Publications by authors named "Thomas Reiberger"

213 Publications

Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score.

J Hepatol 2021 Oct 11. Epub 2021 Oct 11.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria; Christian-Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Background: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need.

Methods: Patients with HCC put on PD-(L)1-based immunotherapy in 6 European centers (training set; n=190) and in 8 European centers (validation set; n=102) were included. We investigated the prognostic value of baseline variables on overall survival by using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n=204).

Results: Baseline serum alpha-fetoprotein ≥100 ng/ml (HR, 1.7; p=0.007) and C-reactive protein ≥1 mg/dl (HR, 1.7; p=0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95%CI, 19.5-35.8) months), followed by those fulfilling one criterion (1 point; CRAFITY-intermediate; 11.3 (95%CI, 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95%CI, 4.8-8.1) months; p<0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low:9%/20%/52%/20% vs. CRAFITY-intermediate:3%/25%/36%/36% vs. CRAFITY-high:2%/15%/22%/61%; p=0.003). These results were confirmed in the independent validation set as well as in different subgroups including Child-Pugh A and B, performance status 0 and ≥1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response.

Conclusions: The CRAFITY score is associated with survival and radiological response. The score may help with patient counseling, but requires prospective validation.

Lay Summary: The immunotherapy based regimen of atezolizumab plus bevacizumab represents the new standard of care in systemic first-line therapy of hepatocellular carcinoma (HCC). Biomarkers to predict treatment outcome are an unmet need in patients undergoing immunotherapy for HCC. We developed and externally validated a score that predicts outcome in patients with HCC undergoing immunotherapy with immune checkpoint blockers.
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http://dx.doi.org/10.1016/j.jhep.2021.09.035DOI Listing
October 2021

Low Serum Cholinesterase Identifies Patients With Worse Outcome and Increased Mortality After TIPS.

Hepatol Commun 2021 Sep 28. Epub 2021 Sep 28.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension-related complications. However, careful selection of patients is crucial. The aim of this study was to evaluate the prognostic value of serum cholinesterase (CHE) for outcomes and mortality after TIPS insertion. In this multicenter study, 389 consecutive patients with cirrhosis receiving a TIPS at Hannover Medical School, University Hospital Essen, or Medical University of Vienna were included. The Hannover cohort (n = 200) was used to initially explore the role of CHE, whereas patients from Essen and Vienna served as a validation cohort (n = 189). Median age of the patients was 58 years and median Model for End-Stage Liver Disease (MELD) score was 12. Multivariable analysis identified MELD score (hazard ratio [HR]: 1.16; P < 0.001) and CHE (HR: 0.61; P = 0.008) as independent predictors for 1-year survival. Using the Youden Index, a CHE of 2.5 kU/L was identified as optimal threshold to predict post-TIPS survival in the Hannover cohort (P < 0.001), which was confirmed in the validation cohort (P = 0.010). CHE < 2.5 kU/L was significantly associated with development of acute-on-chronic liver failure (P < 0.001) and hepatic encephalopathy (P = 0.006). Of note, CHE was also significantly linked to mortality in the subgroup of patients with refractory ascites (P = 0.001) as well as in patients with high MELD scores (P = 0.012) and with high-risk FIPS scores (P = 0.004). After propensity score matching, mortality was similar in patients with ascites and CHE < 2.5 kU/L if treated by TIPS or by paracentesis. Contrarily, in patients with CHE ≥ 2.5 kU/L survival was significantly improved by TIPS as compared to treatment with paracentesis (P < 0.001). Conclusion: CHE is significantly associated with mortality and complications after TIPS insertion. Therefore, we suggest that CHE should be evaluated as an additional parameter for selecting patients for TIPS implantation.
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http://dx.doi.org/10.1002/hep4.1829DOI Listing
September 2021

Therapeutic aspects of bile acid signalling in the gut-liver axis.

Aliment Pharmacol Ther 2021 Sep 23. Epub 2021 Sep 23.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background: Bile acids are important endocrine modulators of intestinal and hepatic signalling cascades orchestrating critical pathophysiological processes in various liver diseases. Increasing knowledge on bile acid signalling has stimulated the development of synthetic ligands of nuclear bile acid receptors and other bile acid analogues.

Aim: This review summarises important aspects of bile acid-mediated crosstalk between the gut and the liver ("gut-liver axis") as well as recent findings from experimental and clinical studies.

Methods: We performed a literature review on bile acid signalling, and therapeutic applications in chronic liver disease.

Results: Intestinal and hepatic bile acid signalling pathways maintain bile acid homeostasis. Perturbations of bile acid-mediated gut-liver crosstalk dysregulate transcriptional networks involved in inflammation, fibrosis and endothelial dysfunction. Bile acids induce enterohepatic feedback signalling by the release of intestinal hormones, and regulate enterohepatic circulation. Importantly, bile acid signalling plays a central role in maintaining intestinal barrier integrity and antibacterial defense, which is particularly relevant in cirrhosis, where bacterial translocation has a profound impact on disease progression. The nuclear bile acid farnesoid X receptor (FXR) is a central intersection in bile acid signalling and has emerged as a relevant therapeutic target.

Conclusions: Experimental evidence suggests that bile acid signalling improves the intestinal barrier and protects against bacterial translocation in cirrhosis. FXR agonists have displayed efficacy for the treatment of cholestatic and metabolic liver disease in randomised controlled clinical trials. However, similar effects remain to be shown in advanced liver disease, particularly in patients with decompensated cirrhosis.
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http://dx.doi.org/10.1111/apt.16602DOI Listing
September 2021

VWF-response to NSBB-therapy - worth to re-read!

Clin Gastroenterol Hepatol 2021 Sep 3. Epub 2021 Sep 3.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab.

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http://dx.doi.org/10.1016/j.cgh.2021.08.043DOI Listing
September 2021

This Letter to the Editor is in response to: 'Non-hemodynamic effects of beta-blockers in decompensated cirrhosis: In search of an ideal marker?'/corresponding author Sanchit SHARMA, M.D. D.M./CGH-01733.

Clin Gastroenterol Hepatol 2021 Aug 25. Epub 2021 Aug 25.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Vienna, Austria.

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http://dx.doi.org/10.1016/j.cgh.2021.08.028DOI Listing
August 2021

COVID-19 pandemic: Impact on the management of patients with hepatocellular carcinoma at a tertiary care hospital.

PLoS One 2021 26;16(8):e0256544. Epub 2021 Aug 26.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background: Patients with hepatocellular carcinoma (HCC) represent a vulnerable population potentially negatively affected by COVID-19-associated reallocation of healthcare resources. Here, we report the impact of COVID-19 on the management of HCC patients in a large tertiary care hospital.

Methods: We retrospectively analyzed clinical data of HCC patients who presented at the Vienna General Hospital, between 01/DEC/2019 and 30/JUN/2020. We compared patient care before (period 1) and after (period 2) implementation of COVID-19-associated healthcare restrictions on 16/MAR/2020.

Results: Of 126 patients, majority was male (n = 104, 83%) with a mean age of 66±11 years. Half of patients (n = 57, 45%) had impaired liver function (Child-Pugh stage B/C) and 91 (72%) had intermediate-advanced stage HCC (BCLC B-D). New treatment, was initiated in 68 (54%) patients. Number of new HCC diagnoses did not differ between the two periods (n = 14 vs. 14). While personal visits were reduced, an increase in teleconsultation was observed (period 2). Number of patients with visit delays (n = 31 (30%) vs. n = 10 (10%); p = 0.001) and imaging delays (n = 25 (25%) vs. n = 7 (7%); p = 0.001) was higher in period 2. Accordingly, a reduced number of patients was discussed in interdisciplinary tumor boards (lowest number in April (n = 24), compared to a median number of 57 patients during period 1). Median number of elective/non-elective admissions was not different between the periods. One patient contracted COVID-19 with lethal outcome.

Conclusions: Changes in patient care included reduced personal contacts but increased telephone visits, and delays in diagnostic procedures. The effects on long-term outcome need to be determined.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256544PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389415PMC
September 2021

Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis.

World J Hepatol 2021 Jul;13(7):731-746

Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna 1090, Austria.

Portal hypertension (PH), a common complication of liver cirrhosis, results in development of esophageal varices. When esophageal varices rupture, they cause significant upper gastrointestinal bleeding with mortality rates up to 20% despite state-of-the-art treatment. Thus, prophylactic measures are of utmost importance to improve outcomes of patients with PH. Several high-quality studies have demonstrated that non-selective beta blockers (NSBBs) or endoscopic band ligation (EBL) are effective for primary prophylaxis of variceal bleeding. In secondary prophylaxis, a combination of NSBB + EBL should be routinely used. Once esophageal varices develop and variceal bleeding occurs, standardized treatment algorithms should be followed to minimize bleeding-associated mortality. Special attention should be paid to avoidance of overtransfusion, early initiation of vasoconstrictive therapy, prophylactic antibiotics and early endoscopic therapy. Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding, and potentially in Child B patients with active bleeding at endoscopy. The use of carvedilol, safety of NSBBs in advanced cirrhosis ( with refractory ascites) and assessment of hepatic venous pressure gradient response to NSBB is discussed. In the present review, we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.
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http://dx.doi.org/10.4254/wjh.v13.i7.731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326161PMC
July 2021

Nuclear receptors in liver fibrosis.

Biochim Biophys Acta Mol Basis Dis 2021 Dec 31;1867(12):166235. Epub 2021 Jul 31.

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Experimental Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. Electronic address:

Nuclear receptors are ligand-activated transcription factors that regulate gene expression of a variety of key molecular signals involved in liver fibrosis. The primary cellular driver of liver fibrogenesis is activated hepatic stellate cells. Different nuclear receptors regulate the hepatic expression of pro-inflammatory and pro-fibrogenic cytokines that promote the transformation of hepatic stellate cells into fibrogenic myofibroblasts. Importantly, nuclear receptors regulate gene expression circuits that promote hepatic fibrogenesis and/or allow liver fibrosis regression. In this review, we highlight the direct and indirect influence of nuclear receptors on liver fibrosis, with a focus on hepatic stellate cells, and discuss potential therapeutic effects of nuclear receptor modulation in regard to anti-fibrotic and anti-inflammatory effects. Further research on nuclear receptors-related signaling may lead to the clinical development of effective anti-fibrotic therapies for patients with liver disease.
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http://dx.doi.org/10.1016/j.bbadis.2021.166235DOI Listing
December 2021

Diet and exercise in NAFLD/NASH: Beyond the obvious.

Liver Int 2021 Oct 21;41(10):2249-2268. Epub 2021 Aug 21.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Lifestyle represents the most relevant factor for non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of the metabolic syndrome. Although a tremendous body of clinical and preclinical data on the effectiveness of dietary and lifestyle interventions exist, the complexity of this topic makes firm and evidence-based clinical recommendations for nutrition and exercise in NAFLD difficult. The aim of this review is to guide readers through the labyrinth of recent scientific findings on diet and exercise in NAFLD and non-alcoholic steatohepatitis (NASH), summarizing "obvious" findings in a holistic manner and simultaneously highlighting stimulating aspects of clinical and translational research "beyond the obvious". Specifically, the importance of calorie restriction regardless of dietary composition and evidence from low-carbohydrate diets to target the incidence and severity of NAFLD are discussed. The aspect of ketogenesis-potentially achieved via intermittent calorie restriction-seems to be a central aspect of these diets warranting further investigation. Interactions of diet and exercise with the gut microbiota and the individual genetic background need to be comprehensively understood in order to develop personalized dietary concepts and exercise strategies for patients with NAFLD/NASH.
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http://dx.doi.org/10.1111/liv.15024DOI Listing
October 2021

Epidemiological trends of HBV and HDV coinfection among Viennese HIV+ patients.

Liver Int 2021 Nov 5;41(11):2622-2634. Epub 2021 Aug 5.

Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background And Aims: Despite vaccination recommendations, hepatitis B (HBV) and D (HDV) coinfections are common in HIV+individuals.

Methods: HBV immunization status (anti-HBs) as well as HBV (HBsAg/HBV-DNA) and HDV (anti-HDV) coinfection rates were assessed in 1870 HIV+individuals at HIV diagnosis (baseline, BL) and last follow-up (FU).

Results: Sixty-eight (3.6%) HIV patients were never tested for HBV. At BL, 89/1802 (4.9%) HIV patients were HBV coinfected. Four hundred and fifteen (23.0%) showed virological HBV clearance [HBsAg(-)/anti-HBc(+)/anti-HBs(+)] and 210 (11.7%) presented with anti-HBc(+) only. Seven hundred and ten (39.4%) were HBV naïve [HBsAg(-)/anti-HBs(-)/anti-HBc(-)/HBV-DNA(-)], but only 378 (21.0%) received vaccinations with detectable anti-HBs(+) titres. Among the 89 HBV/HIV-coinfected patients, only 52 (58.4%) were tested for HDV: 11/49 (22.4%) had anti-HDV(+) and 3/12 (25.0%) showed HDV-RNA viraemia. During a median FU of 6.5 (IQR 7.2) years, 44 (4.6%) of the 953 retested BL HBV-negative patients acquired new HBV infection (including 15/304, 4.9% of vaccinated patients). Of the 89 patients, 22 (24.7%) patients cleared their HBsAg, resulting in 60/1625 (3.7%) HIV/HBV individuals at FU: 34 (56.7%) showed HBV-DNA suppression and 15 (25.0%) were HBV viraemic, while 12/89 (13.5%) remained without a FU test. Vaccinations induced anti-HBs(+) in 137 of the retested 649 (21.1%) BL HBV-naïve patients.

Conclusion: HBV testing is well established among Viennese HIV+patients with HBV coinfection rates around 4%-5%. HBV vaccinations are insufficiently implemented since anti-HBs titres were detected in only 21.1% of HBV-naive HIV(+) patients and new HBV infections occurred in previously vaccinated patients. HDV testing is not systematically performed despite up to 25% of HIV/HBV patients may show HDV coinfection.
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http://dx.doi.org/10.1111/liv.15018DOI Listing
November 2021

Decreasing von Willebrand Factor Levels Upon Nonselective Beta Blocker Therapy Indicate a Decreased Risk of Further Decompensation, Acute-on-chronic Liver Failure, and Death.

Clin Gastroenterol Hepatol 2021 Jul 10. Epub 2021 Jul 10.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Laboratory, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria.

Background & Aims: Nonselective beta blockers (NSBBs) exert beneficial effects beyond lowering hepatic venous pressure gradient (HVPG), which may be particularly relevant in patients with decompensated cirrhosis (DC), in whom bacterial translocation and bacterial-induced systemic inflammation drive the development of complications such as acute-on-chronic liver failure (ACLF). We evaluated whether NSBB-related changes in von Willebrand factor (VWF) may serve as a biomarker for these effects.

Methods: In this retrospective analysis, 159 prospectively characterized patients with clinically stable DC (ie, without acute decompensation) who underwent paired HVPG/VWF assessments before/on NSBB therapy were classified as 'VWF responders' (as defined by a ≥5% decrease in VWF) versus 'VWF nonresponders.'

