosis - Diagnostics and management

Patients with liver cirrhosis often exhibit complex alterations in their hemostatic system that can be associated with both bleeding and thrombotic complications. While prophylactic correction of abnormal coagulation parameters should be avoided, an individualized approach is recommended prior to invasive procedures, whereby specific preventive measures to stabilize hemostasis should be based on the periprocedural bleeding risk. While the haemostatic system of patients with compensated cirrhosis is often in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic factors, a decompensation of liver cirrhosis can lead to destabilization of this fragile equilibrium. Since conventional coagulation tests do not adequately capture the complex changes in the hemostatic system in cirrhosis, functional analysis methods such as viscoelastic tests or thrombin generation assays can be used for evaluating the coagulation status. This review describes the underlying pathophysiological changes in the hemostatic system in liver cirrhosis, provides an overview of diagnostic methods and discusses therapeutic measures in case of bleeding and thrombotic complications.

Direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis: What is the evidence?

In recent years, the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved. Currently, it is known that in cirrhotic patients, the hemostatic system is rebalanced, which involves coagulation factors, fibrinolysis and platelets. These alterations disrupt homeostasis, skewing it toward a procoagulant state, which can lead to thromboembolic manifestations, especially when hemodynamic and endothelial factors co-occur, such as in the portal vein system in cirrhosis. Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease, prognosis of cirrhotic patients and success of liver transplantation. It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function. Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis. In chronic portal vein thrombosis, the role of anticoagulant therapy is still unclear. Traditional anticoagulants, vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis. In the last ten years, direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolic-related diseases, but evidence on their use in cirrhotic patients is very limited. The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.

Commentary on: Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial

Commentary on: Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial

Predictive Value of a Noninvasive Serological Hepatic Fibrosis Scoring System in Cirrhosis Combined with Oesophageal Varices

Objective In recent years, the noninvasive serological scoring system has become a research hotspot in predicting hepatic fibrosis and has achieved good results. However, it has rarely been applied to the prediction of oesophageal varices. The aim of the study was to evaluate the predictive value of the four following scoring systems in cirrhosis combined with oesophageal varices: aspartate and platelet ratio index (APRI), aspartate aminotransferase-alanine aminotransferase ratio (AAR), FIB-4, and S index. Methods A total of 153 patients with cirrhosis were categorized into groups with or without oesophageal varices. In addition, cirrhosis patients with oesophageal varices were further divided into mild, moderate, and severe grades. The rank sum test was used to compare the significant differences of APRI, AAR, FIB-4, and S index between the two groups of cirrhosis patients with or without oesophageal varices. A ROC curve was generated to compare the area under the curve of the three groups and to obtain the corresponding optimal prediction value. Moreover, multivariate logistic regression analysis was employed to assess the predictive factors for cirrhosis combined with oesophageal varices. Results 44 patients had no oesophageal varices and 108 patients had oesophageal varices. Of the 108 patients with oesophageal varices, 43 were mild, 32 were moderate, and 33 were severe. The rank sum test indicated that the APRI, FIB-4, and S index were statistically significant between two groups (P < 0.05), while no significant difference was detected in terms of AAR between the two groups (P > 0.05). In addition, all four scoring systems were statistically significant between nonoesophageal varices group and severe oesophageal varices group (P < 0.05). In the ROC curve of oesophageal varices, the AUC values of APRI, FIB-4, and S index for predicting oesophageal varices were 0.681, 0642, and 0.673, respectively. However, in the ROC curve of severe oesophageal varices, the AUC values of APRI, AAR, FIB-4, and S index were 0.729, 0.648, 0.673, and 0.695, respectively. Multivariate logistic regression analysis indicated that APRI and FIB-4 were predictors of disease progression (P < 0.05). Conclusion AAR harboured a poor predictive value for oesophageal varices, APRI can be used as a reference index for the prediction of severe oesophageal varices, and the S index harboured potential value in predicting the degree of progression of cirrhosis.

Local prothrombotic state in portal venous system in cirrhosis

Local prothrombotic state in portal venous system in cirrhosis

Correlation of Serum Prolactin Level to Child Pugh Scoring System in Cirrhosis of Liver.

