The influence of prehabilitation in patients with liver cirrhosis before liver transplantation: a randomized clinical trial.

BACKGROUND: The high prevalence of liver cirrhosis in Slovakia leads to a great need for transplant treatment. The outcome of liver transplantation is influenced by several factors. AIM: The main objective of this study is to test the effectiveness of prehabilitation compared to standard of care. DESIGN: Prospective, double-arm, randomized, open-registry study. SETTING: Patient in F. D. Roosevelt Teaching Hospital, Slovakia, Banská Bystrica. POPULATION: The participants consisted of patients with liver cirrhosis (55 men, 25 women). METHODS: The patients were randomized to the active prehabilitation group (N.=39) or the standard of care group (SOC) (N.=41). SOC represents the standard of care for patients prior to liver transplantation, consisting of a formal oral interview lasting 30 minutes. In addition to SOC, each patient with decompensated liver cirrhosis also underwent a prehabilitation intervention that included rehabilitation and nutrition support. Patients completed the exercises under the supervision of a physician during hospitalisation. RESULTS: After one month, the liver frailty index improved in the prehabilitation group (P=0.05). No improvement in MELD (Model of End Stage Liver Disease) was found in the group that underwent the prehabilitation program (P=0.28), and no improvement was found in the Child-Pugh score after one month (P=0.13). In the prehabilitation groups compared with the SOC group, differences were not found in the MELD score (P=0.11). Better clinical outcomes according to the Child-Pugh score was found for the prehabilitation group compared with the SOC group (P=0.02). According to LFI, there was no difference between the groups (P=0.26). Very low adherence was found after three months. Only three patients in the SOC group and six patients in the prehabilitation group came to the check-up. Due to low adherence after 3 months in patients with liver cirrhosis, it is not possible to make an adequate comparison between groups after three months. CONCLUSIONS: Despite the great effort to maintain adherence, it was not possible to draw a conclusion about the effectiveness of prehabilitation in patients before liver transplantation compared to standard of care because the main problem in Slovak patients with liver cirrhosis is low adherence. More studies are needed to identify the barriers that lead to low adherence in patients with liver cirrhosis. CLINICAL REHABILITATION IMPACT: A promising result was found due to improvement of the Liver Frailty Index and the Child-Pugh Score after one month in the prehabilitation group.

Predictive value of infliximab trough levels in maintenance therapy for 5-year sustained clinical remission in patients with inflammatory bowel disease.

BACKGROUND: Despite long-term use of infliximab (IFX) in IBD treatment, its optimized use is unclear due to its complicated pharmacokinetics/dynamics. Hence, the predictive value of IFX trough levels (TL) is important in treatment management. METHODS: We performed a prospective, cross-sectional, observational study with 74 IBD patients treated with IFX (mean 9.1 years, SD ± 3). TL was measured during maintenance therapy, in which maintenance of remission was followed for 5 years. RESULTS:  TL > 3 µg/ml during maintenance therapy was a significant predictor of clinical remission in 5 years in UC patients (82 % vs 62 %, p 3 µg/ml during maintenance therapy in a cohort of IBD patients (p = 0.05). Deviations in percentage of remission and fraction of relapses in TL categories were insignificant in a cohort of CD patients (85 % vs 74 %, p > 0.05). CONCLUSIONS:  TL > 3 µg/ml during maintenance therapy is a strong predictor of sustained clinical remission for 5 years in UC patients. The use of combination therapy with AZA, due to its significant association with high TL, may have a practical benefit in achieving better clinical outcomes in UC patients (Tab. 2, Fig. 10, Ref. 20).

Relationship between alcohol consumption and adverse childhood experiences in college students-A cross-sectional study.

Background: Alcohol consumption is an important issue. Adverse childhood experiences (ACEs) can affect alcohol consumption later in life. Therefore, the main objective of this study was to test the association between ACE and the alcohol consumption in college students. Materials and methods: A cross-sectional study on college students was conducted during December 2021 and January 2022, Through the school web system, students received a standard questionnaire on alcohol consumption (AUDIT) and ACEs. The study involved 4,044 participants from three universities in Slovakia. Result: Compared to men, the incidence of emotional abuse by a parent, physical abuse by a parent, and sexual abuse was significantly higher in women (p < 0.001). Furthermore, women reported greater emotional and physical neglect (p < 0.001). The incidence of a high or very high AUDIT score in college students with ACE-0, ACE-1, ACE-2, ACE-3, and ACE-4+ was 3.8, 4.7, 4.1, 6.4, and 9.3%, respectively. Conclusion: More adverse childhood experiences were associated with increased alcohol consumption in both male and female university students. Baseline drinking was higher in male students, but increased drinking in relation to an increase in ACEs was higher in female students. These results point to gender-specific driving forces and targets for intervention.

