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World Journal of Gastroenterology 2015年第1期21卷 60-83页

作者： Nikolaos K Gatselis kalliopi zachou George K Koukoulis George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine School of MedicineUniversity of Thessaly41110 LarissaGreece Department of Pathology School of MedicineUniversity of Thessaly41110 LarissaGreece

Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface *** to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially ***,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of *** has a global distribution affecting any age,both sexes and all ethnic *** manifestations vary from asymptomatic to severe or rarely fulminant *** with selective elevation of IgG is found in most *** attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory ***(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely *** remains a major diagnostic *** should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute *** personnel,hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.

关键词： Autoimmune hepatitis Liver autoimmunity Liver-rela

Individualization of chronic hepatitis C treatment according to the host characteristics

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World Journal of Gastroenterology 2014年第11期20卷 2839-2853页

作者： Nikolaos K Gatselis kalliopi zachou Asterios Saitis Maria Samara George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine School of MedicineUniversity of Thessaly41110 LarissaGreece Department of Pathology School of MedicineUniversity of Thessaly41110 LarissaGreece

Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people *** is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most common cause of liver failure and *** standardof-care treatment for chronic hepatitis C(CHC)has been changed during the last decade and direct acting antiviral drugs have already been ***,understanding of the pathogenesis of CHC has evolved rapidly during the last years and now several host factors are known to affect the natural history and response to *** genome-wide association studies have shown the important role of interleukin-28B and inosine triphosphatase in HCV *** present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment.

关键词： Chronic hepatitis C Hepatitis C virus host factors Interleukin 28B Inosine triphosphatase Single nucleotide polymorphism

Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

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World Journal of Gastroenterology 2012年第34期18卷 4721-4728页

作者： Theodoros A Zografos Nikolaos Gatselis kalliopi zachou Christos Liaskos Stella Gabeta George K Koukoulis George N Dalekos Depart ment of Medicine and Research Laboratory of Internal Medicine Medical SchoolUniversity of Thessaly41110 LarissaGreece Department of Pathology Medical SchoolUniversity of Thessaly41110 LarissaGreece

AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (ANA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). CONCLUSION:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.

关键词： Primary biliary cirrhosis Antimitochondrial antibodies Anti-gp210 Anti-sp100 Liver autoimmunity

Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: A pilot study

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World Journal of Gastroenterology 2005年第4期11卷 482-487页

作者： Nikolaos K.Gatselis Sarah P.Georgiadou Nikolaos Tassopoulos kalliopi zachou Christos Liaskos Angelos Hatzakis Georgios N.Dalekos Department of Internal Medicine Research Laboratory of Internal Medicine Medical SchoolUniversity of Thessaly Larissa Greece Department of Internal Medicine Western Attica Hospital AthensGreece Department of Internal Medicine Research Laboratory of Internal Medicine Medical SchoolUniversity of Thessalv Larissa.Greece Academic Liver UnitDepartment of Internal MedicineMedical SchoolUniversity of Thessaly LarissaGreece Department of Internal Medicine Research Laboratory of Internal Medicine Medical SchoolUniversity of Thessaly LarissaGreece Department of Hygiene and Epidemiology National Retrovirus Reference Center Athens University Medical SchoolAthensGreece Department of Internal Medicine Research Laboratory of Internal Medicine Medical SchoolUniversity of Thessaly LarissaGreece Academic Liver UnitDepartment of Internal MedicineMedical SchoolUniversity of Thessaly LarissaGreece

AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- a may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.

关键词： HCV infection Autoantibodies Interferon-alpha

Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and γ-immunoglobulin infusions

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World Journal of Clinical Cases 2019年第21期7卷 3394-3406页

作者： Sarah Georgiadou Nikolaos K Gatselis Aggelos Stefos kalliopi zachou Konstantinos Makaritsis Eirini I Rigopoulou George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine University Hospital of LarissaLarissa 41110Greece Institute of Internal Medicine and Hepatology University Hospital of LarissaLarissa 41447Greece

BACKGROUND Secondary haemophagocytic lymphohistiocytosis(sHLH)is a rare lifethreatening condition mainly associated with underlying infections,malignancies,and autoimmune or immune-mediated *** To analyse all sHLH cases that were diagnosed and managed under real-world circumstances in our department focusing on the treatment schedule and the *** Prospectively collected data from all adult patients fulfilling the criteria of sHLH who diagnosed and managed from January 1,2010 to June 1,2018,in our department of the tertiary care university hospital of Larissa,Greece,were analysed retrospectively(n=80;52%male;median age:55 years).The electronic records and/or written charts of the patients were reviewed for the demographic characteristics,clinical manifestations,underlying causes of sHLH,laboratory parameters,treatment schedule and 30-d-mortality *** of patients had received after consent intravenousγ-immunoglobulin(IVIG)for 5 d(total dose 2 g/kg)in combination with intravenous steroid pulses followed by gradual tapering of *** Seventy-five patients(94%)reported fever>38.5°C,47(59%)had liver or spleen enlargement and 76(95%)had ferritin>500 ng/mL including 20(25%)having considerably high levels(>10000 ng/mL).Anaemia and thrombocytopenia occurred in 72%and leucopoenia in 47%of *** infections were diagnosed in 59 patients(74%)as follows:leishmaniasis alone in 15/80(18.9%),leishmaniasis concurrently with Coxiella Burnetti or non-Hodgkin lymphoma in 2/80(2.5%),bacterial infections in 14/80(17.5%)including one case with concurrent non-Hodgkin lymphoma,viral infections in 13/80(16.3%),fungal infections in 2/80(2.5%),infections by mycobacteria in 1/80(1.3%)and unidentified pathogens in 12/80(15%).Seventy-two patients(90%)had received combination treatment with IVIG and intravenous ***,sHLH resolved in 76%of patients,15%died within the first month but 82.5%of patients were still alive 6 mo after ***