With the growing incidence of liver cirrhosis among Asians, the use of a biomarker such as prolactin, indicates the severity of the disease, its complications and serves as a tool for early intervention. To compare the efficacy of serum prolactin to the Child Pugh scoring system in cirrhosis of the liver and establish that serum prolactin is an early marker for complications of cirrhosis of the liver. This was a comparative study on 60 patients admitted to the Department of General Medicine, KIMS from June 2014 to November 2015. Patients above the age of 18 years, diagnosed to have cirrhosis of the liver were included in the study. Patients having conditions/medications known to elevate prolactin levels such as cranial surgery/irradiation, pituitary disease, chronic renal failure, drugs such as neuroleptics, metoclopramide, aldosterone antagonists, etc., were excluded. All the patients were subjected to the routine work up for chronic liver disease including serum prolactin levels at admission. In the present study, the most common cause of cirrhosis was found to be alcohol (73%). The complications of cirrhosis were portal hypertension in 50 (83.3%), oesophageal varices in 39 (65%) with upper GI bleed in 22 (36.7%) patients, hepatic encephalopathy in 15 (25%) patients. Serum prolactin levels were elevated in 73% of the patients with highest levels of serum prolactin (>35 ng/ml) seen in patients of Class 'C' Child Pugh. Elevated serum prolactin was found in 66.7% of the patients with oesophageal varices, 90.9% patients with upper GI bleed and in all patients with hepatic encephalopathy (100%). Serum prolactin levels correlated with the Child Pugh score in predicting the severity of the disease. Patients with a higher serum prolactin at admission had a greater incidence of complications of cirrhosis. Hence, serum prolactin is an inexpensive, non invasive blood marker which may be used to estimate the severity and the complications of cirrhosis.

Hemostasis system correction in patients with cirrhosis

Nature of violations of hemostasis system in cirrhosis is difficult, often unpredictable and concerns all its links. Thus both bleedings and thrombosis are possible. Disease decompensation is accompanied by deeper haemostatic imbalance towards thrombophilia. It is connected with that hepatocytes is the main place of synthesis vitamin K dependent pro- and anticoagulant proteins. Respectively, medical tactics should be directed on correction of pathogenetic mechanisms of haemostatic imbalance. Aim. To estimate influence Vikasolum on pro- and anticoagulant link of hemostasis in patients with cirrhosis. Methods and results. 30 patients with cirrhosis were under supervision. Patients received Vikasolum in dose 1.0 ml of 0.01 % solution intramuscularly 3 times a day within 3-4 days, with shift to oral route – on 1 tablet (0.015) twice a day up to 2 weeks. Estimation of procoagulant unit included determination of the number of platelets, prothrombin index, activated partial thromboplastin time, blood-coagulation factor F VIII, fibrinogen levels, «B» and D-dimer fibrinogen. Anticoagulant system was evaluated with activity of coagulation inhibitor of protein C. It is shown that hemostasis condition is characterised by an imbalance towards hyper coagulation on the ground of normal or hyperactivated blood-coagulation factor F VIII in patients with cirrhosis. At appointment of vikasoli increase levels of a protrombin index and the protein C is noted. Conclusion. Vikasolum intake promotes normalisation of a haemostatic imbalance, vitamin K dependent pro- and antikoagulyant factors synthesis.

Cirrhotic cardiomyopathy: Implications for the perioperative management of liver transplant patients.

Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a definitive clinical entity. In the setting of liver cirrhosis, it is characterized by a blunted inotropic and chronotropic response to stress, impaired diastolic relaxation of the myocardium and prolongation of the QT interval in the absence of other known cardiac disease. A key pathological feature is the persistent over-activation of the sympathetic nervous system in cirrhosis, which leads to down-regulation and dysfunction of the β-adrenergic receptor. Diagnosis can be made using a combination of echocardiography (resting and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead electrocardiogram and measurement of biomarkers. There are significant implications of cirrhotic cardiomyopathy in a number of clinical situations in which there is an increased physiological demand, which can lead to acute cardiac decompensation and heart failure. Prior to transplantation there is an increased risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic portosystemic shunt insertion and increased risk of arrhythmias during acute gastrointestinal bleeding. Liver transplantation presents the greatest physiological challenge with a further risk of acute cardiac decompensation. Peri-operative management should involve appropriate choice of graft and minimization of large fluctuations in preload and afterload. The avoidance of cardiac failure during this period has important prognostic implications, as there is evidence to suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy.

Management of disordered hemostasis and coagulation in patients with cirrhosis.

