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.

Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis.

BACKGROUND: Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice. AIMS: This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome. METHODS: A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed. RESULTS: Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target. CONCLUSIONS: The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.

Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.

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).

The Colon Endoscopic Bubble Scale (CEBuS): a two-phase evaluation study.

BACKGROUND: To date, no scale has been validated to assess bubbles associated with bowel preparation. This study aimed to develop and assess the reliability of a novel scale - the Colon Endoscopic Bubble Scale (CEBuS). METHODS: This was a multicenter, prospective, observational study with two online evaluation phases of 45 randomly distributed still colonoscopy images (15 per scale grade). Observers assessed images twice, 2 weeks apart, using CEBuS (CEBuS-0 - no or minimal bubbles, covering < 5 % of the surface; CEBuS-1 - bubbles covering 5 %-50 %; CEBuS-2 - bubbles covering > 50 %) and reporting the clinical action (do nothing; wash with water; wash with simethicone). RESULTS: CEBuS provided high levels of agreement both in evaluation Phase 1 (4 experts) and Phase 2 (6 experts and 13 non-experts), with almost perfect intraobserver reliability: kappa 0.82 (95 % confidence interval 0.75-0.88) and 0.86 (0.85-0.88); interobserver agreement - intraclass correlation coefficient (ICC) 0.83 (0.73-0.89) and 0.90 (0.86-0.94). Previous endoscopic experience had no influence on agreement among experts vs. non-experts: kappa 0.86 (0.80-0.91) vs. 0.87 (0.84-0.89) and ICC 0.91 (0.87-0.94) vs. 0.90 (0.86-0.94), respectively. Interobserver agreement on clinical action was ICC 0.63 (0.43-0.78) in Phase 1 and 0.77 (0.68-0.84) in Phase 2. Absolute agreement on clinical action per scale grade was 85 % (82-88) for CEBuS-0, 21 % (16-26) for CEBuS-1, and 74 % (70-78) for CEBuS-2. CONCLUSION: CEBuS proved to be a reliable instrument to standardize the evaluation of colonic bubbles during colonoscopy. Assessment in daily practice is warranted.

IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease.

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

Artificial Intelligence and Its Application to Minimal Hepatic Encephalopathy Diagnosis.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting. HE manifests as a spectrum of neurological or psychiatric abnormalities. Diagnosis of overt HE (OHE) is based on the typical clinical manifestation, but covert HE (CHE) has only very subtle clinical signs and minimal HE (MHE) is detected only by specialized time-consuming psychometric tests, for which there is still no universally accepted gold standard. Significant progress has been made in artificial intelligence and its application to medicine. In this review, we introduce how artificial intelligence has been used to diagnose minimal hepatic encephalopathy thus far, and we discuss its further potential in analyzing speech and handwriting data, which are probably the most accessible data for evaluating the cognitive state of the patient.

Seroprevalence of Bartonella henselae and Bartonella quintana Infection and Impact of Related Risk Factors in People from Eastern Slovakia.

The genus Bartonella is a rapidly expanding group of ubiquitous bacteria that occur mainly in different animal species, but some can also be transmitted to humans. Three species, B. henselae, B. bacilliformis, and B. quintana, are responsible for the majority of human cases. The severity of the clinical symptoms often depends on the immune status of the patient, but others factors such as the species of the pathogen, virulence factors, and bacterial load also can play an important role. As the information on the occurrence of bartonellosis in the human population in Slovakia is absent, the aim of our pilot study was to determine the seroprevalence against B. henselae and B. quintana in the population of people living in Eastern Slovakia, and to identify the impact of related risk factors. Of 536 people included in the study, 126 (23.5%) showed positivity for anti-B. henselae antibodies and 133 (24.8%) against B. quintana. A statistically higher prevalence was confirmed only in the case of B. quintana in women regardless of the risk group. In analyzing the risk factors, we found significant differences between B. henselae seropositive and seronegative groups only in uric acid levels and serum creatinine, both, however, clinically irrelevant. Significant, but clinically irrelevant differences were observed also in alanine aminotransferase (ALT) levels and creatinine in people seropositive to B. quintana.