关键词： Haemophagocytic syndrome Haemophagocytic lymphohistiocytosis γ-immunoglobulin Leishmaniasis Ferritin

Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients

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World Journal of Gastroenterology 2020年第34期26卷 5130-5145页

作者： Nikolaos K Gatselis Tamás Tornai Zakera Shums kalliopi zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L Norman Mária Papp George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine National Expertise Center of Greece in Autoimmune Liver DiseasesGeneral University Hospital of LarissaLarissa 41110Greece Institute of Internal Medicine and Hepatology Larissa 41447Greece Department of Internal Medicine Division of GastroenterologyUniversity of DebrecenFaculty of MedicineDebrecen H-4032Hungary Department of Research and Development Inova DiagnosticsInc.San DiegoCA 92131United States

BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are *** this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial *** a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in ***,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in *** far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease *** To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease *** GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all *** hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related *** duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted *** particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic *** Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of

关键词： Biomarker Golgi protein-73 Hepatic fibrosis Cirrhosis Hepatocellular carcinoma Hepatitis B Hepatitis C Aspartate aminotransferase/Platelets ratio index score

Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome

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World Journal of Hepatology 2013年第10期5卷 577-583页

作者： Eirini I Rigopoulou kalliopi zachou Nikolaos K Gatselis Georgia Papadamou George K Koukoulis George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine Medical School University of Thessaly Department of Pathology Medical SchoolUniversity of Thessaly

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of ***: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during ***: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.

关键词： Antimitochindrial antibodies Autoimmune liver disease Hepatitis B virus Hepatitis C virus Primary biliary cirrhosis.

Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

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World Journal of Hepatology 2013年第7期5卷 387-392页

作者： kalliopi zachou Alexandros Sarantopoulos Nikolaos K Gatselis Themistoklis Vassiliadis Stella Gabeta Aggelos Stefos Asterios Saitis Panagiota Boura George N Dalekos Department of Medicine and Research Laboratory of Internal Medicine School of Medicine University of Thessaly Clinical Immunology Unit 2nd Department of Internal Medicine Hippokration General Hospital Aristotle University of Thessaloniki First Medical Propedeutic Department Medical School Aristotle University of Thessaloniki AHEPA Hospital Thessaloniki

AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.

关键词： Immunosuppression Hepatitis B Antihepatitis B virus core antibody positivity Occult hepatitis B virus infection Rituximab

Smoking and genital human papilloma virus infection in women attending cervical cancer screening in Greece

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World Journal of Obstetrics and Gynecology 2013年第3期2卷 53-61页

作者： Kimon Chatzistamatiou Taxiarchis Katsamagas Menelaos Zafrakas Konstantia zachou Anastasia Orologa Fani Fitsiou Thomas Theodoridis Theocharis Konstantinidis Theodoros C Konstantinidis Theodoros Agorastos 4th Department of Obstetrics and Gynecology Hippokrateio Hospital Aristotle University of Thessaloniki 54642 Thessaloniki Greece School of Health and Medical Care Alexander Technological Educational Institute of Thessaloniki 55134 Thessaloniki Greece Laboratory of Cytology Hippokrateio Hospital54642 ThessalonikiGreece Center for Family Planning Hippokrateio Hospital 54642 Thessaloniki Greece Peripheral Laboratory of Public Health Hellenic Center for Disease Control and Prevention Ministry of Health 68100 Alexandroupoli Greece Laboratory of Hygiene and Environmental Protection and Laboratory of Microbiology Democritus University of Thrace 68100 Alexandroupoli Greece

AIM: To investigate whether smoking is associated with human papilloma virus(HPV) infection. METHODS: HPV infection is considered to be a neces-sary condition for cervical cancer development. The study population included 1291 women, aged 25-55 years, attending cervical cancer screening. All women had a Papanicolaou(Pap) test, with liquid-based cytology(Thinprep), an HPV-DNA test and an evaluation of smoking habits. The COBAS 4800 system was used for HPV-DNA testing, enabling identifi cation of the following high-risk HPV(hr HPV)-types: each of HPVs 16 and 18 separately, and HPVs 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 as a cocktail. The evaluation of smoking habits was assessed using the smoking intensity index(SII), a variable formed as the product of cigarettes consumed per day by the days(years × 365) that a woman was a smoker, divided by 1000. RESULTS: There were 136 smokers among 238 women tested positive for hr HPV-types(HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and/or 68), and 463 smokers among 1053 hr HPV-negative women(OR = 1.7, P < 0.001). This association was attributed to the youngest age group of women, aged 25-34 years(OR = 2.3, P < 0.001), while there was no association in other age groups. The intensity of smoking(increasing SII) showed no statistically signifi cant association with hr HPV infection. Cervical infection with HPV 16 and/or HPV 18 was also not associated with age or smoking habits. Finally, no association was found between Pap test status and smoking habits or smoking intensity. CONCLUSION: Smoking appears to be associated with hr HPV infection of the uterine cervix, particularly in younger women. Further studies should investigate whether this association is based on causality and evaluate the role of other possible co-factors.

关键词： Human papilloma virus High-risk human papilloma virus Human papilloma virus-DNA test Smok-ing Cervical cancer Screening