Introduction The coagulopathy of cirrhosis and portal hypertension is complicated and often challenging to predict. While patients with cirrhosis are clearly prone to bleed, there is often a concurrent paradoxical propensity toward thrombosis. A finely regulated balance between bleeding and thrombosis is maintained in the healthy individual. When vascular breach or injury occurs, the clotting system activates (Fig. 1). In cirrhosis, a more precarious balance exists with heightened sensitivity to exogenous factors. 7 This rebalanced system is maintained by compensatory mechanisms, such as elevated levels of procoagulant factors like von Willebrand factor, FVIII, and reduced levels of anticoagulant factors like protein C. Additionally, a fibrinolysis pathway (not shown) governs clot dissolution, which may be altered in cirrhosis. Factors like infection, renal dysfunction, and endothelial injury can alter this balance. Tests commonly used to predict bleeding such as the prothrombin time/international normalized ratio do not reliably predict bleeding risk in patients with cirrhosis. Other, more global measures are currently under study and available in some centers (e.g., thromboelastography, thrombin generation assay), but there is no single test available today that can accurately predict bleeding or thrombosis tendency in patients with cirrhosis. Management of the bleeding cirrhosis patient is well studied with established clinical guidelines. Treating cirrhosis patients with thrombosis is less defined and clinicians must currently rely on expert recommendation, inference, and extrapolation from data in other patient populations. As our understanding of the intricacies of the coagulation system in cirrhosis develops, new tests and treatments for thrombosis and bleeding will likely emerge.

The insulin like growth factor system in cirrhosis. Relation to changes in body composition following adrenoreceptor blockade

ObjectiveCirculating levels of IGF-I and IGFBP-3 are low in cirrhosis and are related to liver dysfunction. Metabolic disturbances include malnutrition with altered body composition and osteopenia. Since the effects of IGF-I may be associated to changes in body composition and bone mineral content (BMC) in cirrhotic patients, we investigated the relations between changes in the IGF-system and body composition and the effects of long-term alpha- and beta‐blockade. DesignThe study was designed as a combined cross-sectional and prospective randomised controlled study of 62 patients with cirrhosis. Twenty-three of these patients were randomised to treatment with beta- or combined alpha/beta-blocker for 3months. Haemodynamics, body composition, and systemic and hepatic IGF-I and IGFBP-3 levels were determined in all patients. In the subgroup changes in body composition and IGF-I/IGFBP-3 levels after 3months of beta- or combined alpha/beta-blockade were additionally examined. ResultsBoth the hepatic and the systemic IGF systems were suppressed and correlated with liver dysfunction and anthropometrics (p<0.05–0.001). Multivariate analyses revealed that changes in the IGF-system were determined by metabolic liver dysfunction as well as anthropometrics. In the follow-up study, hepatic venous IGF-I (p=0.05) and IGFBP-3 (p=0.02) increased after 3months only in the group who received beta-blocker. In both groups, fat body mass increased significantly after 3months (p=0.05–0.001). ConclusionsIn cirrhosis, the IGF-system is associated with both anthropometrics and synthetic capacity of the liver. Changes in IGF-I relate to changes in anthropometrics and there seems to be a differential effect depending on the type of adrenoreceptor blockade. Future longitudinal studies are needed to unravel these mechanisms in cirrhosis.

Comparison of endothelin receptors in normal versus cirrhotic human liver and in the liver from endothelial cell-specific ETB knockout mice

AimsEndothelin (ET) antagonists show promise in animal models of cirrhosis and portal hypertension. The aim was to pharmacologically characterise the expression of endothelin receptors in human liver, hepatic artery and portal vein. Main methodsImmunofluorescence staining, receptor autoradiography and competition binding assays were used to localise and quantify ET receptors on hepatic parenchyma, hepatic artery and portal vein in human cirrhotic or normal liver. Additional experiments were performed to determine the affinity and selectivity of ET antagonists for liver ET endothelin receptors. An endothelial cell ETB knockout murine model was used to examine the function of sinusoid endothelial ETB receptors. Key findingsETB receptors predominated in normal human liver and displayed the highest ratio (ETB:ETA 63:47) compared with other peripheral tissues. In two patients examined, liver ETB expression was up-regulated in cirrhosis (ETB:ETA 83:17). Both sub-types localised to the media of normal portal vein but ETB receptors were downregulated fivefold in the media of cirrhotic portal vein. Sinusoid diameter was fourfold smaller in endothelial cell ETB knockout mice. The liver morphology of ETB knockout mice was markedly different to normal murine liver, with loss of the wide spread sinusoidal pattern. In the knockout mice, sinusoids were reduced in both number and absolute diameter, while large intrahepatic veins were congested with red blood cells. SignificanceThese data support a role for the ET system in cirrhosis of the liver and suggest that endothelial ETB blockade may cause sinusoidal constriction which may contribute to hepatotoxicity associated with some endothelin antagonists.

