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Portal hypertension is the consequence of cirrhosis and results from increased sinusoidal vascular resistance and hepatic blood inflow. Etiological therapies represent the first intervention to prevent a significant increase in portal pressure due to chronic liver damage. However, other superimposed pathophysiological drivers may worsen liver disease, including inflammation, bacterial translocation, endothelial dysfunction, and hyperactivation of hemostasis. These mechanisms can be targeted by a specific class of drugs already used in clinical practice. Albumin, rifaximin, statins, aspirin, and anticoagulants have been tested in cirrhosis and were a topic of discussion in the last Baveno consensus as non-etiological therapies. Based on the pathogenesis of portal hypertension in cirrhosis, our review summarizes the main mechanisms targeted by these drugs as well as the clinical evidence that considers them a valid complementary option to manage patients with cirrhosis and portal hypertension. [ABSTRACT FROM AUTHOR]

Background: In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG) > 10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non‐invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol. Methods: Sixty‐six patients with cirrhosis and HVPG ≥ 10 mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh‐performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2‐3 metabolites identifying HVPG responders (HVPG reduction > 10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross‐validation and cut‐offs to classify responders/non‐responders was proposed. Results: A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty‐nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P‐16:0/22:6)) and a free fatty acid (20:2(n‐6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut‐off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut‐off values allowed identifying responders (0.688, PPV 84%) and non‐responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model. Conclusions: The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non‐invasive test to classify the HVPG response to propranolol. [ABSTRACT FROM AUTHOR]

Background & Aims Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation. Results Three hundred and thirteen culture-positive infections (173 community acquired [ CA] and 140 hospital acquired [ HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents ( MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in-hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy ( P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) ( P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death. Conclusions Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background & Aims Portal vein thrombosis ( PVT) is frequently observed in cirrhosis and may be a clinically important complication. In vitro assays for endogenous thrombin potential ( ETP) demonstrated that in cirrhosis plasma has intrinsic resistance to the anticoagulant action of thrombomodulin ( TM- R). This study retrospectively explores the association of TM- R with de novo PVT and its clinical impact on cirrhosis. Methods Fifty-three patients with cirrhosis were tested for ETP-ratio with/without thrombomodulin. Clinical, endoscopic variables, presence/absence of PVT by Doppler- US and/or CT examination were collected at baseline and up to 4 years from baseline. The de novo PVT was the primary clinical end-point. Portal hypertension ( PHT)-related complications and transplantation free survival were secondary end-points. ETP-ratio higher than the 95° percentile of the distribution in 173 healthy controls defined TM- R. Results During 48 months of follow-up, 11 patients developed de novo PVT, with preference for the 36 patients with TM- R after adjusting for Child-Pugh class (HR: 8.354; 90%CI:1.475 - 47.305; P = 0.009). Seventeen patients experienced PHT-related complications, 23 either died or underwent liver transplantation. PHT complications and transplantation free survival were associated with TM- R, but were independently predicted by Child-Pugh class, only. Same results were obtained by considering the MELD score. Conclusions Owing to PVT results from the pro-coagulant imbalance occurring in patients with advanced cirrhosis, TM- R might serve as a predictor and could possibly be a biological mediator of adverse outcome in patients with advanced cirrhosis. [ABSTRACT FROM AUTHOR]

