肠道微生物群失调、免疫反应以及用于评估慢性乙型肝炎病毒感染者肝纤维化的非侵入性模型的性能

R. E Eworo, U. A Fabian, N. A Ntamu, C. C Thomas, U. O Egom, M. C Nsonwu, R. U Basake, A. R Essien, I. M Ekam-Ukere, A. C Nsonwu-Anyanwu
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引用次数: 0

摘要

肠道微生物群失调和脂多糖介导的免疫反应与慢性乙型肝炎病毒感染者并发症和肝损伤的发病机制有关。本病例对照研究评估了慢性乙型肝炎病毒感染(CHBV)患者的C反应蛋白(CRP)、脂多糖(LPS)、血清蛋白、血小板计数(PLT)、天冬氨酸氨基转移酶(AST)水平,以及无创模型球蛋白与血小板比值指数(GPI)、C反应蛋白与白蛋白比值指数(CAR)和天冬氨酸与血小板比值指数(APRI)在评估肝纤维化方面的性能。 该研究招募了 60 名慢性乙型肝炎病毒感染者和 40 名健康对照者。血小板计数用 5 部分 Sysmex XS-1000 血液学自动分析仪测定,脂多糖用夹心-ELISA 法测定,CRP 用乳胶试剂凝集法测定,AST、ALB、TP 用商业比色法测定,计算 C 反应蛋白-白蛋白比值(CAR)、球蛋白-血小板指数(GPI)、天冬氨酸-血小板比值指数(APRI)。 数据分析采用方差分析、Pearson 检验和 DeLong 检验,在 α=0.05 时比较无创标记物的接收者操作特征曲线下面积 (AUROC)。与 CHBV 和对照受试者相比,肝纤维化(LF)受试者的 LPS、CRP、AST、GLO、CAR、GPI 和 APRI 明显较高,而 PLT 和 ALB 较低。试验对象的 Log10 CAR 与 Log10 GPI 分别呈正相关(r= 0.464,P=0.000),CRP 与 LPS 呈正相关,与 PLT 呈负相关(r=0.626,P=0.000 和 r=-0.393,P=0.002)。GPI、CAR 和 APRI 的曲线下面积分别为 0.923、0.940 和 1.000。这项研究表明,肠道微生物群失调和 LPS 介导的免疫激活可能是慢性乙型肝炎病毒感染者肝损伤的发病机制。GPI、CAR和APRI模型是预测明显肝纤维化的良好测试工具,对于无法进行纤维扫描、瞬时弹性成像或肝活检的患者,使用这些模型可能是评估肝损伤的简单而低成本的选择。
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Gut Microbiota Dysbiosis, Immunological Response And The Performance Of Non-Invasive Models For Assessing Liver Fibrosis In Patients With Chronic Hepatitis B Virus
Gut microbiota dysbiosis and lipopolysaccharide-mediated immune response has been linked with pathogenesis of complications and liver injuries in subjects with chronic hepatitis B virus infection. The levels of C-reactive protein (CRP), lipopolysaccharides (LPS), serum protein, platelet count (PLT), aspartate amino transferase (AST), and the performance of non-invasive models globulin to-platelet index (GPI), C-reactive protein to-albumin ratio (CAR), and aspartate to-platelet ratio index (APRI) in assessing fibrosis in patients with chronic hepatitis B virus infection (CHBV) were assessed in this case-control study.  The study enrolled 60 subjects with CHBV and 40 healthy controls. Platelet count was determined by a 5 parts Sysmex XS-1000 haematology automated analyzer, lipopolysaccharide was determined by sandwich-ELISA method, CRP was determined by latex Reagent agglutination method, AST, ALB, TP,  were determined by commercial colorimetric methods, C-reactive protein-albumin ratio (CAR), globulin-platelet index (GPI), aspartate-platelet ratio index (APRI),  were computed.  Data analysis was performed using analysis of variance, Pearson’s and DeLong’s test to compare the area under the receiver operating characteristic curve (AUROC) for the noninvasive markers, at α=0.05. Subjects with liver fibrosis (LF) had significantly higher LPS, CRP, AST, GLO, CAR, GPI and APRI and lower PLT, ALB, when compared with CHBV and control subjects. Log10 CAR correlated positively with Log10 GPI r= 0.464, P=0.000) respectively, CRP correlated positively with LPS and negatively with PLT (r=0.626, P=0.000 and r= -0.393, P=0.002) respectively, in the test subjects. The area under the curve for GPI, CAR and APRI were 0.923, 0.940, and 1.000 respectively. This study has shown that dysbiosis of the gut microbiota and LPS-mediated immune activation may underlie the pathogenesis of liver damage in subjects with chronic hepatitis B virus. The GPI, CAR and APRI models are good test instruments in predicting significant fibrosis and their use may represent simple and low-cost options in assessing liver injury in patients where FibroScan, transient elastography or liver biopsy is not accessible.
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