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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.)

Background and Aim: Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives., Methods: This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry., Results: The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician's recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient., Conclusion: Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here, we investigate the prognostic value of HVPG in MASLD-related compensated ACLD (MASLD-cACLD)., Methods: This European multicentre study included patients with MASLD-cACLD characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest., Results: A total of 340 patients with MASLD-cACLD (56.2% male; median age 62 [55-68] years, median MELD 8 [7-9], 71.2% with diabetes) were included. Clinically significant portal hypertension (CSPH: i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in those with MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio [SHR] 5.13; p <0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (adjusted SHR per mmHg: 1.12, p <0.001). Liver-related mortality occurred in 37 patients at a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (adjusted SHR per mmHg: 1.20, p <0.001)., Conclusion: HVPG measurement is of high prognostic value in MASLD-cACLD. In patients with MASLD-cACLD without CSPH, the short-term risk of decompensation is very low and liver-related mortality is rare, while the presence of CSPH substantially increases the risk of both., Impact and Implications: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD patients, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in patients with MASLD-cACLD without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker., Aims: Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD., Methods: We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients., Results: A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation., Conclusions: Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background & Aims: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality., Methods: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year., Results: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death., Conclusion: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients., Impact and Implications: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD., Aims: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series., Methods: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients., Results: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn's disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients., Conclusions: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.

There is uncertainty regarding Wilson's disease (WD) management., Objectives: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers., Methods: Data on WD patients followed at 32 Spanish hospitals were collected., Results: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response., Conclusions: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Background & Aims: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis., Methods: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD., Results: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH., Conclusions: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD., Methods: Retrospective multicentre study of 79 patients who received LT for PSVD., Results: Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely., Conclusions: LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension., Competing Interests: V.H.-G. received speaker fees from Gore. J.C.G.-P. advises for GORE, Cook, and Shionogi. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reprogramming of immunosuppressive tumor-associated macrophages (TAMs) presents an attractive therapeutic strategy in cancer. The aim of this study was to explore the role of macrophage CD5L protein in TAM activity and assess its potential as a therapeutic target., Methods: Monoclonal antibodies (mAbs) against recombinant CD5L were raised by subcutaneous immunization of BALB/c mice. Peripheral blood monocytes were isolated from healthy donors and stimulated with IFN/LPS, IL4, IL10, and conditioned medium (CM) from different cancer cell lines in the presence of anti-CD5L mAb or controls. Subsequently, phenotypic markers, including CD5L, were quantified by flow cytometry, IF and RT-qPCR. Macrophage CD5L protein expression was studied in 55 human papillary lung adenocarcinoma (PAC) samples by IHC and IF. Anti-CD5L mAb and isotype control were administered intraperitoneally into a syngeneic Lewis Lung Carcinoma mouse model and tumor growth was measured. Tumor microenvironment (TME) changes were determined by flow cytometry, IHC, IF, Luminex, RNAseq and RT-qPCR., Findings: Cancer cell lines CM induced an immunosuppressive phenotype (increase in CD163, CD206, MERTK, VEGF and CD5L) in cultured macrophages. Accordingly, high TAM expression of CD5L in PAC was associated with poor patient outcome (Log-rank (Mantel-Cox) test p = 0.02). We raised a new anti-CD5L mAb that blocked the immunosuppressive phenotype of macrophages in vitro. Its administration in vivo inhibited tumor progression of lung cancer by altering the intratumoral myeloid cell population profile and CD4 + T-cell exhaustion phenotype, thereby significantly modifying the TME and increasing the inflammatory milieu., Interpretation: CD5L protein plays a key function in modulating the activity of macrophages and their interactions within the TME, which supports its role as a therapeutic target in cancer immunotherapy., Funding: For a full list of funding bodies, please see the Acknowledgements., Competing Interests: Declaration of interests A patent protecting a method for the detection of CD5L has been submitted to the European Patent Office (EP3653646A1). Likewise, the RImAb antibody is the object of an EP3476863A1 patent. LK is part of an institutional licensing agreement with SunRock Biopharma, and co-inventor of two patents (EP22382093.7 and 62828195). JB received support from MSD, Grífols and Hipra through institutional grants, and by AlbaJuna Therapeutics S.L. through an Institutional License. He is Founder and CEO of AlbaJuna Therapeutics S.L. from which he owns stock options. He is also consultant for MSD and Nesapor S.L, and received support from Gilead for attending meetings. GT has received honoraria from Takeda for lectures., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Imported schistosomiasis is an emerging issue in European countries as a result of growing global migration from schistosomiasis-endemic countries, mainly in sub-Saharan Africa. Undetected infection may lead to serious long-term complications with an associated high cost for public healthcare systems especially among long-term migrants., Objective: To evaluate from a health economics perspective the introduction of schistosomiasis screening programs in non-endemic countries with high prevalence of long-term migrants., Methodology: We calculated the costs associated with three approaches-presumptive treatment, test-and-treat and watchful waiting-under different scenarios of prevalence, treatment efficacy and the cost of care resulting from long-term morbidity. Costs were estimated for our study area, in which there are reported to reside 74,000 individuals who have been exposed to the infection. Additionally, we methodically