Background/Aims: Cirrhotic patients chronically treated with beta-blockers who achieve a decrease of hepatic venous pressure gradient (HVPG) ⩾20% from baseline or to ⩽12mmHg have a marked reduction of first bleeding or re-bleeding. However, two HVPG measurements are needed to evaluate response. This study was aimed at investigating the predictive role of acute HVPG response to i.v. propranolol for bleeding and survival. Methods: We retrospectively studied 166 cirrhotic patients with varices with HVPG response to i.v. propranolol (0.15mg/kg). All patients subsequently received non-selective beta-blockers to prevent first bleeding (n =78) or re-bleeding (n =88). Results: Thirty-seven patients developed a portal hypertension-related bleeding over 2 years of follow-up. Decrease (12%) in HVPG was the best cut-off for bleeding risk discrimination. This parameter was used to classify patients in responders (n =95) and non-responders (n =71). In primary prophylaxis (54 responders vs. 24 non-responders) the actuarial probability of bleeding was half in responders than in non-responders (12% vs. 23% at 2 years; ns). In secondary prophylaxis (41 responders vs. 47 non-responders) a good hemodynamic response was also significantly and independently associated with a 50% decrease in the probability of re-bleeding (23% at 2 years vs. 46% in non-responders; p =0.032) and a better survival (95% vs. 65%; p =0.003). Conclusion: The evaluation of acute HVPG response to i.v. propranolol before initiating secondary prophylaxis for variceal bleeding is a useful tool in predicting the efficacy of non-selective beta-blockers. If adequately validated, this might be a more cost-effective strategy than the chronic evaluation of HVPG response and might be useful to guide therapeutic decisions in these patients. [Copyright &y& Elsevier]

Keywords: blood group; cirrhosis; factor VIII; portal vein thrombosis; von Willebrand factor EN blood group cirrhosis factor VIII portal vein thrombosis von Willebrand factor 1788 1789 2 06/25/20 20200701 NES 200701 Abbreviations ETPr thrombin potential with/without thrombomodulin ratio FVIII factor VIII PVT portal vein thrombosis VWF von Willebrand factor We read with interest the paper from Scheiner et al, who investigated the influence of AB0 blood group on the risk of portal vein thrombosis (PVT) in patients with cirrhosis and wish to make comments.[1] In the general population, the venous thrombosis risk is 2-4 fold increased in non-0 individuals, likely because of their higher von Willebrand factor (VWF) and factor VIII (FVIII) levels.[2] In cirrhotics, VWF and FVIII are markedly increased.[3] However, Scheiner et al could not find association between non-0 group and PVT in 84 947 cirrhotics listed for liver transplantation in the USA. Blood group, cirrhosis, factor VIII, portal vein thrombosis, von Willebrand factor. [Extracted from the article]

Cirrhosis presents with thrombocytopenia and possibly thrombocytopathy. Previous studies exploring platelet function gave conflicting results and most controversies are explained by the variety of methods employed for investigation. We sought to assess in-vitro the overall platelet function in cirrhosis. We investigated 34 patients by using the following tests. (i)Aggregometry. (ii)Measurement of the content of platelet granules. (iii)Cytometric platelet activation. (iv)Plasmatic markers of in-vivo platelet activation. (v)Platelet procoagulant activity by thrombin generation (TG) in platelet-rich plasma (PRP). TG measured in PRP for patients and controls was similar. Platelets from patients with cirrhosis showed reduction of aggregation and secretion of ATP. Similar results were observed for platelet activation parameters such as P-selectin expression and PAC-1 platelet binding. Plasma levels of βeta-thromboglobulin and soluble P-selectin, were increased in patients- vs -controls. In contrast, there were no patients- vs -controls differences for plasmatic platelet-factor-4. Results are consistent with a state of in-vivo platelet activation and decreased in-vitro aggregation. Since bleeding events following invasive procedures are uncommon in cirrhosis, we speculate that in-vitro aggregometry testing does not reflect the situation occurring in-vivo. Results of the study and pathophysiological considerations support the conclusion that platelet function in cirrhosis as determined by aggregometry, although somewhat impaired, may support the overall hemostatic potential, which is needed for most invasive interventions. These conclusions are in line with the recommendations of international guidelines, warning against indiscriminate use of prophylactic preprocedural administration of platelets before invasive procedures. Decision on platelet support should not be made based on in-vitro laboratory testing for platelet function. • The role of platelet function in cirrhosis during procedures is poorly defined. • We investigated the overall platelet function with an array of laboratory methods. • Platelet function is impaired but does hardly represent the in-vivo situation. • Since perioperative bleeding is uncommon platelet function testing is not advised. [ABSTRACT FROM AUTHOR]