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

Background & 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.

Non-invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response.

BACKGROUND AND AIMS: A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR). METHODS: The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package). RESULTS: Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%. CONCLUSIONS: A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.

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.

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

BACKGROUND AND AIMS: Patients with compensated cirrhosis with clinically significant portal hypertension (CSPH: HVPG > 10 mm Hg) 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 outcomes in these compensated patients. APPROACH AND RESULTS: This is a nested study from the PREDESCI cohort (an RCT of nonselective beta-blockers vs. 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 ultra-high-performance liquid chromatography-mass spectrometry, was performed. Metabolites underwent univariate time-to-event cox regression analysis. Top-ranked metabolites were selected using Log-Rank p -value to generate a stepwise cox model. Comparison between models was done using DeLong test. Eighty-two patients with CSPH were randomized to nonselective beta-blockers 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). The addition of 2 metabolites, ceramide (d18:1/22:0) and methionine (HVPG/Clinical/Metabolite model), significantly improved the model's performance [C-index of 0.808 (CI95% 0.735-0.882); p =0.032]. The combination of these 2 metabolites together with Child-Pugh and the 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.

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

BACKGROUND & 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 people with NC-SVT without an indication for long-term anticoagulation. The second aim was to identify RT risk factors and afterwards verify them in a validation cohort. METHODS: This is a multicentre, retrospective observational study evaluating risk factors for RT in 64 people with NC-SVT of idiopathic/local factor aetiology. In a subgroup of 48 individuals, the potential value of additional thrombophilic parameters to predict RT was analysed. Findings were validated in 70 individuals with idiopathic/local factor NC-SVT. RESULTS: Of the 64 participants in the training cohort, 17 (26%) presented splanchnic and/or extrasplanchnic RT (overall-RT) during follow-up (cumulative incidence: 2, 10, 19, and 34% at 1, 2, 5, and 10 years, respectively). In addition, 53% of people with splanchnic RT were asymptomatic. No clinical or biochemical parameters predicted overall-RT. However, in the 48 people with an additional comprehensive thrombophilic study, factor VIII ≥150% was the only independent factor predicting overall-RT (hazard ratio 7.10, 95% CI 2.17-23.17, p <0.01). In the validation cohort, 19 individuals (27%) presented overall-RT, and it was also independently predicted by factor VIII >150% (hazard ratio 3.71, 95% CI 1.31-10.5, p <0.01). The predictive value of factor VIII was confirmed in both people with idiopathic/local factor aetiology associated NC-SVT. CONCLUSIONS: People with idiopathic/local factor 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 individuals at high risk of overall-RT who could benefit from long-term anticoagulation. IMPACT AND IMPLICATIONS: People with idiopathic/isolated local factor non-cirrhotic portal vein thrombosis were previously thought to be at minimal risk of re-thrombosis and therefore did not receive scheduled follow-up. The results of this study are of special interest for hepatologists treating people with non-cirrhotic splanchnic thrombosis, as they show a 25% incidence of re-thrombosis and support the close follow-up of people with factor VIII >150% to ensure the early identification of new thrombotic events.

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis.

BACKGROUND & AIMS: In individuals with compensated advanced chronic liver disease (cACLD), the severity of portal hypertension (PH) determines the risk of decompensation. Invasive measurement of the hepatic venous pressure gradient (HVPG) is the diagnostic gold standard for PH. We evaluated the utility of machine learning models (MLMs) based on standard laboratory parameters to predict the severity of PH in individuals with cACLD. METHODS: A detailed laboratory workup of individuals with cACLD recruited from the Vienna cohort (NCT03267615) was utilised to predict clinically significant portal hypertension (CSPH, i.e., HVPG ≥10 mmHg) and severe PH (i.e., HVPG ≥16 mmHg). The MLMs were then evaluated in individual external datasets and optimised in the merged cohort. RESULTS: Among 1,232 participants with cACLD, the prevalence of CSPH/severe PH was similar in the Vienna (n = 163, 67.4%/35.0%) and validation (n = 1,069, 70.3%/34.7%) cohorts. The MLMs were based on 3 (3P: platelet count, bilirubin, international normalised ratio) or 5 (5P: +cholinesterase, +gamma-glutamyl transferase, +activated partial thromboplastin time replacing international normalised ratio) laboratory parameters. The MLMs performed robustly in the Vienna cohort. 5P-MLM had the best AUCs for CSPH (0.813) and severe PH (0.887) and compared favourably to liver stiffness measurement (AUC: 0.808). Their performance in external validation datasets was heterogeneous (AUCs: 0.589-0.887). Training on the merged cohort optimised model performance for CSPH (AUCs for 3P and 5P: 0.775 and 0.789, respectively) and severe PH (0.737 and 0.828, respectively). CONCLUSIONS: Internally trained MLMs reliably predicted PH severity in the Vienna cACLD cohort but exhibited heterogeneous results on external validation. The proposed 3P/5P online tool can reliably identify individuals with CSPH or severe PH, who are thus at risk of hepatic decompensation. IMPACT AND IMPLICATIONS: We used machine learning models based on widely available laboratory parameters to develop a non-invasive model to predict the severity of portal hypertension in individuals with compensated cirrhosis, who currently require invasive measurement of hepatic venous pressure gradient. We validated our findings in a large multicentre cohort of individuals with advanced chronic liver disease (cACLD) of any cause. Finally, we provide a readily available online calculator, based on 3 (platelet count, bilirubin, international normalised ratio) or 5 (platelet count, bilirubin, activated partial thromboplastin time, gamma-glutamyltransferase, choline-esterase) widely available laboratory parameters, that clinicians can use to predict the likelihood of their patients with cACLD having clinically significant or severe portal hypertension.

