Outcome of Budd-Chiari Syndrome Patients Treated With Direct Oral Anticoagulants: An Austrian Multicenter Study.

BACKGROUND AND AIMS: Direct oral anticoagulants (DOACs) may simplify management of Budd-Chiari syndrome (BCS). Here, we report our experience with off-label use of DOACs for anticoagulation in BCS. METHODS: The safety of DOAC vs vitamin K antagonist treatment as well as associated clinical outcomes were retrospectively assessed in 47 BCS patients treated at 6 Austrian centers. RESULTS: Mean age at study inclusion was 37.9 ± 14.0 years and mean Model for End-Stage Liver Disease was 13.1 ± 5.1. Overall, 63.8% (n = 30) of patients had decompensated liver disease, and 87.2% (n = 41) showed clinical signs of portal hypertension. During a median follow-up of 82.5 (interquartile range, 43.1-121.8) months, 43 (91.5%) patients received anticoagulation alone or following interventional treatment, including 22 (46.8%) patients treated with DOACs (edoxaban: 10, apixaban: 4, rivaroxaban: 3, dabigatran: 3, more than one DOAC sequentially: 2) for a median of 24.4 (interquartile range, 5.7-35.1) months. While 72.7% (n = 16 of 22) of patients were switched from low-molecular-weight heparin (n = 12) or vitamin K antagonist (n = 4) to DOAC after disease stabilization or improvement, 27.3% (n = 6 of 22) of BCS patients were initially treated with DOAC. Complete response (European Association for the Study of the Liver criteria) was achieved or maintained in 14 (63.6%) of 22 patients, with ongoing response in 2 patients, while disease progressed in 6 patients (including 2 patients with hepatocellular carcinoma). Four major spontaneous bleedings (18.2%; incidence rate 8.8 per 100 patient-years; n = 2 upper gastrointestinal bleeding, n = 1 lower gastrointestinal bleeding, n = 1 hepatocellular carcinoma rupture), 7 minor bleedings, and 1 major procedure-related bleeding (4.5%; 2.2 per 100 patient-years) occurred during DOAC therapy. Overall transplant-free survival was 91.6% at 5 years. CONCLUSIONS: DOACs seem to be effective and safe for long-term anticoagulation in patients with BCS, but confirmation by larger prospective studies is needed.

HCC risk stratification after cure of hepatitis C in patients with compensated advanced chronic liver disease.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) caused by chronic hepatitis C who have achieved sustained virologic response (SVR). We developed risk stratification algorithms for de novo HCC development after SVR and validated them in an independent cohort. METHODS: We evaluated the occurrence of de novo HCC in a derivation cohort of 527 patients with pre-treatment ACLD and SVR to interferon-free therapy, in whom alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. We validated our results in 1,500 patients with compensated ACLD (cACLD) from other European centers. RESULTS: During a median follow-up (FU) of 41 months, 22/475 patients with cACLD (4.6%, 1.45/100 patient-years) vs. 12/52 decompensated patients (23.1%, 7.00/100 patient-years, p <0.001) developed de novo HCC. Since decompensated patients were at substantial HCC risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de novo HCC development during FU than pre-treatment values or absolute/relative changes. Models based on post-treatment AFP, alcohol consumption (optional), age, LSM, and albumin, accurately predicted de novo HCC development (bootstrapped Harrel's C with/without considering alcohol: 0.893/0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low- (~2/3 of patients) and high-risk (~1/3 of patients) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk: 0% vs. 16.5%) and validation (3.3% vs. 17.5%) cohorts. An alternative approach based on alcohol consumption (optional), age, LSM, and albumin (i.e., without AFP) also showed a robust performance. CONCLUSIONS: Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol consumption, accurately stratified patients with cACLD based on their risk of de novo HCC after SVR. Approximately two-thirds were identified as having an HCC risk <1%/year in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC surveillance. LAY SUMMARY: Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately two-thirds) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound.

Noninvasive Risk Stratification After HCV Eradication in Patients With Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of noninvasive surrogates of portal hypertension (liver stiffness measurement [LSM] by vibration-controlled transient elastography and von Willebrand factor/platelet count ratio [VITRO]) for development of hepatic decompensation and hepatocellular carcinoma in patients with pretreatment advanced chronic liver disease (ACLD) who achieved HCV cure. APPROACH AND RESULTS: A total of 276 patients with pretreatment ACLD and information on pretreatment and posttreatment follow-up (FU)-LSM and FU-VITRO were followed for a median of 36.6 months after the end of interferon-free therapy. FU-LSM (area under the receiver operating characteristic curve [AUROC]: 0.875 [95% confidence interval [CI]: 0.796-0.954]) and FU-VITRO (AUROC: 0.925 [95% CI: 0.874-0.977]) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU-LSM < 12.4 kPa and/or FU-VITRO < 0.95) to rule out clinically significant portal hypertension (CSPH, hepatic venous pressure gradient ≥10 mm Hg) at FU assigned most (57.3%) of the patients to the low-risk group; none of these patients developed hepatic decompensation. In contrast, in patients in whom FU-CSPH was ruled in (FU-LSM > 25.3 kPa and/or FU-VITRO > 3.3; 25.0% of patients), the risk of hepatic decompensation at 3 years following treatment was high (17.4%). Patients within the diagnostic gray-zone for FU-CSPH (17.8% of patients) had a very low risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n = 86) and external (n = 162) cohort. CONCLUSION: FU-LSM/FU-VITRO are strongly and independently predictive of posttreatment hepatic decompensation in HCV-induced ACLD. An algorithm combining these noninvasive markers not only rules in or rules out FU-CSPH, but also identifies populations at negligible versus high risk for hepatic decompensation. FU-LSM/FU-VITRO are readily accessible and enable risk stratification after sustained virological response, and thus facilitate personalized management.

Flexible diverticulotomy for Zenker's diverticulum - a bicentric study.

INTRODUCTION: Flexible diverticulotomy is an established procedure for the treatment of Zenker's diverticulum. In a bicentric study, we investigated the development of the procedure since its introduction at the Ordensklinikum Linz Barmherzige Schwestern and Elisabethinen in 2010. METHODS: All flexible diverticulotomies performed between January 2010 and December 2019 at the above-mentioned clinics were evaluated retrospectively. Patients were divided into two 5-year periods (2010-2014 and 2015-2019) and statistical tests were performed for comparison of data. RESULTS: In all, 69 flexible diverticulotomies were performed. The procedure was technically successful in 93.5% of cases. No lethal outcome was encountered. Only 2 (2.9%) interventions led to serious complications which had to be treated in the intensive care unit. Mild complications occurred in 14.5% of cases. 54 patients were evaluated in the follow-up period; 11 (20.3%) patients experienced relapses of dysphagia. The primary intervention resulted in a significant improvement over the observation period. Patients in the second intervention group had shorter average hospital stays and longer recurrence-free intervals. CONCLUSION: Flexible diverticulotomy is a safe and effective procedure for the treatment of Zenker's diverticulum. However, as the success rate appears to depend on the expertise and experience of the department, flexible diverticulotomy should be performed at centers with high caseloads.

[Health status of endoscopy personnel in Austria]. / Gesundheitszustand des Endoskopiepersonals in Österreich.

BACKGROUND: Working in the field of endoscopy is associated with physical and psychological challenges, but we lack data as to whether it influences the health status of endoscopy personnel. The aim of the present survey was to evaluate the health status of endoscopy personnel in Austria and draw comparisons. METHOD: In 2019, a standardized questionnaire of Hogrefe Publishers and a self-designed SurveyMonkey questionnaire were sent online to doctors (n=326) and nursing staff (n=234) working in the field of gastrointestinal endoscopy in Austria. The response rate was 17.9%. The data were compared with those of a standard population, a similar previous survey from 2004, and national sick leave data. RESULTS: Compared to a standard population of identical age and gender distribution, endoscopy personnel in Austria have more health-related complaints. Compared to doctors, nursing staff experience greater adverse effects; foremost among these are fatigue and an excessive need for sleep (p=0.001), a heavy sensation in the legs (p=0.001), hypersensitivity to warmth (p<0.001) and cold (p=0.002). Nursing staff are somewhat more frequently on sick leave than doctors. The days of sick leave were higher than those in 2004, but markedly below the average figures in Austria. Lifestyle had little influence on the respondents' symptoms. CONCLUSION: The results of the survey showed that persons working in endoscopy have slightly greater health problems than the standard population. Nursing staff are affected more severely than doctors. These data may serve as a basis for targeted preventive measures.

[Austrian benchmarking project for ERCP: a 10-year report]. / Österreichisches Benchmarking ERCP: 10-Jahresbericht.

The quality assurance program "Benchmarking ERCP", that his been under the patronage of the ÖGGH for ten years (with a one-year break in 2008), in collaboration with the Institute for Applied Statistics University Linz, has followed patient safety measures and successes while undergoing ERCP in Austria. A total of 28 319 examinations were registered. The participating centers all had different ERCP frequency and variable expertise, thereby enabling them to recognise individual problems in terms of success, cannulation and complication rates (3.9 % post-ERCP pancreatitis, 3.8 % bleeding, 0.6 % perforation, 1.2 % cholangitis, 1.0 % cardiopulmonary complications). The aim of quality assurance measures in medicine is to ensure the best possible patient care.

Drug fever due to a single dose of pantoprazole.

Although proton pump inhibitors (PPI) are generally well tolerated, with most adverse effects being minor and self-limiting, there are singular reports on hypersensitivity immune reactions triggered by a PPI or its metabolites. Here we report a case of acute drug-induced fever with leukocytosis and a transient increase in CRP due to pantoprazole. This was apparently an idiosyncratic reaction (inflammatory fever), showing no cross-sensitivity towards esomeprazole.

Retrospective Analysis of Rectal Endoscopic Submucosal Dissection at Ordensklinikum Linz and Kepler Universitätsklinikum Linz.

Background and study aim: Endoscopic submucosal dissection is a minimally invasive endoscopic procedure for the removal of neoplastic benign and early malignant lesions in the gastrointestinal tract. In this study, we analyse the success and safety of rectal ESD at Linz hospitals, focusing on a specific endoscopist. Additionally, we examine whether there is a learning curve regarding success parameters. Methods: This retrospective study included all 102 patients who underwent endoscopic submucosal dissection of the rectum by a defined endoscopist at Ordensklinikum Hospital and Kepler University Hospital between December 2010 and May 2021. With the collected data, a descriptive statistic was carried out and regression analyses were performed. Results: The en bloc resection rate was 78.4% and the rate of lesions removed in healthy tissue was 55.6%. The average procedure time was 179 min and the complication rate was 7.8%. In total, 26.4% of cases showed carcinoma; in 25.9% of these cases, an oncologically curative resection was achieved with ESD. Follow-up data were available for 61.1% of cases, with recurrence being diagnosed in 3.6% of cases. A learning curve was observed regarding the rate of lesions removed in healthy tissue and the procedure time, but not regarding the en bloc resection rate. Conclusions: Endoscopic submucosal dissection is a safe method for the removal of large rectal adenomas and early carcinomas. The en bloc resection rate of the analysed procedures is within the range of comparable European studies. The rate of lesions removed in healthy tissue is below the R0 resection rate of the comparative literature; however, a learning curve could be observed in this parameter.

Biodegradable biliopancreatic stents could help conserve health care resources during the COVID-19 pandemic: An observational multicenter study.

BACKGROUND: Considering limited resources for follow-up due to COVID-19, we used biodegradable stents (BPBS) for a range of biliopancreatic diseases. AIMS: This observational multicenter study aimed to evaluate technical safety and give first insights into clinical utility. METHODS: Technical success, clinical success, and necessity of follow-up visits for BPBS placed at three Austrian tertiary care hospitals between April 2020 and January 2021 were retrospectively analyzed. RESULTS: 63 stents were deployed in 60 patients. Main indications were prophylaxis of post-ERCP pancreatitis (PEP; n = 30/63; 48%) and bridging of prolonged waiting times to cholecystectomy (n = 21/63; 33%). Median time to surgery was 47 days (range: 136 days). The technical success rate was 94% (n = 59/63; 95% CI [0.84, 0.98]). Technical difficulties primarily arose with dislocations. Clinical success was achieved in 90% (n = 57/63; 95% CI [0.80, 0.96]). Clinical failure despite successful deployment was caused by papillary bleeding (1 patient) and cholestasis (1 patient). Both required reinterventions. No follow-up visits were needed in 97% of cases (n = 57/59; 95% CI [0.88, 1.00]). CONCLUSION: Biodegradable stents could help conserve health care resources without compromising treatment standards for PEP prophylaxis, which is particularly valuable in times of restricted resources. First insights into feasibility as bridging to cholecystectomy indicate a favorable safety profile.

