Management of acute gastrointestinal bleeding. Multidisciplinary guideline proposal. / Heveny gastrointestinalis vérzések ellátása. Multidiszciplináris útmutató javaslat.

Gastrointestinal bleeding has a profound impact on public health due to its high prevalence and severity. With the elderly population taking more anticoagulants/antiaggregants/non-steroid anti-inflammatory drugs, the digestive bleeding will certainly raise more and more challenges in quantity as well as in severity for the public healthcare system. The emergency medicine specialists and gastroenterologists have a central role in the management of patients presenting with gastrointestinal bleeding. In certain cases, radiologists, invasive radiologists, intensive care specialists and surgeons should also be involved in the decision making process and management of patients. Therefore, Hungarian experts felt the need to elaborate a comprehensive, multidisciplinary, practical local guideline reflecting the frequently arisen aspects based on current international guidelines. This guideline proposal covers topics of basic requirements, initial assessment of patients, risk evaluation, laboratory tests, hemodynamic resuscitation in the case of gastrointestinal bleeding followed by its consecutive steps of diagnosis and therapy sorted by location of the source of the hemorrhage. The authors give practical instructions for unsuccessful hemostasis or rebleeding. Finally, the role of surgery is also summarized in the management of gastrointestinal bleeding. Orv Hetil. 2020; 161(30): 1231-1242.

[Incidence of hepatocellular carcinoma and consequent lessons for its management in Northeastern Hungary]. / A hepatocellularis carcinoma elofordulása és kezelésének tanulságai az északkelet-magyarországi régióban.

INTRODUCTION: The increasing incidence and poor prognosis of hepatocellular carcinoma places huge burden on healthcare. AIM: After reviewing literature on epidemiological trends, risk factors, diagnosis and management options for hepatocellular carcinoma, the authors investigated results of treatment and survival data of patients in Northeastern Hungary. METHOD: In a retrospective study, the authors analyzed medical records of 187 patients with hepatocellular carcinoma (etiology, presence of cirrhosis, stage of the tumor, treatment and disease outcome). RESULTS: Seventy-one patients (38%) had known cirrhosis at the diagnosis of hepatocellular carcinoma, while in 52 patients (28%) the presence of cirrhosis was established at the time of the diagnosis of hepatocellular carcinoma. Fifteen patients (8%) had no cirrhosis and in 49 patients (26%) no data were available regarding cirrhosis. Etiological factors were alcohol consumption (52%), viral hepatitis (41%) and metabolic syndrome (44%). In cases of metabolic syndrome, hepatocellular carcinoma frequently occurred without cirrhosis. In 83% of the cases, the tumor was discovered in an advanced stage. Median survival time was significantly associated with tumor stage (Barcelona A stage vs. B/C vs. D: 829 vs. 387 vs. 137 days, respectively p<0.001) but not with disease etiology (virus 282 days, metabolic syndrome 335 days and alcohol 423 days, p = 0.65). CONCLUSIONS: High mortality of hepatocellular carcinoma was mainly attributed to the delayed diagnosis of the disease. Screening of patients with cirrhosis could only result in a partial improvement since in a great proportion cirrhosis was diagnosed simultaneously with the tumor. Screening of diabetic and obese patients by ultrasonography should be considered. Management of baseline liver disease is of importance in the care of hepatocellular carcinoma. Orv. Hetil., 2016, 157(45), 1793-1801.

Macrophage activation marker, soluble CD163, is an independent predictor of short-term mortality in patients with cirrhosis and bacterial infection.

BACKGROUND & AIMS: Innate immune system dysfunction is common in advanced cirrhosis, with a central role of the monocyte/macrophage system. Monocytes and macrophages express the scavenger receptor CD163, which is regulated by inflammatory mediators. Cleavage of the receptor leads to the formation of soluble (s)CD163 that represents an anti-inflammatory response. We aimed to study the clinical importance of sCD163 in cirrhosis. METHODS: Sera of 378 patients were assayed for sCD163 by ELISA [193 outpatients and 185 patients with acute decompensation (AD)]. A 5-year follow-up observational study was conducted to assess the possible association between sCD163 level and poor disease outcomes. RESULTS: sCD163 level was associated with disease severity, but not with the presence of varices or prior variceal bleeding. In outpatients, sCD163 level did not predict the development of disease-specific complications or the long-term mortality. In patients with AD episode, sCD163 level was significantly higher compared to outpatients but only in the presence of bacterial infection (INF) (AD-INF:4586, AD-NON-INF:3792 and outpatients: 3538 ng/ml, P < 0.015 and P = 0.001, respectively). sCD163 level gradually increased according to severity of infection. During bacterial infections, high sCD163 level (>7000 ng/ml) was associated with increased mortality rate (42% vs. 17%, P < 0.001) and was identified as an independent predictor of 28-day mortality (hazard ratio:2.96, 95% confidence intervals:1.27-6.95) in multivariate Cox-regression model comprising aetiology, co-morbidity, model for end-stage liver disease score and leucocyte count as covariates. CONCLUSIONS: High sCD163 level is useful to identify patients with high-risk of death during an AD episode complicated by bacterial infection. This finding serves as an additional hint towards the significance of anti-inflammatory response during bacterial infection.