Cross-regulation of cannabinoid CB1 and CB2 receptors governs hepatic steatosis

Cross-regulation of cannabinoid CB1 and CB2 receptors governs hepatic steatosis

Soluble membrane attack complex in ascites in patients with liver cirrhosis without infections

To study complement activation in 46 patients with alcoholic cirrhosis and ascites but no spontaneous bacterial peritonitis (SBP) and 10 healthy controls. Complement activation was determined by the measurement of soluble membrane attack complex (sMAC) concentrations in ascites and plasma. In patients, metabolic liver function was determined by the galactose elimination capacity and the clinical status assessed by the Model of End-Stage Liver Disease and Child-Pugh scores. Ascites sMAC levels were markedly higher than in the corresponding plasma sample (median (range): 596 (170 - 1519) vs 160 (77 - 848) μg/L; P < 0.01). Ascites sMAC levels correlated positively with liver status. There was no relationship between ascites sMAC and leukocyte count. No relationship between ascites sMAC and blood C-reactive protein, albumin or neutrophile count was found. Plasma sMAC concentrations were slightly higher in patients than in controls [130 μg/L (70 - 204); P = 0.04]. Neither sMAC in ascites nor plasma was related to mortality. The increased sMAC concentration in ascites and plasma indicate an activation of the complement system in cirrhosis even in the absence of SBP. This was particularly evident in the peritoneal fluid and most marked in patients with preserved liver status. The high ascites sMAC levels may reflect transudation of membrane attack complexes from the liver. Whether this complement activation has any clinical implications remains to be clarified.

Fisiopatología de la translocación y la peritonitis bacteriana espontánea en la cirrosis

El mecanismo patogénico clave que inicia la peritonitis bacteriana espontánea (PBE) es la translocación bacteriana (TB), proceso por el cual las bacterias entéricas cruzan la barrera mucosa intestinal e infectan los ganglios linfáticos mesentéricos, y desde donde alcanzan la circulación sanguínea y, posteriormente, el líquido ascítico. La alta tasa de TB en la cirrosis se debe al daño en los 3 pilares que constituyen la barrera mucosa del intestino: equilibrio de la flora bacteriana intraluminal, integridad de la barrera epitelial intestinal y sistema inmunitario local. La diseminación sanguínea y el crecimiento de los gérmenes en el líquido ascítico que se produce en la PBE es consecuencia del daño en el sistema inmunitario que conlleva la cirrosis. La hiperproducción en el líquido ascítico de citocinas proinflamatorias y otras sustancias con propiedades vasoactivas contribuye a la vasodilatación arterial y a la insuficiencia renal que, con frecuencia, complica el curso de la PBE. Aun en ausencia de PBE, la translocación de bacterias y productos bacterianos desde la luz intestinal contribuye a la activación sistémica de las células inmunitarias en la cirrosis. The key pathogenic mechanism initiating spontaneous bacterial peritonitis (SBP) is bacterial translocation (BT), a process through which enteric bacteria cross the intestinal barrier and infect the mesenteric lymph nodes, thus entering the blood circulation and ascitic fluid. The high rate of bacterial translocation in cirrhosis is due to injury to the three pilars composing the intestinal mucosal barrier (the balance of intraluminal bacterial flora, the integrity of the intestinal epithelial barrier, and the local immune system). Blood dissemination and microbial growth in ascitic fluid resulting from SBP are a consequence of damage to the immune system in cirrhosis. Hyperproduction of proinflammatory cytokines and other vasoactive substances contributes to the arterial vasodilation and renal failure that frequently complicate the course of SBP. Even in the absence of SBP, translocation of bacteria and bacterial products from the intestinal lumen contribute to systemic inactivation of immune cells in cirrhosis.

