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| 1 | 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 |
| 2 | 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 |
| 3 | 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 |
| 4 | 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 |
| 5 | Diagnostic Relevance and Clinical Significance of the New Enhanced Performance M2 (MIT3) ELISA for the Detection of IgA and IgG Antimitochondrial Antibodies in Primary Biliary Cirrhosis显示文摘 | Stella Gabeta Gary L. Norman Christos Liaskos Panagiotis A. Papamichalis Theodoros Zografos Athanasios Garagounis Eirini I. Rigopoulou George N. Dalekos | 2007 | Journal of Clinical Immunology2007，，4： | 2 |
| 6 | Diagnostic relevance and clinical significance of the new enhanced performance M2(MIT3)ELISA for the detection of IgA and IgG anti-mitochondrial antibodies in primary biliary cirrhosis显示文摘 | Gabeta S Norman GL Liaskos C | 2007 | Clin Immunol2007，27，： | 1 |
| 7 | Diagnostic Relevance and Clinical Significance of the New Enhanced Performance M2 (MIT3) ELISA for the Detection of IgA and IgG Antimitochondrial Antibodies in Primary Biliary Cirrhosis显示文摘 | Stella Gabeta Gary L. Norman Christos Liaskos Panagiotis A. Papamichalis Theodoros Zografos Athanasios Garagounis Eirini I. Rigopoulou George N. Dalekos | 2007 | Journal of Clinical Immunology2007，，4： | 1 |
| 8 | Diagnostic relevance and clinical significance of the new enhanced performance M2 ( MIT3 ) ELISA for the detection of IgA and IgG antimitochondrial antibodies in primary biliary cirrhosis 显示文摘 | Gabeta S Norman GL Liaskos C | 2007 | J Clin Immunol2007，27，4： | 1 |
| 9 | Clinical significance of the fluctuation of primary biliary cirrhosis-related autoantibodies during the course of the disease*显示文摘 | Nikolaos K. Gatselis Kalliopi Zachou Gary L. Norman Stella Gabeta Panagiotis Papamichalis George K. Koukoulis George N. Dalekos | 2013 | Autoimmunity2013，，7： | 1 |
| 10 | 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： | 1 |
| 11 | Diagnostic Relevance and Clinical Significance of the New Enhanced Performance M2 (MIT3) ELISA for the Detection of IgA and IgG Antimitochondrial Antibodies in Primary Biliary Cirrhosis显示文摘 | Stella Gabeta Gary L. Norman Christos Liaskos Panagiotis A. Papamichalis Theodoros Zografos Athanasios Garagounis Eirini I. Rigopoulou George N. Dalekos | 2007 | Journal of Clinical Immunology2007，，4： | 1 |
| 12 | Clinical significance of the fluctuation of primary biliary cirrhosis-related autoantibodies during the course of the disease*显示文摘 | Nikolaos K. Gatselis Kalliopi Zachou Gary L. Norman Stella Gabeta Panagiotis Papamichalis George K. Koukoulis George N. Dalekos | 2013 | Autoimmunity2013，，7： | 1 |
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