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Lubomir Skladany,1 Jana Vnencakova,1 Lukas Laffers,2 Beata Skvarkova,1 Eva Hrubá,1 Pavol Molcan,1 Tomas Koller3 1Hepatology, Gastroenterology and Transplantation (HEGITO) Department of the 2nd Department of Medicine, Slovak Medical University, FD Roosevelt Hospital, Banska Bystrica, Slovakia; 2Department of Mathematics, Faculty of Natural Sciences, Matej Bel University, Banska Bystrica, Slovakia; 3Gastroenterology and Hepatology Subdiv. of the 5th Department of Medicine, Comenius University Faculty of Medicine, University Hospital Bratislava, Bratislava, SlovakiaCorrespondence: Tomas KollerGastroenterology and Hepatology Subdiv. of the 5th Department of Medicine, Comenius University Faculty of Medicine, University Hospital Bratislava, Ruzinovska 6, Bratislava 82606, SlovakiaTel +42190518692Email koller.tomas@gmail.comPurpose: Patients with advanced chronic liver disease (ACLD) often have a poor nutritional status. In the management, current guidelines recommend dietary counseling and oral nutritional supplements (ONS). Nutritional goals and adherence to ONS are difficult to achieve while studies addressing adherence are scarce. We aimed to evaluate adherence to ONS, the associated factors, and its impact on outcome among ALCD patients who are discharged from the hospital.Patients and Methods: We identified consecutive hospitalized patients with ACLD from the cirrhosis registry and ONS prescription at discharge. Baseline demographics, anthropometrics, hand-grip strength (HGS), nutritional, and laboratory parameters were recorded. Adherence was assessed at 30, 90, and 180 days, but not in patients who did not survive or in those who underwent liver transplantation (LT) before the time-point.Results: From the registry containing 1004 patients, we included 450 cases, the median age was 56.3 (IQR 47– 62), 60% were males, 63.8% had alcoholic etiology, and the median model for end-stage liver disease score (MELD) was 16 (11– 21). During follow-up, 13.6%, 23.6%, and 31.1% of patients have died within 30, 90, and 180 days, respectively, and 21 underwent LT. Adherence to ONS in surviving patients was observed in 46%, 26.1%, and 16.9% within 30, 90, and 180 days, respectively. Baseline refractory ascites (HR=0.43, 0.24– 0.76), HGS (HR=1.03, 1.01– 1.06), and mid-arm circumference (HR=0.93, 0.88– 0.99) were independently associated with 30-day adherence. Among patients who survived beyond 30 days, adherents for > 30 days had improved synthetic liver function, HGS, a higher probability of LT (HR=1.7, 1.03– 2.8) and lower risk of death (HR=0.65, 0.45– 0.89), particularly those with MELD> 16 (OR=0.55, 0.36– 0.85) and low HGS (OR=0.61, 0.39– 0.93).Conclusion: In ACLD patients after discharge, adherence to ONS steeply declined and was associated with baseline refractory ascites and low muscle strength. Adherence to ONS also improved liver function, muscle strength, and survival.Keywords: adherence, nutritional supplements, malnutrition, cirrhosis, outcome, prognosis

In hospitalized patients with advanced chronic liver disease (ACLD), we aimed to evaluate the association between myostatin and muscle mass, its relation to inflammation and to assess the added prognostic value of myostatin for survival. In a prospective single-center cohort study, inclusion criteria were: consecutive hospitalization for ACLD and Child-Pugh score ≥ 7 points. Baseline parameters were myostatin, C-reactive protein (CRP), hand-grip strength (HGS), mid-arm muscle circumference (MAC), transversal psoas muscle index (TPMI). Patients were followed-up for at least 400 days. We included 198 men, 157 women, and 40 controls, median myostatin levels in pg/ml were 1790.1 in women, 1959.4 in men, and 3850.0 and 2996.o in healthy men and women. Myostatin positively correlated with TPMI, but weakly with MAC and HGS, and not in women. Myostatin negatively correlated with CRP in both genders. In cases with CRP 10 mg/l, regression analysis of myostatin versus HGS, MAC or TPMI showed steeper dependence curve. During follow up, 85 men and 64 women (42.9% versus 40.8%) have died, 22 men and 19 women (11.1% versus 12.1%) underwent liver transplantation. Cumulative incidence of death was higher in men with myostatin levels < 1600.0 pg/ml, but not in women. In men, MELD score and myostatin cut-off were independent predictors of worse survival but did not predict survival in women. In men, myostatin levels directly reflect the muscle mass and low levels independently predict worse survival. In women, myostatin is not associated with muscle mass or survival. [ABSTRACT FROM AUTHOR]

