The portal vein in patients with cirrhosis is not an excessively inflammatory or hypercoagulable vascular bed, a prospective cohort study

Background A hypercoagulable state is not associated with development of portal vein thrombosis in cirrhosis, as we previously demonstrated. However, some groups demonstrated elevated levels of inflammatory markers and activation of hemostasis in the portal vein (PV) compared to posthepatic veins, but because the liver is involved in clearance of these markers, we hypothesize that interpretation of these data is not straightforward. Aim To determine whether the PV has particular proinflammatory/hypercoagulable characteristics by comparing plasma sampled in the PV, hepatic vein (HV), and the systemic circulation. Methods Plasma samples from 51 cirrhotic patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt placement, were taken from the PV, HV, and jugular vein (JV). Markers of inflammation (lipopolysaccharide, tumor necrosis factor-alpha, interleukin-6, thiobarbituric acid-reactive substances), neutrophil-extracellular-traps (cfDNA, MPO-DNA), endothelial damage (von Willebrand factor [VWF]), and hemostasis were determined and compared among the three vascular beds. Results Markers of inflammation were slightly, but significantly higher in the PV than in the HV and systemic circulation. VWF and markers of hemostasis were modestly elevated in the PV. Levels of multiple markers were lower in the HV compared with the PV and systemic circulation. Higher model for end-stage liver disease score was associated with a more prothrombotic state in all three sample sites. Conclusion In contrast to published studies, we did not detect a clear proinflammatory or prothrombotic environment in the PV of cirrhotic patients. Many markers are lowest in the HV, indicating that the low levels of these markers in the HV, at least in part, reflect clearance of those markers in the liver

A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement

Background & Aims To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). Methods We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. Results One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. Conclusions A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Lay summary Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Porto-sinusoidal vascular disorder in chronic HBV: A significant coexistence not to be overlooked

Background &amp; Aims: Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. Methods: This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. Results: We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p <0.0001 and 20% vs. 9.1%, p <0.0001, respectively). Patients with CHB had a significant delay in PSVD diagnosis compared to those without CHB (11 [5–25] vs. 1 [0–3] years, p = 0.002) and had a more advanced disease (MELD score 12 [9–17] vs. 9 [7–11], p = 0.012) at the time of PSVD diagnosis. The clinical evolution of PSVD in patients with CHB was marked by a significantly higher transplantation rate at the last follow-up (33% vs. 4.1%, p = 0.001). Conclusions: Recognizing the coexistence of PSVD and CHB is important for timely diagnosis and optimal management, highlighting the potential benefits of specialized care for potentially improved outcomes. Impact and implications: The new diagnostic criteria for porto-sinusoidal vascular disorder (PSVD) allow for coexistence with other liver diseases. The results of the present study highlight, for the first time, a non-negligible prevalence of chronic hepatitis B in the PSVD population that was previously unknown. Coexistence may challenge and delay the PSVD diagnosis and is associated with a more unfavorable clinical course. Our findings will increase awareness of this coexistence and improve PSVD diagnosis and management. Furthermore, the data will encourage new studies to determine the prevalence and clinical behavior of other chronic liver diseases that coexist with PSVD

Clinical course and treatment of incidentally detected splanchnic vein thrombosis: an individual patient data meta-analysis

Background: The clinical relevance and management of incidental splanchnic vein thrombosis (SVT) remain poorly defined. Objectives: The objectives of this study were to evaluate the clinical course of incidental SVT in comparison with symptomatic SVT and assess the safety and effectiveness of anticoagulant treatment in incidental SVT. Methods: Individual patient data meta-analysis of randomized controlled trials or prospective studies published up to June 2021. Efficacy outcomes were recurrent venous thromboembolism (VTE) and all-cause mortality. The safety outcome was major bleeding. Incidence rate ratios and 95% CIs for incidental vs symptomatic SVT were estimated before and after propensity-score matching. Multivariable Cox models were used considering anticoagulant treatment as a time-varying covariate. Results: In total, 493 patients with incidental SVT and 493 propensity-matched patients with symptomatic SVT were analyzed. Patients with incidental SVT were less likely to receive anticoagulant treatment (72.4% vs 83.6%). Incidence rate ratios (95% CI) for major bleeding, recurrent VTE, and all-cause mortality in patients with incidental SVT compared with symptomatic SVT were 1.3 (0.8, 2.2), 2.0 (1.2, 3.3), and 0.5 (0.4, 0.7), respectively. In patients with incidental SVT, anticoagulant therapy was associated with a lower risk of major bleeding (hazard ratio [HR] 0.41; 95% CI, 0.21 to 0.71), recurrent VTE (HR 0.33; 95% CI, 0.18 to 0.61), and all-cause mortality (HR 0.23; 95% CI, 0.15 to 0.35). Conclusion: Patients with incidental SVT appeared to have a similar risk of major bleeding, a higher risk of recurrent thrombosis, but lower all-cause mortality than patients with symptomatic SVT. Anticoagulant therapy seemed safe and effective in patients with incidental SVT

Incidence and factors predictive of recurrent thrombosis in patients with non-cirrhotic portal vein thrombosis.

