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Presepsin teardown- pitfalls of biomarkers in the diagnosis and prognosis of bacterial infection in cirrhosis

World Journal of Gastroenterology 2016年第41期22卷 9172-9185页

作者： Maria Papp Tamas Tornai Zsuzsanna Vitalis Istvan Tornai David Tornai Tamas Dinya Andrea Sumegi peter antal-szalmas Department of Internal Medicine Division of Gastroenterology University of Debrecen Faculty of Medicine Department of Laboratory Medicine University of Debrecen Faculty of Medicine Debrecen Institute of Surgery University of Debrecen Faculty of Medicine Vascular Biology Thrombosis and Haemostasis Research Group Hungarian Academy of Sciences

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 *** Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without(median, 1002 pg/m L vs 477 pg/m L, P 1206 pg/m L 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/m L compared to those with ≤ 1277 pg/m L(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 *** 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.

关键词： Presepsin Cirrhosis Bacterial infection Organ failure Mortality

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Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

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World Journal of Gastroenterology 2017年第29期23卷 5412-5421页

作者： Tamas Tornai Eszter Palyu Zsuzsanna Vitalis Istvan Tornai David Tornai peter antal-szalmas Gary L Norman Zakera Shums Gabor Veres antal Dezsofi Gabriella Par Alajos Par peter Orosz Ferenc Szalay peter Laszlo Lakatos Maria Papp Institute of Internal Medicine Department of Gastroenterology University of Debrecen Faculty of Medicine Department of Laboratory Medicine University of Debrecen Faculty of Medicine Debrecen Inova Diagnostics Inc.San Diego 1^st Department of Pediatrics Semmelweis University 1^st Department of Medicine University of Pecs Gastroenterology Department of Medicine Borsod-Abauj Zemplen County Hospital 1^st Department of Medicine Semmelweis University

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. METHODSSera 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. RESULTSA 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 AAA IgA posvsneg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various micr

关键词： Primary sclerosing cholangitis Gut barrier dysfunction Intestinal fatty acid-binding protein Anti-F-actin antibody Anti-gliadin antibody

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Immune dysfunction in cirrhosis

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World Journal of Gastroenterology 2014年第10期20卷 2564-2577页

作者： Nora Sipeki peter antal-szalmas peter L Lakatos Maria Papp Institute of Medicine Department of Gastroenterology University of Debrecen H-4032 DebrecenHungary Department of Laboratory Medicine University of Debrecen H-4032 Debrecen Hungary 1st Department of Medicine Semmelweis University H-1083 Budapest Hungary

Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver *** the evolution of the disease,acute decompensation events associated with organ failure(s),so-called acute-on chronic liver failure,and chronic decompensation with progression of liver fibrosis and also development of disease specific complications,comprise distinct clinical entities with different immunopathology *** bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical *** and chronic exposure to bacteria and/or their products,however,can result in variable clinical *** immune status of patients is not constant during the illness;consequently,alterations of the balance between pro-and anti-in-flammatory processes result in very different dynamic *** this review we give a detailed overview of acquired immune dysfunction and its consequences for *** demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory ***,we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver *** and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications,delaying progression and reducing mortality.

关键词： Cirrhosis Immune dysfunction Endotoxemia

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Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

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World Journal of Gastroenterology 2015年第22期21卷 6952-6964页

作者： Nora Sipeki Laszlo Davida Eszter Palyu Istvan Altorjay Jolan Harsfalvi peter antal szalmas Zoltan Szabo Gabor Veres Zakera Shums Gary L Norman peter L Lakatos Maria Papp Division of Gastroenterology Department of Internal Medicine Faculty of Medicine University of Debrecen Clinical Research Center Faculty of MedicineUniversity of Debrecen Department of Laboratory Medicine Faculty of Medicine University of Debrecen Division of Emergency Medicine Department of Internal Medicine Faculty of Medicine University of Debrecen 1~(st) Department of Medicine Semmelweis University Inova Diagnostics Inc. San Diego California

AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) ***: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ELISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally,we provide an overview of studies, performed so far, in which significance of APLAs in IBD were ***: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p < 0.0001 and10.2%, p = 0.004) and HC(2.9%, p < 0.0001 and15.5%, p = NS). No difference was found for the prevalence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the *** of a

关键词： Crohn's disease Ulcerative colitis Diseaseprogression Antiphospholipid antibodies Anti-β2-Glycoprotein-I antibodies Anti-phosphatidylserine/prothrombin Anti-cardiolipin antibodies Thrombosis

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Budesonide induces complete remission in autoimmune hepatitis

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World Journal of Gastroenterology 2006年第9期12卷 1362-1366页

作者： antal Csepregi Christoph R(o|¨)cken Gerhard Treiber peter Malfertheiner Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke UniversityLeipziger Str 4439120 MagdeburgGermany Institute of Pathology Otto-von-Guericke University Leipziger Str 4439120 MagdeburgGermany

AIM： Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis （AIH）. However, only 65% of the patients enter complete histological remission. Recently, budesonide （BUD） was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH. METHODS： Eighteen patients （12 women, 6 men; mean age 45.4±21 years） with AIH were treated with BUD （Budenofalk） 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis （n = 5） or primary sclerosing cholangitis （n = 2）. Advanced liver fibrosis or cirrhosis was present in RESULTS： Fifteen （83%） patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis, were given BUD as first-line therapy, of which seven enter remission. Three patients, two with liver cirrhosis, did not improve. All patients with second-line therapy experienced long-term remission. A histological remission was also seen in three patients. Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis （n = 4）. CONCLUSION： BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

关键词： Budesonide Autoimmune hepatitis Complete remission Adverse events

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Acute exacerbation of autoimmune hepatitis induced by Twinrix

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World Journal of Gastroenterology 2005年第26期11卷 4114-4116页

作者： antal Csepregi Gerhard Treiber Christoph R(o|¨)cken peter Malfertheiner Department of Gastroenterology Hepatology and Infectious Diseases Department of Pathology Otto-von-Guericke University Leipziger Str. 44 Magdeburg 39120 Germany

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix? In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid, and led to complete normalization of the pathological liver function tests. We believe that Twinrix led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

关键词： Twinrix Autoimmune hepatitis Budesonide

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Immune phenotype in children with therapy-nave remitted and relapsed Crohn’s disease

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World Journal of Gastroenterology 2010年第47期16卷 6001-6009页

作者： Aron Cseh Barna Vasarhelyi Kriszta Molnar Balazs Szalay peter Svec Andras Treszl antal Dezsofi peter Laszlo Lakatos Andras Arato Tivadar Tulassay Gabor Veres Research Group for Pediatrics and Nephrology Semmelweis University Hungarian Academy of Sciences Department of Laboratory Medicine Semmelweis University First Department of Pediatrics Semmelweis University First Department of Medicine Semmelweis University

AIM: To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy-nave childhood Crohn's disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease. METHODS: We enrolled 26 pediatric patients with CD. 14 therapy-nave CD children; of those, 10 children remitted on conventional therapy and formed the remission group. We also tested another group of 12 chil-dren who relapsed with conventional therapy and were given infliximab; and 15 healthy children who served as controls. The prevalence of Th1 and Th2, nave and memory, activated and regulatory T cells, along with the members of innate immunity such as natural killer (NK), NK-T, myeloid and plasmocytoid dendritic cells (DCs), monocytes and Toll-like receptor (TLR)-2 and TLR-4 expression were determined in peripheral blood samples. RESULTS: Children with therapy-nave CD and those in relapse showed a decrease in Th1 cell prevalence. Simultaneously, an increased prevalence of memory and activated lymphocytes along with that of DCs and monocytes was observed. In addition, the ratio of myeloid /plasmocytoid DCs and the prevalence of TLR-2 or TLR-4 positive DCs and monocytes were also higher in therapy-nave CD than in controls. The majority of alterations diminished in remitted CD irrespective of whether remission was obtained by conventional or biological therapy. CONCLUSION: The finding that immune phenotype is normalized in remission suggests a link between immune phenotype and disease activity in childhood CD. Our observations support the involvement of members of the adaptive and innate immune systems in childhood CD.

关键词： Crohn’s disease Dendritic cell Infliximab Lymphocyte Monocyte Regulatory T cell Relapse Remission Therapy-nave Toll-like receptor

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