Hepatolymphomania

After three years of penning Landmarks in Hepatology, it is a unique pleasure to have the occasion to respond to a letter to the editor from an avid fan, albeit one who is a little miffed by her perception that lymphology was given short shrift in a couple of articles. Although the writer's letter would probably not pass muster for inclusion in a collection of letters to the editor of The Times,1 like the curate's egg it was good in parts. I am grateful that Dr. Witte has offered the opportunity for greater recognition of the role of the lymphatic system in cirrhosis than was possible in “My Cup Runneth Over,” the main focus of which was intended to be The Overflow Hypothesis, proposed by Telfer Reynolds, as a landmark in hepatology from an historical perspective. Perforce, such a format undoubtedly may overlook competing hypotheses, and scholarly scientific reviews should be consulted for a more balanced account of any given topic. Of course, as the writer reminds us, ascites only accumulates if there is an imbalance between the rate of formation and absorption of visceral lymph, as described so elegantly in the cited reference 2 by her late illustrious husband, Charles L. Witte, herself, and Allan Dumont. Finally, Gaspar Asellius did indeed rediscover the lymphatic system in the postprandial dog by seeing the glistening chyliferous vessels that Hippocrates before him saw as “white blood,” Aristotle described as vessels containing a colorless fluid, and both Herophilus and Erasistratus noticed too. The eminent Danish physician, naturalist, physiologist, and anatomist Thomas Bartholin's contribution was to confirm the existence of the human thoracic duct, in the cadavers of two criminals (donated by the king), following Jean Pecquet's discovery of this structure in dogs. Adrian Reuben M.B.B.S., F.R.C.P.*, * Division of GI/Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC.

The answer: angiotensin II. The question: what do inflammation, oxidant stress and fibrogenesis have in common?

The answer: angiotensin II. The question: what do inflammation, oxidant stress and fibrogenesis have in common?

Disturbed synthesis of insulinlike growth factor I and its binding proteins may influence renal function changes in liver cirrhosis.

Insulinlike growth factor-1 (IGF-1) is an anabolic hormone synthesized by the liver upon stimulation by growth hormone (GH). IGF-1 exerts important effects on renal hemodynamics and renal sodium handling. The bioactivity of this hormone is influenced by its binding proteins (BP) of which IGF-BP3 favors retention in the capillary lumen while IGF-BP1 facilitates the transport to the target tissues. IGF-BP1 modulates the actions of IGF-1 on target cells including renal tubules. Although a number of reports have dealt with disturbances of the IGF-1/IGF-BP system in cirrhosis, no studies have yet addressed the relationship between alterations in this system and renal function changes in cirrhosis. In the present study we have included 20 patients with cirrhosis and 10 healthy subjects (control group). As compared with the controls, patients showed lower circulating levels of IGF-1 and IGF-BP3, higher IGF-BP1 levels, and a tendency to higher insulinemia and GH values. The index IGF-1 x IGF-BP1/IGF-BP3 (IGF-1-IGF-BP index, reflecting the accessibility of circulating IGF-1 to target cells) was higher in patients with ascites. IGF-1 directly correlated with renal blood flow (P < 0.05), with IGF-BP3 (P < 0.001) and inversely with the Pugh's score (P < 0.02). A negative correlation was found between IGF-1-IGF-BP index and fractional sodium excretion (P < 0.01) and between IGF-BP1 and urinary sodium excretion (P < 0.02). Our findings support the hypothesis that the disturbance of the IGF-1/IGF-BP axis may be related to the degree of renal vasodilation and renal sodium retention in cirrhotic patients.

Chronic blockade of endothelin receptors in cirrhotic rats: Hepatic and hemodynamic effects

Background & Aims: Because controversial roles have been attributed to activation of the hepatic paracrine endothelin (ET) system in cirrhosis, this study assessed whether chronic ET receptor blockade modifies the development of portal hypertension in cirrhotic rats. Methods: Cirrhotic and control rats received the mixed ET receptor antagonist RO 48-5695 or vehicle daily for 10 weeks. At the end of the treatment period, portal pressure, systemic hemodynamics, standard renal and liver function tests, hepatic concentration of hydroxyproline, and liver messenger RNA (mRNA) expression of procollagen type I were measured. Results: Cirrhotic rats had portal hypertension and hyperdynamic circulation with no differences between animals treated or not treated with the ET-receptor antagonist. However, cirrhotic rats receiving ET-receptor blockade long-term showed a higher hepatic hydroxyproline content and procollagen type I mRNA expression than cirrhotic animals receiving vehicle. Conclusions: The results indicate that the liver paracrine ET system does not play a major role in the pathogenesis of portal hypertension and support the concept that this system takes part in an autocrine loop that counteracts the development of liver fibrogenesis. GASTROENTEROLOGY 1999;116:161-167