Endovascular Assessment of Liver Hemodynamics in Patients with Cirrhosis Complicated by Portal Hypertension.

The hepatic venous pressure gradient (HVPG) is currently considered the gold standard to assess portal hypertension (PH) in patients with cirrhosis. A meticulous technique is important to achieve accurate and reproducible results, and values obtained during measurement are applied in risk stratification of patients with PH, allocating treatment options, monitoring follow-up, and deciding management options in surgical patients. The use of portosystemic pressure gradients in patients undergoing placement of transjugular intrahepatic portosystemic shunts has been studied extensively and has great influence on decisions on shunt diameter. The purpose of this study was to describe the recommended technique to measure HVPG and portosystemic pressure gradient and to review the existing literature describing the importance of these hemodynamic measurements in clinical practice.

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-α, 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.

The Pathophysiology of Portal Vein Thrombosis in Cirrhosis: Getting Deeper into Virchow's Triad.

Portal vein thrombosis (PVT) is a common complication among patients with cirrhosis. However, its pathophysiology is not well established and there are currently very few predictive factors, none of which are actually useful, from a clinical perspective. The contribution of each of the vertices of Virchow's triad, e.g., blood hypercoagulability, blood flow, and portal vein endothelial damage in the development of PVT is not clear. In this review, we aim to recapitulate the latest studies on the field of PVT development in order to understand its mechanisms and discuss some of the future directions in the study of this important complication of cirrhosis.

Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases.

BACKGROUND & AIMS: Vascular liver diseases (VLDs) are represented mainly by portosinusoidal vascular disease (PSVD), noncirrhotic splanchnic vein thrombosis (SVT), and Budd Chiari syndrome (BCS). It is unknown whether patients with VLDs constitute a high-risk population for complications and greater coronavirus disease 2019 (COVID-19)-related mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLDs, as well as to assess its impact on hepatic decompensation and survival. METHODS: This is an observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLDs between March 2020 and March 2021, compared with the general population (GP). Patients from Spain (5 centers; n = 493) and France (1 center; n = 475) were included. RESULTS: Nine hundred sixty-eight patients were included: 274 with PSVD, 539 with SVT, and 155 with BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 with PSVD, 77 with SVT, and 8 with BCS. The prevalence of SARS-CoV-2 infection in patients with PSVD (19%) and SVT (14%) was significantly higher than in the GP (6.5%; P < .05), whereas it was very similar in patients with BCS (5%). In terms of infection severity, patients with VLDs also presented a higher need of hospital admission (14% vs 7.3%; P < .01), intensive care unit admission (2% vs 0.7%; P < .01), and mortality (4% vs 1.5%; P < .05) than the GP. Previous history of ascites (50% vs 8%; P < .05) and post-COVID-19 hepatic decompensation (50% vs 4%; P < .05) were associated with COVID-19 mortality. CONCLUSIONS: Patients with PSVD and SVT could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease.

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.

Risk of non-tumoural portal vein thrombosis in patients with HCV-induced cirrhosis after sustained virological response.

