Alcoholic Liver Disease-Related Hepatocellular Carcinoma: Characteristics and Comparison to General Slovak Hepatocellular Cancer Population.

Hepatocellular carcinoma (HCC) has multiple molecular classes that are associated with distinct etiologies and, besides particular molecular characteristics, that also differ in clinical aspects. We aim to characterize the clinical aspects of alcoholic liver disease-related HCC by a retrospective observational study that included all consequent patients diagnosed with MRI or histologically verified HCC in participating centers from 2010 to 2016. A total of 429 patients were included in the analysis, of which 412 patients (96%) had cirrhosis at the time of diagnosis. The most common etiologies were alcoholic liver disease (ALD) (48.3%), chronic hepatitis C (14.9%), NAFLD (12.6%), and chronic hepatitis B (10%). Patients with ALD-related HCC were more commonly males, more commonly had cirrhosis that was in more advanced stages, and had poorer performance status. Despite these results, no differences were observed in the overall (median 8.1 vs. 8.5 months) and progression-free survival (median 4.9 vs. 5.7 months). ALD-HCC patients within BCLC stage 0-A less frequently received potentially curative treatment as compared to the control HCC patients (62.2% vs. 87.5%, p = 0.017); and in patients with ALD-HCC liver function (MELD score) seemed to have a stronger influence on the prognosis compared to the control group HCC. Systemic inflammatory indexes were strongly associated with survival in the whole cohort. In conclusion, alcoholic liver disease is the most common cause of hepatocellular carcinoma in Slovakia, accounting for almost 50% of cases; and patients with ALD-related HCC more commonly had cirrhosis that was in more advanced stages and had poorer performance status, although no difference in survival between ALD-related and other etiology-related HCC was observed.

Inflammatory Indexes as Prognostic Factors of Survival in Geriatric Patients with Hepatocellular Carcinoma: A Case Control Study of Eight Slovak Centers.

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.

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).

Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Clinical Patterns, Outcomes, and Prognostic Factors for Overall Survival-A Retrospective Analysis of a Slovak Cohort.

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.

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.

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.

Chronic hepatitis C virus infection in the Czech Republic and Slovakia: an analysis of patient and virus characteristics.

OBJECTIVES: The MOSAIC study gathered data on chronic hepatitis C virus (HCV) infection and its treatment in various countries worldwide. Here we summarise patient and HCV characteristics in the Czech Republic and Slovakia. METHODS: MOSAIC was an observational study that included patients with chronic HCV infection untreated at the time of enrolment. Study collected and descriptively analysed patient demographics, disease stage and viral characteristics. Data were collected between February 2014 to October 2014. RESULTS: Among 220 patients enrolled, 51.4% were treatment-naïve. The most prevalent HCV genotype was G1 (78.4%), followed by G3 (19.7%). Higher prevalence of G1 was found in treatment-experienced patients (94.3%) compared to treatment-naïve (63.4%). Most participants (67.7%) presented viral RNA load of ≥ 800,000 IU/mL. Liver cirrhosis was reported in 24.5% of patients. Higher HCV RNA load and duration of HCV infection correlated with the degree of liver fibrosis. Anti-HCV interferon-based treatments were initiated in 88.2% of participants. CONCLUSIONS: The study confirmed significant changes in the HCV genotypes partition with G3 genotype rapidly increasing in both countries, with possible impact on the WHO eradication initiative and treatment selection.

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.

[Acute decompensation (AD) of advanced chronic liver disease (ACLD) and hepatitis E virus (HEV) infection as the trigger].

