Prehliadanie podľa Autor "Havaj, Daniel Jan"
Teraz sa zobrazuje 1 - 3 z 3
Výsledky na stránku
Možnosti zoradenia
Položka 3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation(Springer Nature Switzerland AG : Cham, 2024) Skladaný, Ľubomír; Kubánek, Natália; Adamcová - Selčanová, Svetlana; Žilinčanová, Daniela; Havaj, Daniel Jan; Šulejová, Karolína; Šoltys, Katarína; Messingerová, Lucia; Lichvár, Michal; Lafférs, Lukáš; Žilinčan, Michal; Honsová, Eva; Lipták, Peter; Bánovčin, Peter; Bureš, Jan; Koller, Tomáš; Golubnitschaja, Olga; Arab, Juan-PabloRationale: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients’ needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy. Methods: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at − 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH — such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) — to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management. Results: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS. Conclusions and recommendations in the framework of 3PM: In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa — to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH’s pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof.Položka Does the change in Liver Frailty Index over the first week of hospitalisation predict mortality in patients with acute-on- chronic liver failure? A prospective cohort study from a Slovak liver centre(BMJ Group : Londýn, 2025) Skladaný, Ľubomír; Líška, Dávid; Mesíková, Klaudia; Havaj, Daniel Jan; Adamcová - Selčanová, Svetlana; Šulejová, Karolína; Žilinčanová, Daniela; Kohout, PavelObjective Hospital admissions for advanced chronic liver disease (ACLD) are associated with increased mortality, disability, a decline in quality of life and significant economic costs. Being admitted to the hospital usually indicates a triggering event that disrupted a previously stable condition, leading to decompensation or complications of ACLD. The most acute and severe manifestation of this imbalance is acute-on-chronic liver failure (ACLF), a syndrome representing a critical juncture. Reliable prognostic stratification of patients admitted with ACLF could facilitate the systematic delivery of tailored care, ranging from palliative care to intensive interventions like extracorporeal liver support devices and prioritised liver transplantation. Disease-specific prognostic tools, such as the Model for End-Stage Liver Disease score, are effective but have limitations, particularly in reflecting a patient’s potential for recovery. The concept of the body’s functional reserve in the context of ACLD/ACLF is gaining attention, with the Liver Frailty Index (LFI) potentially emerging as a recommended diagnostic tool. Methods Patients were selected from our cirrhosis registry (RH7). The LFI serves as an indicator of the patient’s prognosis. The LFI measurement takes place at two time intervals: on the patient’s admission and after 7 days of hospitalisation. Results Our RH7 registry included 154 patients (15.1%) who were diagnosed with ACLF. The primary cause of the underlying ACLD was alcohol-associated liver disease in the majority (79.8%) of cases. The mean value of LFI at admission was 4.50 (± 0.94). When patients with liver cirrhosis were categorised into three subgroups based on the LFI on day 7, survival exhibited a statistically significant decrease (p≤0.05) across all three ACLF grades. This decline in survival was observed from the ‘improved LFI’ cohort, through the ‘stable LFI’ group, to the ‘worsened LFI’ group. Conclusion The impact of day 7 LFI on the survival of patients with ACLF is notable. Nevertheless, it does not markedly enhance the predictive capability of the LFI assessed on admission. Consequently, the initial LFI on day 1 continues to be the most valuable and commonly used instrument for promptly recognising individuals with ACLF.Položka Telemedicine in the tertiary liver unit: A feasibility study(Termedia Publishing House : Poznań, 2024) Havaj, Daniel Jan; Adamcová - Selčanová, Svetlana; Mesíková, Klaudia; Vnenčáková, Janka; Žilinčanová, Daniela; Kubánek, Natália; Šulejová, Karolína; Mesárošová, Zuzana; Šváč, Juraj; Lapuník, Radovan; Ďurajová, Viktória; Skladaný, ĽubomírAim of the study: Chronic liver disease is a global cause of morbidity and mortality. Slovakia has a high prevalence but an inadequate hepatology network. The COVID-19 pandemic catalysed telemedicine (TM) as a potential solution, which we aimed to investigate. Material and methods: We conducted a retrospective cohort study to evaluate the feasibility and benefits of TM for liver cirrhosis and posttransplant patients, consisting of two phases, TM1 and TM2. The main outcomes were 1) cumulative endpoint of feasibility, uptake/acceptance, adherence (TM1), and fidelity (TM1, TM2), 2) the po- tential to reduce the length of hospital stay, avert unnecessary hospital admissions, and expedite the search/recall process in case of serious signals mediated by TM. Although not analysed in this study, we have recorded variables necessary for investigating associations of TM use with clinical outcomes and healthcare expenditure. Results: The study included 95 patients. The adherence documented by the termination of monitoring at the designated time was higher in TM2 (81.7% vs. 58.3%). The proportion of patients terminated due to death or the physician’s decision decreased (16.9% vs. 29.2%) and was based on their discretion, unrelated to any health complications (1.4% vs. 12.5%). The clinical impact was reflected in the hospitalization rate, particularly shortened hospitalization in 11.3%, averted/prevented hospital admissions in 14.1%, and accelerated rehospitalization in 11.3% in the subsequent phase with alert-based interventions. Conclusions: This study showed that adherence to TM was high and integrating TM helps to reduce hospitalization rates. Despite the identified limitations, TM has the potential to improve the quality and substantially reduce the cost of care.