Effectiveness of controlled-expansion transjugular intrahepatic portosystemic shunt (CX-TIPS) in an interdisciplinary setting at a large tertiary center.

Introduction: The use of controlled-expansion transjugular intrahepatic portosystemic shunt (CX-TIPS) effectively controls portal hypertension (PH)-related complications while reducing risks related to fully expanded stents. We evaluated the effectiveness of CX-TIPS in a large Viennese patient cohort.

Method: We assessed the number of patients evaluated for CX-TIPS placement by interdisciplinary discussion at the Medical University of Vienna and included all patients from the prospective AUTIPS registry undergoing CX-TIPS placement between June 2018 - December 2024.

Smoking Aggravates Inflammation, Fibrogenesis, Angiogenesis and Cancer Risk in Patients With Cirrhosis.

Background And Aims: Smoking induces a proinflammatory state, yet its role in advanced chronic liver disease (ACLD) remains understudied. This study evaluated its impact on disease-driving mechanisms and clinical outcomes in ACLD patients.

Methods: ACLD patients undergoing hepatic venous pressure gradient measurements from 2017 to 2021 were included.

Diagnostic and Clinical Implications of High Spleen-To-Liver Stiffness Ratio in MASH-A Prospective, Comparative Study.

Background: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) represent non-invasive surrogates of portal hypertension (PH) that both correlate with hepatic venous pressure gradient (HVPG). SSM may overcome limitations of HVPG and LSM in detecting presinusoidal PH components. We investigated the SSM/LSM ratio as a PH surrogate and its relationship to HVPG and spleen diameter across different liver disease aetiologies.

Clinical Features of Portal Hypertension and Their Prognostic Implications in Patients With Autoimmune Hepatitis.

Background And Aims: Autoimmune hepatitis (AIH) may progress to advanced chronic liver disease (ACLD) with clinically significant portal hypertension (CSPH). In this study, we evaluated the prevalence of different clinical CSPH features and their prognostic impact regarding decompensation, liver transplantation (LTX) and death in patients with AIH.

Method: Patients with confirmed AIH diagnosis (sIAIHG-Score ≥ 6) managed at the Vienna General Hospital between 2005 and 2023 were retrospectively analysed.

FXR adapts hepatic mitochondrial function to increased substrate oxidation in patients with obesity.

Metabolic pressure shifts signaling pathways of nuclear receptors, including the bile acid receptor FXR, which are sensitive to nutritional inputs. We performed an FXR ChIP-seq-centered multiomic analysis of liver biopsy samples from individuals with or without obesity, who were treated with either placebo or the FXR agonist obeticholic acid, to define metabolic adaptions of FXR signaling pathways. FXR occupied substantially more DNA binding sites in individuals with obesity, and FXR activation by OCA robustly changed the transcriptional output.

MRI-derived quantification of hepatic vessel-to-volume ratios in chronic liver disease using a deep learning approach.

Background: We aimed to quantify hepatic vessel volumes across chronic liver disease stages and healthy controls using deep learning-based magnetic resonance imaging (MRI) analysis, and assess correlations with biomarkers for liver (dys)function and fibrosis/portal hypertension.

Methods: We assessed retrospectively healthy controls, non-advanced and advanced chronic liver disease (ACLD) patients using a 3D U-Net model for hepatic vessel segmentation on portal venous phase gadoxetic acid-enhanced 3-T MRI. Total (TVVR), hepatic (HVVR), and intrahepatic portal vein-to-volume ratios (PVVR) were compared between groups and correlated with: albumin-bilirubin (ALBI) and "model for end-stage liver disease-sodium" (MELD-Na) score) and fibrosis/portal hypertension (Fibrosis-4 (FIB-4) Score, liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), platelet count (PLT), and spleen volume.

Association between CMR-derived hepatic T1-time, tricuspid regurgitation and survival.

Background: Cardiac magnetic resonance (CMR) derived hepatic T1-time is associated with outcome. However, the interplay between tricuspid regurgitation (TR), which can cause congestive hepatopathy and liver T1-time is unclear.

Methods: We measured hepatic T1-time in CMR all-comers, who underwent echocardiography within 3 weeks of CMR.

Successful AAV8 gene therapy on hepatic ex situ machine perfusion for mitochondrial neurogastrointestinal encephalomyopathy.