Background and Aims: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification., Patients and Methods: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180 days. Additional risk refinement by F-CAL was tested for both groups., Results: We enrolled 263 cases in the study group with a median age of 57.2 years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92 × ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR] = 1.05, p < 0.001) and F-CAL terciles (HR = 1.413, p = 0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR = 2.49, p = 0.013) and Child stages A and B (HR = 1.706, p = 0.025), in whom high F-CAL (cut-off >11 × ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group., Conclusion: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Alcohol-associated hepatitis (AH) is a severe inflammatory form of alcohol-associated liver disease (ALD) that carries a high mortality rate. Early liver transplantation for severe AH is increasingly available. However, specific criteria for referral and selection remain a subject of debate., Aims: To provide a narrative review of the natural history, diagnostic criteria and indications for referral for early liver transplantation for severe AH., Methods: We searched PubMed for articles published through August 2023. Key search terms were 'alcoholic hepatitis,' 'alcohol-associated hepatitis,' 'abstinence,' 'alcohol relapse,' and 'liver transplantation.', Results: Previously, a six-month period of alcohol abstinence was required before patients with ALD were considered for liver transplantation. However, studies in recent years have demonstrated that, among carefully selected patients, patients who received early transplants have much higher survival rates than patients with similarly severe disease who did not undergo transplants (77% vs. 23%). Despite these successes, early liver transplantation remains controversial, as these patients have typically not undergone treatment for alcohol use disorder, with the ensuing risk of returning to alcohol use., Conclusions: While early liver transplantation for AH has survival benefits, many patients would not have received treatment for alcohol use disorder. An integrated approach to evaluating candidacy for early liver transplantation is needed., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

One of the most prevalent influenceable risk factors for poor cardiovascular outcome is arterial hypertension.This is a prospective analysis of liver transplant recipients in which 24-hour blood pressure (BP) measurement was performed. The primary aim was to identify post-LT (liver transplantation) patients without a history of arterial hypertension who meet the criteria for arterial hypertension using 24-hour BP monitoring. Secondary objectives were to determine how many patients with known treated arterial hypertension had suboptimal BP control. The group included 88 patients (men, 52.3%, history of arterial hypertension group: n=56, no history of arterial hypertension group: n=32) with an average age at the time of measurement of 62.4 years±11. The average time since LT at the time of measurement was 45.2 months. De novo arterial hypertension using 24-hour BP monitoring was diagnosed in 28%. Hypertonic changes in the fundus oculi were confirmed as predictor for suboptimally controlled hypertension [OR 5,1265, p=0.0279]. On the other hand, male sex [OR 3.1840, p=0.0311], together with age [OR 1.3347, p=0.0153] and waist circumference [OR 4.3490, p=0.0418] predicted the need of intensification of antihypertensive treatment. Male sex, age and waist circumference should increase the index of suspicion and lead to zoom-in on a possibility of poorly controlled blood pressure. Where automated blood pressure monitoring is unavailable, regular examination of the fundus could serve as an available surrogate marker of suboptimally controlled arterial hypertension (Tab.6, Fig. 1, Ref. 36). Text in PDF www.elis.sk Keywords: liver transplantation, arterial hypertension, automated blood pressure monitoring.

Aim of the Study: We tried to assess the influence of concomitant diverticulosis and other factors, e.g., Child-Pugh (C-P) and MELD scores, viral etiology, and presence of alcoholic disease, on short-term results of liver transplantation (LT) with an emphasis on duration of patient's hospitalization., Material and Methods: This prospective study was performed on 206 cirrhotic patients who were selected for LT. In order to assess the presence of diverticculosis we performed colonoscopy., Results: The duration of hospitalization after LT did not differ significantly between patients with and without diverticulosis (27.5 [21.0-33.5] vs. 24.0 [18.0-32.0] days, p = 0.28). Patients with C-P class C were hospitalized longer in comparison to the class B patients. It is reflected in the positive correlation between C-P score and days of hospitalization ( r = 0.22, p = 0.002). Patients with diverticulosis were significantly older (59.6 [51.1-63.3] vs. 52.9 [43.8-59.2] years, p = 0.03). Alcoholic liver disease (ALD) was associated with a greater risk of diverticulosis (OR = 3.89, 95% CI [1.13-15.87], p = 0.04)., Conclusions: Presence of diverticulosis among subjects undergoing LT did not influence the duration of hospitalization after the procedure. Significantly longer hospitalization was observed in patients with the most advanced liver disease according to C-P score. To determine the exact impact of diverticulosis on short-term results of LT additional studies are required., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Clinical and Experimental Hepatology.)

