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. (c) 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

We evaluated the application of quantitative phase imaging (QPI) with digital holographic microscopy (DHM) for the assessment of histopathological inflammation in patients with ulcerative colitis (UC).

Das akut-auf-chronische Leberversagen (ACLF) bezeichnet das Endstadium chronischer Lebererkrankungen und ist durch eine hohe Mortalität gekennzeichnet. In dieser Übersichtsarbeit sollen Pathophysiologie, Definition und Prognoseabschätzung des ACLF erläutert werden. Literaturrecherche, Analyse und Diskussion bestehender Grundlagenarbeiten zum Thema des ACLF. Das ACLF entsteht in Folge einer schweren systemischen Inflammation, die durch verschiedene Auslöser (Infektionen, akute Alkoholhepatitis, Blutungen) induziert wird und in einem Circulus vitiosus den Krankheitsprozess unterhält und vorantreibt. Neue Prognosescores, bestehend aus Lebersynthesemarkern und elastographischen Verfahren, können dabei helfen, Risikopatienten zu identifizieren. Krankheitsdefinierend für das ACLF ist eine dekompensierte Leberzirrhose mit neu aufgetretenem (Mehr‑)Organversagen. Die möglichen Organversagen werden anhand des abgewandelten Chronic-liver-failure(CLIF)-sequential-organ-failure-assessment(SOFA)-Scores festgelegt (Leber, Gerinnung, Niere, Enzephalopathie, Atmung und Kreislauf) und gehen zusammen mit Patientenalter und Markern der systemischen Inflammation in den CLIF-consortium(C)-ACLF-Score ein. Nierenversagen und hepatische Enzephalopathie zeigen eine besondere Relevanz und sind mit einer schlechten Prognose assoziiert. Der CLIF-C-ACLF-Score ist dafür geeignet, Patienten mit einem ACLF zu identifizieren und deren 30-Tage-Mortalität abzuschätzen. Das ACLF ist ein lebensbedrohliches Krankheitsbild. Prognosescores können in Zukunft dazu beitragen, Risikopatienten zu identifizieren. Die frühzeitige Diagnose eines ACLF sowie der individuellen Auslöser ist entscheidend für die Therapie.

Metabolic dysfunction-associated Steatohepatitis (MASH), is a prominent cause for liver cirrhosis. MASH-cirrhosis is responsible for liver complications and there is no specific treatment. To develop new therapeutic approaches, animal models are needed. The aim of this study was to develop a fast animal model of MASH-cirrhosis in rats reflecting the human disease. Carbon tetrachloride (CCl4) injections in combination with a high-fat Western diet (WD) were used to induce MASH-cirrhosis. To accelerate liver injury, animals received phenobarbital (PB) in their drinking water using two different regimens. Rats developed advanced MASH-cirrhosis characterized by portal hypertension, blood biochemistry, hepatic ballooning, steatosis, inflammation and fibrosis. Importantly, rats receiving low-dose PB for the long term (LT) showed ascites after 6 weeks, whereas rats with high-dose short-term (ST) PB developed ascites after 8 weeks. ST- and LT-treated rats showed increased portal pressure (PP) and decreased mean arterial pressure (MAP). Of note, hepatocyte ballooning was only observed in the LT group. The LT administration of low-dose PB with CCl4 intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl4 + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis.

Aims Upper gastrointestinal bleeding (UGIB) is the most common manifestation of gastrointestinal (GI) bleedings. In recent years, local hemostatic agents became more widely available and are associated with a high rate of successful immediate yet short-term hemostasis. However, the clinical efficacy on UGIB recurrence is unknown. This study aims to evaluate the clinical efficacy of bentonite and synthetic peptides on immediate endoscopic hemostasis and UGIB recurrence.

In the spring of 2020, the SARS-CoV-2 pandemic presented a formidable challenge to national and global healthcare systems. Immunocompromised individuals or those with relevant pre-existing conditions were particularly at risk of severe coronavirus disease 2019 (COVID-19). Thus, understanding the immunological processes in these patient groups is crucial for current research. This study aimed to investigate humoral immunity following vaccination and infection in liver transplant recipients. Humoral immunity analysis involved measuring IgG against the SARS-CoV-2 spike protein (anti-S IgG) and employing a surrogate virus neutralization test (sVNT) for assessing the hACE2 receptor-binding inhibitory capacity of antibodies. The study revealed that humoral immunity post-vaccination is well established, with positive results for anti-S IgG in 92.9% of the total study cohort. Vaccinated and SARS-CoV-2-infected patients exhibited significantly higher anti-S IgG levels compared to vaccinated, non-infected patients (18,590 AU/mL vs. 2320 AU/mL, p < 0.001). Additionally, a significantly elevated receptor-binding inhibitory capacity was observed in the cPassTMTM sVNT (96.4% vs. 91.8%, p = 0.004). Furthermore, a substantial enhancement of anti-S IgG levels (p = 0.034) and receptor-binding inhibition capacity (p < 0.001) was observed with an increasing interval post-transplantation (up to 30 years), calculated by generalized linear model analysis. In summary, fully vaccinated liver transplant recipients exhibit robust humoral immunity against SARS-CoV-2, which significantly intensifies following infection and with increasing time after transplantation. These findings should be considered for booster vaccination schemes for liver transplant recipients.

Background: Acute-on-chronic liver failure (ACLF), as the end-stage of chronic liver diseases, is characterized by very high short-term mortality. Objectives: In this work, pathomechanisms of ACLF development, diagnostic as well as prognostic criteria are discussed. Methods: Review of the literature related to ACLF, analyses and discussion of the results. Results: Severe systemic inflammation, as a response to precipitating events (infections, acute alcoholic hepatitis, bleeding), is the main pathomechanism for the development and progression of ACLF. Novel prognostic scoring tests using liver function markers and elastography can be useful for the identification of patients at risk to develop ACLF. ACLF is defined as single or multiorgan failure in patients with decompensated liver cirrhosis. Organ failures are classified using the modified chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score (liver, coagulation, kidney, brain, lung, circulation). The CLIF-C-ACLF score is a combination of CLIF-SOFA, age and inflammatory markers at the time of ACLF diagnosis. Kidney and brain failure are relevant markers and determinants of poor patient outcome. CLIF-C-ACLF score is useful to identify patients with ACLF and predict individual 30-day short-term mortality. Conclusions: ACLF is a life-threatening disease. Prognostic scoring tests might be suitable to identify patients at risk. Early diagnosis of ACLF and identification of individual precipitating events is crucial for timely treatment decisions.