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Background & Aims: Despite several recent international guidelines, no consensus exists on the bleeding risk nor haemostatic parameter thresholds that define the safety of invasive procedures in patients with cirrhosis. The aim of this study was to establish a position paper on the bleeding risk associated with invasive procedures in patients with cirrhosis among the experts involved in various guidelines. Methods: All experts involved in recent guidelines on the management of invasive procedures in patients with cirrhosis were invited to classify 80 procedures as ''high risk'' or ''low risk'' with respect to bleeding. Procedures were considered high risk when the estimated risk of major bleeding was 1.5% or more, or when even minor bleeding might lead to significant morbidity or death. The experts were also asked to choose safety thresholds for laboratory test values at which elective invasive procedures could be safely performed. The predetermined threshold considered as “consensus” was ≥75% agreement. Results: Fifty-two experts participated in the study. Out of 80 procedures, a consensus opinion was reached for 52 procedures (65%): 17 procedures were classified as “high risk”, primarily interventional endoscopic procedures, percutaneous organ biopsies, or procedures involving the central nervous system; and 35 as “low risk”, primarily “diagnostic” procedures. The lowest platelet counts at which performance of a low-risk procedure or a high-risk procedure/surgery were deemed acceptable were 30 × 109/L and 50 × 109/L, respectively. Experts did not believe that international normalised ratio should be considered before performing low-risk procedures; 71% also indicated that it should not be considered before performing high-risk procedures. Conclusions: This experience-based classification may be helpful to refine future study designs and to guide clinical decision making regarding invasive procedures in patients with cirrhosis. Impact and implications: Several risk classifications and management guidelines for invasive procedures in patients with cirrhosis have been proposed, but with conflicting recommendations. By providing a position paper, based on the opinion of a broad panel of experts, on the bleeding risk associated with 52 invasive procedures in patients with cirrhosis, this survey will help to provide a framework for future study design. The consensus on platelet count, international normalised ratio, fibrinogen and activated partial thromboplastin time identified in this survey will inform physicians regarding the laboratory test values considered acceptable by the experts prior to the performance of an elective invasive procedure in patients with cirrhosis.

Background and Aims: Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension., Approach and Results: We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value., Conclusions: This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Autoimmune liver diseases (AILD) involve dysregulated CD4 T cell responses against liver self-antigens, but how these autoreactive T cells relate to liver tissue pathology remains unclear. Here we perform single-cell transcriptomic and T cell receptor analyses of circulating, self-antigen-specific CD4 T cells from patients with AILD and identify a subset of liver-autoreactive CD4 T cells with a distinct B-helper transcriptional profile characterized by PD-1, TIGIT and HLA-DR expression. These cells share clonal relationships with expanded intrahepatic T cells and exhibit transcriptional signatures overlapping with tissue-resident T cells in chronically inflamed environments. Using a mouse model, we demonstrate that, following antigen recognition in the liver, CD4 T cells acquire an exhausted phenotype, play a crucial role in liver damage, and are controlled by immune checkpoint pathways. Our findings thus suggest that circulating autoreactive CD4 T cells in AILD are imprinted by chronic antigen exposure to promote liver inflammation, thereby serving as a potential target for developing biomarkers and therapies for AILD., Competing Interests: Competing interests: The authors declare no competing interest., (© 2025. The Author(s).)