The Epidemiology of Primary Biliary Cholangitis in European Countries: A Systematic Review and Meta-Analysis.

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease with wide ranges of reported incidence and prevalence. Aim: To map the incidence and prevalence of PBC in European countries from 2000 through 2020. Methods: Following PRISMA recommendations, we searched the Medline and Scopus databases for studies with information on either the incidence or prevalence of PBC. After data extraction, we used a random-effects model to estimate both the pooled annual incidence rate and pooled point-prevalence rate and performed subgroup analyses to identify components contributing to between-study heterogeneity. Results: We performed a qualitative and quantitative analysis of 18 studies. The pooled point-prevalence rate was 22.27 cases per 100,000 inhabitants (95% CI: 17.98-27.01), and the pooled annual incidence rate was 1.87 new cases per 100,000 inhabitants (95% CI: 1.46-2.34). In the subgroup analyses, we proved that a small part of the between-study heterogeneity is significantly associated with a history of being part of the Eastern Bloc.

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.

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.

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.

Comparison of Two Diagnostic Methods for the Detection of Hepatitis B Virus Genotypes in the Slovak Republic.

The hepatitis B virus (HBV), belonging to the Hepadnaviridae family, is responsible for a global health concern still in the 21st century. The virus is divided into 10 genotypes, which differ in geographical distribution and in their effect on disease progression and transmission, susceptibility to mutations, and response to treatment. There are many methods for diagnostics of HBV and differentiating its genotypes. Various commercial kits based on real-time polymerase chain reaction (RT PCR) and hybridization available, as well as whole genome sequencing or the sequencing of only individual parts of the genomes. We compared a commercial kit AmpliSens HBV-genotype-FRT, based on RT PCR, with an adapted method of amplification of the surface genomic region combined with Sanger sequencing. In the examined samples we identified the A, B, C, D, and E genotypes. By PCR with Sanger sequencing, the genotypes were determined in all 103 samples, while by using the commercial kit we successfully genotyped only 95 samples, including combined genotypes, which we could not detect by sequencing.

Roma Ethnicity and Sex-Specific Associations of Serum Uric Acid with Cardiometabolic and Hepatorenal Health Factors in Eastern Slovakian Population: The HepaMeta Study.

Background: Health characteristics associated with uric acid (UA) in the Roma minority remain less well known. The study sought to determine the ethnicity- and sex-specific associations of serum UA with health factors in Eastern Slovakian Roma and non-Roma populations. Methods: Data from the comparative cross-sectional HepaMeta study conducted in Slovakia in 2011 were used. The study enrolled 452 Roma subjects (35.2% men) and 403 non-Roma individuals (45.9% men) aged 18-55 years. Results: All study parameters differed between the sexes in both the Roma and non-Roma participants (p < 0.05). UA was related to sex with odds ratio for female sex 0.873, 95% CI 0.853-0.893 (p < 0.0001) per 10-unit increase of UA. Average level of UA ± standard deviation was lower in Roma than in non-Roma (226.54 ± 79.8 vs. 259.11 ± 84.53 umol/L; p < 0.0001). The Roma population presented with greater levels of high-sensitivity C-reactive protein (hsCRP) (3.07 ± 4 mg/L vs. 1.98 ± 2.83 mg/L; p < 0.0001) and ferritin in Roma males (403.78 ± 391.84 vs. 302.67 ± 236.26 mg/L; p < 0.0001). Conclusions: Serum UA is sex- and ethnicity specific. Elevated levels of hsCRP and ferritin particularly in Roma males can reflect low-grade systemic inflammation and thus serve as a marker of an increased cardiovascular risk.

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.

