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Az akut pancreatitis a szerv steril gyulladásával kezdődik, amely, ha a szervben necrosis alakul ki, felülfertőződhet. Ez a betegek kis hányadát (5%-át) érinti, azonban súlyos betegséget jelent, és magas halálozással jár. Valószínűleg ezzel magyarázható, hogy az orvosok nagy része az infekció bizonyítása nélkül is antibiotikumkezelést indít, amely a pancreatitis kimenetelét nem javítja, ugyanakkor a felesleges antibiotikumkezelésnek számos negatív hatása van. A döntést általában a magas gyulladásos paraméterekre (C-reaktív protein, fehérvérsejtszám) és a láz jelentkezésére alapozzák, pedig ezek bármelyikét okozhatja a hasnyálmirigy steril gyulladása is. Az antibiotikum indítása előtt tisztázni kell az infekció lokalizációját, lehetőleg tenyésztést kell kérni. A pancreasnekrózis elfertőződése elsősorban a második héttől kezdve merül fel, ilyenkor a betegnek általában sokszervi elégtelensége is van. Első lépésként bizonyítani szükséges a hasnyálmirigy-necrosis tényét képalkotóval. A döntésben segít a prokalcitoninszint meghatározása. Bizonyított vagy valószínű felülfertőződés esetén széles spektrumú, a nekrotikus szövetbe penetráló antibiotikumot kell választani.

Májzsugoros beteg felső tápcsatornai vérzése esetén varixvérzést kell feltételezni, mivel jóval gyakoribb, mint az egyéb lokalizációból származó vérzések. Légútbiztosítás után az első lépés a keringés stabilizálása és a szükséges laboratóriumi vizsgálatok elvégzése, köztük a vércsoport meghatározása. Két branülön át vénát kell biztosítani, és el kell indítani az intravénás folyadékpótlást, amely során a restriktív töltés elvét kell érvényesíteni. A beteget a súlyos alapbetegsége miatt lehetőleg intenzív osztályon kell elhelyezni. A felső tápcsatornai vérzés észlelésekor, még az endoszkópiát megelőzően el kell indítani az oktreotid- vagy terlipressinkezelést, illetve az antibiotikumprofilaxist. A keringésstabilizálást követően, de mindenképpen 12 órán belül meg kell hogy történjen a gasztroszkópia és a lokális vérzéscsillapítás. Varixvérzés esetén akkor is el kell végezni a ligációt (szkleroterápiát), cianoakrilát-kezelést, ha aktuálisan vérzés már nem észlelhető. Amennyiben a Hgb 70 g/l alatti, amint a vér megérkezik, a transzfúziót el kell indítani, de az értékét 90 g/l fölé lehetőleg ne emeljük! Az antibiotikumot legalább 5 napig, az intravénás vazopresszorokat minimum 3 napig kell alkalmazni.

Májcirrózisban a véralvadás több ponton is sérül: gyakran csökken a thrombocytaszám, az alvadási fehérjék, az antikoagulánsok és a fibrinolízisben részt vevő faktorok szintje is. Emellett számolni kell a májzsugorban jellemző krónikus gyulladásos állapot provokálta fokozott alvadékonysággal. Ezen változások következtében a haemostasis egy új, a normálisnál labilisabb egyensúlyi állapotba kerül, amely eltolódhat a hiperkoagulábilis vagy hipokoagulábilis állapot irányába. Az összetett változások miatt a klasszikus alvadási vizsgálatok nem használhatóak cirrózisos betegben, helyettük a komplex alvadási vizsgálatokat kell választani. A változások megértése fontos a beavatkozások előtti vagy a fokozott trombózisveszéllyel járó állapotok esetén alkalmazandó profilaxis megválasztásához, illetve a vérzések vagy trombózisok optimális kezelésének meghatározásához. Bár a súlyos májzsugort korábban a szerzett vérzékenység csoportjába sorolták, az utóbbi időben egyre nyilvánvalóbbá vált, hogy sokkal inkább egy trombózisra hajlamosító állapotról van szó. Ráadásul egyre több adat utal arra, hogy a kialakuló kis thrombusoknak szerepük van a betegség patofiziológiájában, prog­ressziójában, és a profilaktikusan alkalmazott antitrombotikus kezelés javítja a betegség prognózisát.