BACKGROUND & AIMS: Sustained virological response (SVR) to direct-acting antivirals ameliorates portal hypertension, improves hepatic function and may reverse the procoagulant state observed in patients with cirrhosis. However, an unexpected incidence of portal vein thrombosis (PVT) immediately after antiviral therapy has recently been reported. Therefore, we analysed the long-term impact of SVR on the development of non-tumoural PVT. METHODS: Our study comprised of two well-characterized prospective cohorts (hepatitis C virus '(HCV)-Cured': n = 354/'HCV-Active': n = 179) of patients with HCV cirrhosis who underwent standardized ultrasound surveillance. In the main analysis, the event of interest was de novo non-tumoural PVT and events known to modify its natural history (orthotopic liver transplantation, transjugular intrahepatic portosystemic shunt, death, tumoural PVT and anticoagulation) were considered as competing risk. Adjusted models were built using propensity scores for baseline covariates. Moreover, predictive factors were investigated by conventional multivariate analysis. RESULTS: Ten (2.8%) patients in the 'HCV-Cured' cohort developed a non-tumoural PVT during a median follow-up of 37.1 months, while 8 (4.5%) patients in the 'HCV-Active' cohort were diagnosed with non-tumoural PVT during a median follow-up of 42.2 months. High Child-Pugh score was the only independent risk factor for non-tumoural PVT development and stage A patients were at low risk. Importantly, HCV cure did not decrease the risk of non-tumoural PVT in inverse probability of treatment-weighted (IPTW) analysis (subdistribution hazard ratio: 1.31 (95% confidence interval [95% CI]: 0.43-3.97); P = .635). In contrast, SVR was associated with a substantial reduction in mortality (IPTW-adjusted sHR: 0.453 [95% CI: 0.287-0.715]; P < .001). CONCLUSIONS: The risk of non-tumoural PVT persists after HCV cure in patients with cirrhosis, despite improving survival. Even after aetiological cure, severity of liver disease remains the main determinant of non-tumoural PVT development.

Autoimmune biomarkers in porto-sinusoidal vascular disease: Potential role in its diagnosis and pathophysiology.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) is a rare disease that requires excluding cirrhosis and other causes of portal hypertension for its diagnosis because it lacks a specific diagnostical test. Although it has been occasionally associated with autoimmune diseases, the pathophysiology of PSVD remains unknown. The aim of this study was to evaluate the potential role of autoimmunity in the pathophysiology and diagnosis of PSVD. METHODS: Thirty-seven consecutive patients with PSVD and 39 with cirrhosis matched by gender, signs of portal hypertension and liver function were included (training set). By using Indirect Immunofluorescence, ELISA and slot-blot methods data 22 autoantibodies were identified in patients with PSVD and cirrhosis. Presence of anti-endothelial cells antibodies (AECA) was assayed by a cell-based ELISA. Thirty-one PSVD, 40 cirrhosis patients, 15 patients with splenomegaly associated with haematological disease and 14 healthy donors were included in a validation set. FINDINGS: The proportion of patients with at least one positive antibody was statistically significantly higher in patients with PSVD compared with cirrhosis (92% vs 56%; P < .01). Specifically, AECA were significantly more frequent in PSVD than in cirrhosis (38% vs 15%; P = .013). Results were confirmed in the validation set. In the overall population, presence of AECA had a 63% positive predictive value for diagnosing PSVD and a 71% negative predictive value, with a specificity of 94% when the 1/16 level is used as cut-off. AECA positive serum samples react with a 68-72 kDa protein of human liver endothelial sinusoidal cells.

Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease.

BACKGROUND & AIMS: Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD. METHODS: We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group). RESULTS: Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis. CONCLUSION: PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. LAY SUMMARY: Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

BACKGROUND & AIMS: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis. METHODS: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization. RESULTS: A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9). CONCLUSION: Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade. LAY SUMMARY: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

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.

Agreement between wedged hepatic venous pressure and portal pressure in non-alcoholic steatohepatitis-related cirrhosis.