Confocal Laser Endomicroscopy vs Biopsies in the Assessment of Persistent or Recurrent Intestinal Metaplasia/Neoplasia after Endoscopic Treatment of Barrett's Esophagus related Neoplasia.

BACKGROUND AND AIMS: Patients after endoscopic treatment of Barrett's esophagus (BE) related neoplasia (BORN) should enter endoscopic surveillance with biopsies to detect persistent or recurrent neoplasia or intestinal metaplasia (IM). Probe-based confocal laser endomicroscopy (pCLE) serves as a virtual biopsy and could replace standard biopsies. However, the role of pCLE in patients after endoscopic treatment of BORN has not been systematically assessed. The aim of this study was to compare pCLE with biopsies in detecting persistent/recurrent IM/neoplasia. METHODS: A single center, prospective and pathologist-blinded study was performed. Patients after endoscopic treatment of BORN (endoscopic resection or dissection, radiofrequency ablation) underwent surveillance endoscopy with pCLE followed by biopsies. RESULTS: A total of 56 patients were enrolled: initial diagnoses were low-grade dysplasia (LGD) in 24 patients (43%), high-grade dysplasia (HGD) in 12 patients (21%) and early adenocarcinoma (EAC) in 20 patients (36%). Only one patient (2%) experienced recurrent neoplasia (LGD), which was diagnosed by pCLE only. Twenty patients (35.7%) experienced persistent/recurrent IM, diagnosed by both pCLE and biopsies in 17 patients (17/30, 85%) and by pCLE only in 3 pts (3/30, 15%). Sensitivity, specificity, positive and negative predictive values to diagnose recurrent/persistent IM did not differ significantly between pCLE and biopsies; diagnostic accuracy was 100% (95%CI 93.6-100) for pCLE and 94.6 (95%CI 85.1-98.9%) for biopsies, p=0.25. In patients with IM detected by both tested methods, pCLE detected significantly more goblet cells (median 43 per patient) than biopsies (median 12 per patient), p=0.01. CONCLUSION: pCLE is at least as effective as standard biopsies in the detection of persistent/recurrent IM after endoscopic treatment of BORN.

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology.

BACKGROUND & AIMS: Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. METHODS: A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. RESULTS: Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). CONCLUSIONS: Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS. GOV NUMBER: NCT03056612. LAY SUMMARY: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.

Epidemiology and clinical course of primary biliary cholangitis in Eastern Slovakia.

OBJECTIVE: To determine both the incidence and the prevalence of primary biliary cholangitis (PBC) in Eastern Slovakia and to describe its clinical course and the response to ursodeoxycholic acid (UDCA). METHODS: We recorded data of patients with PBC, who were followed up in gastroenterology and hepatology centers in Eastern Slovakia during the period from June 30, 1999, through June 30, 2019. RESULTS: The annual incidence of PBC varied from 0.7 to 1.5 cases per 100,000 inhabitants between 2014 and 2018. PBC prevalence steadily increased from initial 10.2 cases per 100,000 inhabitants in 2014 to 14.9 cases per 100,000 inhabitants in June 2019. The mean age at the time of diagnosis was 56.3 ± 10.9 years. 95.7% of patients were females, and female/male gender ratio was 22.3:1. In June 2019, prevalence in the female population was 28 cases per 100,000 women. At the time of diagnosis, three-quarters of patients were symptomatic and 10% of patients had liver cirrhosis. The mean follow-up was 7.3 ± 5.2 years. Response to UDCA was observed in 72.1% of patients. Patients with higher baseline alkaline phosphatase (ALP) levels, liver cirrhosis at entry or at the end of follow-up and women younger than 45 years responded worse to UDCA. One-quarter of patients had liver cirrhosis at the end of follow-up. During follow-up, 1.6% of patients underwent liver transplantation and 5.5% of patients died. Five-year and 10-year liver-related mortalities were 2.7% and 4.3%, respectively. CONCLUSION: PBC prevalence in Eastern Slovakia is increasing, and most of the patients respond to therapy with UDCA.