High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis.

BACKGROUND & AIMS: Anti-neutrophil cytoplasmic antibodies (ANCA) are a non-uniform family of antibodies recognizing diverse components of neutrophil granulocytes. ANCA formation might be induced by protracted bacterial infections or probably reflect an abnormal immune response to commensal microorganisms. Bacterial infections are common complications in cirrhosis with high incidence of episodes caused by enteric organisms, therefore, we sought to study the presence and clinical importance of ANCA in cirrhosis. METHODS: Sera of 385 patients with cirrhosis of different etiologies were assayed for ANCA of IgG, IgA, IgA1, IgA2, and secretory IgA subtypes by indirect immunofluorescence and ELISAs. The control group comprised 202 patients with chronic liver diseases without cirrhosis and 100 healthy subjects. In cirrhosis, a 2-year follow-up, observational study was conducted to assess a possible association between the presence of ANCA and clinically significant bacterial infections. RESULTS: Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p<0.001 for both). ANCA IgA subtyping assays revealed marked increase in the proportion of IgA2 subtype (46% of total ANCA IgA) and presence of the secretory component concurrently. Presence of ANCA IgA was associated with disease-specific clinical characteristics (Child-Pugh stage and presence of ascites, p<0.001). During a 2-year follow-up period, risk of infections was higher among patients with ANCA IgA compared to those without (41.8% vs. 23.4%, p<0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank <0.001) in Kaplan-Meier analysis and was identified as an independent predictor in multivariate Cox-regression analysis (HR:1.74, 95% CI: 1.18-2.56, p=0.006). CONCLUSIONS: Presence of IgA type ANCA is common in cirrhosis. Involvement of gut mucosal immune system is in center of their formation and probably reflects sustained exposure to bacterial constituents.

Pancreatic autoantibodies are associated with reactivity to microbial antibodies, penetrating disease behavior, perianal disease, and extraintestinal manifestations, but not with NOD2/CARD15 or TLR4 genotype in a Hungarian IBD cohort.

BACKGROUND: Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. Conventional antibodies and carbohydrates (glycans) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Our aim was to determine the accuracy of PAB and GAB autoantibodies as well as to study relevant phenotype-serotype associations. METHODS: A Hungarian study cohort of 1092 subjects, including 689 well-characterized, unrelated IBD patients (CD: 579, m/f ratio: 274/305, duration: 7.9 +/- 11.2 years; UC: 110, m/f ratio: 53/57, duration: 8.9 +/- 9.8 years), 139 celiac patients, 100 healthy, and 64 non-IBD gastrointestinal controls were investigated. Sera were assayed for PAB-GAB IgA/IgG, anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCA), and anti-glycans. TLR4 and NOD2/CARD15 was tested by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined. RESULTS: The prevalence of PAB was significantly more frequent in CD (41.1%) versus UC (22.7%), celiac (22.3%), and controls (8% and 4.6%, P < 0.01 for each), while GAB detection was poor in all groups except UC (15.4%). In CD the combination of PAB and/or anti-glycans/ASCA increased the sensitivity to 72% and 59%, respectively, for isolated colonic disease. PAB was associated to gylcans (odds ratio [OR] 1.74,P = 0.002), ASCA IgG/IgA (OR 1.75, P = 0.002), Omp (OR 1.86, P = 0.001) as well as perforating, perianal disease, arthritis, ocular, and cutaneous manifestations (P = 0.002-0.032). In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery. No associations were found in UC. CONCLUSIONS: PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.