Questionnaire for risk factors of alcoholic and nonalcoholic fatty liver disease.

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).

Patients with COVID-19 pneumonia with 25(OH)D levels lower than 12 ng/ml are at increased risk of death.

OBJECTIVES: There is no consensus on specific serum 25-hydroxy vitamin D (25(OH) D) levels associated with higher risk of severe outcome in patients with coronavirus disease 2019 (COVID-19). According to the literature patients with serum 25(OH) D levels <12 ng/ml are clearly deficient at all ages. Our aim was to assess COVID-19 mortality in the settings of severe 25(OH) D deficiency. A cohort study of 357 patients with COVID-19 was conducted. Subjects were monitored until discharge or in-hospital death. At admission, severity parameters (C-reactive protein (CRP), IL-6, Charlson comorbidity index, etc.) were assessed. These parameters were compared regarding 25(OH) D levels threshold 12 ng/ml, where values below 12 ng/ml were considered absolute vitamin D deficiency. RESULTS: 25(OH) D levels at the time of admission were independently associated with mortality (p <0.05). Nonsurvivors (N = 168) had lower 25(OH) D levels, SO2, higher age, CRP, viral load, and Charlson comorbidity index in comparison to survivors. Patients with serum 25(OH) D levels <12 ng/ml had higher mortality (55% vs 45 %), viral load (21.5 vs 23.1), and Charlson comorbidity index (5.3 vs 4.4) than those with serum 25(OH) D levels >12 ng/ml (p <0.05). CONCLUSIONS: Patients with COVID-19 with serum 25(OH) D levels <12 ng/ml have higher mortality. Among other factors, severe vitamin D deficiency likely leads to poor outcome.

Prognostic Factors in Primary Biliary Cholangitis: A Retrospective Study of Joint Slovak and Croatian Cohort of 249 Patients.

OBJECTIVE: To identify pretreatment laboratory parameters associated with treatment response and to describe the relationship between treatment response and liver decompensation in patients with primary biliary cholangitis treated with ursodeoxycholic acid. METHODS: We defined treatment response as both ALP ≤ 1.67 × ULN and total bilirubin ≤ 2 × ULN. Multiple logistic regression analyses were performed to adjust for confounding effects of sociodemographic variables. RESULTS: Pretreatment total bilirubin ((TB); OR = 0.3388, 95%CI = 0.1671-0.6077), ALT (OR = 0.5306, 95%CI = 0.3830-0.7080), AST (OR = 0.4065, 95%CI = 0.2690-0.5834), ALP (OR = 0.3440, 95%CI = 0.2356-0.4723), total cholesterol ((TC); OR = 0.7730, 95%CI = 0.6242-0.9271), APRI (OR = 0.3375, 95%CI = 0.1833-0.5774), as well as pretreatment albumin (OR = 1.1612, 95%CI = 1.0706-1.2688) and ALT/ALP (OR = 2.4596, 95%CI = 1.2095-5.5472) were associated with treatment response after six months of treatment. Pretreatment TB (OR = 0.2777, 95%CI = 0.1288-0.5228), ALT (OR = 0.5968, 95%CI = 0.4354-0.7963), AST (OR = 0.4161, 95%CI = 0.2736-0.6076), ALP (OR = 0.4676, 95%CI = 0.3487-0.6048), APRI (OR = 0.2838, 95%CI = 0.1433-0.5141), as well as pretreatment albumin (OR = 1.2359, 95%CI = 1.1257-1.3714) and platelet count (OR = 1.0056, 95%CI = 1.0011-1.0103) were associated with treatment response after 12 months of treatment. Treatment response after 6 months of UDCA therapy is significantly associated with treatment response after 12 months of UDCA therapy (OR = 25.2976, 95% CI = 10.5881-68.4917). Treatment responses after 6 and 12 months of UDCA therapy decrease the risk of an episode of liver decompensation in PBC patients (OR = 12.1156, 95%CI = 3.7192-54.4826 and OR = 21.6000, 95%CI = 6.6319-97.3840, respectively). CONCLUSIONS: There are several pretreatment laboratory parameters associated with treatment response in patients with primary biliary cholangitis. Treatment response after six months is significantly associated with treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy. Treatment responses after 6 and 12 months of UDCA decrease the risk of an episode of liver decompensation.

External Validation of UDCA Response Score in Slovak and Croatian Patients with Primary Biliary Cholangitis.

Background: Ursodeoxycholic acid response score (URS) is a prognostic model that estimates the baseline probability of treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cholangitis (PBC). Aim: To independently evaluate the predictive performance of the URS model. Methods: We used a cohort of Slovak and Croatian treatment-naïve PBC patients to quantify the discrimination ability using the area under receiver operating characteristic curve (AUROC) and its 95% confidence interval (CI). Furthermore, we evaluated the calibration using calibration belts. The primary outcome was treatment response after 12 months of UDCA therapy defined as values of alkaline phosphatase ≤1.67 × upper limit of normal. Results: One hundred and ninety-four patients were included. Median pretreatment age was 56 years (interquartile range 49-62). Treatment response was achieved in 79.38% of patients. AUROC of the URS was 0.81 (95% CI 0.73-0.88) and the calibration belt revealed that response rates were correctly estimated by predicted probabilities. Conclusion: Our results confirm that the URS can be used in treatment-naïve PBC patients for estimating the treatment response probability after 12 months of UDCA therapy.

Frailty in Nonalcoholic Fatty Liver Cirrhosis: A Comparison with Alcoholic Cirrhosis, Risk Patterns, and Impact on Prognosis.

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.

Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review.

BACKGROUND: Muscle growth promoters are being developed for the treatment of disease-induced loss of muscle mass. Ligandrol and ostarine are selective androgen receptor modulators (SARMs) with a non-steroidal structure and a presumably more favorable side effect profile. In recent years, these substances with or without "post-cycle therapy" (PCT) are often misused by amateur athletes aiming to promote muscle growth. At the same time, reports on their toxic effects on organ systems are emerging. CASE SUMMARY: We report two cases of liver injury in young men who used ligandrol and/or ostarine for a few weeks followed by the use of substances for PCT. Acute liver injury occurred in both cases after stopping SARMs while on PCT. The clinical picture was dominated by jaundice and fatigue. The biochemical pattern showed a mixed type of injury with normal alkaline phosphatase and high concentrations of bilirubin and serum bile acids. Histological evidence showed predominantly cholestatic injury with canalicular bile plugs, ductopenia, and mild hepatocellular damage without significant fibrosis. The patients recovered from the condition after 3 mo. The off target effects of SARMs were likely idiosyncratic, but our report highlights the yet unrecognized effects of other toxic substances used for PCT, supra-therapeutic doses, and the complete absence of monitoring for adverse effects. CONCLUSION: Among muscle-building amateur athletes, SARMs (ligandrol or ostarine) and/or substances in PCT may cause cholestatic liver injury with prolonged recovery.

Applicability and prognostic value of frailty assessment tools among hospitalized patients with advanced chronic liver disease.

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.

Challenging management of severe chronic disorders in acute pandemic situation: Chronic liver disease under COVID-19 pandemic as the proof-of-principle model to orchestrate the measures in 3PM context.

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.

Irisin in Liver Cirrhosis.

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.

Adherence to Oral Nutritional Supplements After Being Discharged from the Hospital is Low but Improves Outcome in Patients with Advanced Chronic Liver Disease.

PURPOSE: 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.

Alcohol Use Relapse Following Liver Transplantation for Alcoholic Liver Disease.

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.

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.

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.

Decrease of trabecular bone score reflects severity of Crohn's disease: results of a case-control study.

OBJECTIVES: Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD). PATIENTS AND METHODS: The study was designed as a case-control study with the aim to assess and compare bone quantity and quality in patients with Crohn's disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy. RESULTS: The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-α therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups. CONCLUSION: For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.

Less strict intervention thresholds for the FRAX and TBS-adjusted FRAX predict clinical fractures in osteopenic postmenopausal women with no prior fractures.

Little is known about the clinical relevance of treating post-menopausal women with no prior history of fragility fracture and bone mineral densities (BMD) within the osteopenic range. In recent years, in addition to BMD and FRAX fracture probability assessments, a surrogate measure of bone micro-architecture quality, called the trabecular bone score (TBS), has been proven to predict future fragility fractures independently of both BMD and the FRAX. In this retrospective analysis of a follow-up study, we compared three risk assessment instruments-the FRAX, the TBS, and a TBS-adjusted FRAX score-in their ability, to predict future fragility fractures over a minimum of five years of follow-up among post-menopausal osteopenic women with no prior fragility fractures. We also sought to determine if more- versus less-stringent criteria were better when stratifying patients into higher-risk patients warranting osteoporosis-targeted intervention versus lower-risk patients in whom intervention would usually be deemed unnecessary. Over a mean 5.2 years follow-up, 18 clinical fragility fractures were documented among 127 women in the age 50 years and older (mean age = 66.1). On multivariate analysis utilizing regression models and Kaplan-Meier curve analysis, less-stringent criteria for the FRAX and TBS-adjusted FRAX were capable of predicting future fractures (with sensitivity/specificity of 83/31; 39/77 and 78/50% for TBS, FRAX and TBS-adjusted FRAX, respectively), while more-stringent criteria were incapable of doing so (with sensitivity/specificity of 56/60; 39/77 and 39/74 for TBS, FRAX and TBS-adjusted FRAX, respectively). Neither TBS threshold alone was a significant predictor of future fracture in our study. However, hazard ratio analysis revealed slight superiority of the TBS-adjusted FRAX over the FRAX alone (HR = 3.09 vs. 2.79). Adjusting the FRAX tool by incorporating the TBS may be useful to optimize the detection of post-menopausal osteopenic women with no prior fractures who warrant osteoporosis-targeted therapy.

Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study.

AIM: To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients. METHODS: During a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury. RESULTS: Two hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued. CONCLUSION: Liver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.

[Hemosuccus pancreaticus - rare complication of chronic pancreatitis]. / Hemosuccus pancreaticus - raritná komplikácia chronickej pankreatitídy.

Hemosuccus pancreaticus is a rare cause of upper digestive tract bleeding, it is hemorrhage to the pancreatic duct. A case report is about 56-years old man who was repeatedly hospitalized and suffered from melena and enterorrhagia during 3 years. Imaging studies did not clearly identified etiology of bleeding or source of hemorrhage was wrong identified. Finally, hemosuccus pancreaticus from collaterals of pseudoaneurysm after embolization was suspected because of repeating hemorrhage and embolization of a gastroduodenal artery in history. The interventional procedure was made in a the proximal part of the gastroduodenal artery with a good clinical response. This disease causes severe diagnostic and therapeutic problems, the unrecognized one can be fatal.Key words: enterorrhagia - hemosuccus pancreaticus - chronic pancreatitis - melena.

[Hepatic transit times and liver elasticity compared with meld in predicting a 1 year adverse clinical outcome of a clinically diagnosed cirrhosis]. / Význam merania obehových casov a elasticity pecene v porovnaní s MELD pri odhade jednorocného rizika nepriaznivého priebehu klinicky diagnostikovanej cirhózy.

INTRODUCTION AND OBJECTIVES: Hepatic transit times measured by the contrast enhanced ultrasonography and liver elasticity were found to predict a clinically significant portal hypertension. However, these modalities we not yet sufficiently evaluated in predicting adverse clinical outcome in patients with clinically diagnosed cirrhosis (D´Amico stages > 1), having a clinically significant portal hypertension. The aim of our study was to assess the predictive power of the liver transit times and the liver elasticity on an adverse clinical outcome of clinically diagnosed cirrhosis compared with the MELD score. METHODS: The study group included 48 consecutive outpatients with cirrhosis in the 2., 3. and 4. DAmico stages. Patients with stage 4 could have jaundice, patients with other complications of portal hypertension were excluded. Transit times were measured from the time of intravenous administration of contrast agent (Sonovue) to a signal appearance in a hepatic vein (hepatic vein arrival time, HVAT) or time difference between the contrast signal in the hepatic artery and hepatic vein (hepatic transit time, HTT) in seconds. Elasticity was measured using the transient elastography (Fibroscan). The transit times and elasticity were measured at baseline and patients were followed for up for 1 year. Adverse outcome of cirrhosis was defined as the appearance of clinically apparent ascites and/or hospitalization for liver disease and/or death within 1 year. RESULTS: The mean age was 61 years, with female/male ratio 23/25. At baseline, the median Child-Pugh score was 5 (IQR 5.0-6.0), MELD 9.5 (IQR 7.6 to 12.1), median HVAT was 22 s (IQR 19-25) and HTT 6 (IQR 5-9). HTT and HVAT negatively correlated with Child-Pugh (-0.351 and -0.441, p = 0.002) and MELD (-0.479 and -0.388, p = 0.006) scores. The adverse outcome at 1-year was observed in 11 cases (22.9 %), including 6 deaths and 5 hospitalizations. Median HVAT in those with/without the adverse outcome was 20 seconds (IQR 19.3-23.5) compared with 22 s (IQR 19-26, p = 0.32). Cases with adverse outcome had significantly higher MELD (12.9 vs 8.5), Child-Pugh score (7.0 vs 5.0) and the liver elasticity (52.5 vs 21.5 kPa) (p < 0.05). The AUROC of the HVAT, liver elasticity and MELD for the prediction of the adverse outcome was 0.60 (95% CI 0.414 to 0.785), 0.767 (0.56 to 0.98) and 0.813 (0.66 to 0.97). Unlike HVAT, the liver elasticity > 35.3 kPa increased the risk of the adverse outcome 10.3-times and MELD score > 11 points 8.5-times. CONCLUSION: In patients with clinically diagnosed cirrhosis having a clinically significant portal hypertension hepatic transit times do not predict the 1-year adverse clinical outcome. However, the liver elasticity > 35.3 kPa appears clinically useful with a prognostic value comparable with MELD. KEY WORDS: clinically diagnosed cirrhosis - hepatic transit times - liver elasticity - MELD - portal hypertension.