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on the lives of millions of people, especially those with other concomitant diseases, such as chronic liver diseases. To date, seven coronaviruses have been identified to infect humans. The main site of pathological action of these viruses is lung tissue. However, a substantial number of studies have proven that SARS-CoV-2 shows affinity towards several organs, including the gastrointestinal tract and the liver. The current state of evidence points to several proposed mechanisms of liver injury in patients with COVID-19 and their combination. Liver impairment is considered to be the result of the direct effect of the virus on the hepatic tissue cells, a systemic reaction consisting of inflammation, hypoxia and cytokine storm, drug-induced liver injury, with the possible contribution of a perturbed gut-liver axis. Reactivation of chronic hepatic disease could be another factor for liver impairment in patients with SARS-CoV-2 infection. Acute-on-chronic liver failure (ACLF) is a relatively new syndrome that occurs in 10%-30% of all hospitalized patients with chronic liver disease. It is crucial to recognize high-risk patients due to the increased morbidity and mortality in these cases. Several published studies have reported virus infection as a trigger factor for ACLF. However, to date, there are few relevant studies describing the presence of ACLF in patients with acute SARS-CoV-2 infection. In this minireview we summarize the current state of knowledge regarding the relation between ACLF and acute SARS-CoV-2 infection., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior authors or other coauthors who contributed their efforts to this manuscript., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The COVID-19 pandemic has caused several negative changes. Increased alcohol consumption has been reported in some studies. This study aimed to compare the level of alcohol consumption among college students in the central and eastern regions of Slovakia., Materials and Methods: This cross-sectional study was conducted during the COVID-19 pandemic. Three Slovak universities were included in the study. The Alcohol Use Disorders Identification Test (AUDIT) was used to determine alcohol consumption., Results: The total number of college students was 3,647. The overall AUDIT score was significantly higher in the eastern region (p 0.05). During a typical drinking day, more alcohol was consumed in the eastern region compared to the central region of Slovakia in men (p < 0.028). Excess drinking by men has been reported in the eastern region compared to the central region (p 0.05). Inability to remember what happened on a night of drinking was a significant difference in eastern men (p = 0.047)., Conclusion: Alcohol consumption is a significant problem in Slovakia. The number of students with a high AUDIT score from the eastern region is higher than the number of students with a high AUDIT score from the central region. More significant differences were found between men compared to women from eastern and central Slovakia (Tab. 5, Fig. 2, Ref. 34). Text in PDF www.elis.sk Keywords: alcohol consumption, AUDIT, pandemic, COVID-19, Slovakia.

Chemerin is one of the specialized pro-resolving mediators that participate in the early phase of inflammation and contribute to the initiation of the pro-resolving response. There is a paucity of data regarding the time course of chemerin during acute infections. We aimed to evaluate the sequence of inflammatory responses in the acute COVID-19 phase throughout onset and resolution of inflammation. We evaluated changes in selected biomarkers in COVID-19 survivors on the 7-day and 28-day follow up. Chemerin was lower in patients with baseline moderate/severe disease at day 7 compared with asymptomatic patients and individuals with mild illness (7265 [5526−9448] vs. 8730 [6888−11,058] pg/mL; p = 0.03). Only in patients with moderate/severe disease, but not in those with mild symptoms, were chemerin concentrations decreased one week after infection onset compared with baseline (7265 [5526−9448] vs. 8866 [6383−10,690] pg/mL; p < 0.05) with a subsequent increase on the 28-day follow up (9313 [7353−11,033] pg/mL; p < 0.05). Resolution of inflammation in the group of moderate/severe SARS-CoV2 infection was associated with increasing serum concentrations of chemerin, contrary to pro-inflammatory cytokines and adipokines (pentraxin 3, TNFα, resistin, leptin). A similar pattern of angiopoietin-2 dynamics may suggest signs of enhanced vascularization as a consequence of acute SARS-CoV2 infection.

