Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity

Mandorfer, Mattias; Schwabl, Philipp; Paternostro, Rafael; Pomej, Katharina; Bauer, Dávid; Thaler, Johannes; Ay, Cihan; Quehenberger, Peter; Fritzer‐Szekeres, Monika; Peck‐Radosavljevic, Markus; Trauner, Michael; Reiberger, Thomas; Ferlitsch, Arnulf

doi:10.1111/apt.14522

Cited by 87 publications

(101 citation statements)

References 44 publications

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“…Nevertheless, when restricting the analysis to patients with pretreatment CSPH in order to evaluate the regression of CSPH, the AUROC of TE numerically decreased, whereas the AUROC of VITRO increased. This might be a consequence of liver stiffness being less strongly correlated with HVPG at values ≥ 10‐12 mm Hg in patients without NSBB treatment, and VWF may show a better correlation with HVPG in this patient population …”

Section: Discussionmentioning

confidence: 87%

“…Thus, we aimed to assess the impact of pretreatment HVPG, changes in HVPG, and posttreatment values on the development of hepatic decompensation in patients with PH who achieved SVR to IFN‐free therapy. Moreover, we investigated the use of transient elastography (TE) and von Willebrand factor (VWF) for monitoring the evolution of PH and the impact of HCV cure on markers of bacterial translocation and inflammation …”

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confidence: 99%

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Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon‐Free Therapy

et al. 2019

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Background and Aims Sustained virologic response (SVR) to interferon (IFN)‐free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN‐free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH. Approach and Results The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow‐up [FU]) IFN‐free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08‐1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC], < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86‐0.92) in most patients, especially if assessed in a sequential manner. Conclusions Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An “immediate” HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.

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Section: Discussionmentioning

confidence: 87%

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confidence: 99%

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon‐Free Therapy

et al. 2019

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“…In the present retrospective study the authors observe, in a group of 225 cirrhotic patients, that VWF levels are associated with markers of bacterial translocation (LBP, r = .201; P = 0.021) and systemic inflammation (IL‐6, r = .426; P < 0.001 and C reactive protein, r = .249; P < 0.001), independently of HVPG. These interesting results may indicate that the presence of a pro‐coagulant state in the intestinal microcirculation of cirrhosis patients may favour enterocyte ischaemia, intestinal barrier dysfunction and bacterial translocation .…”

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confidence: 51%

“…These interesting results may indicate that the presence of a pro‐coagulant state in the intestinal microcirculation of cirrhosis patients may favour enterocyte ischaemia, intestinal barrier dysfunction and bacterial translocation . Indeed a relationship between VWF and the pro‐coagulant state (factor VIII/protein C ratio, P = 0.507; P < 0.001) is also present . This vicious circle may perpetuate the chronic systemic inflammation, independently from portal hypertension (Figure ).…”

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confidence: 92%

“…The work by Mandorfer et al examines the complex link between endothelial dysfunction and systemic inflammation in liver cirrhosis and provides some clinical evidence for a correlation between increased levels of Von Willebrand factor (VWF), bacterial translocation, systemic inflammation, pro‐coagulant imbalance and complications of cirrhosis, independently of the severity of portal hypertention.…”

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confidence: 99%

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Editorial: von Willebrand factor and CRP levels may predict survival in liver cirrhosis

Merli

Gregorio

2018

Aliment Pharmacol Ther

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The von Willebrand Factor Facilitates Model for End‐Stage Liver Disease–Independent Risk Stratification on the Waiting List for Liver Transplantation

et al. 2020

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Background and Aims The Model for End‐Stage Liver Disease (MELD) is used for clinical decision‐making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD‐Na). However, MELD‐Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF‐Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF‐Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT. Approach and Results Hence, WF‐Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD‐Na, and mortality on the waiting list were recorded. Prediction of 3‐month waiting‐list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF‐Ag (P < 0.001). MELD‐Na and vWF‐Ag were comparable and independent in their predictive potential for 3‐month mortality on the waiting list (area under the curve [AUC], vWF‐Ag = 0.739; MELD‐Na = 0.764). Importantly, a vWF‐Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD‐Na of 20 points (vWF‐Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD‐Na, OR = 7.594, 95% CI, 2.578, 22.372; P < 0.001, respectively). Ultimately, inclusion of vWF‐Ag into the MELD‐Na equation significantly improved prediction of 3‐month waiting‐list mortality (AUC, MELD‐Na–vWF = 0.804). Conclusions A single measurement of vWF‐Ag at listing for OLT predicts early mortality. Combining vWF‐Ag levels with MELD‐Na improves risk stratification and may help to prioritize organ allocation to decrease waiting‐list mortality.

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Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity

Abstract: SummaryBackground: Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate

Cited by 87 publications

References 44 publications

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon‐Free Therapy

Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon‐Free Therapy

Editorial: von Willebrand factor and CRP levels may predict survival in liver cirrhosis

The von Willebrand Factor Facilitates Model for End‐Stage Liver Disease–Independent Risk Stratification on the Waiting List for Liver Transplantation

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