Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

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).

Von Willebrand factor for outcome prediction within different clinical stages of advanced chronic liver disease.

Background And Aims: The prognostic performance of von Willebrand factor (VWF) may vary across clinical stages of advanced chronic liver disease (ACLD). Therefore, we investigated the evolution of VWF and other biomarkers throughout the full ACLD spectrum and evaluated their stage-specific prognostic utility.

Methods: We retrospectively included Viennese ACLD patients with available information on hepatic venous pressure gradient (HVPG), C-reactive protein (CRP)/VWF levels and outcomes.

Platelet adhesion assessed by PFA-100 is not linked to progression of ACLD.

Background & Aims: Increased aggregation of individual platelets upon activation, as assessed by whole blood aggregometry standardised to platelet count (PLT), has recently been linked to progression of advanced chronic liver disease (ACLD). Moreover, changes in primary haemostasis have been implicated in bleeding and thrombosis in patients with ACLD.We aimed (i) to identify the determinants of the primary haemostatic capacity - as assessed by Platelet Function Analyzer 100 (PFA-100) (' bleeding time') - in patients with ACLD and (ii) to investigate its potential association with clinical outcomes.

Von Willebrand factor processing in patients with advanced chronic liver disease and its relation to portal hypertension and clinical outcome.

Background And Aims: Endothelial dysfunction and portal hypertension (PH) are reflected by increased von Willebrand factor antigen (VWF-Ag) levels in advanced chronic liver disease (ACLD). This study investigated VWF release and cleavage and their association with PH and clinical outcomes.

Methods: Levels of VWF-Ag, VWF-N (VWF-propeptide), and VWF-A (VWF processed by the main VWF-cleaving protease ADAMTS13) were assessed in 229 patients with clinically stable ACLD (hepatic venous pressure gradient [HVPG] ≥ 6 mmHg; absence of bacterial infections or acute decompensation) undergoing HVPG-measurement.

Diabetes impairs the haemodynamic response to non-selective betablockers in compensated cirrhosis and predisposes to hepatic decompensation.

Background: Non-selective betablockers (NSBBs) reduce the risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD). Metabolic co-morbidities (MetC) are increasingly observed in cACLD patients.

Aims: To investigate the impact of MetC on the haemodynamic effects of NSBB and hepatic decompensation in cACLD.

Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol-related cirrhosis.

Background & Aims: Removing the primary aetiological factor in decompensated cirrhosis may lead to a restoration of hepatic function. In this study, we investigated the clinical implications of recompensation and the subsequent survival in patients with decompensated alcohol-related cirrhosis.

Methods: The rate of recompensation was evaluated in patients with decompensated alcohol-related cirrhosis and persistent alcohol abstinence undergoing a hepatic venous pressure gradient (HVPG) measurement.

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis.

Background: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

Methods: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD.

Etiological cure prevents further decompensation and mortality in patients with cirrhosis with ascites as the single first decompensating event.

Background And Aims: Removal/suppression of the primary etiological factor reduces the risk of decompensation and mortality in compensated cirrhosis. However, in decompensated cirrhosis, the impact of etiologic treatment is less predictable. We aimed to evaluate the impact of etiological treatment in patients with cirrhosis who developed ascites as single index decompensating event.

Bacterial growth and ceftriaxone activity in individual ascitic fluids in an model of spontaneous bacterial peritonitis.

The environment of the infection site affects bacterial growth and antibiotic activity. When bacterial growth and antibiotic activity are studied in body fluids, samples of multiple subjects are usually pooled, averaging out potentially relevant differences in composition. The ascitic fluid (AF) environment is frequently associated with spontaneous bacterial peritonitis (SBP) in cirrhotic patients.

Disturbances in sodium and chloride homeostasis predict outcome in stable and critically ill patients with cirrhosis.

Background: Hyponatremia has prognostic implications in patients with cirrhosis, and thus, has been incorporated in the 2016 MELD-UNOS update. Changes in serum chloride are commonly perceived as 'just' parallel to changes in serum sodium. However, these are less well studied in the context of cirrhosis.

Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease.

Background & Aims: Ammonia levels predicted hospitalisation in a recent landmark study not accounting for portal hypertension and systemic inflammation severity. We investigated (i) the prognostic value of venous ammonia levels (outcome cohort) for liver-related outcomes while accounting for these factors and (ii) its correlation with key disease-driving mechanisms (biomarker cohort).