Ex situ normothermic machine perfusion (NMP) is rapidly emerging as a novel platform for testing therapeutics in human donor livers. Recently perfusion of explanted patient livers was achieved, raising the possibility of using these diseased organs to increase the fidelity and resolution of drug testing and development. Here, we provide proof-of-principle for the feasibility of this approach in the context of gene therapy.

UDFF and Auto pSWE accurately assess liver steatosis and fibrosis risk in obese patients with MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) can progress to fibrosis and cirrhosis. Fibrosis and steatosis assessment with vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) requires a dedicated device and time to obtain ≥10 reliable measurements. Auto pSWE allows for the simultaneous collection of 15 ARFI-based liver stiffness measurements (LSM) and UDFF-based steatosis assessment in a single acquisition.

Refining Prognosis in Cirrhosis Patients With Ascites: Impact of Acute vs. Non-Acute Decompensation.

Background: A more granular understanding of hepatic decompensation in cirrhosis has led to the classification of acute decompensation (AD) and non-acute decompensation (NAD). In this study, we assessed differences in the clinical course of AD versus NAD in patients with ascites as the first decompensation event.

Methods: 505 cirrhosis patients with ascites as first decompensation were included in this single-center longitudinal cohort study and followed until further decompensation, orthotopic liver transplantation (OLT), or death.

Molecular patterns of the NO-sGC-cGMP pathway in progressive and regressive liver fibrosis models.

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine-monophosphate (cGMP) pathway is impaired in liver fibrosis. We investigated expression patterns of NO-sGC-cGMP components via RT-qPCR in various rat models of liver fibrosis and murine models of liver fibrosis regression. Hepatic cGMP-levels were measured chromatographically.

Identifying signatures of image phenotypes to track treatment response in liver disease.

Quantifiable image patterns associated with disease progression and treatment response are critical tools for guiding individual treatment, and for developing novel therapies. Here, we show that unsupervised machine learning can identify a pattern vocabulary of liver tissue in magnetic resonance images that quantifies treatment response in diffuse liver disease. Deep clustering networks simultaneously encode and cluster patches of medical images into a low-dimensional latent space to establish a tissue vocabulary.

Risk of portal hypertensive complications preventable by TIPS in patients with ascites.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment of recurrent/refractory ascites in patients with cirrhosis. The aim of this study is to identify patients with ascites as index decompensation who are at risk of developing portal hypertension (PH)-related complications within 12 months that seem preventable by TIPS.

Methods: We included 451 patients from two tertiary care centres (Vienna and Padua, derivation cohort) with clinically significant ascites (grade 2/3) as a single first decompensating event and without contraindications for TIPS placement.

Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.

Progress in our understanding of the molecular basis of bile acid (BA) transport in the liver, bile ducts, intestine, and kidney has not only advanced our understanding of the pathophysiology of cholestasis and metabolic dysfunction-associated liver disease but also led to novel therapeutic approaches targeting BA transport and signaling within the entero-nephro-hepatic circulation. This includes BA transport modulators such as inhibitors of the apical BA-transport system in the terminal ileum and proximal renal tubule (IBAT/ASBT inhibitors) and basolateral (sinusoidal) BA uptake in hepatocytes (NTCP inhibitors). In addition to altering membrane transporter function by targeting IBAT/ASBT and NTCP, there is an array of potentially additive therapeutic approaches which include receptor agonists acting via nuclear receptor (FXR, PPAR)-mediated transcriptional modification of BA synthesis and transport genes and BA analogs such as norucholic acid (previously known as norUDCA) that undergo cholehepatic shunting.

Pathogenic aspects of fructose consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): A narrative review.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to non-alcoholic fatty liver disease (NAFLD), has become a global health concern with a still increasing prevalence. One of the major contributing factors to its pathogenesis is overnutrition. In recent years, a discussion has been started that not only general overnutrition but also specific dietary patterns like the so-called 'Western diet' composed of foods rich in saturated fats, cholesterol, and sugar (especially fructose) but low in fiber and polyunsaturated fats, may contribute to the development of MASLD.

The history and future of bile acid therapies.

Animal bile has been regarded as a potential remedy for liver diseases for millennia in ancient Eastern cultures. The application of bile acids, as major organic components of bile, for gallstone dissolution and of ursodeoxycholic acid (UDCA) for cholestatic liver diseases began in the second half of the 20 century. Currently, UDCA is regarded as an effective first-line treatment for primary biliary cholangitis, the most common chronic cholestatic liver disease, and is also applied in other cholestatic disorders, including primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy.

Severe alpha-1 antitrypsin deficiency is associated with a higher risk of complications after first decompensation than other aetiologies of cirrhosis.

Background & Aims: Alpha-1 antitrypsin deficiency (AATD) causes/predisposes to advanced chronic liver disease. However, the role of the Pi∗ZZ genotype in patients with decompensated cirrhosis is unclear. Thus, we evaluated the impact of the Pi∗ZZ genotype on the disease course after the first hepatic decompensation event.

Minimal residual ascites 3 months after TIPS implantation implicates worse clinical outcomes in patients with cirrhosis.

Background & Aims: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is indicated for recurrent/refractory ascites in patients with cirrhosis. The prognostic impact of residual minimal ascites after TIPS implantation has not yet been investigated.

Methods: We included patients with cirrhosis undergoing covered TIPS implantation for refractory ascites in Vienna (2000-2022) and Hannover (2009-2021) with available abdominal ultrasound 3 months after TIPS insertion (3M).

Primary biliary cholangitis and the narrowing gap towards optimal disease control.

Although infrequent, primary biliary cholangitis is not indolent and remains a burdensome chronic autoimmune biliary disease. Progressive biliary injury and cholestasis results in complications of biliary cirrhosis, with reduced quality and quantity of life. Treatment advances beyond ursodeoxycholic acid and liver transplantation are notable, as efforts grow to prevent end-stage liver disease.

The Vasopressin Biomarker Copeptin is Linked to Systemic Inflammation and Refines Prognostication in Decompensated Cirrhosis.

Background & Aims: Copeptin, an arginine-vasopressin biomarker, may confer prognostic information in patients with advanced chronic liver disease (ACLD).

Methods: Patients with ACLD included in the Vienna Cirrhosis Study (NCT03267615) between January 2017 and April 2023 and available copeptin levels were prospectively recruited and classified into 6 predefined clinical ACLD stages from S0 (subclinical portal hypertension) to S5 (further decompensation). A prognostic score (MELD-copeptin score) in patients with decompensated ACLD (dACLD) was developed in a derivation cohort (n = 150) and validated in an internal (n = 148) and an external validation cohort (n = 771).

Acute liver failure in patients admitted to the intensive care unit-a Viennese retrospective single-center analysis.

Background: Acute liver failure (ALF) is characterized by a rapid deterioration of liver function and a high mortality without transplantation depending on etiology and onset. Immediate transfer to a dedicated intensive care unit (ICU) and evaluation for high-urgency liver transplantation (HU-LTx) is recommended to maximize chances of survival. Data on ALF epidemiology are limited, particularly for Central Europe.

Enteronephrohepatic circulation of bile acids and therapeutic potential of systemic bile acid transporter inhibitors.

Together with carriers in the liver and small intestine, kidney transporters function to conserve and compartmentalise bile acids in the enteronephrohepatic circulation. In patients with liver disease, systemic bile acid levels are elevated, undergo increased renal glomerular filtration, and contribute to the pathogenesis of cholemic nephropathy and acute kidney injury. In this review, we describe mechanisms for renal bile acid transport and highlight very recent discoveries that challenge current paradigms on the pathogenesis of cholemic nephropathy and renal tubule cast formation.

Effect of Cecal Intubation Rate on Post Colonoscopy Colorectal Cancer Deaths and Detection of Colorectal Cancer Precursors.

Background & Aims: The visualization of the whole colonic mucosa with complete colonoscopy including cecal intubation has been accepted as a quality parameter for screening colonoscopy. However, there is little evidence regarding the cecal intubation rate (CIR) and its association with long-term patient outcome.

Methods: We did a linkage of individuals that participated in an Austrian Colonoscopy Quality Assurance Program to the Austrian death registry to obtain information on deaths of post-colonoscopy colorectal cancer (PCCRC).

No increase of biopsy rates despite high rates of probable eosinophilic esophagitis in patients with esophageal food impaction.

Introduction: Eosinophilic esophagitis (EoE) is one of the main causes of esophageal food impaction (EFI). Since only few endoscopists take biopsies during the emergency endoscopy at EFI presentation, as is recommended by current guidelines, a high number of patients will not have a proper diagnosis after EFI. Hence, we investigated the change of biopsy rates and the etiology of EFI over 11 years.