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Gut 2004;53:143-148 Recurrent variceal bleeding is very frequent after variceal haemorrhage and pharmacological therapy is the first choice treatment. Recently, baseline and repeat measurements of hepatic venous pressure gradient (HVPG) [...]

Methods: TIPSS has been compared to large volume paracenthesis (LVP) in 4 randomised controlled trials with mostly poor results. We performed TIPSS in 49 carefully selected cirrhotic patients with refractory [...]

Presents a response to a letter on the influence of bacterial infection on the pathophysiology of cirrhosis.

Background: Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics., Methods: This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used., Results: Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047)., Conclusions: In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called "gut-liver axis", with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet., Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 non-cirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC)., Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleeding but was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)]., Conclusions: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.

Since the original description of the effectiveness of β-blockers in lowering the portal pressure and therefore the risk of variceal bleeding, more than 500 articles in the English literature on the use of non selective β-blockers (NSBB) in cirrhosis have been published. The use of NSBB in pre-primary prophylaxis of variceal bleeding is currently not indicated. In primary prophylaxis, patients with high risk small varices or large/medium varices should receive primary prophylaxis either with NSBB or with endoscopic band ligation if there are contraindications to NSBB. For secondary prophylaxis the current recommendation is to receive a combination of NSBB and endoscopic variceal ligation. In addition to lowering portal pressure, NSBB can also reduce bacterial translocation, potentially exerting multiple beneficial effects which go beyond the reduction of bleeding risk. Carvedilol is a NSBB with intrinsic anti-α(1)-adrenergic activity, possibly more effective than propranolol in lowering portal hypertension. A potential harmful effect of propranolol in patients with cirrhosis with refractory ascites deserves further confirmation. NSBB remain the cornerstone of therapy in cirrhotic patients with portal hypertension.

Introduction: Acute variceal bleeding is a medical emergency and one of the main causes of mortality in patients with cirrhosis. Timely and effective treatment of the acute bleeding episode results in increased survival, and appropriate prophylactic treatment can prevent bleeding or rebleeding from varices., Areas Covered: We discuss the prevention of development and growth of varices, the primary and secondary prophylaxis of bleeding, the treatment of acute bleeding, and the management of gastric varices. We systematically reviewed studies, without time limits, identified through Medline and searches of reference lists, and provide an overview of the evidence underlying the -treatment options in the management of varices in cirrhosis., Expert Opinion: The management of variceal hemorrhage relies on nonspecific interventions (e.g., adequate fluid resuscitation, airway protection) and on specific interventions. These are routine prophylactic antibiotics, vasoactive drugs and endoscopic treatment. Procedures such as the placement of a Sengstaken-Blakemore tube or a transjugular intrahepatic portosystemic shunt (TIPS) can be lifesaving. The primary and secondary prophylaxis of bleeding is based on nonselective beta-blockers and endoscopy, even though TIPS or, less frequently, surgery have a role in selected cases.

Portal hypertension (PH) is a severe complication of liver cirrhosis. Measurement of the degree of portal hypertension is usually performed by measuring the hepatic venous pressure gradient (HVPG) which is the difference between the free hepatic venous pressure (FHVP) and the wedged hepatic venous pressure (WHPG). The HVPG accurately reflects the degree of PH in the majority of liver diseases. PH is defined by an increase of HVPG values above the normal upper limit of 5 mm Hg, while clinically significant PH is defined by an HVPG to ≥10 mm Hg. Although measurement of HVPG potentially has several applications, in clinical practice its major use has been related to the assessment of hemodynamic response to pharmacological therapy, in order to evaluate the efficacy of treatment and to predict the risk of rebleeding from esophageal varices. When properly performed, HVPG is a reliable, safe and good predictive tool in the management of portal hypertension. However, the need for appropriate equipment, sufficient and reliable operators and costs, have discouraged its use outside Liver Units specifically devoted to the clinical management of portal hypertension. This has diminished its applicability. Combining its use with transjugular liver biopsy and using the prognostic value of HVPG may help encourage its use., (Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and beta-blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of beta-blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites., Materials and Methods: Extensive search of the literature including randomized controlled trial (RCT) and non-RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using beta-blockers were evaluated. We performed a meta-analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model., Results: Three RCT and three retrospective studies in which beta-blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non-responders., Conclusions: This analysis suggests a role of beta-blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding.

Purpose: Transjugular intrahepatic portosystemic shunt (TIPS) has been reported superior to large-volume paracentesis for refractory ascites, but post-TIPS encephalopathy is a major complication. We intended to assess the outcome of limited diameter TIPS on ascites control, mortality, and encephalopathy in patients with refractory ascites at our centre., Methods: TIPS was successfully performed on 56 patients. Initial stent dilatation was to 6 mm, if there was a reduction in portal pressure gradient (PPG) >25%, further dilatation was not proposed., Results: Either complete or partial response was obtained in 58%, 81%, 83%, and 93% of patients at 1, 3, 6, and 12 months, respectively. Mortality was 10%, 29%, 37%, and 50% at 1, 3, 6, and 12 months, respectively. In 27 patients (48%), a new episode of encephalopathy developed, but only 6 (22%) were grade III or IV and 23 (85%) responded quickly to treatment., Conclusions: The results of our study confirm the efficacy of TIPS for refractory ascites. The use of narrow-diameter dilatation without aiming at lowering the PPG below a certain threshold might simplify the procedure and the follow-up for these patients.

Objective: In patients with cirrhosis and bacterial infection there is impaired coagulation and a heparin effect on thromboelastography (TEG). Our aim was to assess the presence of a heparin effect on heparinase I-modified TEG in patients before and after transjugular intrahepatic portosystemic shunt (TIPS). Our hypothesis was that, given the presence of a portosystemic gradient of endotoxaemia, and the role of endotoxaemia on the release of heparinoids, the inflow of portal blood after TIPS might reveal heparinoids through a heparin effect on TEG., Material and Methods: Blood samples for heparinase I-modified TEG were taken before, 1 h after, 6 h after and the morning after TIPS, with further daily samples being taken until any TEG changes had reverted to baseline. A heparin effect was defined as an improvement of > or =20% in a TEG variable after addition of heparinase I., Results: We studied 10 patients (six males, mean age 48.8 years, mean Child score 8.8). The aetiology of liver disease was alcohol in six patients, Budd-Chiari syndrome in two, and hepatitis C virus and cryptogenic cirrhosis in one each. Indications for TIPS were recurrent variceal bleeding in four patients, refractory ascites or hydrothorax in four and Budd-Chiari syndrome in two. There was a statistically significant worsening in TEG parameters after TIPS placement. In eight patients a heparin effect appeared after TIPS and disappeared within 24-48 h., Conclusions: We report the appearance of a transient heparin effect in systemic venous blood after TIPS in patients with cirrhosis or Budd-Chiari syndrome, suggesting the presence of heparinoid substances in the portal venous system in these patients.