reviewed the potential factors that could affect the cost/benefit ratio of a schistosomiasis screening program and need therefore to be ascertained., Results: Assuming a 24% prevalence of schistosomiasis in the exposed population and 100% treatment efficacy, the estimated associated cost per infected person of a watchful waiting strategy would be €2,424, that of a presumptive treatment strategy would be €970 and that of a test-and-treat strategy would be €360. The difference in averted costs between test-and-treat and watchful waiting strategies ranges from nearly €60 million in scenarios of high prevalence and treatment efficacy, to a neutral costs ratio when these parameters are halved. However, there are important gaps in our understanding of issues such as the efficacy of treatment in infected long-term residents, the natural history of schistosomiasis in long-term migrants and the feasibility of screening programs., Conclusion: Our results support the roll-out of a schistosomiasis screening program based on a test-and-treat strategy from a health economics perspective under the most likely projected scenarios, but important knowledge gaps should be addressed for a more accurate estimations among long-term migrants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Roure et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE., Patients and Methods: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation., Results: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients., Conclusion: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission., Competing Interests: Competing interests: CB has received speaker fees from GORE and is a board member in Alfa Wassemran/Norgine. VH-G, AG, JB, AA, DT and FN have received speaker fees from GORE. J-CG-P has consultant fees from GORE, and Shionogi and Cook grants from GORE and Novartis. JT has speaking and/or consulting fees from GORE, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis and Martin Pharmaceuticals. RB has received speaker fees from GORE and Grifols, unrelated to the submitted work., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bacterial infections remain one of the main complications in cirrhosis and worsen patients' prognosis and quality of life. An increase in multidrug resistant microorganism (MDRM) infections among patients with cirrhosis, together with infection-related mortality rates, have been reported in recent years. Therefore, adaptation of the initial empiric antibiotic approach to different factors, particularly the local epidemiology of MDRM infections, has been recommended. We aim to describe the main features, outcomes and risk factors of MDRM infections in patients with cirrhosis., Methods: Prospective registry of all episodes of in-hospital infections occurring among cirrhotic patients admitted within a 2-year period at a single center. Clinical and microbiological data were collected at the time of infection diagnosis, and the in-hospital mortality rate of the infectious episode was registered., Results: A total of 139 infectious episodes were included. The disease-causing microorganism was identified in 90 episodes (65%), of which 31 (22%) were caused by MDRM. The only two factors independently associated with MDRM infections were rectal colonization by MDRM and a nosocomial or healthcare-associated source. The infection-related mortality rate was 18.7%. MDRM infection and a past history of hepatic encephalopathy were independently associated with in-hospital mortality., Conclusions: Almost one fourth of bacterial infections occurring in admitted cirrhotic patients were due to MDRM. Rectal colonization was the most important risk factor for MDRM infections in decompensated cirrhosis. Screening for MDRM rectal colonization in patients admitted for decompensated cirrhosis should be assessed as a tool to improve local empiric antibiotic strategies., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Background & Aims: Bleeding from gastric fundal varices (isolated gastric varices type 1/gastroesophageal varices type 2) represents a major problem because of a high incidence of rebleeding and death with standard-of-care therapy (endoscopic obliteration with tissue adhesives plus pharmacological therapy). Transjugular intrahepatic portosystemic shunts (TIPSs) are recommended as a rescue therapy. Pre-emptive 'early' TIPS (pTIPS) significantly improves control of bleeding and survival in patients at high-risk of dying or rebleeding from esophageal varices., Methods: This randomised controlled trial investigate whether the use of pTIPS improves rebleeding-free survival in patients with gastric fundal varices (isolated gastric varices type 1 and/or gastroesophageal varices type 2) compared with standard therapy., Results: The study did not achieve the predefined sample size because of low recruitment. Nevertheless, pTIPS (n = 11) was more effective compared with combined endoscopic and pharmacological therapy (n = 10) in improving rebleeding-free survival (per protocol analysis: 100 vs . 28%; p  = 0.017). This was mainly because of a better outcome in patients with Child-Pugh B or C scores. There were no differences in serious adverse events or in the incidence of hepatic encephalopathy among the different cohorts., Conclusion: The use of pTIPS should be considered in patients with Child-Pugh B or C scores bleeding from gastric fundal varices., Impact and Implications: The first-line treatment of gastric fundal varices (GOV2 and/or IGV1) is the combination of pharmacological therapy and endoscopic obliteration with glue. TIPS is considered the main rescue therapy. Recent data suggest that, in patients at high-risk of dying or rebleeding (Child-Pugh C or B scores + active bleeding at endoscopy) from esophageal varices, the use of pTIPS, performed during the first 72 h from admission, results in an increased rate of control of bleeding and survival compared with combined endoscopic and pharmacological therapy. Herein, we present a randomised controlled trial comparing pTIPS with combined endoscopic (injection of glue) and pharmacological therapy (first, somatostatin or terlipressin; carvedilol after discharge) in the treatment of patients bleeding from GOV2 and/or IGV1. Although we were not able to include the calculated sample size because of the scarcity of these patients, our results show that the use of pTIPS is associated with a significantly higher actuarial rebleeding-free survival when analysed as per protocol. This is because of the greater efficacy of this treatment in patients with Child-Pugh B or C scores., Competing Interests: AE/CV: travel grant from Gore. JCGP: Cook advisory board member, travel grants from Gore and Mallinkrodt; JB: consultant/advisory board member for Astra Zeneca, BioVie, 10.13039/100001003Boehringer Ingelheim, NovoNordisk, and Resolution Therapeutics. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Background & Aims: Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension-related decompensation in patients with advanced NAFLD (aNAFLD)., Methods: Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels., Results: Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P = .019) than in the aHCV group. For any of the HVPG cutoff analyzed (&lt;10, 10-12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group., Conclusions: Patients with aNAFLD have higher prevalence of portal hypertension-related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)