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Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed due to complications of portal hypertension (PH) or infections. Von Willebrand factor antigen (vWF-Ag) and C-reactive protein (CRP) are simple, broadly available markers of these processes. We determined whether addition of vWF-Ag and CRP to the MELD-Na score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in 2 independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD-Na and mortality on the waiting list were recorded. Prediction of 3-month waiting list mortality was assessed by receiver operating characteristics curve (ROC-AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF-Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (N=269) vWF-Ag and CRP both improved the predictive value of MELD-Na for 3-month waitlist mortality and showed the highest predictive value when combined (AUC: MELD-Na: 0.764, MELD-Na+CRP: 0.790, MELD-Na+vWF: 0.803, MELD-Na+CRP+vWF-Ag: 0.824). Results were confirmed in an independent validation cohort (N=129, AUC: MELD-Na: 0.677, MELD-Na+CRP+vWF-Ag: 0.882). vWF-Ag was independently associated with PH and inflammatory biomarkers, while CRP closely, and MELD-independently, correlated with biomarkers of bacterial translocation/inflammation. Conclusion: The addition of vWF-Ag and CRP -reflecting central pathophysiological mechanisms of PH, bacterial translocation and inflammation, that are all drivers of mortality on the waiting list for LT -to the MELD-Na score improves prediction of waitlist mortality. Using the vWFAg-CRP-MELD-Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.

Aim Anticoagulation was associated with improved survival of hospitalized COVID-19 patients in large-scale studies. Yet, the development of COVID-19 associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low molecular weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence. Methods and Results Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K antagonist oral anticoagulants (NOAC) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox-regression (hazard ratio = 0.561, 95% confidence interval: 0.348-0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization and curtailed viral persistence was observed in patients using LMWH leading to a four-day reduction of virus positivity upon quantitative polymerase chain reaction (13 [interquartile range: 6-24] versus 9 [interquartile range: 5-16] days, p = 0.009). Conclusions Time courses of hemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on hemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond hemostasis, which encourages use of LMWH in COVID-19 patients without contraindications. Translational Perspective The data gathered in this retrospective multicenter observational study could confirm an association of improved survival and anticoagulation and could link LMWH use to improved biomarkers of cell death and curtailed persistence of SARS-CoV-2. This encourages the use of this drug in patients without known contraindications in case this effect can be consolidated in randomized controlled trials. Currently performed prospective trials using LMWH in COVID-19 should focus on viral persistence in order to explore an additional field of application for LMWH during this pandemic.

Introduction Despite important advances in many areas of hepatobiliary surgical practice during the past decades, posthepatectomy liver failure (PHLF) still represents an important clinical challenge for the hepatobiliary surgeon. The aim of this review is to present the current body of evidence regarding different aspects of PHLF. Methods A literature review was conducted to identify relevant articles for each topic of PHLF covered in this review. The literature search was performed using Medical Subject Heading terms on PubMed for articles on PHLF in English until May 2022. Results Uniform reporting on PHLF is lacking due to the use of various definitions in the literature. There is no consensus on optimal preoperative assessment before major hepatectomy to avoid PHLF, although many try to estimate future liver remnant function. Once PHLF occurs, there is still no effective treatment, except liver transplantation, where the reported experience is limited. Discussion Strict adherence to one definition is advised when reporting data on PHLF. The use of the International Study Group of Liver Surgery criteria of PHLF is recommended. There is still no widespread established method for future liver remnant function assessment. Liver transplantation is currently the only effective way to treat severe, intractable PHLF, but for many indications, this treatment is not available in most countries.