Purpose: Human carcinoma cells with different p53 status exposed to a combination of bioactive substances, resveratrol and berberine, revealed different responses in cell viability via p53-dependant apoptosis pathway activation., Materials and Methods: Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, we investigated various and opposing effects in hepatocellular carcinoma cells, Hep-G2 and Hep-3B with different p53-status., Results: Cells decreased in viability after treatment with dose-dependent concentrations of resveratrol and berberine. Hep-3B p53 mutants were more sensitive in comparison to the p53 wild type Hep-G2 cell line. A synergistic effect was observed after treatment of Hep-3B cells with a combination of resveratrol/berberine ratios in favor of resveratrol (2:1, 3:1). The results suggest that an effective concentration of berberine, in the presence of resveratrol, could be decreased even to 50% (half the IC 50 for berberine) in cancer treatment. Combined treatment with berberine and resveratrol, at the investigated concentrations and fractions, significantly reduces the viability of wild type p53 Hep-G2 and null p53-mutant Hep-3B cells by 20% and 40%, respectively., Conclusions: Stronger toxic effects on viability and proliferation were observed in Hep-3B cells what is consistent with the assumptions that null p53-mutants activate apoptosis canonical pathway. In conclusion, p53 status in human hepatocellular cancer cell lines modulates responses to plant-derived therapies., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Hepatocellular cancer (HCC) often occurs in geriatric patients. The aim of our study was to compare overall survival and progression-free survival between geriatric patients (>75 years) and patients younger than 75 years and to identify predictive factors of survival in geriatric patients with HCC. Material and Methods: We performed a retrospective analysis of patients with HCC diagnosed in Slovakia between 2010−2016. Cases (HCC patients ≥75 years) were matched to controls (HCC patients <74 years) based on the propensity score (gender, BCLC stage and the first-line treatment). Results: We included 148 patients (84 men, 57%) with HCC. There were no differences between cases and controls in the baseline characteristics. The overall survival in geriatric patients with HCC was comparable to younger controls (p = 0.42). The one-, two-, and three-year overall survival was 42% and 31%, 19% and 12%, and 12% and 9% in geriatric patients and controls, respectively (p = 0.2, 0.4, 0.8). Similarly, there was no difference in the one- and two-year progression-free survival: 28% and 18% vs. 10% and 7% in geriatric HCC patients and controls, respectively (p = 0.2, 1, -). There was no case−control difference between geriatric HCC patients and younger HCC controls in the overall survival in the subpopulation of patients with no known comorbidities (p = 0.5), one and two comorbidities (p = 0.49), and three or more comorbidities (p = 0.39). Log (CRP), log (NLR), log (PLR), and log (SII) were all associated with the three-year survival in geriatric HCC patients in simple logistic regression analyses. However, this time, only log (NLR) remained associated even after controlling for the age and BCLC confounding (OR 5.32, 95% CI 1.43−28.85). Conclusions. We found no differences in overall survival and progression-free survival between older and younger HCC patients. Parameters of subclinical inflammation predict prognosis in geriatric patients with HCC. A limitation of the study is small number of the treated patients; therefore, further investigation is warranted.

Objectives: Non-communicable diseases are estimated to account for 90 % of total deaths and 19 % of premature deaths in Slovakia. Major preventable risk factors of premature mortality are overweight, obesity and alcohol consumption., Background: Screening of risk factors related to alcoholic and nonalcoholic fatty liver diseases (AFLD and NAFLD, respectively) in Slovak outpatients with liver disease., Methods: A total group of 923 patients, aged 19-91 years were included in the study. Self-administered anonymous questionnaires (Q) were filled in by them. Twelve questions were included relating to age, gender, education, BMI, intake of vegetable, fruit, fish, alcohol, and coffee, as well as to smoking and physical exercise., Results: Overweight/obesity was detected in 59 % of patients, insufficient fiber intake in 87 % of patients, insufficient fish intake in 85 % of patients, and insufficient physical exercise in 68 % of patients. BMI over 25 together with the risk of alcohol consumption was present in 68 % of patients. Smoking was present in 19 % of patients and insufficient coffee intake (from its hepatoprotective point of view) was in 35 % of patients. A total proportion of 75 % of patients were at risk for NAFLD. The risk of alcohol consumption was present in 64 % of patients., Conclusions: An anonymous questionnaire is a useful screening tool for searching for the risks of NAFLD and AFLD in general practice. Recommendation of a screening schedule for general practitioners is implemented (Tab. 2, Fig. 4, Ref. 36).

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity., (© 2021. The Author(s).)

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

Objective: To compare NAFLD-related HCC and other etiology-related HCC and to describe predictive factors for survival in patients with NAFLD-related HCC independent of the BCLC staging system., Methods: We performed a multicenter longitudinal retrospective observational study of patients diagnosed with HCC during the period from 2010 through 2016., Results: 12.59% of patients had NAFLD-related HCC, and 21.91% had either NAFLD or cryptogenic etiology. NAFLD-related HCC patients were younger ( p = 0.0007), with a higher proportion of women ( p < 0.001) compared to other etiology-related HCC patients. The NAFLD group had a significantly lower proportion of patients with liver cirrhosis at the time of HCC diagnosis ( p < 0.0001), and they were more frequently diagnosed with both diabetes and metabolic syndrome when compared to other etiology-related HCC ( p < 0.0001). We did not find any difference in the overall survival or in the progression-free survival between NAFLD-related and other etiology-related HCC patients staged as BCLC B and BCLC C. NAFLD-related HCC patients with three or more liver lesions had a shorter overall survival when compared to patients with one or two liver lesions ( p = 0.0097), while patients with baseline CRP values of ≥5 mg/L or with PLR ≥ 150 had worse overall survival ( p = 0.012 and p = 0.0028, respectively). ALBI Grade 3 predicted worse overall survival compared to ALBI Grade 1 or 2 ( p = 0.00021). In NAFLD-related HCC patients, PLR and ALBI remained significant predictors of overall survival even after adjusting for BCLC., Conclusion: NAFLD-related HCC patients have a similar prognosis when compared to other etiology-related HCC. In NAFLD-related HCC patients, ALBI and PLR are significant predictors of the overall survival independent of the BCLC staging system.