BACKGROUND AND AIMS Clinical guidelines do not recommend long-term anticoagulation in non-cirrhotic splanchnic vein thrombosis (NC-SVT) without underlying thrombophilia because it is assumed that there is a very low risk of recurrent thrombosis (RT). Our first aim was to describe the incidence of RT in patients with NC-SVT without indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort. METHODS Multicenter retrospective observational study evaluating risk factors for RT in 64 patients with NC-SVT of idiopathic/local etiology. In a subgroup of 48 patients the potential value of additional thrombophilic parameters to predict RT was analyzed. Findings were validated in 70 independent patients with idiopathic/local NC-SVT. RESULTS Of the 64 patients, 17 (26%) presented splanchnic and/or extra-splanchnic RT (overall-RT) during follow-up (cumulative incidence: 2%, 10%, 19% and 34% at 1, 2, 5 and 10 years). 53% of splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 patients with additional comprehensive thrombophilic study, factor VIII ≥ 150% was the only independent factor predicting overall-RT (HR 7.10 (CI 2.17 - 23.17) p 150% (HR 3.71 (1.31 - 10.5), p < 0.01). The predictive value of factor VIII was confirmed both in patients with idiopathic and with local etiology. CONCLUSIONS Patients with idiopathic/local NC-SVT are at risk of overall-RT. Splanchnic RT can be asymptomatic and requires screening for its detection. Values of factor VIII ≥ 150% may help identify patients at high risk of overall-RT who could benefit from long-term anticoagulation. LAY SUMMARY Patients with idiopathic/isolated local factor non cirrhotic splanchnic vein thrombosis (NC-SVT) were previously thought to be at minimal risk of rethrombosis. Our results show a 25% incidence of rethrombosis and support the indication of close follow-up to identify new thrombotic events, specially in patients with factor VIII >150%

Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors.

BACKGROUND & AIMS Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis

Metabolomics as a tool to predict the risk of decompensation or liver related death in patients with compensated cirrhosis.

BACKGROUND AIMS Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG >10 mmHg) have a high risk of decompensation. HVPG is, however, an invasive procedure not available in all centers. The present study aims to assess whether metabolomics can improve the capacity of clinical models in predicting clinical outcome in these compensated patients. APPROACH RESULTS This is a nested study from the PREDESCI cohort (a RCT of non-selective beta blockers (NSBB) versus placebo in 201 patients with compensated cirrhosis and CSPH) including 167 patients for whom a blood sample was collected. A targeted metabolomic serum analysis, using UHPLC-MS, was performed. Metabolites underwent univariate time-to event cox regression analysis. Top ranked metabolites were selected using LogRank P-value to generate a stepwise cox model. Comparison between models was done using DeLong's test. Eighty-two patients with CSPH were randomized to NSBB and 85 to placebo. Thirty-three patients developed the main endpoint (decompensation/liver-related death). The model including HVPG, Child-Pugh and treatment received (HVPG/Clinical model) had a C-index of 0.748 [CI95% 0.664-0.827]. Addition of two metabolites, Ceramide (d18:1/22:0) and Methionine (HVPG/Clinical/Metabolite model) significantly improved model's performance (C-index of 0.808 [CI95% 0.735-0.882]; P=0.032). The combination of these two metabolites together with Child-Pugh and type of treatment received (Clinical/Metabolite model) had a C-Index of 0.785 [CI95% 0.710-0.860] not significantly different from the HVPG based models including or not metabolites. CONCLUSIONS In patients with compensated cirrhosis and CSPH, metabolomics improves the capacity of clinical models and achieves similar predictive capacity than models including HVPG

Impact of SARS-CoV-2 pandemic on vascular liver diseases

Vascular liver diseases (VLD) are represented mainly by portosinusoidal vascular disease (PSVD), non-cirrhotic splanchnic vein thrombosis (SVT) and Budd Chiari syndrome (BCS). It is unknown whether patients with VLD constitute a high-risk population for complications and greater COVID-19-related mortality from SARS-CoV-2 infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLD, as well as to assess its impact on hepatic decompensation and survival.This is a observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLD between March 2020-March 2021 comparing with the general population (GP). Patients from Spain (5 centers, n = 493) and France (1 center, n = 475) were included.Nine hundred and sixty-eight patients were included: 274 PSVD, 539 SVT and 155 BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 PSVD, 77 SVT and 8 BCS. The prevalence of SARS-CoV-2 infection in PSVD (19%) and SVT (14%) was significantly higher than in GP (6.5%, p < 0.05), while it was very similar in BCS (5%). In terms of infection severity, patients with VLD also presented a higher need of hospital admission (14% vs 7.3%, p<0.01), ICU admission (2% vs 0.7%, p< 0.01) and mortality (4% vs 1.5%, p < 0.05) than GP. Previous history of ascites (50% vs 8%, p < 0.05) and post-COVID-19 hepatic decompensation (50% vs 4%, p < 0.05) were associated to COVID-19 mortality.PSVD and SVT patients could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease.Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved