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.

Prevalence of Subclinical Cardiovascular Disease in Patients with Non-Alcoholic-Fatty Liver Disease: Analysis of the Paracelsus 10.000 Cohort Study.

BACKGROUND: In patients with non-alcoholic fatty liver disease (NAFLD) cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. METHODS: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing non-alcoholic steatohepatitis Index (FNI) and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. RESULTS: Results revealed an association between liver steatosis/fibrosis and CAC. A FLI > 60 was associated with higher odds of NAFLD (OR 3.38, 95% CI: 2.61-4.39, p < 0.01) and increased prevalence of CAC-Score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude odds ratios of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became non-significant after adjusting for age, sex, and MetS. CONCLUSION: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.

Iron, Oxidative Stress, and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Excess free iron is a substrate for the formation of reactive oxygen species (ROS), thereby augmenting oxidative stress. Oxidative stress is a well-established cause of organ damage in the liver, the main site of iron storage. Ferroptosis, an iron-dependent mechanism of regulated cell death, has recently been gaining attention in the development of organ damage and the progression of liver disease. We therefore summarize the main mechanisms of iron metabolism, its close connection to oxidative stress and ferroptosis, and its particular relevance to disease mechanisms in metabolic-dysfunction-associated fatty liver disease and potential targets for therapy from a clinical perspective.

Prevalence and Characteristics of Metabolic Hyperferritinemia in a Population-Based Central-European Cohort.

BACKGROUND: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. METHODS: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40-77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. RESULTS: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. CONCLUSION: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF.

Feasibility of Continuous Monitoring of Endoscopy Performance and Adverse Events: A Single-Center Experience.

BACKGROUND: We integrated a standardized questionnaire focusing on adverse events and performance measures in gastrointestinal endoscopy as a mandatory component of the electronical medical record. METHODS: This retrospective study was conducted using prospectively collected data on quality parameters and adverse events (AEPM) for all diagnostic and therapeutic endoscopic procedures at our center between 2018 and 2020. RESULTS: A total of 7532 consecutive endoscopic procedures were performed in 5035 patients. The proportion of high-risk examinations and high-risk patients was 20% and 23%, respectively. Severe adverse events (AEs, n = 21) occurred in 0.3% of procedures and significantly more often in patients with an ASA score > II (0.6%, p < 0.01). We observed no long-term morbidity after severe AEs. Mortality was 0.03% (n = 2). Following screening colonoscopy (n = 242), four endoscopists documented AEPM in more than 98% of the examinations. The cecal intubation rate was 97%, and the mean adenoma detection rate 60%. The quality of lavage was documented in 97% (rated as good in 70% and moderate in 24%). CONCLUSIONS: The risk of adverse events is significantly increased in patients with an ASA score > II, which should be considered when choosing treatment methods and precautionary measures. Continuous recording of AEPM can be effectively integrated into the clinical reporting process, enabling analysis of the data and feedback to be provided to endoscopists.

Relationships between education and non-alcoholic fatty liver disease.

INTRODUCTION: Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle choices. However, the association between non-alcoholic fatty liver disease (NAFLD) and educational level remains unclear. Therefore, the aim of this study was to investigate whether there is an independent relationship between NAFLD and educational level as a surrogate marker for socioeconomic status (SES). METHODS: This cross-sectional study included 8,727 participants from the Paracelsus 10,000 study. The association between NAFLD and educational level was assessed using multivariable logistic regression models and multivariable linear regression. The primary endpoints were NAFLD (FLI score > 60) and liver fibrosis (FIB-4 score > 1.29). Further subgroup analysis with liver stiffness measurement was done. RESULTS: In the study, NAFLD prevalence was 23% among participants with high education, 33% among intermediate, and 40% among those with low education (p<0.01). Importantly, a significantly reduced risk of NAFLD was observed in individuals with higher education, as indicated by an adjusted relative risk of 0.52 (p < 0.01). Furthermore, higher education level was associated with significantly lower odds of NAFLD and fibrosis. Additionally, a subgroup analysis revealed that higher liver stiffness measurements were independently associated with lower levels of education. CONCLUSION: The study's findings indicate that a lower education level increases the risk of NAFLD independent of confounding factors. Therefore, these findings highlight the potential impact of educational attainment on NAFLD risk and emphasize the need for targeted interventions in vulnerable populations.

Genetic Variants Determine Treatment Response in Autoimmune Hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare entity; in addition, single-nucleotide polymorphisms (SNPs) may impact its course and outcome. We investigated liver-related SNPs regarding its activity, as well as in relation to its stage and treatment response in a Central European AIH cohort. METHODS: A total of 113 AIH patients (i.e., 30 male/83 female, median 57.9 years) were identified. In 81, genotyping of PNPLA3-rs738409, MBOAT7-rs626238, TM6SF2-rs58542926, and HSD17B13-rs72613567:TA, as well as both biochemical and clinical data at baseline and follow-up, were available. RESULTS: The median time of follow-up was 2.8 years; five patients died and one underwent liver transplantation. The PNPLA3-G/G homozygosity was linked to a worse treatment response when compared to wildtype [wt] (ALT 1.7 vs. 0.6 × ULN, p < 0.001). The MBOAT7-C/C homozygosity was linked to non-response vs. wt and heterozygosity (p = 0.022). Male gender was associated with non-response (OR 14.5, p = 0.012) and a higher prevalence of PNPLA3 (G/G vs. C/G vs. wt 41.9/40.0/15.0% males, p = 0.03). The MBOAT7 wt was linked to less histological fibrosis (p = 0.008), while no effects for other SNPs were noted. A polygenic risk score was utilized comprising all the SNPs and correlated with the treatment response (p = 0.04). CONCLUSIONS: Our data suggest that genetic risk variants impact the treatment response of AIH in a gene-dosage-dependent manner. Furthermore, MBOAT7 and PNPLA3 mediated most of the observed effects, the latter explaining, in part, the predisposition of male subjects to worse treatment responses.