Results: There were no major differences in baseline characteristics between VWF responders (61%) and VWF nonresponders. VWF responders showed more pronounced decreases in inflammation (procalcitonin), whereas rates of HVPG response were similar. In line, NSBB-related changes in VWF correlated with the dynamics of bacterial translocation/inflammation (lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin), rather than those of HVPG. Interestingly, VWF responders also showed less pronounced NSBB-related decreases in mean arterial pressure, suggesting an amelioration of systemic vasodilatation. Finally, VWF response was associated with decreased risks of further decompensation (adjusted hazard ratio [aHR], 0.555; 95% confidence interval [CI], 0.337-0.912; P = .020), ACLF (aHR, 0.302; 95% CI, 0.126-0.721; P = .007), and liver-related death (aHR, 0.332; 95% CI, 0.179-0.616; P < .001) in Cox regression models adjusted for prognostic factors including changes in HVPG.

Conclusions: Decreases in VWF upon NSBB therapy reflect their anti-inflammatory activity, are accompanied by less pronounced adverse effects on systemic hemodynamics, and are independently associated with a decreased risk of further decompensation, ACLF, and death. VWF response may discriminate between decompensated patients who benefit from NSBB treatment and have a favorable prognosis versus patients with poor outcomes.
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http://dx.doi.org/10.1016/j.cgh.2021.07.012DOI Listing
July 2021

Polyploidy control in hepatic health and disease.

J Hepatol 2021 Nov 3;75(5):1177-1191. Epub 2021 Jul 3.

Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), 1090 Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Electronic address:

A balanced increase in DNA content (ploidy) is observed in some human cell types, including bone-resorbing osteoclasts, platelet-producing megakaryocytes, cardiomyocytes or hepatocytes. The impact of increased hepatocyte ploidy on normal physiology and diverse liver pathologies is still poorly understood. Recent findings suggest swift genetic adaptation to hepatotoxic stress and the protection from malignant transformation as beneficial effects. Herein, we discuss the molecular mechanisms regulating hepatocyte polyploidisation and its implication for different liver diseases and hepatocellular carcinoma. We report on centrosomes' role in limiting polyploidy by activating the p53 signalling network (via the PIDDosome multiprotein complex) and we discuss the role of this pathway in liver disease. Increased hepatocyte ploidy is a hallmark of hepatic inflammation and may play a protective role against liver cancer. Our evolving understanding of hepatocyte ploidy is discussed from the perspective of its potential clinical application for risk stratification, prognosis, and novel therapeutic strategies in liver disease and hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.jhep.2021.06.030DOI Listing
November 2021

COVID-19-Related Downscaling of In-Hospital Liver Care Decreased Patient Satisfaction and Increased Liver-Related Mortality.

Hepatol Commun 2021 10 1;5(10):1660-1675. Epub 2021 Jul 1.

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

The coronavirus disease 2019 (COVID-19) pandemic necessitated down-scaling of in-hospital care to prohibit the spread of severe acute respiratory syndrome-coronavirus-2. We (1) assessed patient perceptions on quality of care by telesurvey (cohort 1) and written questionnaire (cohort 2), and (2) analyzed trends in elective and nonelective admissions before (December 2019 to February 2020) and during (March to May 2020) the COVID-19 pandemic in Austria. A total of 279 outpatients were recruited into cohort 1 and 138 patients into cohort 2. All admissions from December 2019 to May 2020 to the Division of Gastroenterology/Hepatology at the Vienna General Hospital were analyzed. A total of 32.6% (n = 91 of 279) of cohort 1 and 72.5% (n = 95 of 131) of cohort 2 had telemedical contact, whereas 59.5% (n = 166 of 279) and 68.2% (n = 90 of 132) had face-to-face visits. A total of 24.1% (n = 32 of 133) needed acute medical help during health care restrictions; however, 57.3% (n = 51 of 89) reported that contacting their physician during COVID-19 was difficult or impossible. Patient-reported satisfaction with treatment decreased significantly during restrictions in cohort 1 (visual analog scale [VAS] 0-10: 9.0 ± 1.6 to 8.6 ± 2.2; P < 0.001) and insignificantly in cohort 2 (VAS 0-10: 8.9 ± 1.6 to 8.7 ± 2.1; P = 0.182). Despite fewer hospital admissions during COVID-19, the proportion of nonelective admissions (+6.3%) and intensive care unit admissions (+6.7%) increased. Patients with cirrhosis with nonelective admissions during COVID-19 had significantly higher Model for End-Stage Liver Disease (MELD) (25.5 [14.2] vs. 17.0 [interquartile range: 8.8]; P = 0.003) and ΔMELD (difference from last MELD: 3.9 ± 6.3 vs. 8.7 ± 6.4; P = 0.008), required immediate intensive care more frequently (26.7% vs. 5.6%; P = 0.034), and had significantly increased 30-day liver-related mortality (30.0% vs. 8.3%; P = 0.028). Conclusion: The COVID-19 pandemic's effects on quality of liver care is evident from decreased patient satisfaction, hospitalization of sicker patients with advanced chronic liver disease, and increased liver-related mortality. Strategies for improved telemedical liver care and preemptive treatment of cirrhosis-related complications are needed to counteract the COVID-19-associated restrictions of in-hospital care.
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http://dx.doi.org/10.1002/hep4.1758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239672PMC
October 2021

Outcomes of an HCV elimination program targeting the Viennese MSM population.

Wien Klin Wochenschr 2021 Jul 28;133(13-14):635-640. Epub 2021 Jun 28.

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Background And Aims: Recent reports suggest an increasing incidence of hepatitis C virus (HCV) infections among MSM (men-who-have-sex-with-men). Early treatment with direct-acting antivirals (DAAs) achieves high cure rates and prevents further HCV transmission. We offered barrier-free HCV screening in the Viennese MSM population and immediate access to DAA treatment.

Methods: In collaboration with gay health specialists, we screened for HCV seropositivity in Viennese MSM between 2019 and 2020. Barrier-free HCV-RNA-PCR tests, transient elastography (TE) and immediate access to DAA treatment were offered.

Results: A total of 310 HCV-seropositive patients were identified. Of those, 145 could be contacted and 109 attended their appointment at our clinic. HIV-coinfection was highly prevalent in our cohort (n = 86/145; 78.9%), while pre-exposure prophylaxis (PrEP) was taken by 21.7% (n = 5/23) of non-HIV patients. Sexual risk behavior and (history of) intravenous drug use was reported by 32.1% and 13.8% of patients, respectively. Most MSM had already achieved sustained virological response (SVR) to previous antiviral treatment (n = 72, 66.1%) or experienced spontaneous clearance (n = 10, 9.2%). Advanced fibrosis was only detected in 3/109 (2.8%) patients. 30 MSM tested positive for HCV-RNA and DAA treatment was initiated in 29 patients - all achieved SVR.

Conclusion: A targeted HCV test-and-treat program revealed a high prevalence of HCV seropositivity among Viennese MSM, potentially associated with high-risk sexual behavior and drug use. Early DAA treatment seems warranted in viremic HCV-MSM as SVR was 100%, which in turn prevents further HCV transmission.
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http://dx.doi.org/10.1007/s00508-021-01898-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237255PMC
July 2021

Safety of direct oral anticoagulants in patients with advanced liver disease.

Liver Int 2021 09 10;41(9):2159-2170. Epub 2021 Jul 10.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background & Aims: While direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited.

Methods: Liver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low-molecular-weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti-Xa peak levels and thrombomodulin-modified thrombin generation assays (TM-TGAs) were measured in a subgroup of 35/28 DOAC patients.

Results: Among patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child-Pugh-stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure-related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow-up of 10.5 (IQR: 4.0-27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS-B/C (at 12 months: 36.9% vs CPS-A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59-6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00-16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82-9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti-Xa peak levels were higher in patients with CPS-B/C (345 [95% CI: 169-395] vs CPS-A: 137 [95% CI: 96-248] ng/mL, P = .048) and were associated with lower TM-TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients.

Conclusions: Anticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.
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http://dx.doi.org/10.1111/liv.14992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456813PMC
September 2021

Recent advances in the understanding and management of hepatorenal syndrome.

Fac Rev 2021 21;10:48. Epub 2021 May 21.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Renal dysfunction occurs frequently in hospitalized patients with advanced chronic liver disease (ACLD)/cirrhosis and has profound prognostic implications. In ACLD patients with ascites, hepatorenal syndrome (HRS) may result from circulatory dysfunction that leads to reduced kidney perfusion and glomerular filtration rate (in the absence of structural kidney damage). The traditional subclassification of HRS has recently been replaced by acute kidney injury (AKI) type of HRS (HRS-AKI) and non-AKI type of HRS (HRS-NAKI), replacing the terms "HRS type 1" and "HRS type 2", respectively. Importantly, the concept of absolute serum creatinine (sCr) cutoffs for diagnosing HRS was partly abandoned and short term sCr dynamics now may suffice for AKI diagnosis, which facilitates early treatment initiation that may prevent the progression to HRS-AKI or increase the chances of AKI/HRS-AKI reversal. Recent randomized controlled trials have established (a) the efficacy of (long-term) albumin in the prevention of complications of ascites (including HRS-AKI), (b) the benefits of transjugular intrahepatic portosystemic shunt placement in patients with recurrent ascites, and (c) the superiority of terlipressin over noradrenaline for the treatment of HRS-AKI in the context of acute-on-chronic liver failure. This review article aims to summarize recent advances in the understanding and management of HRS.
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http://dx.doi.org/10.12703/r/10-48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170686PMC
May 2021

Directly observed therapy at opioid substitution facilities using sofosbuvir/velpatasvir results in excellent SVR12 rates in PWIDs at high risk for non-adherence to DAA therapy.

PLoS One 2021 4;16(6):e0252274. Epub 2021 Jun 4.

Department of Internal Medicine IV, Klinik Ottakring, Vienna, Austria.

Background & Aims: We evaluated the effectiveness of sofosbuvir/velpatasvir (SOF/VEL) in difficult-to-treat PWIDs with presumed high risk for non-adherence to antiviral therapy using an innovative concept involving their opioid agonist therapy (OAT) facility.

Methods: N = 221 patients (m/f: 168/53; median age: 44.7 years (IQR 16.9); HCV-genotype 3: 45.2%; cirrhosis: 33.9%) treated with SOF/VEL were included. PWIDs at high risk for non-adherence to DAA therapy (n = 122) received HCV treatment alongside OAT under the supervision of medical staff ("directly observed therapy", DOT). These patients were compared to patients with presumed excellent drug compliance, who were treated in a "standard setting" (SS) of SOF/VEL prescription at a tertiary care center (n = 99).

Results: DOT-patients (n = 122/221; 55.2%) were younger than SS-patients (median age: 41.3 vs. 53.0 years), all had psychiatric comorbidities and most had a poor socioeconomic status. 83/122 (68.0%) reported ongoing intravenous drug use. Within the DOT-group, SVR12 was achieved in 99.1% (95% CI: 95.0-100; n = 109/110) with one patient experiencing treatment failure, while n = 12/122 (9.8%) patients were excluded due to loss of follow-up (FU). 5 patients showed HCV reinfection after achieving SVR12. SS-patients achieved SVR in 96.6% (95% CI: 90.3-99.3%; n = 84/87) after exclusion of 10/99 (10.1%) patients who were lost to FU and 2 patients who died prior to SVR12 due to reasons not related to DAA therapy.

Conclusions: SOF/VEL given as DOT along with OAT in PWIDs at high risk of non-adherence to antiviral therapy including those with ongoing intravenous drug use resulted in excellent SVR rates similar to patients with presumed "excellent compliance" under standard drug intake.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252274PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177501PMC
October 2021

Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute-on-chronic liver failure.

United European Gastroenterol J 2021 May;9(4):427-437

Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.

Introduction: Recently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on-chronic liver failure (pre-ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real-life cohort of hospitalized patients with cirrhosis.

Methods: Patients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis.

Results: Two hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre-ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1-year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90-day mortality: pre-ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C-reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre-ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre-ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis.

Discussion: The recently proposed pathophysiological/prognostic EF-CLIF subgroups are also reproduceable in a real-life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre-ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.
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http://dx.doi.org/10.1002/ueg2.12089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259248PMC
May 2021

Individualized treatment options for patients with non-cirrhotic and cirrhotic liver disease.

World J Gastroenterol 2021 May;27(19):2281-2298

Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, United Kingdom.

The obesity pandemic has led to a significant increase in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). While dyslipidemia, type 2 diabetes mellitus and cardiovascular diseases guide treatment in patients without signs of liver fibrosis, liver related morbidity and mortality becomes relevant for MAFLD's progressive form, non-alcoholic steatohepatitis (NASH), and upon development of liver fibrosis. Statins should be prescribed in patients without significant fibrosis despite concomitant liver diseases but are underutilized in the real-world setting. Bariatric surgery, especially Y-Roux bypass, has been proven to be superior to conservative and/or medical treatment for weight loss and resolution of obesity-associated diseases, but comes at a low but existent risk of surgical complications, reoperations and very rarely, paradoxical progression of NASH. Once end-stage liver disease develops, obese patients benefit from liver transplantation (LT), but may be at increased risk of perioperative infectious complications. After LT, metabolic comorbidities are commonly observed, irrespective of the underlying liver disease, but MAFLD/NASH patients are at even higher risk of disease recurrence. Few studies with low patient numbers evaluated if, and when, bariatric surgery may be an option to avoid disease recurrence but more high-quality studies are needed to establish clear recommendations. In this review, we summarize the most recent literature on treatment options for MAFLD and NASH and highlight important considerations to tailor therapy to individual patient's needs in light of their risk profile.
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http://dx.doi.org/10.3748/wjg.v27.i19.2281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130039PMC
May 2021

The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes.

Hepatol Int 2021 Oct 21;15(5):1160-1173. Epub 2021 May 21.

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background And Aims: The cardiovascular hormones renin/angiotensin/aldosterone (RAA), brain-type natriuretic peptide (BNP)and arginine-vasopressin (AVP) are key regulators of systemic circulatory homeostasis in portal hypertension (PH). We assessed (i) the activation of renin, BNP and AVP across distinct stages of PH and (ii) whether activation of these hormones correlates with clinical outcomes.

Methods: Plasma levels of renin, proBNP and copeptin (AVP biomarker) were determined in 663 patients with advanced chronic liver disease (ACLD) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 11/2011 and 02/2019. We stratified for Child stage (A-C), HVPG (6-9 mmHg, 10-15 mmHg, ≥ 16 mmHg) and compensated vs. decompensated ACLD.

Results: With increasing PH, hyperdynamic state was indicated by higher heart rates (6-9 mmHg: median 71.0 [IQR 18.0] bpm, 10-15 mmHg: 76.0 [19.0] bpm, ≥ 16 mmHg: 80.0 [22.0] bpm; p < 0.001), lower mean arterial pressure (6-9 mmHg: 103.0 [13.5] mmHg, 10-15 mmHg: 101.0 [19.5] mmHg, ≥ 16 mmHg: 99.0 [21.0] mmHg; p = 0.032) and lower serum sodium (6-9 mmHg: 139.0 [3.0] mmol/L, 10-15 mmHg: 138.0 [4.0] mmol/L, ≥ 16 mmHg: 138.0 [5.0] mmol/L; p < 0.001). Across HVPG strata (6-9 mmHg vs. 10-15 mmHg vs ≥ 16 mmHg), median plasma levels of renin (21.0 [50.5] vs. 25.1 [70.9] vs. 65.4 [219.6] µIU/mL; p < 0.001), proBNP (86.1 [134.0] vs. 63.6 [118.0], vs. 132.2 [208.9] pg/mL; p = 0.002) and copeptin (7.8 [7.7] vs. 5.6 [8.0] vs. 10.7 [18.6] pmol/L; p = 0.024) increased with severity of PH. Elevated renin levels independently predicted first hepatic decompensation (adjusted hazard ratio [aHR]: 1.69; 95% confidence interval [95% CI] 1.07-2.68; p = 0.025) and mortality in compensated patients (aHR: 3.15; 95% CI 1.70-5.84; p < 0.001) and the overall cohort aHR: 1.42; 95% CI 1.01-2.01; p = 0.046). Elevated copeptin levels predicted mortality in decompensated patients (aHR: 5.77; 95% CI 1.27-26.33; p = 0.024) and in the overall cohort (aHR: 3.29; 95% CI 1.36-7.95; p = 0.008). ProBNP levels did not predict clinical outcomes.

Conclusions: The cardiovascular hormones renin, proBNP and AVP are activated with progression of ACLD and PH. Renin activation is a risk factor for hepatic decompensation and mortality, especially in compensated patients. Increased plasma copeptin is a risk factor for mortality, in particular in decompensated patients.
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http://dx.doi.org/10.1007/s12072-021-10203-9DOI Listing
October 2021

Intraperitoneal Activation of Coagulation and Fibrinolysis in Patients with Cirrhosis and Ascites.

Thromb Haemost 2021 May 21. Epub 2021 May 21.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Development of ascites is the most common form of decompensation of cirrhosis. We aimed to investigate the coagulation system in ascitic fluid and plasma of patients with cirrhosis. We determined coagulation parameters and performed clotting and fibrinolysis experiments in ascitic fluid and plasma of thoroughly characterized patients with cirrhosis and ascites ( = 25) and in plasma of patients with cirrhosis but without ascites ( = 25), matched for severity of portal hypertension. We also investigated plasma D-dimer levels in an independent cohort of patients ( = 317) with clinically significant portal hypertension (HVPG ≥ 10 mmHg), grouped according to ascites severity. Ascitic fluid was procoagulant in a clotting assay. The procoagulant potential of ascitic fluid was abolished by depletion of extracellular vesicles from ascitic fluid by filtration or by addition of a tissue factor-neutralizing antibody. Compared with plasma, extracellular vesicle-associated tissue factor activity was high in ascitic fluid, while activities of other coagulation factors were low. The extracellular vesicle-depleted fraction of ascitic fluid induced fibrinolysis, which was prevented by aprotinin, indicating the presence of plasmin in ascitic fluid. Plasma peak thrombin generation and parameters reflecting fibrinolysis were independently associated with the presence of ascites. Finally, plasma D-dimer levels were independently linked to ascites severity in our second cohort comprising 317 patients. In conclusion, coagulation and fibrinolysis become activated in ascites of patients with cirrhosis. While tissue factor-exposing extracellular vesicles in ascitic fluid seem unable to pass the peritoneal membrane, fibrinolytic enzymes get activated in ascitic fluid and may re-enter the systemic circulation and induce systemic fibrinolysis.
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http://dx.doi.org/10.1055/a-1515-9529DOI Listing
May 2021

Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease.

Am J Gastroenterol 2021 04;116(4):723-732

1Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; 3Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; 4Vienna Hepatic Hemodynamic Laboratory, Medical University of Vienna, Vienna, Austria; 5Service d'Hépatologie CHU Toulouse Rangueil, Institut Cardiomet et Université Paul Sabatier, Toulouse, France; 6UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Centre, Royal Free Hospital and UCL, London, United Kingdom; 7Swiss Liver Center, UVCM, Inselspital, Department of Biomedical Research, University of Bern, Bern, Switzerland; 8Liver Unit, Regional Institute of Gastroenterology and Hepatology "Octavian Fodor," University of Medicine and Pharmacy "Iuliu Hatieganu," Cluj-Napoca, Romania; 9Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada; 10Division of Internal Medicine II, Krankenhaus Barmherzige Brüder, Vienna, Austria; 11Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.

Introduction: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice.

Methods: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH.

Results: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 10/L ruled out CSPH in most etiologies.

Discussion: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.
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http://dx.doi.org/10.14309/ajg.0000000000000994DOI Listing
April 2021

Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR.

J Pers Med 2021 Apr 7;11(4). Epub 2021 Apr 7.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria.

Genetic variants including and have been shown to influence progression to advanced chronic liver disease (ACLD) in patients with chronic hepatitis C (CHC). We aimed to investigate their impact on disease regression (i.e., changes in hepatic venous pressure gradient [HVPG] and non-invasive surrogates [liver stiffness measurement (LSM), von Willebrand factor (VWF), and VWF/platelet count ratio (VITRO)]) and clinical outcomes after CHC cure in 346 patients with pre-treatment ACLD. Patients carrying the minor allele had more advanced liver disease prior to antiviral therapy, confirming its impact on liver disease progression. In a subgroup of 88 patients who underwent paired HVPG-measurements and were genotyped for all SNP/indels, genotypes were not associated with changes in HVPG. In line, changes in non-invasive surrogates of portal hypertension (LSM/VWF/VITRO) were comparable between carriers and non-carriers of the -allele in the overall cohort. Finally, carriage of -allele was not associated with the development of hepatic decompensation, de-novo hepatocellular carcinoma, or transplant-free mortality during a median follow-up of 42 months after the end of antiviral treatment. Therefore, genetic variants in do not impact the regression of portal hypertension and clinical outcomes in patients with pre-treatment ACLD after CHC cure.
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http://dx.doi.org/10.3390/jpm11040281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067986PMC
April 2021

Reply to: "Presepsin as a biomarker of inflammation and prognosis in decompensated liver disease".

J Hepatol 2021 07 20;75(1):234-236. Epub 2021 Apr 20.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.03.027DOI Listing
July 2021

Influenza vaccination uptake and factors influencing vaccination decision among patients with chronic kidney or liver disease.

PLoS One 2021 13;16(4):e0249785. Epub 2021 Apr 13.

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Introduction: Seasonal influenza is a major global health problem causing substantial morbidity and health care costs. Yet, in many countries, the rates of influenza vaccination remain low. Chronic kidney or liver diseases (CKLD) predispose patients to severe influenza infections, but data on vaccination acceptance and status is limited in this risk population. We investigated the influenza vaccination awareness considering sociodemographic factors in CKLD patients.

Patients And Methods: This cross-sectional, questionnaire-based study recruited CKLD patients managed at three Viennese tertiary care centers between July and October 2020. CKLD was defined as chronic kidney- (all stages) or compensated/decompensated liver disease, including kidney/liver transplant recipients. Questionnaires assessed sociodemographic and transplant- associated parameters, patients vaccination status and the individuals self-perceived risks of infection and associated complications.

Results: In total 516 patients (38.1% female, mean age 56.4 years) were included. 43.9% of patients declared their willingness to be vaccinated in the winter season 2020/2021, compared to 25.4% in 2019/2020 and 27.3% in 2016-2018. Vaccination uptake was associated with the self-perceived risks of infection (OR: 2.8 (95%CI: 1.8-4.5), p<0.001) and associated complications (OR: 3.8 (95%CI: 2.3-6.3), p<0.001) as well as with previously received influenza vaccination (2019/2020: OR 17.1 (95%CI: 9.5-30.7), p<0.001; season 2016-2018: OR 8.9 (95%CI: 5.5-14.5), p<0.001). Most frequent reasons for not planning vaccination were fear of a) graft injury (33.3%), b) complications after vaccination (32.4%) and c) vaccine inefficiency (15.0%).

Conclusion: While influenza vaccination willingness in patients with CKLD is increasing in the 2020/2021 season, vaccination rates may still remain <50%. Novel co-operations with primary health care, active vaccination surveillance and financial reimbursement may substantially improve vaccination rates in high-risk CKLD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249785PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043408PMC
October 2021

Complications of Cirrhosis.

Clin Liver Dis 2021 05 10;25(2):xiii-xiv. Epub 2021 Mar 10.

Universitätsklinikum AKH Wien, Gastroenterology Office 7I Red Tower, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.cld.2021.02.002DOI Listing
May 2021

Prevention of Variceal Bleeding and Rebleeding by Nonselective Beta-Blockers: A Tailored Approach.

Clin Liver Dis 2021 05 10;25(2):311-326. Epub 2021 Mar 10.

Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria. Electronic address:

Nonselective beta-blockers represent the mainstay of medical therapy in the prophylaxis of variceal bleeding and rebleeding in patients with portal hypertension. Their efficacy has been demonstrated by numerous trials; however, there exist safety concerns in advanced disease, such as in patients with refractory ascites. Importantly, nonselective beta-blockers also exert nonhemodynamic beneficial effects that may contribute to a prolonged decompensation-free survival, as recently shown in the PREDESCI trial. This review summarizes the current evidence on nonselective beta-blocker therapy and proposes a tailored, patient-centered approach for the use of nonselective beta-blockers in patients with portal hypertension.
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http://dx.doi.org/10.1016/j.cld.2021.01.004DOI Listing
May 2021

The Addition of C-Reactive Protein and von Willebrand Factor to Model for End-Stage Liver Disease-Sodium Improves Prediction of Waitlist Mortality.

Hepatology 2021 Sep 29;74(3):1533-1545. Epub 2021 Aug 29.

Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN.

Background And Aims: Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of 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.

Approach And Results: We determined whether addition of vWF-Ag and CRP to the Model for End-Stage Liver Disease-Sodium (MELD-Na) score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in two 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, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation.

Conclusions: 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.
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http://dx.doi.org/10.1002/hep.31838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518408PMC
September 2021

Author's reply to "Thromboelastometry in patients with advanced chronic liver disease: a complex interplay".

Hepatol Int 2021 Apr 17;15(2):522-524. Epub 2021 Feb 17.

Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.1007/s12072-021-10145-2DOI Listing
April 2021
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