Predictive value of gastrointestinal symptoms and patient risk factors for NSAID-associated gastrointestinal ulcers defined by endoscopy? Insights from a pooled analysis of two naproxen clinical trials.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain and rheumatic conditions. To facilitate patient management, we determined the predictive value of gastrointestinal (GI) symptoms and risk factors for the development of NSAID-associated GI injuries. METHODS: Post-hoc analysis of pooled data from naproxen treatment arms of two identical, randomized, double-blind, controlled phase 3 trials in arthritis patients at risk of GI adverse events. Endoscopic incidence of GI ulcers at baseline, and 1, 3, and 6 months was employed as a surrogate parameter for GI injury. For GI symptom analysis, Severity of Dyspepsia Assessment questionnaire was used. For GI risk factor analysis, the high risk factors: previous GI injury, concomitant selective serotonin reuptake inhibitors or corticosteroids, ulcer history, concomitant low-dose aspirin, and age >65 years were employed. RESULTS: Data of 426 naproxen patients were analyzed. Distribution of GI symptoms between patients with and without ulcer was similar; about one third of patients developing an ulcer reported no GI pain symptoms. GI symptoms experienced under naproxen treatment were thus not indicative of GI injury. The proportion of patients developing an ulcer increased with the number of risk factors present, however, about a quarter of patients without any of the analyzed risk factors still developed an ulcer. CONCLUSION: GI symptoms and the number of risk factors are not reliable predictors of NSAID-induced GI injury to decide which patients need gastroprotection and will lead to a large group of patients with GI injuries. A preventive rather than reactive approach should be taken.

Austrian consensus on the diagnosis and management of portal hypertension in advanced chronic liver disease (Billroth IV).

The Billroth IV consensus was developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on the 26th of November 2022 in Vienna.Based on international recommendations and considering recent landmark studies, the Billroth IV consensus provides guidance regarding the diagnosis and management of portal hypertension in advanced chronic liver disease.

Hereditary pancreatitis in childhood: course of disease and complications.

BACKGROUND: Hereditary pancreatitis is rare. Pain therapy for juvenile symptom onset, child development and the risk of pancreatic carcinoma in adulthood must be considered. PATIENTS, MATERIAL AND METHODS: Data from a cohort of 11 patients with disease onset in childhood (< 16 years) were analyzed retrospectively. The gene encoding cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1) and cystic fibrosis transmembrane conductance regulator (CFTR) genes were investigated as genetic factors. Treatment concept and complications were registered. Prognosis, treatment success and quality of life were objectified using the chronic pancreatitis prognosis score and a standardized questionnaire (KIDSCREEN-10 index). RESULTS: The mean age of symptom onset was 7.5 ±4.2 years. The PRSS1 and SPINK1 mutations each occurred with 36.4%, 3 patients had a pancreas divisum and 2 a long common channel. The course of pancreatitis was obstructive in 90.9%. Exocrine pancreatic insufficiency occurred in seven patients so far (mean age 12.5 years). Stenting was performed in 72.7% and 18.2% needed pancreatic surgery. Currently the chronic prognosis score is on average 7.5 points, pain on numerical rating scale 0 (no pain). The mean KIDSCREEN­T score of 66.9 confirms a very good quality of life. CONCLUSION: Patients with genetically caused chronic pancreatitis are rare. Their care ranges from pain therapy in childhood and adolescence to questions concerning family planning and pancreatic cancer prevention from mid-adulthood onward. The disease is challenging for the interdisciplinary cooperation. We found the step-up strategy to be a good option for pain therapy. A national registry monitored by scientific societies with active recruitment for screening examinations will further improve and ensure care in the long term.

A multicenter prospective study on the diagnostic performance of a new liquid rapid urease test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. Rapid urease tests (RUT) are well established for the point-of-care, invasive diagnosis of H. pylori infection. The study aimed to evaluate the diagnostic performance of a new liquid RUT, the preOx-HUT, within a prospective cohort of treatment-naïve patients. METHODS: The multicenter prospective clinical trial was conducted at nine Austrian centers for gastrointestinal endoscopy. Patients referred for a diagnostic upper gastrointestinal endoscopy underwent gastric biopsy sampling for routine histological evaluation, and in parallel, the preOx-HUT. Histology served as reference standard to evaluate the diagnostic performance of the preOx-HUT. RESULTS: From January 2015 to January 2016, a total of 183 consecutive patients (54 males and 129 females, median age 50 years) were included. Endoscopy revealed pathological findings in 149/183 cases (81%), which were mostly gastritis (59%) and gastro-esophageal reflux disease (27%). H. pylori infection was detected by histology in 41/183 (22%) cases. In relation to histology, the preOx-HUT had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 96%. Performance of preOx-HUT was not affected significantly by concomitant PPI-use as present in 15% of cases (P = 0.73). CONCLUSIONS: This was the first study evaluating the preOx-HUT in a prospective, multicenter clinical setting. We found a high diagnostic accuracy for the point-of-care, invasive diagnostic test of H. pylori infection. Hence, this test may be a valuable diagnostic adjunct to the clinical presentation of patients with suspected H. pylori infection. Trial registration number EK 1548/2014, Name of registry: Register der Ethikkommission der Medizinischen Universität Wien, URL of registry: https://ekmeduniwien.at/core/catalog/2012/, Date of registration: 24.09.2014, Date of enrolment of the first participant to the trial: 15.01.2015.

Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth III).

The Billroth III guidelines were developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on 18 February 2017 in Vienna. Based on international guidelines and considering recent landmark studies, the Billroth III recommendations aim to help physicians in guiding diagnostic and therapeutic strategies in patients with portal hypertension.

[Pancreatic Diseases]. / Pankreaserkrankungen: eine subjektive Auswahl praxisrelevanter Publikationen 2014-2015.

The author presents his personal choice of practical relevant papers of pancreatic diseases from 2014 to 2015. Nutritional factors and hypertriglycidemia are discussed as causes of acute pancreatitis. Tools to avoid post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis are described and the natural course of fluid collections and pseudocysts is demonstrated. The value of secretin-MRCP(magnetic resonance cholangiopancreatography) for diagnosis of chronic pancreatitis is illustrated. Data help to choose the minimally effective prednisolone dose in autoimmune pancreatitis. The increased prevalence of fractures in patients with chronic pancreatitis highlights the necessity of screening for bone density loss. The association of vitamin D intake with pancreatic cancer is described. The probability of cancer in IPNM is shown and innovative surgical concepts to reduce the loss of pancreatic function are presented. Finally neoadjuvant concepts for the treatment of pancreatic cancer are highlighted.

The VITRO Score (Von Willebrand Factor Antigen/Thrombocyte Ratio) as a New Marker for Clinically Significant Portal Hypertension in Comparison to Other Non-Invasive Parameters of Fibrosis Including ELF Test.

BACKGROUND: Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio) instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients. AIM: This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement. METHODS: All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D'Amico stage, VITRO score, APRI and transient elastography (TE). RESULTS: The analysis included 236 patients; 170 (72%) were male, and the median age was 57.9 (35.2-76.3; 95% CI). Disease aetiology included ALD (39.4%), HCV (23.4%), NASH (12.3%), other (8.1%) and unknown (11.9%). The CPS showed 140 patients (59.3%) with CPS A; 56 (23.7%) with CPS B; and 18 (7.6%) with CPS C. 136 patients (57.6%) had compensated and 100 (42.4%) had decompensated cirrhosis; 83.9% had HVPG ≥10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001). ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI. CONCLUSION: The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis.