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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 | Quality of life, work productivity impairment and healthcare resources in inflammatory bowel diseases in Brazil显示文摘BACKGROUND Inflammatory bowel diseases(IBD)have been associated with a low quality of life(QoL)and a negative impact on work productivity compared to the general population.Information about disease control,patient-reported outcomes(PROs),treatment patterns and use of healthcare resources is relevant to optimizing IBD management.AIM To describe QoL and work productivity and activity impairment(WPAI),treatment patterns and use of healthcare resources among IBD patients in Brazil.METHODS A multicenter cross-sectional study included adult outpatients who were previously diagnosed with moderate to severe Crohn’s disease(CD)or ulcerative colitis(UC).At enrolment,active CD and UC were defined as having a Harvey Bradshaw Index≥8 or a CD Activity Index≥220 or calprotectin>200μg/g or previous colonoscopy results suggestive of inadequate control(per investigator criteria)and a 9-point partial Mayo score≥5,respectively.The PRO assessment included the QoL questionnaires SF-36 and EQ-5D-5L,the Inflammatory Bowel Disease Questionnaire(IBDQ),and the WPAI questionnaire.Information about healthcare resources and treatment during the previous 3 years was collected from medical records.Chi-square,Fisher’s exact and Student’s t-/Mann-Whitney U tests were used to compare PROs,treatment patterns and the use of healthcare resources by disease activity(α=0.05).RESULTS Of the 407 patients in this study(CD/UC:64.9%/35.1%,mean age 42.9/45.9 years,54.2%/56.6%female,38.3%/37.1%employed),44.7%/25.2%presented moderate-to-severe CD/UC activity,respectively,at baseline.Expressed in median values for CD/UC,respectively,the SF-36 physical component was 46.6/44.7 and the mental component was 45.2/44.2,the EQ-visual analog scale score was 80.0/70.0,and the IBDQ overall score was 164.0/165.0.Moderate to severe activity,female gender,being unemployed,a lower educational level and lower income were associated with lower QoL(P<0.05).Median work productivity impairment was 20%and 5%for CD and UC patients,respectively,and activity impairment was 30%,the latter being higher among patients with moderate to severe disease activity compared to patients with mild or no disease activity(75.0%vs 10.0%,P<0.001).For CD/UC patients,respectively,25.4%/2.8%had at least one surgery,38.3%/19.6%were hospitalized,and 70.7%/77.6%changed IBD treatment at least once during the last 3 years.The most common treatments at baseline were biologics(75.3%)and immunosuppressants(70.9%)for CD patients and 5-ASA compounds(77.5%)for UC patients.CONCLUSION Moderate to severe IBD activity,especially among CD patients,is associated with a substantial impact on QoL,work productivity impairment and an increased number of IBD surgeries and hospitalizations in Brazil. | Rogerio Serafim Parra Julio MF Chebli Heda MBS Amarante Cristina Flores Jose ML Parente Odery Ramos Milene Fernandes Jose JR Rocha Marley R Feitosa Omar Feres Antonio S Scotton Rodrigo B Nones Murilo M Lima Cyrla Zaltman Carolina D Goncalves Isabella M Guimaraes Genoile O Santana Ligia Y Sassaki Rogerio S Hossne Mauro Bafutto Roberto LK Junior Mikaell AG Faria Sender J Miszputen Tarcia NF Gomes Wilson R Catapani Anderson A Faria Stella CS Souza Rosana F Caratin Juliana T Senra Maria LA Ferrari | 2019 | World Journal of Gastroenterology2019,25,38: | 2 |
| 3 | Murine model to study brain,behavior and immunity during hepatic encephalopathy显示文摘AIM:To propose an alternative model of hepatic encephalopathy(HE) in mice,resembling the human features of the disease.METHODS:Mice received two consecutive intraperitoneal injections of thioacetamide(TAA) at low dosage(300 mg/kg).Liver injury was assessed by serum transaminase levels(ALT) and liver histology(hematoxylin and eosin).Neutrophil infiltration was estimated by confocal liver intravital microscopy.Coagulopathy was evaluated using prolonged prothrombin and partial thromboplastin time.Hemodynamic parameters were measured through tail cuff.Ammonia levels were quantified in serum and brain samples.Electroencephalography(EEG) and psychomotor activity score were performed to show brain function.Brain edema was evaluated using magnetic resonance imaging.RESULTS:Mice submitted to the TAA regime developed massive liver injury,as shown by elevation of serum ALT levels and a high degree of liver necrosis.An intense hepatic neutrophil accumulation occurred in response to TAA-induced liver injury.This led to mice mortality and weight loss,which was associated with severe coagulopathy.Furthermore,TAA-treated mice presented with increased serum and cerebral levels of ammonia,in parallel with alterations in EEG spectrum and discrete brain edema,as shown by magnetic resonance imaging.In agreement with this,neuropsychomotor abnormalities ensued 36 h after TAA,fulfilling several HE features observed in humans.In this context of liver injury and neurological dysfunction,we observed lung inflammation and alterations in blood pressure and heart rate that were indicative of multiple organ dysfunction syndrome.CONCLUSION:In summary,we describe a new murine model of hepatic encephalopathy comprising multiple features of the disease in humans,which may provide new insights for treatment. | Lindisley Ferreira Gomides Pedro Elias Marques Bruno Engler Faleiros Rafaela Vaz Pereira Sylvia Stella Amaral Thais Reis Lage Gustavo Henrique Souza Resende Patricia Alves Maia Guidine Giselle Foureaux Fabíola Mara Ribeiro Fabiana Paiva Martins Marco Antonio Peliky Fontes Anderson José Ferreira Remo Castro Russo Mauro Martins Teixeira Márcio Flávio Moraes Antonio Lúcio Teixeira Gustavo Batista Menezes | 2014 | World Journal of Hepatology2014,6,4: | 2 |
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