Background and Aims: In patients with noncirrhotic chronic extrahepatic portal vein obstruction (EHPVO), data on the morbimortality of abdominal surgery are scarce., Approach and Results: We retrospectively analyzed the charts of 76 patients (78 interventions) with EHPVO undergoing abdominal surgery within the Vascular Disease Interest Group network. Fourteen percent of the patients had ≥1 major bleeding (unrelated to portal hypertension) and 21% had ≥1 Dindo-Clavien grade ≥3 postoperative complications within 1 month after surgery. Fifteen percent had ≥1 portal hypertension-related complication within 3 months after surgery. Three patients died within 12 months after surgery. An unfavorable outcome (ie, ≥1 abovementioned complication or death) occurred in 37% of the patients and was associated with a history of ascites and with nonwall, noncholecystectomy surgical intervention: 17% of the patients with none of these features had an unfavorable outcome, versus 48% and 100% when one or both features were present, respectively. We then compared 63/76 patients with EHPVO with 126 matched (2:1) control patients without EHPVO but with similar surgical interventions. As compared with control patients, the incidence of major bleeding ( p <0.001) and portal hypertension-related complication ( p <0.001) was significantly higher in patients with EHPVO, but not that of grade ≥3 postoperative complications nor of death. The incidence of unfavorable postoperative outcomes was significantly higher in patients with EHPVO than in those without (33% vs. 18%, p =0.01)., Conclusions: Patients with EHPVO are at high risk of major perioperative or postoperative bleeding and postoperative complications, especially in those with ascites or undergoing surgery other than wall surgery or cholecystectomy., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background & Aims: Current knowledge of the natural history of patients with porto-sinusoidal vascular disorder (PSVD) is derived from small studies. The aim of the present study was to determine the natural history of PSVD and prognostic factors in a large multicenter cohort of patients., Methods: We performed a retrospective study on patients with PSVD and signs of portal hypertension (PH) prospectively registered in 27 centers., Results: A total of 587 patients were included, median age of 47 years and 38% were women. Four-hundred and one patients had an associated condition, which was graded as severe in 157. Median follow-up was 68 months. At diagnosis, 64% of patients were asymptomatic while 36% had a PH-related complication: PH-related bleeding in 112 patients, ascites in 117, and hepatic encephalopathy in 11. In those not presenting with bleeding, the incidence of first bleeding was 15% at 5 years, with a 5-year rebleeding rate of 18%. The 5-year cumulative incidence of new or worsening ascites was 18% and of developing portal vein thrombosis was 16%. Fifty (8.5%) patients received a liver transplantation and 109 (19%) died, including 55 non-liver-related deaths. Transplant-free survival was 97% and 83% at 1 and 5 years, respectively. Variables independently associated with transplant-free survival were age, ascites, serum bilirubin, albumin and creatinine levels at diagnosis and severe associated conditions. This allowed for the creation of a nomogram that accurately predicted prognosis., Conclusions: The prognosis of PSVD is strongly determined by the severity of the associated underlying conditions and parameters of liver and renal function., Impact and Implications: Porto-sinusoidal vascular liver disorder (PSVD) is a rare entity that usually affects young people, frequently causes severe complications of portal hypertension, and may reduce life expectancy. To date, there is scarce information regarding its clinical manifestations, natural history and prognostic factors. The present study, including the largest number of patients with PSVD reported so far, shows that overall, when managed at centers of expertise, the prognosis of patients with PSVD is good, with LT-free survival rates of 83% and 72% at 5 and 10 years, respectively. Presence and severity of an underlying associated condition, presence of ascites, age and bilirubin, albumin and creatinine levels were associated with poor prognosis. These results are important to know for hepatologists. A final model combining these parameters enabled development of a nomogram that predicts prognosis with good discrimination and calibration capacity and can be easily applied in clinical practice., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: We conducted a systematic review and meta-analysis (PROSPERO ID: CRD42023401796) of randomized placebo-controlled trials evaluating the effectiveness and safety of naltrexone as a standalone pharmacotherapy for amphetamine-type stimulant use disorder (ATSUD)., Methods: We searched EMBASE, MEDLINE, EBM Reviews, PsycINFO, CINAHL, Google Scholar, and trial registries on April 11, 2023, and updated on September 24, 2024, to identify randomized placebo-controlled trials evaluating the effectiveness of naltrexone for the treatment of ATSUD. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed for reporting the study. Risk of bias and quality of evidence were assessed with the Cochrane Risk-of-bias Assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation. Risk ratios (RRs) or Peto odds ratio were estimated for binary outcomes as appropriate. Standardized mean differences were calculated for continuous outcomes., Results: Five studies (n = 419 participants) were eligible. We found no significant difference between naltrexone and placebo for amphetamine-type stimulant use (RR = 0.903, 95% confidence interval [CI] = 0.698 to 1.167, P = 0.44, I2 = 96.1%; 4 studies), study retention (RR = 1.055, 95% CI = 0.942 to 1.182, P = 0.35, I2 = 45.0%; 4 studies), end-of-treatment craving (standardized mean difference = 0.069, 95% CI = -0.272 to 0.410, P = 0.69, I2 = 0.0%; 2 studies), and serious adverse events (odds ratio = 1.086, 95% CI = 0.414 to 2.849, P = 0.87, I2 = 0.0%; 3 studies). The quality of evidence was low to very low., Conclusions: The available evidence does not support the use of standalone naltrexone to treat ATSUD. Significant research efforts must be put toward to identify effective pharmacotherapies to complement psychosocial interventions for ATSUD., Competing Interests: LE is a shareholder and employee of OneCare Inc, which is a biotechnology mental health company. OneCare Inc, biotechnologies’ work does not relate to the contents of the present article. DJA received investigational products from Cardiol Therapeutics and Exka for clinical trials funded by the Quebec Ministry of Health and Social Services (2022-2024). GB, CM, HS, AM, DZ, SB, and LCJ report no conflict of interests., (Copyright © 2024 American Society of Addiction Medicine.)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a dimensional framework for psychopathology advanced by a consortium of nosologists. In the HiTOP system, psychopathology is grouped hierarchically from super-spectra, spectra, and subfactors at the upper levels to homogeneous symptom components and maladaptive traits and their constituent symptoms, and maladaptive behaviors at the lower levels. HiTOP has the potential to improve clinical outcomes by planning treatment based on symptom severity rather than heterogeneous diagnoses, targeting treatment across different levels of the hierarchy, and assessing distress and impairment separately from the observed symptom profile. Assessments can be performed according to this framework with the recently developed HiTOP-Self-Report (HiTOP-SR). Examples of how to use HiTOP in clinical practice are provided for the internalizing spectrum, including the use of the Unified Protocol and other modularized treatments, measurement-based care, psychopharmacology, and in traditionally underserved populations. Future directions are discussed in this State of the Science review including HiTOP's use in further developing transdiagnostic treatments, extending the model to include other information such as environmental factors, establishing the treatment utility of clinical assessment for the HiTOP-SR, developing new treatments, and disseminating the model., (Copyright © 2024 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Introduction: Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD., Methods: A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables., Results: Five RCTs ( N  = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p  = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p  = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p  = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p  = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p  = 0.029)., Conclusion: There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LE is a shareholder and employee of OneCare Inc., which is a biotechnology mental health company. OneCare Inc., biotechnologies’ work does not relate to the contents of the present article. DJA received study materials from Cardiol Therapeutics and Exka for clinical trials not related to the present article (2022–2024). The other authors have no potential conflicts to declare.

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis., Methods: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility., Results: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%)., Conclusion: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Relapse after immunosuppression (IS) treatment withdrawal is frequent in patients with Autoimmune Hepatitis (AIH), and non-invasive biomarkers predictive of this risk are lacking. We assessed the frequency of circulating T cell subsets as potential biomarkers of disease activity and predictor of the risk of relapse after IS withdrawal. Serum levels of the cytokine B-cell Activating Factor (BAFF) were also investigated. Blood samples from 58 patients with active AIH, 56 AIH patients in remission, and 31 patients with NASH were analyzed. The frequency of activated CD4+ T peripheral helper (TPH) cells (CD4+CD45RA-CXCR5-PD1+CD38+) and of activated CD8+ T cells (CD8+CD45RA-PD1+CD38+) were assessed by flow cytometry. BAFF levels were determined by ELISA. Activated TPH and CD8+ T cell frequencies were significantly increased in patients with active AIH compared to remission AIH or NASH (TPH: 0.88% of total CD3+ vs. 0.42% and 0.39% respectively, p < 0.0001; CD8+ subset: 1.42% vs. 0.09% and 0.11% p < 0.0001). Among patients in remission undergoing treatment withdrawal (n = 18), those with increased frequencies of activated TPH (> 0.5% of total CD3+) and/or activated CD8+ T cells (> 0.18% total CD3+) had a higher risk of relapse (80% vs. 15% after 2 years, p = 0.0071). High BAFF serum concentration (> 213pg/ml) was also associated to a higher risk of relapse (57% vs. 11%, p = 0.0452). In conclusion, high frequency of activated TPH and of activated CD8+, as well as high levels of BAFF, before IS discontinuation, were significantly associated to a greater risk of relapse during the first two years. Thus, they represent promising biomarkers to provide personalized clinical follow-up for patients with AIH., (© 2024. The Author(s).)

Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory-Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several KRT8/18 genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of KRT8/18 in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several KRT8 (rs2070910, rs137898974, rs1065306) and KRT18 (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several KRT18 variants appeared associated with a poorer prognosis. These results highlight the possible role of KRT18 variants in ALD., (Copyright © 2024. Published by Elsevier Inc.)

Portal vein thrombosis (PVT) refers to the development of a non-malignant obstruction of the portal vein, its branches, its radicles, or a combination. This Review first provides a comprehensive overview of all aspects of PVT, namely the specifics of the portal venous system, the risk factors for PVT, the pathophysiology of portal hypertension in PVT, the interest in non-invasive tests, as well as therapeutic approaches including the effect of treating risk factors for PVT or cause of cirrhosis, anticoagulation, portal vein recanalisation by interventional radiology, and prevention and management of variceal bleeding in patients with PVT. Specific issues are also addressed including portal cholangiopathy, mesenteric ischaemia and intestinal necrosis, quality of life, fertility, contraception and pregnancy, and PVT in children. This Review will then present endpoints for future clinical studies in PVT, both in patients with and without cirrhosis, agreed by a large panel of experts through a Delphi consensus process. These endpoints include classification of portal vein thrombus extension, classification of PVT evolution, timing of assessment of PVT, and global endpoints for studies on PVT including clinical outcomes. These endpoints will help homogenise studies on PVT and thus facilitate reporting, comparison between studies, and validation of future studies and trials on PVT., Competing Interests: Declaration of interests VHG has received speaker fees from Gore Medical and Cook Medical. ADG has received consulting fees from Astrazeneca and Swedish Orphan Biovitrum. MR serves as consultant from Quantum Surgical (fees paid to institution) and has received speaker fees from Servier, Guerbet, GE Healthcare, Ipsen, Angiodynamics, and AstraZeneca. FN has received speaker fees from Advanz and Permanyer. VML serves as consultant from AstraZaneca and has received speaker fees and travel support from Albireo Ipsen. AB serves as consultant for Boehringer Ingelheim and has received speaker fees from GE Healthcare and Hologic. AA has served as a lecturer for Boehringer-Ingelheim and Gore Medical. AN has received research funding from MSD-Avenir and consulting fees from Abbvie and Janssen. MM serves as a lecturer for AbbVie, Ipsen, Echosens, Gilead Sciences, and Gore Medical, and has received travel support from AbbVie and Gilead Sciences. DP has served as lecturer for Boehringer-Ingelheim and Gore Medical. DT has received research grants from Boehringer-Ingelheim and Novartis and has served as lecturer for Gore Medical. JCGP has received speaker fees from Gore Medical and research grants from Mallinkrodt and AstraZeneca. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension-related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre-therapeutic assessment, in the procedure itself and in the follow-up have led the board of the French Association for the Study of the Liver to establish recommendations., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objective: To evaluate the impact of depressive symptom severity on opioid use and treatment retention in individuals with prescription-type opioid use disorder (POUD)., Method: We analyzed data from a multi-centric, pragmatic, open-label, randomized controlled trial comparing buprenorphine/naloxone to methadone models of care in 272 individuals with POUD. Opioid use was self-reported every two weeks for 24 weeks using the Timeline Followback. Depressive symptom severity was self-reported with the Beck Depression Inventory at baseline, week 12 and week 24., Results: Baseline depressive symptom severity was not associated with opioid use nor treatment retention. At week 12, moderate depressive symptoms were associated with greater opioid use while mild to severe depressive symptoms were associated with lowered treatment retention. At week 24, moderate depressive symptoms were associated with greater opioid use., Conclusions: Ongoing depressive symptoms lead to poorer outcomes in POUD. Clinicians are encouraged to use integrative approaches to optimize treatment outcomes. This study was registered in ClinicalTrials.gov (NCT03033732) on January 27 th , 2017, prior to participants enrollment.