Prostaglandin production in cirrhosis and portal hypertension—Experimental and clinical study

Disease-related changes in prostaglandin (PG) levels may contribute to a bleeding tendency and local vasodilation in the portal circulation in patients with liver cirrhosis. We measured the plasma and tissue PG metabolite levels (6-keto PGF1 α and thromboxane TXB 2) in the systemic and portal circulation in 12 rats with CCl 4-induced liver cirrhosis (LC rats) and ten with portal hypertension induced by 2 weeks of partial portal ligation (PH rats) and compared them with normal control rats ( n=10). We also compared the plasma PG metabolite levels in the systemic and portal circulations in 11 cirrhotic patients with hepatocellular carcinoma (HCC) and five patient controls without liver disease. In the animal study, LC rats had significantly higher portal blood 6-keto PGF1 α ( P<0.01) and TXB 2 ( P<0.05) levels than the control rats; and significantly higher systemic blood TXB 2 level than PH rats ( P<0.05) and control rats ( P<0.05), but the systemic blood 6-keto PGF1 α levels were not significantly different among the three groups. PH and LC rats had significantly higher portal vein tissue 6-keto PGF1 α levels than the control rats ( P<0.01 and P<0.05), and the level in PH rats was higher than that in LC rats ( P<0.05). LC rats had significantly higher portal vein tissue TXB 2 level than control rats ( P<0.05). The liver tissue levels of both metabolites did not differ among the three groups. Compared with control rats, LC rats had significantly higher 6-keto PGF1 α/TXB 2 ratios in the portal circulation ( P<0.01) and liver tissue ( P<0.05); and PH rats had significantly higher ratios in the portal vein ( P<0.01), systemic circulation ( P<0.05) and liver tissue ( P<0.05). In the clinical study, both PG metabolite levels were significantly higher in the portal circulation than in the systemic circulation in cirrhotic patients with HCC, whereas the levels were only slightly higher in the portal circulation in control patient without liver disease. The PG metabolite ratio was significantly higher in the portal circulation than in the systemic circulation in cirrhotic patients (2.0±0.1 vs. 1.5±0.1, P<0.05), but the ratios were not significantly different in patient controls (1.8±0.3 vs. 1.3±0.1). These results suggest that the production of PG, especially of prostacycline, may be enhanced in the portal system in cirrhosis and may in part evoke portal pressure increase and other vascular alterations.

Effect of extracellular volume expansion on erythrocyte cation transport in cirrhotic rats.

Erythrocyte intracellular Na+ and K+, and ouabain- and bumetanide-inhibitable Na+ efflux and 86Rb uptake have been measured in control and cirrhotic rats with or without extracellular volume expansion (EVE, saline, 3% body wt., 3 h). Non-expanded, cirrhotic rats showed a lower Na+ excretion (UNaV) than controls. After EVE, control rats showed a significantly higher UNaV (90%) and urinary flow (40%), than non-expanded controls. In cirrhotics, the increases in urinary flow (10%) and UNaV (17%) were not significant. No differences in intracellular Na+ and K+ levels between control and cirrhotic rats were observed. In controls none of these values changed with volume expansion, but in cirrhotic rats intracellular Na+ was significantly higher in expanded than in non-expanded rats. No differences in 86Rb uptake between non-expanded control and cirrhotic rats were observed. In controls EVE induced a decrease of pump-mediated 86Rb influx, but in cirrhotic rats, total and pump-mediated 86Rb influxes were lower in expanded than in non-expanded animals. By contrast, EVE induced a decrease in ouabain-inhibitable 86Rb uptake. In conclusion, in spite of the limitations imposed by considering the erythrocyte as representative of the renal cells, these results do not support an alteration in the response of the ouabain-inhibitable sodium pump as responsible for the lack of natriuretic response to extracellular volume expansion in cirrhotic rats. However, modification of the cotransport system in cirrhosis could play some role in this impaired response.