Methods: (i) The outcome cohort included 549 clinically stable outpatients with evidence of advanced chronic liver disease.

The impact of transmembrane 6 superfamily 2 (TM6SF2) rs58542926 on liver-related events in patients with advanced chronic liver disease.

Background & Aims: Genetic factors such as the transmembrane 6 superfamily 2 (TM6SF2) rs58542926 single nucleotide variant(SNV) modulate the susceptibility for (advanced) chronic liver disease ([A]CLD). However, the impact of this variant in patients who have already progressed to ACLD is unknown.

Methods: The association between TM6SF2-rs58542926 genotype and liver-related events was evaluated in 938 ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement.

The systemic and hepatic alternative renin-angiotensin system is activated in liver cirrhosis, linked to endothelial dysfunction and inflammation.

We aimed to assess the systemic and hepatic renin-angiotensin-system (RAS) fingerprint in advanced chronic liver disease (ACLD). This prospective study included 13 compensated (cACLD) and 12 decompensated ACLD (dACLD) patients undergoing hepatic venous pressure gradient (HVPG) measurement. Plasma components (all patients) and liver-local enzymes (n = 5) of the RAS were analyzed using liquid chromatography-tandem mass spectrometry.

The Sequential Application of Baveno VII Criteria and VITRO Score Improves Diagnosis of Clinically Significant Portal Hypertension.

Background & Aims: Baveno VII proposed liver stiffness measurement (LSM)/platelet count (PLT)-based criteria ('ruled out,' LSM ≤15 kPa plus PLT ≥150 G/L; 'ruled in': LSM ≥25 kPa) for clinically significant portal hypertension (CSPH) in compensated advanced chronic liver disease (cACLD). However, a substantial proportion of patients remains 'unclassified.'

Methods: Patients with evidence of cACLD (LSM ≥10 kPa) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital 2004 to 2021 (derivation [2004-2016], n = 221; validation [2017-2021], n = 81) were included.

Alpha-1 antitrypsin Pi∗Z allele is an independent risk factor for liver transplantation and death in patients with advanced chronic liver disease.

Background & Aims: Alpha-1 antitrypsin (AAT) deficiency causes/predisposes individuals to advanced chronic liver disease (ACLD). However, the role of the Pi∗Z allele in patients who have already progressed to ACLD is unclear. Thus, we aimed to evaluate the impact of the Pi∗Z allele on the risk of liver transplantation/liver-related death in patients with ACLD, while adjusting for the severity of liver disease at inclusion.

Clinical significance of substantially elevated von Willebrand factor antigen levels in patients with advanced chronic liver disease.

Background: Von Willebrand factor antigen (VWF) is a non-invasive marker for clinically significant portal hypertension (HVPG≥10 mmHg) and confers HVPG-independent prognostic information. While quantification of increased VWF-levels is not relevant in the context of von Willebrand disease, highly elevated VWF may be of clinical significance in ACLD. Thus, we have modified our analytical approach to quantify very high VWF-levels (i.

Carvedilol Achieves Higher Hemodynamic Response and Lower Rebleeding Rates Than Propranolol in Secondary Prophylaxis.

Background & Aims: Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding.

Methods: Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis.

Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease.

Background & Aims: Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic liver disease (ACLD).

Methods: Serum biomarkers of SI (CRP, IL-6, procalcitonin [PCT]) and extracellular matrix (ECM) turnover (i.

Acute hemodynamic response to propranolol predicts bleeding and nonbleeding decompensation in patients with cirrhosis.

Nonselective beta-blockers are used as prophylaxis for variceal bleeding in patients with advanced chronic liver disease (ACLD). The acute hemodynamic response to intravenous propranolol (i.e.

Current treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of pathologies ranging from non-alcoholic fatty liver (NAFL), characterized by simple steatosis without inflammation, to non-alcoholic steatohepatitis (NASH), characterized by steatosis of the liver accompanied by inflammation and hepatocyte ballooning, which can lead to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Apart from lifestyle modifications such as weight loss, a Mediterranean diet and physical activity, only a few NAFLD-specific pharmacological treatment options such as Vitamin E and Pioglitazone are considered by current international guidelines. However, recently randomized controlled trials with GLP-1 agonists, FXR and PPAR ligands as well as other agents have been published and may expand the therapeutic armamentarium for NAFLD in the near future.