Absztrakt: A gastrointestinalis vérzés gyakori előfordulása, súlyossága miatt kiemelkedő népegészségügyi jelentőséggel bír. Az antikoagulált és/vagy rendszeres thrombocytaaggregáció-gátló készítményeket, nemszteroid gyulladásgátlókat szedő, idősödő populáció arányának növekedésével az emésztőszervi vérzés a jövőben várhatóan számban és súlyosságban is egyre növekvő terhet ró az egészségügyi ellátórendszerre. A gastrointestinalis vérzés ellátásában a sürgősségi szakember mellett a gasztroenterológus-endoszkóposnak van alapvető szerepe. A társszakmák (radiológus, invazív radiológus, intenzív terapeuta, sebész) képviselői sok esetben nem mellőzhetők a döntéshozatalban, a betegek ellátásában. Az érintett szakterületek képviselői szükségét érezték egy átfogó, multidiszciplináris, közösen elfogadott szemléletet tükröző, gyakorlati szemléletű hazai iránymutatás összeállításának az érvényes nemzetközi irányelvek alapján. A szerzők részletesen tárgyalják a gastrointestinalis vérzés ellátásának feltételeit, a kezdeti betegészlelést, a rizikóbecslést, a laborvizsgálatokat, a betegek resuscitatióját, valamint a vérzések diagnosztikájának és terápiájának lépéseit a vérzésforrás lokalizációja szerint külön csoportosítva. A szerzők iránymutatást adnak az elsődleges ellátás sikertelensége, illetve az ismételten fellépő vérzés eseteiben, végül a sebészet mai helyét is definiálják a gastrointestinalis vérzésekben. Orv Hetil. 2020; 161(30): 1231–1242.

A primer biliaris cholangitis (PBC) egy krónikus gyulladással járó ismeretlen eredetű autoimmun cholesta­ticus májbetegség, amely kezeletlen esetben végstádiumú biliaris cirrózis kialakulásához vezet. A diagnó­zis a cholestaticus májenzimek emelkedett szintjén és ezzel egyidejűleg a szérumban kimutatható anti­mi­tokondriális (AMA) és/ vagy PBC specifikus antinukleáris antitestek (ANA) jelenlétén alapszik. A májbiopszia elvégzése a diagnózis felállításához ritka esetektől eltekintve nem szükséges. Az AMA­pozitivitás önmagában normál májenzimértékek esetén nem elégséges a PBC diagnózisának felállításához. A PBC a betegekre mind a májbetegség progressziója (májcirrózis kialakulása), mind pedig tünetei révén (cholestaticus viszketés, sic­ca komplex, fáradtság) hatással van. A betegség klinikai megjelenése és lefolyása különböző lehet, ezért a betegek személyre szabott kezelésének és gondozásának biztosítása fontos élethosszig tartóan. A kezelés és a gondozás célja a végstádiumú májbetegség kialakulásának megelőzése és az ezzel összefüggő tünetek eny­hítése. Az elsővonalbeli kezelésre az urzodeoxikólsav (UDCA) javasolt. Az orális obetikólsav­ (OCA) kezelést feltételesen jóváhagyták PBC­betegek kezelésére, UDCA­val kombinációban azon esetekre, akik nem meg­felelően reagálnak az UDCA­ra, vagy monoterápiaként azon betegekben, akiknél UDCA­intolerancia észlel­hető. Magyarországon társadalombiztosítási keretek között nem elérhető. A betegek májtranszplantációs előkészítése szükséges, ha a májcirrózis szövődményei alakulnak ki, vagy ha a betegség progrediál, mint pl. folyamatosan emelkedett bilirubinérték vagy MELD­pontszám >15, vagy súlyos, kezelésre nem reagáló visz­ketés jelentkezik. Minden PBC­s betegnél figyelembe kell venni, hogy fokozott osteoporosis­kockázat állhat fenn, ezért ennek szűrése és kezelése szükséges. Jelen összefoglaló az EASL klinikai gyakorlati útmutatója nyomán ismerteti a PBC­s betegek ellátásának strukturált, élethosszig tartó és egyéni megközelítését, amely keretet nyújt az ellátó hepatológusnak a diagnózis felállításához, a hatékony kezeléséhez és gondozásához.

Introduction Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP. Methods The Hungarian Pancreatic Study Group prospectively collected multicentre clinical data on 1435 adult AP patients between 2012 and 2017. Pain was characterized by its intensity (mild or intense), duration prior to admission (hours), localization (nine regions of the abdomen) and type (sharp, dull or cramping). Results 97.3% of patients (n = 1394) had pain on admission. Of the initial population with acute abdominal pain, 727 patients answered questions about pain intensity, 1148 about pain type, 1134 about pain localization and 1202 about pain duration. Pain was mostly intense (70%, n = 511/727), characterized by cramping (61%, n = 705/1148), mostly starting less than 24 h prior to admission (56.7%, n = 682/1202). Interestingly, 50.9% of the patients (n = 577/1134) had atypical pain, which means pain other than epigastric or belt-like upper abdominal pain. We observed a higher proportion of peripancreatic fluid collection (19.5% vs. 11.0%; p = 0.009) and oedematous pancreas (8.4% vs. 3.1%; p = 0.016) with intense pain. Sharp pain was associated with AP severity (OR = 2.481 95% CI: 1.550-3.969) and increased mortality (OR = 2.263, 95% CI: 1.199-4.059) compared to other types. Longstanding pain (>72 h) on admission was not associated with outcomes. Pain characteristics showed little association with the patient's baseline characteristics. Conclusion A comprehensive patient interview should include questions about pain characteristics, including pain type. Patients with sharp and intense pain might need special monitoring and tailored pain management. Significance Acute abdominal pain is the leading presenting symptom in acute pancreatitis; however, we currently lack specific guidelines for pain assessment and management. In our cohort analysis, intense and sharp pain on admission was associated with higher odds for severe AP and several systemic and local complications. Therefore, a comprehensive patient interview should include questions about pain characteristics and patients with intense and sharp pain might need closer monitoring.

Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (AD-No ACLF), or with ACLF phenotype (AD-ACLF) defined by organ failure(s). Precipitants may induce AD. This multicenter, prospective, observational PREDICT study (NCT03056612) analyzes and characterizes the precipitants leading to both of these AD phenotypes., info:eu-repo/semantics/published

Although excessive alcohol consumption is by far the most frequent cause of recurrent acute pancreatitis (AP) cases, specific therapy is still not well established to prevent recurrence. Generally, psychological therapy (e.g., brief intervention (BI)) is the cornerstone of cessation programs; however, it is not yet widely used in everyday practice. We conducted a post-hoc analysis of a prospectively collected database. Patients suffering from alcohol-induced AP between 2016 and 2021 received 30 min BI by a physician. Patient-reported alcohol consumption, serum gamma-glutamyl-transferase (GGT) level, and mean corpuscular volume (MCV) of red blood cells were collected on admission and at the 1-month follow-up visit to monitor patients’ drinking habits. Ninety-nine patients with alcohol-induced AP were enrolled in the study (mean age: 50 ± 11, 89% male). A significant decrease was detected both in mean GGT value (294 ± 251 U/L vs. 103 ± 113 U/L, p < 0.001) and in MCV level (93.7 ± 5.3 U/L vs. 92.1 ± 5.1 U/L, p < 0.001) in patients with elevated on-admission GGT levels. Notably, 79% of the patients (78/99) reported alcohol abstinence at the 1-month control visit. Brief intervention is an effective tool to reduce alcohol consumption and to prevent recurrent AP. Longitudinal randomized clinical studies are needed to identify the adequate structure and frequency of BIs in alcohol-induced AP.

Introduction:Pain is the most common symptom in acute pancreatitis(AP) and is part of the diagnostic criteria. Its clinical characteristics in APhave not been detailed.Aims:Therefore, we aimed to characterize acute abdominal pain in AP.Materials and Methods:The Hungarian Pancreatic Study Group hasprospectively collected multicenter clinical data of 1435 adult AP patientsbetween 2012 and 2017. The pain was characterized by its intensity (mild, intense), duration prior to admission (hours), localization (9 regions of theabdomen), and type (sharp, dull, cramping). Associations between paincategory groups and outcome parameters were investigated.Results:97.3% of patients (n¼1394) had pain on admission. Pain wasmostly intense (70%, n¼511), cramping (61%, n¼705), and epigastric (48%, n¼687). More intense pain was associated with disease severity (p¼0.021), and we observed higher proportion of peripancreaticfluid collection(19.5% vs 11.0% ; p¼0.009) and edematous pancreas (8.4% vs 3.1% ; p¼0.016)on on-admission imaging with intense pain. Sharp pain was associatedAbstracts / Pancreatology 21 (2021) S18eS119S36 N. GedeS. KissA. VinczeJ. BajorI. SzaboZ. SzepesF.IzbekiJ. GervainJ. HamvasZ. VitalisE. FeherS.CraiV. SallinenE.Ramirez MoldandoA. MeczkerP.VarjúG. PoropatD. StimacN.FaluhegyiA. MisetaT. NagyA. VereczkeiZ.MartonP.J. HegyiP. HegyiA.ParniczkyA. Szentesi with AP severity (OR¼2.481 95% CI: 1.550-3.969) and increased mortality(OR¼2.263, 95% CI: 1.199e4.059) compared to other pain types. Long- standing pain (>72 h) on admission was not associated with outcomes ; however, it was associated with milder (p