INTRODUCTION: HEV infection is perceived as the cause of acute hepatitis in endemic areas. In addition, it may also manifest as a possible trigger of AD or acute-on-chronic liver failure (ACLF). OBJECTIVES: To determine the prevalence of HEV infection as a trigger of AD/ACLF in patients admitted for decompensated ACLD (dACLD). METHODS: A retrospective study; data analysis of consecutive patients with dACLD admitted to a liver unit. Study interval: August 2016 - October 2017. INCLUSION CRITERIA: AD, defined as the interval between the first manifestations of decompensation and admission ≤ 4 weeks; an anti-HEV ELISA antibody assay in the IgG and IgM classes (HEV Ab ELISA, DRG Instruments GmbH, Germany). EXCLUSION CRITERIA: chronic decompensation of liver cirrhosis, insufficient data. Recorded variables: gender, age, etiology of ACLD, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh score (CTPS), anti-HEV IgG and IgM, ACLF 0-3, length of stay (LOS) in the hospital, mortality: in-hospital mortality (IHM), 30-day, 6-month, 1-year and overall mortality. RESULTS: Over the 15-month study interval, a total of 212 patients (pts) were admitted for dACLD, including 115 with AD (54 %). The final analysis comprised 91 pts with a mean age of 53.3 years (y); 56 % were men. ETIOLOGY: ALD 81 %, autoimmune diseases 7 %, HCV 5 %, non-alcoholic steatohepatitis 3 %, HBV 2 %, others 2 %. The mean MELD score and CTPS were 22.5 and 10.5 points (p), respectively. HEV infection as a possible trigger of AD was found in 9 % of pts (AD 75 %, ACLF 1-12.5 %, ACLF 3-12.5 %). Between HEV-positive and HEV-negative patients, there were no significant differences in age (p = 0.11), gender (p = 0.13), median MELD score (p = 0.42), median CTPS (p = 0.57), LOS (p = 0.56), overall survival (p = NS), IHM (p = NS), 30-day (p = NS), 6-month (p = NS), 1-year (p = NS) and overall mortality (p = NS). CONCLUSION: The prevalence of HEV infection as a trigger of AD was 9 %. There were no significant differences in recorded variables, including mortality, between HEV-negative and HEV-positive patients.

[Spontaneous bacterial peritonitis].

AIM OF STUDY: Spontaneous bacterial peritonitis (SBP) is the most frequent infectious complication of liver cirrhosis with serious consequences. Initially, SBP is always treated with empirical, not targeted, antibiotic therapy. Since a retrospective study performed in our department showed suboptimal effectiveness (only 40 %) of empirical antibiotic therapy in accordance with the EASL guidelines, a decision was made to change the protocol. The aims of this prospective study were to determine: (1) the incidence and characteristics of SBP in real clinical practice - in a liver unit of a tertiary hospital, (2) the effectiveness of new antibiotic therapy selected based on analysis of the spectrum of pathogens and their resistance to antibiotics as identified in a retrospective cohort study on SBP carried out in our department, (3) mortality, and to compare these findings with the literature data. MATERIAL AND METHODS: A prospective cohort observational pragmatic study. SETTING: Department of Hepatology, Gastroenterology and Liver Transplantation, 2nd Internal Clinic, Slovak Medical University and F. D. Roosevelt Teaching Hospital with Polyclinic in Banska Bystrica. Time interval: November 2012-August 2013. INCLUSION CRITERIA: hospitalization for liver cirrhosis, ascites ≥ grade 2, informed consent. The study was approved by the local ethics committee. EXCLUSION CRITERIA: malignancy, secondary bacterial peritonitis. DIAGNOSIS: SBP was defined by the count of neutrophil leukocytes in ascites ≥ 250/mm3). Positive ascitic fluid culture was not a necessary condition for the diagnosis. From each patient, 10 mL of ascitic fluid were sampled into two blood culture bottles, anaerobic and aerobic. Therapeutic response: defined as a decrease in NeA to 25 % of the baseline value after 48-72 hours, in accordance with the EASL guidelines. The absence of response was indication for change of the antibiotic therapy strategy. Empirical antibiotic therapy: The drug of choice was piperacillin/tazobactam 4 g/0.5 g i.v. every 8 hours for 5 days. Additionally, 20% human albumin at doses of 1.5 g/kg of patient weight on day 1 and 1.0 g/kg of patient weight on day 3 from the diagnosis was administered. If there was no response, (a) second choice antibiotic therapy according to analysis of the spectrum of pathogens and their resistance as identified in the former retrospective study on SBP, that is, ertapenem 1g i.v. every 24 hours for 5 days, or (b) targeted antibiotic therapy according to analysis of ascitic fluid culture performed in the meantime was initiated. RESULTS: The inclusion criteria were met by 65 patients (99 episodes); the incidence of SBP was 9 out of 99 episodes (9.1 %); 5 out of the 9 cases had positive bacterial culture (56 %), with most of bacteria being Gram-positive (4 out of 5 cases, 89 %). Therapeutic response was documented in 7 out of the 9 cases (78 %). The in-hospital mortality of patients with SBP was 11 %. CONCLUSIONS: SBP was detected in one out of ten patients with cirrhotic ascites. The selection of empirical therapy in accordance with the principles of antibiotic stewardship led to an increase in therapeutic response to more than 75 %. Effective treatment of SBP is a prerequisite for reduction of mortality.