Background and Aim: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases., Approach and Results: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001)., Conclusions: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Partial splenic embolization (PSE) has been proposed to treat the consequences of hypersplenism in the context of portal hypertension, especially thrombocytopenia. However, a high morbidity/mortality rate has made this technique unpopular. We conducted a multicenter retrospective nationwide French study to reevaluate efficacy and tolerance., Methods: All consecutive patients who underwent PSE for hypersplenism and portal hypertension in 7 tertiary liver centers between 1998 and 2023 were included., Results: The study population consisted of 91 procedures in 90 patients, with a median age of 55.5 years [range 18-83]. The main cause of portal hypertension was cirrhosis (84.6 %). The main indications for PSE were (1) an indication of medical treatment or radiological/surgical procedure in the context a severe thrombocytopenia (59.3 %), (2) a chronic hemorrhagic disorder associated with a severe thrombocytopenia (18.7 %), and (3) a chronic pain associated with a major splenomegaly (9.9 %). PSE was associated with a transjugular intrahepatic portosystemic shunt in 20 cases. Median follow-up after PSE was 41.9 months [0.5-270.5]. Platelet count increased from a median of 48.0 G/L [IQR 37.0; 60.0] to 100.0 G/L [75.0; 148]. Forty-eight patients (52.7 %) had complications after PSE; 25 cases were considered severe (including 7 deaths). A Child-Pugh B-C score (p < 0.02) was significantly associated with all complications, a history of portal vein thrombosis (p < 0.01), and the absence of prophylactic antibiotherapy (p < 0.05) with severe complications., Conclusion: Our results strongly confirm that PSE is very effective, for a long time, although a quarter of the patients experienced severe complications. Improved patient selection (exclusion of patients with portal vein thrombosis and decompensated cirrhosis) and systematic prophylactic antibiotherapy could reduce morbidity and early mortality in the future., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study.", Methods: Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures., Results: From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27)., Conclusions: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described., Research Question: What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients?, Study Design and Methods: In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU., Results: One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022)., Interpretation: LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background & Aims: In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicle (lEV) concentrations reflect disease activity, but their ability to predict liver-related events is unknown., Methods: We measured plasma keratin-18 and hepatocyte lEV concentrations in 500 patients with Child-Pugh class A alcohol-related cirrhosis. The ability of these hepatocyte-derived biomarkers, alone or combined with model for end-stage liver disease (MELD) and FibroTest scores, to predict liver-related events at 2 years was analyzed, taking into account the alcohol consumption at inclusion and during follow-up., Results: Keratin-18 and hepatocyte lEV concentrations increased with alcohol consumption. In patients without active alcohol consumption at enrollment (n = 419), keratin-18 concentration predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both keratin-18 concentrations >285 U/L and FibroTest >0.74 had a 24% cumulative incidence of liver-related events at 2 years, vs. 5% to 14% in other groups of patients. Similar results were obtained when combining keratin-18 concentrations >285 U/L with MELD >10. In patients with active alcohol consumption at enrollment (n = 81), hepatocyte lEVs predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both hepatocyte lEV concentrations >50 U/L and FibroTest >0.74 had a 62% cumulative incidence of liver-related events at 2 years, vs. 8% to 13% in other groups of patients. Combining hepatocyte lEV concentrations >50 U/L with MELD >10 had a lower discriminative ability. Similar