Background: Physical frailty increases susceptibility to stressors and predicts adverse outcomes of cirrhosis. Data on disease course in different etiologies are scarce, so we aimed to compare the prevalence and risk factors of frailty and its impact on prognosis in nonalcoholic fatty liver (NAFLD) and alcoholic (ALD) cirrhosis. Patients and Methods . Cirrhosis registry RH7 operates since 2014 and includes hospitalized patients with decompensated cirrhosis, pre-LT evaluation, or curable hepatocellular carcinoma (HCC). From the RH7, we identified 280 ALD and 105 NAFLD patients with at least 6 months of follow-up., Results: Patients with NAFLD compared with ALD were older and had a higher proportion of females, higher body mass index (BMI) and mid-arm circumference (MAC), lower MELD score, CRP, and lower proportion of refractory ascites. The liver frailty index did not differ, and the prevalence of HCC was higher (17.1 vs. 6.8%, p =0.002). Age, sex, serum albumin, and C-reactive protein (CRP) were independent predictors of frailty. In NAFLD, frailty was also associated with BMI and MAC and in ALD, with the MELD score. The Cox model adjusted for age, sex, MELD, CRP, HCC, and LFI showed that NAFLD patients had higher all-cause mortality (HR = 1.88 95% CI 1.32-2.67, p < 0.001) and were more sensitive to the increase in LFI (HR = 1.51, 95% CI 1.05-2.2)., Conclusion: Patients with NAFLD cirrhosis had a comparable prevalence of frailty compared to ALD. Although prognostic indices showed less advanced disease, NAFLD patients were more sensitive to frailty, which reflected their higher overall disease burden and led to higher all-cause mortality., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Lubomir Skladany et al.)

Chronic liver disease management is a comprehensive approach requiring multi-professional expertise and well-orchestrated healthcare measures thoroughly organized by responsible medical units. Contextually, the corresponding multi-faceted chain of healthcare events is likely to be severely disturbed or even temporarily broken under the force majeure conditions such as global pandemics. Consequently, the chronic liver disease is highly representative for the management of any severe chronic disorder under lasting pandemics with unprecedented numbers of acutely diseased persons who, together with the chronically sick patient cohorts, have to be treated using the given capacity of healthcare systems with their limited resources. Current study aimed at exploring potentially negative impacts of the SARS CoV-2 outbreak on the quality of the advanced chronic liver disease (ACLD) management considering two well-classified parameters, namely, (1) the continuity of the patient registrations and (2) the level of mortality rates, comparing pre-COVID-19 statistics with these under the current pandemic in Slovak Republic. Altogether 1091 registrations to cirrhosis registry (with 60.8% versus 39.2% males to females ratio) were included with a median age of 57 years for patients under consideration. Already within the very first 3 months of the pandemic outbreak in Slovakia (lockdown declared from March 16, 2020, until May 20, 2020), the continuity of the patient registrations has been broken followed by significantly increased ACLD-related death rates. During this period of time, the total number of new registrations decreased by about 60% (15 registrations in 2020 versus 38 in 2018 and 38 in 2019). Corresponding mortality increased by about 52% (23 deaths in 2020 versus 10 in 2018 and 12 in 2019). Based on these results and in line with the framework of 3PM guidelines, the pandemic priority pathways (PPP) are strongly recommended for maintaining tertiary care uninterrupted. For the evidence-based implementation of PPP, creation of predictive algorithms and individualized care strategy tailored to the patient is essential. Resulting classification of measures is summarized as follows:The Green PPP Line is reserved for prioritized (urgent and comprehensive) treatment of patients at highest risk to die from ACLD (tertiary care) as compared to the risk from possible COVID-19 infection.The Orange PPP Line considers patients at middle risk of adverse outcomes from ACLD with re-addressing them to the secondary care. As further deterioration of ACLD is still probable, pro-active management is ascertained with tertiary center serving as the 24/7 telemedicine consultation hub for a secondary facility (on a physician-physician level).The Red PPP Line is related to the patients at low risk to die from ACLD, re-addressing them to the primary care. Since patients with stable chronic liver diseases without advanced fibrosis are at trivial inherent risk, they should be kept out of the healthcare setting as far as possible by the telemedical (patient-nurse or patient- physician) measurements. The assigned priority has to be monitored and re-evaluated individually-in intervals based on the baseline prognostic score such as MELD. The approach is conform with principles of predictive, preventive and personalized medicine (PPPM / 3PM) and demonstrates a potential of great clinical utility for an optimal management of any severe chronic disorder (cardiovascular, neurological and cancer) under lasting pandemics., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2021.)