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.

Disturbance of consciousness (DOC) may develop in acute pancreatitis (AP). In clinical practice, it is known that DOC may worsen the patient's condition, but we have no exact data on how DOC affects the outcome of AP.From the Hungarian Pancreatic Study Groups' AP registry, 1220 prospectively collected cases were analyzed, which contained exact data on DOC, included patients with confusion, delirium, convulsion, and alcohol withdrawal, answering a post hoc defined research question. Patients were separated to Non-DOC and DOC, whereas DOC was further divided into non-alcohol related DOC (Non-ALC DOC) and ALC DOC groups. For statistical analysis, independent sample t-test, Mann-Whitney, Chi-squared, or Fisher exact test were used.From the 1220 patients, 47 (3.9%) developed DOC, 23 (48.9%) cases were ALC DOC vs. 24 (51.1%) Non-ALC DOC. Analysis between the DOC and Non-DOC groups showed a higher incidence of severe AP (19.2% vs. 5.3%, p 0.001), higher mortality (14.9% vs. 1.7%, p 0.001), and a longer length of hospitalization (LOH) (Me = 11; IQR: 8-17 days vs. Me = 9; IQR: 6-13 days, p = 0.049) respectively. Patients with ALC DOC developed more frequently moderate AP vs. Non-ALC DOC (43.5% vs. 12.5%), while the incidence of severe AP was higher in Non-ALC vs. ALC DOC group (33.3% vs. 4.4%) (p 0.001). LOH showed a tendency to be longer in Non-ALC DOC compared to ALC DOC, respectively (Me:13; IQR:7-20 days vs. Me:9.5; IQR:8-15.5 days, p = 0.119).DOC during AP is associated with a higher rate of moderate and severe AP and increases the risk of mortality.

IntroductionAcute pancreatitis (AP) is a life-threatening inflammatory disease of the exocrine pancreas which needs acute hospitalisation. Despite its importance, we have significant lack of knowledge whether the lifestyle factors elevate or decrease the risk of AP or influence the disease outcome. So far, no synthetising study has been carried out examining associations between socioeconomic factors, dietary habits, physical activity, chronic stress, sleep quality and AP. Accordingly, LIFESPAN identifies risk factors of acute pancreatitis and helps to prepare preventive recommendations for lifestyle elements.Methods and analysisLIFESPAN is an observational, multicentre international case–control study. Participating subjects will create case and control groups. The study protocol was designed according to the SPIRIT guideline. Patients in the case group (n=1700) have suffered from AP (alcohol-induced, n=500; biliary, n=500; hypertriglyceridemiainduced, n=200; other, n=500); the control group subjects have no AP in their medical history. Our study will have three major control groups (n=2200): hospital-based (n=500), population-based (n=500) and aetiology-based (alcohol, n=500; biliary, n=500 and hypertriglyceridemia, n=200). All of them will be matched to the case group individually by gender, age and location of residence. Aggregately, 3900 subjects will be enrolled into the study. The study participants will complete a complex questionnaire with the help of a clinical research administrator/study nurse. Analysis methods include analysis of the continuous and categorical values.Ethics and disseminationThe study has obtained the relevant ethical approval (54175-2/2018/EKU) and also internationally registered (ISRCTN25940508). After obtaining the final conclusions, we will publish the data to the medical community and will also disseminate our results via open access.Trial registration numberISRCTN25940508; Pre-results.

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., info:eu-repo/semantics/published

Patients with cirrhosis are susceptible to bacterial infections (BIs) that are major causes of specific complications and mortality. However, the diagnosis of BIs can often be difficult in advanced disease stage since their symptoms may overlap with the ones of acute decompensation (AD). Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from monocytes/macrophages and neutrophils during activation and has been reported to correlate with activity of various inflammatory processes. We investigated its diagnostic and prognostic performance in patients with cirrhosis and BI.Sera of 269 patients were assayed for sTREM-1 by ELISA (172 outpatients and 97 patients with AD of whom 56 had BI). We investigated capacity of sTREM-1 to identify patients with BI and conducted a 90-day follow-up observational study to assess its possible association with short-term mortality.sTREM-1 levels were significantly higher in patients with more severe liver disease, BI, and acute-on-chronic liver failure than in patients without these conditions. sTREM-1 had similar accuracy to CRP identifying BI [sTREM-1: AUROC (95%CI) 0.804 (0.711-0.897), p 0.0001; CRP: 0.791 (0.702-0.881), p 0.0001)] among AD patients. The combination of these two molecules and the presence of ascites into a composite score significantly increased their discriminative power (AUROC: 0.878, 95%CI: 0.812-0.944, p 0.0001). High sTREM-1 level (660 pg/mL) was an independent predictor of 90-day mortality in patients with BI [HR: 2.941, (95%CI: 1.009-8.573), p = 0.048] in our multivariate model.Use of sTREM-1 could increase the recognition of BIs in cirrhosis and help clinicians in mortality risk assessment of these patients.

Abstract: Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50–57.

OBJECTIVES Proton pump inhibitors(PPIs) are widely prescribed to patients with liver cirrhosis. We hypothesized that long-standing PPI use is associated with spontaneous bacterial peritonitis(SBP) and accelerated development of disease-specific complications and liver-related death. METHODS A 5-year follow-up observational cohort study assessed the impact of long-standing PPI use on the clinical course of cirrhosis in a large referral patient cohort. Three hundred fifty patients with cirrhosis (alcohol:69.1%, Child-Pugh stage A/B/C:206/108/36) were assigned to two groups: regular PPI users (n=196) and nonusers (n=154). Occurrence of SBP, decompensation events (ascites, hepatic encephalopathy and variceal bleeding), and liver-related death were assessed. RESULTS Regular PPI use was associated with an increased cumulative probability of SBP compared to nonusers [55% vs. 24.8%, hazard ratio(HR):4.25; P=0.05], in patients without previous SBP episode (n=84). A similar association was found between regular PPI use and decompensation events. The risk of the development of a first decompensation was higher in regular PPI users compared with nonusers, in patients with compensated clinical stage at enrollment (HR: 2.81, P= 0.008, n=146). The risk of liver-related death was also significantly increased among regular PPI users (P

AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections. METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacterial infections and level of plasma presepsin, serum C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Patients were followed for three months to assess the possible association between presepsin level and short-term mortality. RESULTS Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without (median, 1002 pg/mL vs 477 pg/mL, P < 0.001), increasing with the severity of infection [organ failure (OF): Yes vs No, 2358 pg/mL vs 710 pg/mL, P < 0.001]. Diagnostic accuracy of presepsin for severe infections was similar to PCT and superior to CRP (AUC-ROC: 0.85, 0.85 and 0.66, respectively, P = NS for presepsin vs PCT and P < 0.01 for presepsin vs CRP). At the optimal cut-off value of presepsin > 1206 pg/mL sensitivity, specificity, positive predictive values and negative predictive values were as follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however, decreased in advanced stage of the disease or in the presence of renal failure, most probably because of the significantly elevated presepsin levels in non-infected patients. 28-d mortality rate was higher among patients with > 1277 pg/mL compared to those with ≤ 1277 pg/mL (46.9% vs 11.6%, P < 0.001). In a binary logistic regression analysis, however, only PCT (OR = 1.81, 95%CI: 1.09-3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for 28-d mortality after adjusting with MELD score and leukocyte count. CONCLUSION Presepsin is a valuable new biomarker for defining severe infections in cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of short-term mortality.