results were obtained when using decompensation of cirrhosis, defined according to Baveno VII criteria, as an endpoint., Conclusion: In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers with FibroTest or MELD scores identifies patients at high risk of liver-related events, and could be used for risk stratification and patient selection in clinical trials., Impact and Implications: In patients with compensated alcohol-related cirrhosis, reliable predictors of outcome are lacking. In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers (keratin-18 and hepatocyte-large extracellular vesicles) with FibroTest or MELD scores identifies those at high risk of liver-related events at 2 years. The identified patients at high risk of liver-related events are the target-of-choice population for intensive surveillance (e.g., referral to tertiary care centers; intensive control of risk factors) and inclusion in clinical trials., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax., Methods: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management., Results: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001)., Conclusions: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The diagnosis of clinically significant portal hypertension is crucial for prognosis and treatment guidance in patients with compensated advanced chronic liver disease (ACLD). Spleen stiffness measurement (SSM) might improve the non-invasive diagnosis of clinically significant portal hypertension, but previous studies have reported heterogeneous SSM cutoffs. We aimed to evaluate the accuracy of SSM and SSM-based algorithms in this setting., Methods: In this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from database inception to Dec 31, 2022, for articles, abstracts, and letters, with no restrictions on language. Cross-sectional studies reporting hepatic venous pressure gradient and SSM by different techniques (transient elastography; two-dimensional shear-wave elastography [2D-SWE]; point shear-wave elastography [p-SWE]) in adults (≥18 years) with compensated ACLD were eligible for inclusion. The main outcome was the diagnostic performance of two SSM-based algorithms, with the Baveno VII model as a reference, evaluating sensitivity and specificity, as well as summary negative predictive values (NPVs) and positive predictive values (PPVs). In the Baveno VII model, clinically significant portal hypertension was ruled out if patients had a liver stiffness measurement (LSM) of 15 kPa or less and a platelet count of 150 × 10 9 platelets per L or higher and ruled in if they had an LSM of greater than 25 kPa. The two SSM-based models combined these same cutoffs with additional criteria. In the Baveno VII-SSM single cutoff model, clinically significant portal hypertension was ruled out if at least two of the following were present: LSM of 15 kPa or less, platelet count of 150 × 10 9 platelets per L or higher, and SSM of 40 kPa or less; and ruled in if at least two were present: LSM of greater than 25 kPa, platelet count of less than 150 × 10 9 platelets per L, and SSM of greater than 40 kPa. The Baveno VII-SSM dual cutoff model used the same criteria, but with a cutoff of SSM of less than 21 kPa to rule out, and greater than 50 kPa to rule in, clinically significant portal hypertension. This study is registered with PROSPERO, CRD42019127164., Findings: Of the 44 records assessed for eligibility, 17 studies (with 1245 patients) were included in the meta-analysis. In the transient elastography cohort (n=600), the Baveno VII algorithm was validated for both ruling out (NPV 100%, 95% CI 64-100; sensitivity 100%, 95% CI 70-100) and ruling in (PPV 95%, 85-98; specificity 94%, 95% CI 87-97) clinically significant portal hypertension, but the proportion of patients with indeterminate results (grey zone) was 48% (95% CI 44-52); 57% (95% CI 52-62) of patients with clinically significant portal hypertension were included in the rule-in zone. The Baveno VII-SSM dual cutoff model had adequate NPV (98%, 95% CI 58-100; sensitivity 100%, 95% CI 91-100) and PPV (93%, 95% CI 84-97; specificity 89%, 95% CI 84-93), with 32% (95% CI 28-36) of patients in the grey zone; 76% (95% CI 72-80) of the patients with clinically significant portal hypertension were in the rule-in zone. The Baveno VII-SSM single cutoff model had a sensitivity of 93% (95% CI 85-97) and a NPV of 85% (95% CI 60-96) for ruling out, and a specificity of 86% (95% CI 80-91) and a PPV of 92% (95% CI 83-95) for ruling in, clinically significant portal hypertension. 