Aim: To assess and compare the feasibility and prognostic value of various frailty assessment tools among decompensated cirrhosis inpatients., Methods: Our prospective observational registry included consecutive patients admitted for cirrhosis between June 2017 and July 2018. Exclusion criteria were intensive-care unit admission, hepatocellular carcinoma outside of the Milan criteria, and other malignancies. Frailty at baseline was assessed with the Liver Frailty Index (LFI), Clinical Frailty Scale (CFS), Fried Frailty Score (FFS), and Short Physical Performance Battery test (SPPB). The follow-up lasted for at least 180 days., Results: The study enrolled 168 patients (35.1% women, median age 57.9 years). The most frequent primary etiology was alcohol-related liver disease (78.6%). The Median Model for End-Stage Liver Disease (MELD) was 16. The 80th percentile of frailty scores was LFI>5.4, CFS>4, FFS>3, and SPPB<5, and it identified patients with higher mortality. LFI and CFS had the highest numerical prognostic value for in-hospital, and 90- and 180-day mortality. In a bivariate analysis of the risk of death or liver transplantation, the combination of MELD and LFI had the highest concordance (0.771±0.04). In a multivariate model, MELD score (HR 1.17, 95% CI 1.12-1.22), overt encephalopathy (2.39, 1.27-4.48), infection at baseline (2.32, 1.23-4.34), and numerical LFI (1.41, 1.02-1.95) were independent predictors of overall mortality., Conclusion: Frailty assessment using the evaluated tools is feasible among hospitalized cirrhotic patients, identifying those with worse prognosis. CFS had the highest applicability and accuracy for the initial assessment and LFI for the initial and follow-up assessments.

Background: Sarcopenia is a prevalent muscle abnormality characterized by progressive and generalized loss of skeletal muscle mass and strength, common among patients with decompensated advanced chronic liver disease (dACLD). Irisin is a recently identified myokine, which is mainly expressed and secreted by skeletal muscle. Pointing to the essential role of irisin in metabolic regulation and energy expenditure we hypothesize that it plays an important role in cirrhosis development and progression., Aim: To assess irisin serum levels in patients with dACLD, with different cirrhosis stage and etiology. To analyze relationship between sarcopenia and irisin serum levels., Methods: Serum irisin concentrations were measured with commercially available ELISA kits in 88 cirrhotic patients. Recorded parameters of muscle mass were hand-grip strength (HGS), mid-arm muscle circumference (MAC), and transversal psoas muscle index (TPMI)., Results: There was no difference in serum irisin levels between cirrhotic patients with different Child-Pugh (CTP) and model of end-stage liver disease (MELD) score, and those with and without ascites. The Liver Frailty Index (LFI) was significantly higher in patients with more advanced liver disease according to CTP and MELD. There was no association between serum irisin level with MAC (r = 0.04, p = 0.74) nor with TPMI (r = 0.20, p = 0.06). We observed significant negative correlation between serum irisin level and age (r = -0.35, p < 0.001)., Conclusions: Serum irisin levels did not correlate with sarcopenia. There was no difference in serum irisin levels between cirrhotic patients with and without diabetes. There was no difference in serum irisin levels among patients with more severe dACLD, although we observed significant LFI increase among patients with more advanced liver disease.

Background: The liver transplantation is a standard treatment method for the indicated group of patients with a final hepatic failure. The aim of this paper was to compare two reperfusion methods of implanted liver, non-venting and venting vena cava, and to evaluate the impact of both techniques on the post reperfusion syndrome., Methods: We compared two groups of patients: non-venting (n = 42) and venting (n = 41). We monitored bilirubin, liver enzymes and hemodynamic changes after reperfusion. We recorded monitored parameters immediately prior to the transplantation, during and after the reperfusion and on the 1st postoperative day. All liver grafts were used from the donors after a brain death., Results: We did not find a statistically significant difference in input monitored parameters. We detected significant changes of pH after reperfusion in both monitored groups. We determined a significantly better saturation in the non-venting group, bigger consumption of fresh frozen plasma and thrombo-concentrate in the non-venting group, a significantly higher value of total bilirubin and a lower value of Quick's time in the non-venting group., Conclusion: Venting via vena cava inferior did not impact the perioperative and early postoperative course of liver transplantation in our group of patients. However, further analyses are required (Tab. 2, Fig. 3, Ref. 20).

BACKGROUND Alcohol use disorders affect 10% of the European population. Alcohol-related liver disease (ALD) is the most common indication for liver transplantation in Slovakia. The aim of this study was to determine the proportion of patients with ALD who received a liver transplant who had alcohol relapsed, and the risk factors for alcohol relapse, as well as to compare clinical outcomes according to relapse. MATERIAL AND METHODS A retrospective study of consecutive patients with ALD, who underwent liver transplantation in a single transplant center between May 2008 and December 2017. We included adult patients who received a liver transplant due to ALD and excluded those who died <1 month after liver transplantation. We recorded demographic and clinical characteristics, graft injury, and overall mortality and compared them between relapsers and abstainers. RESULTS During the study period, we reviewed 196 cases of liver transplantation in 191 patients. We excluded 87 patients for non-ALD etiology and 15 patients by predefined criteria. The final analysis was carried out in 89 patients, mean aged 55 years; 24.7% were female. We diagnosed relapse in 23 patients (26%) with harmful drinking in 52% and occasional drinking in 48% of relapsers. The independent risk factors associated with relapse were: smoking (OR=5.92, P=0.006), loss of social status (OR=7.61, P=0.002), and time after liver transplantation (OR=1.0008, P=0.015). Graft injury was more frequent in relapsers with 2 independent risk factors: occasional drinking (OR=12.7, P=0.0005), and harmful drinking (OR=36.6, P<0.0001); overall survival was unaffected. CONCLUSIONS We found relapse to alcohol drinking in 26% of patients who received a liver transplant for ALD. Risk factors associated with alcohol drinking relapse were time, cigarette smoking, and loss of social status. Graft injury was more frequent in relapsers, but mortality was similar between relapsers and non-relapsers.

Aim of the Study: To determine the seroprevalence of hepatitis C virus (HCV) in outpatients with chronic kidney disease (CKD) attending a nephrology clinic., Material and Methods: Prospective observational study on consecutive outpatients attending a nephrology clinic. Inclusion criteria were age > 18 years, CKD, informed consent. There were no exclusion criterias. Recorded variables were age, gender, CKD grade and etiology, anti-HCV antibodies (Ab). Patients with positive HCV Abs were tracked for HCV RNA detection. Study interval was from November 2015 to March 2016. The study has been approved by the Ethic committee of F.D. Roosevelt University Hospital. Funded by Restricted Grant of AbbVie Slovakia., Results: One hundred and thirty-four patients were enrolled, with median age 70 years (19.7-91), 52% women. CKD grades: G1/2 - 52 patients (39%), G3a - 34 patients (25%), G3b - 32 patients (24%), G4 - 8 patients (6%), G5 - 8 patients (6%); CKD etiology: tubulointerstitial nephritis (TIN) - 53 patients (40%), nephrosclerosis (NS) - 30 patients (22%), diabetic nephropathy (DN) - 23 patients (17%), glomerulonephritis (GN) - 23 patients (17%), others - 5 patients (4%). Anti-HCV antibodies were detected in 8 patients (6%). There were no significant differences in CKD grades between HCV+ and HCV- patients; Heymann nephritis and GN were significantly more frequent in HCV- patients, as was male gender. Of 8 HCV Ab positive patients, 5 were available for HCV RNA testing (2 died after completion of the study, 1 was lost to follow-up); of them, 1 patient tested positive., Conclusions: Prevalence of anti-HCV antibodies in CKD patients was 6%, which is 4 times higher than in the general population of Slovakia; HCV RNA was detected in 1 patient (12.5%) of anti-HCV positive patients. Based on this result, multicentric, a larger-scale study is considered to be warranted.

Background and Aims: Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C., Methods: We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals., Results: We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis., Conclusion: We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.