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

BACKGROUND & AIMS Pattern recognition receptors (PRRs) have a key role in the innate host defense. Functional polymorphisms of various PRRs have been established to contribute to an increased susceptibility to spontaneous bacterial peritonitis (SBP). Their role in the development of cirrhosis-associated bacterial infections (BI), beyond SBP or progressive disease course related to pathological bacterial translocation (BT) remains unknown. METHODS Three hundred and forty-nine patients with cirrhosis were genotyped for common NOD2 (R702W, G908R and L1007PfsinsC), TLR2 (-16934T>A), and TLR4 (D299G) variants. Incidence of BIs, decompensating events and liver-related death were assessed in a 5-year follow-up observational study. Pathological BT was assessed based on the presence of antimicrobial antibodies or lipopolysaccharide-binding protein (LBP) level. RESULTS In patients with ascites (n = 88) only NOD2 gene variants were associated with an increased cumulative probability of SBP (76.9% ± 19.9%) compared to wild-type (30.9% ± 6.9%, PLogRank = .047). Individual or combined PRR genetic profiles were associated with the risk of non-SBP type BI. Advanced disease stage (HR [95% CI]: 2.11 [1.38-3.25]) and prior history of a BI episode (HR: 2.42 [1.58-3.72]) were the major clinical risk factors of a subsequent BI. The risk of a non-SBP type BI in patients with advanced disease and a prior BI was even higher (HR: 4.74 [2.68-8.39]). The frequency of antimicrobial antibodies and LBP levels did not differ between various PRR genotypes. Correspondingly, PRR genetic profile was not able to predict the long-term disease course. CONCLUSIONS In cirrhosis, functional polymorphisms of PRRs did not improve the identification of patients with high risk of BI beyond SBP or progressive diseases course.

Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

AIM To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODS Sera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. RESULTS A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P < 0.001, for both) and AGA IgG (P = 0.01, for both) but not AGA IgA were significantly higher compared to both of the HCONT and the UC groups. In survival analysis, AAA IgA-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15 (1.27-20.86), P = 0.022 or for the Mayo risk score (HR = 4.24 (0.99-18.21), P = 0.052]. AAA IgA-positivity was significantly associated with higher frequency of anti-microbial antibodies (P < 0.001 for EndoCab IgA and P = 0.012 for anti-OMP Plus IgA) and higher level of the enterocyte damage marker (median I-FABPAAA IgA pos vs neg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSION Presence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage further highlighting the importance of the gut-liver interaction in PSC.

Background&Aims Lectin pathway molecules of the complement system are synthesized by hepatocytes and have pivotal role in innate host defense against infectious organisms. Ficolins(FCNs) act as soluble pattern recognition molecules, while mannan-binding lectin serine proteases(MASPs) do as effector molecules in elimination of pathogens. We aimed to study the significance of low level of these molecules in the development of cirrhosis-associated bacterial infections, which has not been elucidated so far. Methods Sera of 266 stable outpatients with cirrhosis and 160 healthy subjects were assayed for a panel of lectin molecules (FCN-2, FCN-3 and MASP-2) by ELISA. In cirrhosis, a 5-year follow-up observational study was conducted to assess a possible association between lectin levels and development of clinically significant bacterial infections(CSI). Results FCN-2, FCN-3 and MASP-2 levels were significantly lower in cirrhosis compared to healthy subjects and decreased according to disease severity (p

Hyperdynamic circulation, systolic and diastolic left ventricular dysfunction and certain electrophysiological abnormalities have been associated with cirrhosis and known for a long time. These clinical features have been introduced as cirrhotic cardiomyopathy (CCM), which is characterized by blunted myocardial contractile responsiveness to physical, physiological and pharmacological stress. Importantly, cardiac dysfunction can be reversible and can improve due to effective medical treatment and also after liver transplantation. Echocardiography and electrocardiography are essential tools for recognizing the characteristic changes in the myocardial function and also the alterations in the electrophysiological properties of the heart. Laboratory markers are auxiliary modalities further aiding the establishment of the correct diagnosis. In this review, we aimed to collect the pathophysiological background and clinical characteristics of CCM with the intention of summarizing the current possibilities for the diagnosis establishment and treatment of this cardio-hepatic disorder.Abbreviations: A: late diastolic transmitral peak flow velocity; ACE: angiotensin converting enzyme; ANP: atrial natriuretic peptide; ARB: angiotensin receptor blocker; BNP: brain natriuretic peptide; cAMP: cyclic adenosine monophosphate; CCM: cirrhotic cardiomyopathy; CGRP: calcitonin gene-related peptide; CO: carbon monoxide; DD: diastolic dysfunction; DT: deceleration time; E: early diastolic transmitral peak flow velocity; Ea: early diastolic velocity of the septal mitral annulus; EF: ejection fraction; MUGA: Multi Gated Acquisition Scan; NO: nitric oxide; NSBB: non-selective beta-blocker; pro-BNP: pro-brain natriuretic peptide; QTc: corrected QT interval; RAAS: renin-angiotensin aldosterone system; RALES: Randomized Aldactone Evaluation Study; suPAR: urokinase-type plasminogen activator receptor; TDI: Tissue Doppler Imaging; TIPS: transjugular intrahepatic portosystemic shunt; TNF-alpha: tumor necrosis factor-alpha.