BACKGROUND & AIMS: Wedge hepatic vein pressure (WHVP) accurately estimates portal pressure (PP) in alcohol- or viral hepatitis-related cirrhosis. Whether this also holds true in cirrhosis caused by non-alcoholic steatohepatitis (NASH) is unknown. We aimed to evaluate the agreement between WHVP and PP in patients with NASH cirrhosis in comparison to patients with alcohol- or HCV-related cirrhosis. METHODS: All consecutive patients with NASH cirrhosis treated with a transjugular intrahepatic portosystemic shunt (TIPS) in 3 European centres were included (NASH group; n = 40) and matched with 2 controls (1 with alcohol-related and 1 with HCV-related cirrhosis) treated with TIPS contemporaneously (control group; n = 80). Agreement was assessed by Pearson's correlation (R), intra-class correlation coefficient (ICC), and Bland-Altman method. Disagreement between WHVP and PP occurred when both pressures differed by >10% of PP value. A binary logistic regression analysis was performed to identify factors associated with this disagreement. RESULTS: Correlation between WHVP and PP was excellent in the control group (R 0.92; p <0.001; ICC 0.96; p <0.001) and moderate in the NASH group (R 0.61; p <0.001; ICC 0.74; p <0.001). Disagreement between WHVP and PP was more frequent in the NASH group (37.5% vs. 14%; p = 0.003) and was mainly because of PP underestimation. In uni- and multivariate analyses, only NASH aetiology was associated with disagreement between WHVP and PP (odds ratio 4.03; 95% CI 1.60-10.15; p = 0.003). CONCLUSIONS: In patients with decompensated NASH cirrhosis, WHVP does not estimate PP as accurately as in patients with alcohol- or HCV-related cirrhosis, mainly because of PP underestimation. Further studies aimed to assess this agreement in patients with compensated NASH cirrhosis are needed. LAY SUMMARY: Portal pressure is usually assessed by measuring wedge hepatic vein pressure because of solid evidence demonstrating their excellent agreement in alcohol- and viral hepatitis-related cirrhosis. Our results show that in patients with decompensated cirrhosis caused by non-alcoholic steatohepatitis, wedge hepatic vein pressure estimates portal pressure with less accuracy than in patients with other aetiologies of cirrhosis, mainly because of portal pressure underestimation.

Estudio de la calidad asistencial prestada en consultas externas a pacientes con cirrosis hepática / No disponible

INTRODUCCIÓN: la calidad de la asistencia prestada a los pacientes cirróticos se puede medir analizando una serie de indicadores. Los estudios publicados hasta la actualidad muestran una tasa de adherencia a las indicaciones de las guías clínicas del 40-80 %. OBJETIVO: valorar la calidad de la asistencia prestada en un hospital docente de tercer nivel. MÉTODOS: estudio observacional retrospectivo en pacientes cirróticos controlados durante un semestre en consultas externas. Se han revisado 324 historias clínicas recogiendo 14 indicadores de calidad de cinco dominios diferentes y se ha estudiado la adherencia global y en relación a la experiencia del médico responsable. RESULTADOS: excelentes (más del 90 % de adherencia) en indicadores relacionados con documentación de la etiología de la cirrosis y profilaxis de la hemorragia digestiva por varices; aceptables (60-90 %) en despistaje del carcinoma hepatocelular y valoración de la gravedad de la enfermedad; y malos (menos del 50 %) en vacunaciones. Los residentes obtuvieron significativamente mejores resultados que los adjuntos en etiología, valoración de la gravedad y dos indicadores de profilaxis de hemorragia digestiva. Por su parte, los adjuntos presentaron mejores resultados en el despistaje de carcinoma hepatocelular. CONCLUSIONES: a pesar de haber obtenido excelentes resultados en algunos indicadores, muchos deben ser mejorados, especialmente las vacunaciones. La calidad asistencial prestada por los residentes es igual o incluso mejor que la prestada por los adjuntos. Analizar la calidad asistencial es esencial para medir y mejorar la atención prestada a los pacientes cirróticos, y puede ser una herramienta muy eficaz para supervisar a los especialistas en formación

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Quality of care provided to outpatients with hepatic cirrhosis in a teaching hospital.

INTRODUCTION: a set of indicators to measure the quality of care of cirrhotic patients has been established and previously published studies report an adherence rate to clinical guide indications of 40-80 %. OBJECTIVE: to assess the adherence to quality indicators in a tertiary teaching hospital. METHODS: a retrospective observational study was performed of all cirrhotic outpatients seen during one semester in 2017. The charts were studied of 324 patients and quality indicators related to five domains were collected. An overall adherence to 14 quality indicators was recorded and analyzed based on the attending physician's experience. RESULTS: the results were excellent (more than 90 % adherence) for quality indicators related to prophylaxis of variceal bleeding and documentation of cirrhosis etiology, acceptable (60-90 % adherence) for hepatocellular carcinoma screening and disease severity assessment, and poor (less than 50 %) for vaccinations. Residents had significantly better results than experienced physicians in etiology, disease severity assessment and two indicators of prophylaxis of bleeding. Experienced physicians only presented a better adherence to hepatocellular carcinoma screening. CONCLUSIONS: despite excellent results for some quality indicators, most required improvement, especially vaccinations. The quality of care achieved by residents is equal to and even better than that of experienced physicians. Measuring quality of care is essential to analyze and improve the health care of cirrhotic outpatients and may be a useful tool for supervising specialists in training.