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| 1 | Autoimmune hepatitis,one disease with many faces:Etiopathogenetic,clinico-laboratory and histological characteristics显示文摘Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface hepatitis.Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially difficult.Therefore,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of AIH.AIH has a global distribution affecting any age,both sexes and all ethnic groups.Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis.Hypergammaglobulinemia with selective elevation of IgG is found in most cases.Autoimmune attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory cells.Histology(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely diagnosis.AIH remains a major diagnostic challenge.AIH should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute hepatitis.Laboratory 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. | Nikolaos K Gatselis Kalliopi Zachou George K Koukoulis George N Dalekos | 2015 | World Journal of Gastroenterology2015，21，1： | 36 |
| 2 | Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients显示文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In 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 cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS 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 patients.Two 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 disorders.The 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 guidelines.In 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 patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases. | Nikolaos K Gatselis Tamás Tornai Zakera Shums Kalliopi Zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L Norman Mária Papp George N Dalekos | 2020 | World Journal of Gastroenterology2020，26，34： | 21 |
| 3 | Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome显示文摘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 PBC.RESULTS: 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 follow-up.CONCLUSION: 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. | Eirini I Rigopoulou Kalliopi Zachou Nikolaos K Gatselis Georgia Papadamou George K Koukoulis George N Dalekos | 2013 | World Journal of Hepatology2013，5，10： | 7 |
| 4 | Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma显示文摘AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.RESULTS: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P < 0.001), advanced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P < 0.001), alanine aminotransferase(P < 0.02), γ-glutamyl transpeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P < 0.05), international normalized ratio(P = 0.002) and alpha-fetoprotein levels(P < 0.02), and lower albumin(P < 0.001), and platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U/L vs 9.8(4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis(OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development(P = 0.007) and higher incidence of liver-related death(P < 0.001). CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs. | Gary L Norman Nikolaos K Gatselis Zakera Shums Christos Liaskos Dimitrios P Bogdanos George K Koukoulis George N Dalekos | 2015 | World Journal of Hepatology2015，7，14： | 7 |
| 5 | Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat显示文摘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. | Kalliopi Zachou Alexandros Sarantopoulos Nikolaos K Gatselis Themistoklis Vassiliadis Stella Gabeta Aggelos Stefos Asterios Saitis Panagiota Boura George N Dalekos | 2013 | World Journal of Hepatology2013，5，7： | 6 |
| 6 | Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients显示文摘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. | Theodoros A Zografos Nikolaos Gatselis Kalliopi Zachou Christos Liaskos Stella Gabeta George K Koukoulis George N Dalekos | 2012 | World Journal of Gastroenterology2012，18，34： | 4 |
| 7 | Reversion of severe hepatopulmonary syndrome in a non cirrhotic patient after corticosteroid treatment for granulomatous hepatitis:A case report and review of the literature显示文摘肝肺症候群(HPS ) 包括肺内的脉管的膨胀的肝疾病,反常肺的煤气的交换和证据被定义为一个临床的三个一组。我们报导在最后年与疲劳,长持续的发烧,体重减轻,门静脉高血压的符号,肝脾大,胆汁郁积和进步 dyspnoea 介绍的 61 岁的男性。临床,实验室和组织检查所见证实了肉芽肿肝炎的诊断。由于肝的导致 granuloma 的门静脉高血压的 HPS 被证明是由提高对比的回响心动描记法证实了的病人的严重血氧不足的原因。在皮质甾治疗以后的 HPS 的回复被新提高对比的回响心动描记法与胆汁郁积的酶的正规化和病人的条件的改进一起证实。这是在有肝的肉芽肿的一个非肝脏硬化症的病人的 HPS 的完全的回复的第一个案例,显示在肝疾病的那肺内分流是功能的现象, HPS 能甚至在象在这种情况中的其他的肝参与被开发。 | Nikolaos Tzovaras Aggelos Stefos Sarah P Georgiadou Nikolaos Gatselis Georgia Papadamou Eirini Rigopoulou Maria Ioannou Ioannis Skoularigis Georgios N Dalekos | 2006 | World Journal of Gastroenterology2006，12，2： | 3 |
| 8 | In vivo anti-salmonella activity of aqueous extract of Euphorbia prostrata Aiton(Euphorbiaceae) and its toxicological evaluation显示文摘Objective: To investigate the in vivo anti-salmonella activity and the safety of aqueous extract of Euphorbia prostratra(E. prostratra), a plant commonly used in Cameroon by traditional healers.Methods: A Salmonella typhimurium-infected rat model was used for the study. The physiological, biochemical and histopathological markers of possible side effects of this extract were studied using standard methods.Results: The extract had a significant effect on the number of viable Salmonella typhimurium recovered from faeces, and could stop salmonellosis after 8 and 10 days of treatment for male and female rats, respectively, with non-toxic doses. However, the biochemical and histopathological analyses revealed that at relatively high doses(≥ 73.48 mg/kg for female and ≥ 122.71 mg/kg for male) the extract could induce liver damage, as illustrated by a rise of serum transaminases' levels and significant inflammation of the parenchyma and portal vein.Side effects were also observed on the kidneys, as shown by both serum and urinary creatinine,and urinary proteins.Conclusions: The overall results indicate that the aqueous extract of E. prostrata has the potential to provide an effective treatment for salmonellosis, including typhoid fever. However,it is necessary to extrapolate these results in large animals, in further studies. | Donald Sédric Tala Donatien Gatsing Siméon Pierre Chegaing Fodouop Charles Fokunang Fabrice Kengni Merline Namekong Djimeli | 2015 | Asian Pacific Journal of Tropical Biomedicine2015，5，4： | 3 |
| 9 | Adiponectin: a key playmaker adipocytokine in non-alcoholic fatty liver disease显示文摘 | Nikolaos K. Gatselis George Ntaios Konstantinos Makaritsis George N. Dalekos | 2014 | Clinical and Experimental Medicine2014，，2： | 3 |
| 10 | Individualization of chronic hepatitis C treatment according to the host characteristics显示文摘Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people worldwide.It is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most common cause of liver failure and transplantation.The standardof-care treatment for chronic hepatitis C(CHC)has been changed during the last decade and direct acting antiviral drugs have already been used.Besides,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 treatment.Recent genome-wide association studies have shown the important role of interleukin-28B and inosine triphosphatase in HCV infection.The present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment. | Nikolaos K Gatselis Kalliopi Zachou Asterios Saitis Maria Samara George N Dalekos | 2014 | World Journal of Gastroenterology2014，20，11： | 2 |
| 11 | IgA Anti-b2GPI Antibodies in Patients with Autoimmune Liver Diseases显示文摘 | Stella Gabeta Gary L. Norman Nikolaos Gatselis Christos Liaskos Panagiotis A. Papamichalis Athanasios Garagounis Kalliopi Zachou Eirini I. Rigopoulou George N. Dalekos | 2008 | Journal of Clinical Immunology2008，，5： | 2 |
| 12 | Descriptive epidemiology ofchronic hepatitis B by using data from a hepatitis registry in CentralGreece 显示文摘 | Stefos A Gatselis N Zachou K | 2009 | Eur J Intern Med2009，20，1： | 1 |
| 13 | Adiponectin: a key playmaker adipocytokine in non-alcoholic fatty liver disease显示文摘 | Gatselis NK Ntaios G Makaritsis K | 2014 | Clin Exp Med2014，14，2： | 1 |
| 14 | Intrafamil- ial spread of hepatitis B virus infection in Greece显示文摘 | ZERVOU E K GATSELIS N K XANTHI E | 2005 | European Journal of Gastroenterology & Hepatology2005，17，9： | 1 |
| 15 | Safety and efficacy of transcatheter arterial ehemoemholiazatiotl in the real-life maa- agement of unresectable hepatocellular carcinoma 显示文摘 | Mazioti A Gatselis NK Rountas C | 2013 | Hepat Mon2013，13，70： | 1 |
| 16 | Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir显示文摘 | George V. Papatheodoridis George N. Dalekos Cihan Yurdaydin Maria Buti John Goulis Pauline Arends Vana Sypsa Spilios Manolakopoulos Giampaolo Mangia Nikolaos Gatselis Onur Kesk?n Savvoula Savvidou Bettina E. Hansen Christos Papaioannou Kostantinos Galanis | 2014 | Journal of Hepatology2014，，： | 1 |
| 17 | Intrafamilial spread of hepatitis B virus infection in Greece显示文摘 | ZERVOI E K GATSELIS N K XANTHI E | 2005 | European Jour- nal of Gastroenterology & Hepatology2005，17，9： | 1 |
| 18 | Spontaneous spondy- lodiscitis: presentation, risk factors, diagnosis, management, and outcome显示文摘 | Kapsalaki E Gatselis N Stefos A | 2009 | Int J Infect Dis2009，13，5： | 1 |
| 19 | Clinical significance of the fluctuation of primary biliary cirrhosisrelated autoantibodies during the course of the disease显示文摘 | Gatselis NK Zachou K Norman GL | | 0，，7： | 1 |
| 20 | Adipokines as mediators of endothelial function and atherosclerosis显示文摘 | George Ntaios Nikolaos K. Gatselis Konstantinos Makaritsis George N. Dalekos | 2013 | Atherosclerosis2013，，： | 1 |
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