The increasing incidence and poor prognosis of hepatocellular carcinoma places huge burden on healthcare.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.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).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 p0.001) but not with disease etiology (virus 282 days, metabolic syndrome 335 days and alcohol 423 days, p = 0.65).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.

The α-chain alleles 1 and 2 of haptoglobin (Hp) molecule account for three phenotypes, which have biologically important differences in their antioxidant, scavenging, and immunomodulatory properties and may thereby influence the course of inflammatory diseases. A follow-up observational study was conducted to assess the association between haptoglobin phenotype and the development of clinically significant bacterial infections in patients with liver cirrhosis. Sera of 336 patients with liver cirrhosis of various etiologies and 384 healthy subjects were investigated. Haptoglobin phenotypes were determined by gel electrophoresis and assigned corresponding genotype. Haptoglobin phenotype distributions of patients and controls was similar (Hp1-1: 10.7% vs 11.5%, Hp2-1: 47.9% vs 46.1% and Hp2-2: 41.4% vs 42.4%). The probability of clinically significant bacterial infections was calculated for each haptoglobin phenotype (Hp1-1: 50.0%, Hp2-1: 36.0% and Hp2-2: 26.6%, p = 0.039). In a logistic regression analysis, Hp1-1 phenotype (p = 0.015, OR: 2.74, 95% CI: 1.22-6.13), Child-Pugh stage (p = 0.038, OR: 1.40, 95% CI: 1.02-1.91) and presence of co-morbidities (p < 0.001, OR: 2.64, 95% CI: 1.63-4.27) were independently associated with infections. In a Cox regression analysis, Hp1-1 phenotype (p = 0.014), Child-Pugh stage C (p < 0.001), and presence of co-morbidities (p = 0.004) were associated with time to first infectious episode. Phenotypic haptoglobin polymorphism was independent predictor for risk and time to first clinically significant bacterial infectious episode.

Mannose-binding lectin (MBL) is a serum lectin synthesized by the liver and involved in innate host defense. MBL deficiency increases the risk of various infectious diseases mostly in immune-deficient conditions. Bacterial infections are a significant cause of morbidity and mortality in liver cirrhosis due to the relative immuncompromised state.Sera of 929 patients with various chronic liver diseases [autoimmune liver diseases (ALD), 406; viral hepatitis C (HCV), 185; and liver cirrhosis (LC) with various etiologies, 338] and 296 healthy controls (HC) were assayed for MBL concentration. Furthermore, a follow-up, observational study was conducted to assess MBL level as a risk factor for clinically significant bacterial infections in cirrhotic patients.MBL level and the prevalence of absolute MBL deficiency (100 ng/ml) was not significantly different between patients and controls (ALD: 14.5%, HCV: 11.9%, LC: 10.7%, HC: 15.6%). In cirrhotic patients, the risk for infection was significantly higher among MBL deficient subjects as compared to non-deficient ones (50.0% vs. 31.8%, p=0.039). In a logistic regression analysis, MBL deficiency was an independent risk factor for infections (OR: 2.14 95% CI: 1.03-4.45, p=0.04) after adjusting for Child-Pugh score, co-morbidities, gender, and age. In a Kaplan-Meier analysis, MBL deficiency was associated with a shorter time to develop the first infectious complication (median days: 579 vs. 944, pBreslow=0.016, pLogRank=0.027) and was identified as an independent predictor in a multivariate Cox-regression analysis (p=0.003, OR: 2.33, 95% CI: 1.34-4.03).MBL deficiency is associated with a higher probability and shorter time of developing infections in liver cirrhosis, further supporting the impact of the MBL molecule on the host defense.