Background: One of the pathogenic mechanisms of the progression non-alcoholic liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is the accumulation of reactive oxygen species (ROS). So, antioxidant therapy is necessary for successful treatment of the liver injury. We have paid attention to melanin produced by yeast Nadsoniella nigra strain X-1 as novel antioxidant and anti-inflammatory agents with low toxicity. In current study we aimed to investigate the preventive effect of melanin on the monosodium glutamate (MSG) induced NAFLD model in rats., Methods: The study was carried out on 45 Wistar rats that were divided into 3 groups: intact, MSG- and MSG+melanin groups (n=15 in each group). Newborn rats of MSG- and MSG+melanin groups were administered with MSG (4mg/g, 8μl/g, subcutaneously) at 2nd-10th days of life. Since the age of 1 month, rats of MSG-group were treated with water (0.25ml/100g), rats of MSG+melanin groups-with melanin (1mg/kg) dissolved in water (0.25ml/100g)., Introduction: had been performed intermittently (two-week courses alternated with two-week breaks) for 3 months. In 4-month rats anthropometrical parameters and visceral adipose tissue (VAT) mass were estimated. To assess morphological changes in liver we used NAS (NAFLD activity score). The content of pro-inflammatory cytokines (interleukin (IL)-1β, IL-12Bp40, interferon (INF)-γ) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor (TGF)-β) were measured by ELISA., Results: We found significantly lower total score (1.0±0.19 vs 3.33±0.36, p<0.001), degree of steatosis (0.73±0.18 vs 1.80±0.17, p<0.001) and manifestation of lobular inflammation (0.27±0.11 vs 1.20±0.17, p<0.001) due to NAFLD activity score in MSG+melanin group compared to MSG-obesity. NASH we confirmed only in 33.3% of rats with MSG-obesity that was significantly higher than after melanin (6.7%) administration (p=0.033). Melanin administration reduce amount of visceral fat on 44.5% (p<0.001) as compared to MSG-obesity group. Melanin reduced the content of IL-1β in rat serum and restored the level of anti-inflammatory cytokines (IL-10, TGF-β) to the control values., Conclusion: Thus, the administration of melanin can prevent development of NAFLD/NASH in rats with MSG-induced obesity and can be considered as possible novel therapeutic agents but further studies to confirm its action needed., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

In our previous works, the important therapeutic properties of nanocrystalline cerium dioxide such as strong antioxidant ability, prebiotical and antibiotic activity were shown. Such properties were obtained due to stabilization of nanoparticles with precise size 3-7nm. Such modification of nanocrystalline cerium dioxide has contributed to its remarkable efficacy and low toxicity. We have carried out the investigation of toxicity of the nanodrug and revealed that in the condition of the acute toxicity test, LD 50 was 2000mg/kg when it was administered per os. This indicator is approximately 1000 times greater than effective dose of the compound that proved the possibility of its usage for humans. Considering the strong antioxidant properties of this substance, we have performed the investigation of the influence of nanocrystalline cerium dioxide on the erosive-ulcerative lesions in gastric mucosa of rats induced by Selye's restraint stress. It was established that the studied compound significantly reduced the lesions area by 58.3% (p<0.05) induced by Selye's restraint stress. The attenuation of inflammation and decrease of lipid peroxidation in the conditions of gastric lesions and prophylactic administration of nanocrystalline cerium dioxide were shown. That was confirmed by the decrease of pro-inflammatory cytokines content (interleukin (IL) 1β, 12B p40) and raise of anti-inflammatory cytokines content (IL-10 and transforming growth factor β). Measurement of lipid peroxidation products has proved the antioxidant properties of nanocrystalline cerium dioxide as it decreased the content of conjugated dienes and thiobarbituric acid active products in the conditions of gastric ulceration induced by stress., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: Transplant hepatologists convened in Warsaw on 20-21 November 2015 at a meeting of the Initiative Group for Central European Hepatologic Collaboration to exchange their experience in liver transplantation in their respective countries., Material and Methods: The description is based on narration of individual country representatives, supplemented by data from additional queries, and from publicly accessible sources., Results: Liver transplantation programs were launched, in the Czech Republic in 1983, in Poland in 1990 (paediatric) followed by the adult program 1994; the first liver transplant in Hungary was performed in 1995, with Slovakia launching its liver transplantation program in 2008. Currently, there are 2 centres for liver transplantation in Slovakia, 1 centre in Hungary, 6 centres in Poland, and 2 centres in the Czech Republic. The rates of liver transplantation correspond to the number of cadaveric donations being the highest in the Czech Republic (15.8 per million population) and the lowest in Slovakia (4.2 per million population) (2014 data). Live donation is utilized systematically in Poland. Indications vary from country to country, but the 3 most frequent ones include hepatitis C and B cirrhosis, alcoholic cirrhosis, and cholestatic liver disorders. There is a growing incidence of hepatocellular carcinoma among adult liver transplant recipients. Biliary atresia and hereditary diseases are the most frequent indications among children. Hungary became a member of Eurotransplant, other countries are not a part of any international organization for organ sharing., Conclusions: Despite some differences, liver transplant programs seem to be compatible honouring the same values and principles universal to liver transplant programs in most parts of the world.