Seroreactivity to microbial components in Crohn's disease is associated with ileal involvement, noninflammatory disease behavior and NOD2/CARD15 genotype, but not with risk for surgery in a Hungarian cohort of IBD patients.

BACKGROUND: Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients. METHODS: In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC. CONCLUSIONS: Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.

Haptoglobin polymorphisms are associated with Crohn's disease, disease behavior, and extraintestinal manifestations in Hungarian patients.

Functional differences and association with inflammatory disorders were found relating to three major haptoglobin (Hp) phenotypes. Our aim was to investigate Hp polymorphisms in Hungarian patients with Crohn's disease (CD). Four hundred sixty-eight CD patients and 384 healthy controls were examined. Hp phenotypes were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of the sera. The frequency of the Hp(1) allele was significantly higher in CD (0.395; OR, 1.24; 95% CI, 1.02-1.52; P=0.03) compared to controls (0.345). In CD, Hp phenotype was associated with disease behavior (OR [Hp(2-1) vs other], 2.06; 95% CI, 1.29-3.28 for inflammatory behavior). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in the Hp 2-2 compared to the Hp 1-1 phenotype (6.5% vs. 0.0%; P=0.039). We conclude that the Hp polymorphism is associated with CD, inflammatory disease behavior, and primary sclerosing cholangitis in Hungarian patients. Further studies are required to evaluate the significance of Hp polymorphisms in other populations from geographically diverse regions.

[Haptoglobin polymorphism in patients with inflammatory bowel diseases]. / Haptoglobin polimorfizmus vizsgálata gyulladásos bélbetegségekben.

BACKGROUND: Since functional differences were found among three major haptoglobin phenotypes, haptoglobin polymorphism was reported to be associated with the risk and clinical course of different inflammatory diseases. The aim of the study was to investigate the Hp polymorphism distribution in Hungarian Crohn's disease patients. METHODS: 511 Hungarian IBD patients were investigated (Crohn's disease patients: 468, m/f ratio: 233/235, duration 8.2 +/- 6.7 ys, and ulcerative colitis patients: 43, m/f: 22/21, duration: 9.5 +/- 10.6 ys) and 384 healthy subjects served as controls. Hp phenotypes were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis of sera followed by immunoblotting. Clinical data were come by the questionnaires prepared by the physicians. RESULTS: The frequency of haptoglobin-1 allele was significantly higher in Crohn's disease (0.395) compared to the controls (0.345; OR: 1.24, 95%CI: 1.02-1.52, p = 0.03), but the phenotype distribution showed no such differences. Haptoglobin phenotype was associated to disease behavior in Crohn's disease (B1 and B2, in haptoglobin 1-1 and 2-2: 36.6%-34.3% and 32.4%-32.5% vs. in 2-1: 44.9% and 20.3%; ORB1Hp2-1 vs. others: 2.06, 95%CI: 1.29-3.28). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in haptoglobin 2-2, compared to the 1-1 (6.5% vs. 0.0%, p = 0.039). No associations were found in ulcerative colitis. CONCLUSIONS: haptoglobin-1 allele was associated with Crohn's disease, whereas the phenotypes with the disease behavior and frequency of primary sclerosing cholangitis, exhibiting a disease-modifying effect.

[Prevention and treatment of esophageal variceal bleeding]. / A nyelocsovarix-vérzés megelozése és kezelése.

Portal hypertension leads to special complications, which tend to progression. Increase in the size of varices, and variceal-wall tension may cause life-threatening bleeding, which affects mortality. Therefore the reduction of portal hypertension is essential. For prevention of the first bleeding (primary prevention) beta-blockers must be given. For estimation of the effectiveness of this drug, patients should be followed. In case of inefficiency or intolerability variceal ligation or sclerotherapy can prevent bleeding. In case of acute variceal hemorrhage, hemodynamic stabilization of the patient is the first step. Transfusion if necessary, somatostatin or terlipressin should be given for reduction of portal hypertension and also endoscopic treatment of varices is mandatory. Early antibiotic administration for prophylaxis or treatment of infections is associated with a significant reduction in mortality. Up to now in absence of exact data, correction of haemostasis is suggested by the administration of fresh frozen plasma. For secondary prevention i. e. to prevent repeated bleeding beta-blockers (probably with nitrates) can be used. If necessary, drug administration should be complemented with varix ligation or sclerotherapy. In case of inefficiency TIPS implantation or liver transplantation must be considered.