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.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.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, P0.015 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%, P0.001) 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.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.

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.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.Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p0.001 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, p0.001). 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%, p0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank0.001) 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).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.

Background Bacterial infections are common cause of morbidity and mortality in patients with cirrhosis. The early diagnosis of these infections is rather difficult. Aims To assess the accuracy of acute phase proteins in the identification of bacterial infections. Methods Concentration of C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP), sCD14 and antimicrobial antibodies were measured in serum of 368 well-characterized patients with cirrhosis of whom 139 had documented infection. Clinical data was gathered by reviewing the patients’ medical charts. Results Serum levels of CRP, PCT and LBP were significantly higher in patients with clinically overt infections. Among the markers, CRP – using a 10 mg/L cut-off value– proved to be the most accurate in identifying patients with infection (AUC: 0.93). The accuracy of CRP, however, decreased in advanced stage of the disease, most probably because of the significantly elevated CRP levels in non-infected patients. Combination of CRP and PCT increased the sensitivity and negative predictive value, compared with CRP on its own, by 10 and 5% respectively. During a 3-month follow-up period in patients without overt infections, Kaplan–Meier and proportional Cox-regression analyses showed that a CRP value of >10 mg/L (P = 0.035) was independently associated with a shorter duration to progress to clinically significant bacterial infections. There was no correlation between acute phase protein levels and antimicrobial seroreactivity. Conclusions C-reactive protein on its own is a sensitive screening test for the presence of bacterial infections in cirrhosis and is also a useful marker to predict the likelihood of clinically significant bacterial infections in patients without overt infections.

BACKGROUND: Bacterial translocation plays important role in the complications of liver cirrhosis. Antibody formation against various microbial antigens is common in Crohn's disease and considered to be caused by sustained exposure to gut microflora constituents. We hypothesized that anti-microbial antibodies are present in patients with liver cirrhosis and may be associated with the development of bacterial infections. METHODOLOGY/PRINCIPAL FINDINGS: Sera of 676 patients with various chronic liver diseases (autoimmune diseases: 266, viral hepatitis C: 124, and liver cirrhosis of different etiology: 286) and 100 controls were assayed for antibodies to Saccharomyces cerevisiae (ASCA) and to antigens derived from two intestinal bacterial isolates (one gram positive, one gram negative, neither is Escherichia coli). In patients with liver cirrhosis, we also prospectively recorded the development of severe episodes of bacterial infection. ASCA and anti-OMP Plus™ antibodies were present in 38.5% and 62.6% of patients with cirrhosis and in 16% and 20% of controls, respectively (p

Ruptured gastroesophageal varices are the most severe and frequent causes of upper gastrointestinal bleeding in patients suffering from liver cirrhosis, accounting for 80% of all bleeding episodes. Despite recent progress in treatment strategies, variceal bleeding is still considered the most severe type of gastrointestinal bleeding associated with a mortality of 20% at 6 weeks. The most widely accepted explanation for the rupture is the "explosion hypothesis": bleeding is a result of the elevated intravariceal pressure and increased wall-straining due to a rapid increase in the portal pressure gradient. The rupture of the varices and the early rebleeding cannot be attributed solely to mechanical changes. Furthermore, the factors involved in the sudden increase of portal pressure gradient are yet to be discovered. Recently it was postulated that various humoral factors may also play an important role in the pathomechanism of the rupture. The pivotal role of bacterial infection and consequent endotoxaemia must be emphasized. Passage of both viable microbes and microbial products, such as endotoxins from the intestinal lumen to peripheral and portal circulation in cirrhotic patients can be explained by the intestinal bacterial overgrowth, the intestinal dysmotility and the increased intestinal permeability. Endotoxaemia can be a critical factor that triggers a cascade of humoral events, resulting in a further increase of portal pressure, impairment of liver function and worsening of haemostasis, and eventually leads to variceal bleeding. Early administration of prophylactic antibiotics to variceal bleeders recently became an integral and important part of therapeutic strategy. Antibiotics are not only useful in the prevention of early rebleeding but also they are proven to significantly decrease the rate of mortality. The improvement in mortality is equivalent to that seen with terlipressine.

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; OROmp = 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. (Inflamm Bowel Dis 2007)

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.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.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.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.