PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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

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

The Roma Population Living in Segregated Settlements in Eastern Slovakia Has a Higher Prevalence of Metabolic Syndrome, Kidney Disease, Viral Hepatitis B and E, and Some Parasitic Diseases Compared to the Majority Population

Background: The Roma population is one of the largest marginalized population groups in Europe. The aim of our work was to summarize the morbidity of lifestyle-related diseases and infectious diseases in the Roma population living in segregated settlements. Methods: We used data from the cross-sectional study HepaMeta, in which we examined 452 Roma subjects with an average age of 34.7 ± 9.1 years, 35.2% of which were men, and 403 non-Roma subjects with an average age of 33.5 ± 7.4 years, 45.9% of which were men. We collected data by means of a questionnaire, anthropometric measures, and we analyzed blood and urine samples. Results: Roma subjects had a higher incidence of metabolic syndrome (RR: 1.478 (1.159–1.885), p < 0.0001), obesity or waist circumference >94 cm in men/80 cm in women (RR: 1.287 (1.127–1.470), p < 0.0001), and HDL-C < 1.03 mmol/L in men or <1.29 in women (RR: 2.004 (1.730–2.321), p < 0.0001) than their non-Roma counterparts. Subjects of the Roma population were more frequently diagnosed with kidney disease (RR: 1.216 (1.096–1.349), p < 0.0001), HBsAg positivity (RR: 4.468 (2.373–8.415), p < 0.0001), anti HBc IgG positivity (RR: 3.13 (2.598–4.224), p < 0.0001), and anti HEV positivity (RR: 2.972 (1.226–7.287), p < 0.0001). Serological markers of Toxoplasma gondii infection and Toxocara spp. were observed much more frequently among Roma than non-Roma subjects (RR: 1.868 (1.520–2.296), p < 0.0001, for Toxoplasma gondii; and RR: 21.812 (8.097–58.761), p < 0.0001, for Toxocara spp.). Conclusions: Poor socio-economic conditions, an unhealthy lifestyle, and barriers precluding access to healthcare are factors that affect the Roma population in settlements and lead to an increased prevalence of metabolic syndrome and its components, kidney disease, viral hepatitis B and E, and some parasitic diseases

Prevalence and Risk Factors for Hepatitis B Virus Infection in Roma and Non-Roma People in Slovakia

Prevalence of Hepatitis B is relatively low in developed European countries. However specific subpopulations may exist within each country with markedly different Hepatitis B burden. Roma minority is very numerous in Slovakia and their lifestyle is completely different to non-Roma population. The aim of this study is to map Hepatitis B prevalence in Roma and compare it to non-Roma population and to explore potential socio-economic and health related risk factors. Cross-sectional epidemiology study was performed in Slovakia that included randomly sampled Roma population and geographically corresponding random sampled non-Roma population. Comprehensive questionnaire about risk factors was administered and blood samples were drawn for Hepatitis B serology and virology tests. Altogether 855 participants were included. Global Hepatitis B surface Antigen (HBsAg) positivity rate was 7.7% (i.e., active Hepatitis B) and anti Hepatitis B core IgG antibody (antiHBcIgG) positivity rate was 34.6%. Roma population had significantly higher prevalence of Hepatitis B, both active chronic infection (12.4%; 95% Confidence Interval (CI) 9.58%–15.97% versus 2.8%; 95% CI 1.56%–4.91%; p < 0.0001) and antiHBcIgG positivity (52.8%; 95% CI 48.17%–57.44% versus 25.9%; 95% CI 12.56%–20.02%; p < 0.0001) Main risk factors for HBsAg positivity were Roma ethnicity, male sex and tattoo. Conclusion: There is a very high prevalence of Hepatitis B in Roma communities in Slovakia, with potential for grave medical consequences

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 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