88% (95% CI 84-91) of patients with clinically significant portal hypertension were included in the rule-in zone and 9% (95% CI 7-12) of patients were in the grey zone. In the 2D-SWE cohort (n=225), all three algorithms could safely rule in clinically significant portal hypertension with adequate PPV (≥90%), but NPV was inadequate for ruling out clinically significant portal hypertension. Insufficient data were available to evaluate the performance of SSM assessed by p-SWE. Heterogeneity was low (I 2 <25%) for most estimates., Interpretation: Algorithms combining Baveno VII criteria with SSM showed good performance and reduced the diagnostic grey zone for clinically significant portal hypertension compared with Baveno VII criteria alone. Future studies should evaluate whether SSM-based diagnosis allows for the identification of patients who would benefit from non-selective β-blocker treatment., Funding: None., Competing Interests: Declaration of interests P-ER has received research funding from Terrafirma; acted as a consultant for Hemostod, Mursla, Genfit, Boehringer Ingelheim, and Abbelight; and received speaker fees from Tillotts Pharma and AbbVie. TR received grant support from AbbVie, Boehringer Ingelheim, Gilead, Gore, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, and Siemens; speaking honoraria from AbbVie, Gilead, Gore, Intercept, Roche, and MSD; consulting or advisory board fees from AbbVie, Bayer, Boehringer Ingelheim, Gilead, Intercept, MSD, and Siemens; and travel support from AbbVie, Boehringer Ingelheim, Gilead, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background & Aims: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a risk factor for splanchnic vein thrombosis (SVT) is unknown. This study aims to assess the impact of SARS-CoV-2 infection on the presentation and prognosis of recent SVT and to identify specific characteristics of SARS-CoV-2-associated SVT., Methods: This is a retrospective study collecting health-related data of 27 patients presenting with recent SVT in the context of SARS-CoV-2 infection in 12 Vascular Liver Disease Group (VALDIG) centres and in comparison with 494 patients with recent SVT before the SARS-CoV-2 pandemic., Results: Twenty-one patients with SARS-CoV-2 had portal vein thrombosis with or without thrombosis of another splanchnic vein, two had superior mesenteric vein thrombosis, one had splenic vein thrombosis, and three had hepatic vein thrombosis. Diagnosis of SVT was made 10 days (95% CI 0-24 days) after the diagnosis of SARS-CoV-2 infection. Fever (52 vs . 15%; p <0.001) and respiratory symptoms (44 vs . 0%; p <0.001) were more frequent, and median lymphocyte count was lower (1.1 × 10 3 /mm 3 vs . 1.6 × 10 3 /mm 3 ; p  = 0.043) in patients with infection than in those without SARS-CoV-2 infection. A prothrombotic condition was identified in 44 and 52% of patients with and without SARS-CoV-2 infection, respectively ( p  = 0.5). All patients with SARS-CoV-2 received anticoagulation therapy. During a median follow-up of 250 days, three SARS-CoV-2-infected patients (11%) required intestinal resection for infarction 1 to 3 months after diagnosis of SVT compared with 13 (2.6%) controls ( p  = 0.044). Partial or complete recanalisation of the thrombosed splanchnic vein was performed in 33% of patients with SARS-CoV-2., Conclusions: SARS-CoV-2 infection can be associated with recent SVT. Intestinal infarction leading to intestinal resection might be more frequent in patients with SARS-CoV-2., Impact and Implications: SARS-CoV-2 infection can be associated with recent SVT. SVT occurring during SARS-CoV-2 infection is characterised by a higher frequency of respiratory symptoms and a lower lymphocyte count. Intestinal infarction leading to intestinal resection appears to occur more frequently in patients with SARS-CoV-2., Competing Interests: The authors have no competing interests to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)