血清胱抑素C对慢加急性肝衰竭患者肾损伤的早期诊断意义

目的研究血清胱抑素C(CysC)水平对慢加急性肝衰竭(ACLF)患者急性肾损伤(AKI)的早期诊断意义。方法选取2011年8月-2012年10月于本院住院的慢性乙型肝炎相关慢加急性肝衰竭(ACLF)、慢性乙型肝炎(CHB)的患者各60例,同期60例健康者作为对照。肝衰竭患者随访至出院,动态收集患者血清。采用胶乳增强免疫比浊法测定血清CysC水平。通过绘制CysC、肌酐和血钠浓度诊断AKI的受试者工作特征曲线(ROC),获得其曲线下面积(AUC)及最佳临界值。正态分布的计量资料,多组间比较采用单因素方差分析(One-way ANOVA),2组间比较采用双侧t检验;否则,组间比较采用Mann-Whitney U检验。计数资料采用χ2检验。相关分析采用Pearson相关检验。AUC及最佳临界值的计算采用Medcal 12.7.1.0进行分析。结果肝衰竭患者血清CysC水平为(1050±444)ng/ml,显著高于健康对照组(638±275)ng/ml(P=0.016)和CHB组患者(661±225)ng/ml(P=0.028)。ACLF患者血清CysC水平与肌酐水平相关性不显著(r=0.311,P0.05),但与MELD评分呈显著正相关(r=0.529,P0.01)。住院期间,共有8名肝衰竭患者(13.3%)发展为急性肾损伤,多元Logistic回归分析结果显示,血清CysC水平是ACLF患者发生肾损伤的独立影响因素(OR=1.008,P=0.021)。AUC分析显示早期诊断ACLF患者急性肾损伤的血清CysC水平建议值为1210 ng/ml。结论血清CysC检测有助于ACLF伴肌酐水平正常患者住院期间发生急性肾损伤的早期预测。     

血清胱抑素C对肝硬化患者肾损伤的诊断效能研究

目的 探讨应用血清胱抑素C水平诊断肝硬化患者并发急性肾损伤（AKI）的临床价值。方法 2015年1月~2017年2月我院接受治疗的114例肝硬化患者,按照血清肌酐水平在48 h内≥25.5 μmol/L诊断,结果并发AKI患者62例【其中急性肾小管坏死（ATN)8例,肝肾综合症（HRS）16例和前性氮质血症(PRA)38例】,非AKI患者52例。采用增强免疫比浊法检测血清胱抑素C。结果 AKI组合并冠心病19例,糖尿病17例,高血压16例,显著高于非AKI组的12例、10例和11例（P<0.05）;AKI组血清胱抑素C水平为（2.4±0.2） mg/L,显著高于非AKI组的（0.9±0.1） mg/L,白蛋白为（28.3±4.8） g/L,显著低于非AKI组的（34.1±7.3） g/L（P<0.05）;尿素氮为（15.3±5.4） mmol/L,血小板计数为（73.1±11.3）×10⁹/L,总胆红素为（43.8±9.5） μmol/L,血肌酐为（127.6±23.5） μmol/L,与非AKI组的（6.4±3.3） mmol/L、（90.6±12.7）×10⁹/L、（23.6±6.4） μmol/L和（73.4±15.2） μmol/L比,差异显著（P<0.05）;ATN组血胱抑素C水平为（3.6±1.6） mg/L,血小板计数为（102.6±21.7）×10⁹/L,总胆红素为（73.2±16.8） μmol/L,血肌酐为（346.8±30.7） μmol/L,均显著高于HRS组或PRA组（P<0.05）;血清胱抑素C诊断AKI的准确度为92.1%,特异度为95.7%,显著高于血肌酐或尿素氮。结论 血胱抑素C水平检测可帮助早期诊断肝硬化患者并发AKI,或有利于临床早期处理。     

HBsAg levels in HBeAg-positive chronic hepatitis B patients with different immune conditions

AIM:To investigate hepatitis B surface antigen(HBsAg)levels in patients with HBeAg-positive chronic hepatitis B(CHB)and different immune conditions.METHODS:HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study.These patients were grouped according to the following criteria:immune-tolerant patients,IT group;patients with a mild immune response in the immune clearance phase,IC-Mild group;and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure(ACLF),ACLF group.All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of2:2:1.Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus(HBV)DNA level were evaluated in these groups.RESULTS:In total,180 HBeAg-positive CHB patients[IT group(n=72),IC-Mild group(n=72),and ACLF group(n=36)]were enrolled in this study.The median serum HBsAg levels varied among the groups(P<0.001):IT,4.86 log10IU/mL;IC-Mild,3.97 log10IU/mL;and ACLF,3.57 log10IU/mL.Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group(r=0.60,P<0.001),but exhibited a weaker correlation in the IT(r=0.52,P<0.001)and ACLF groups(r=0.51,P=0.001).The ratio of HBsAg/HBV DNA did not differ significantly among the IT,IC-Mild,and ACLF groups(medians:0.56,0.55,and 0.56,respectively;P=0.179).CONCLUSION:Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions.These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients.     

血清NGAL和Cys C对慢加急性肝衰竭患者并发肝肾综合征早期诊断价值研究

目的 研究血清中性粒细胞明胶酶相关载脂蛋白（NGAL）和光抑素C（Cys-C）诊断慢加急性肝衰竭（ACLF）患者并发肝肾综合征（HRS）的价值。方法 2010年1月~2017年1月收治的204例ACLF患者,并发HRS 58例。采用固相夹心酶联免疫吸附法检测血清NGAL,常规检测血清Cys-C、β2-微球蛋白（β2-MG）。绘制受试者工作特征曲线（ROC）评估血清指标诊断ACLF患者并发HRS的价值。结果 HRS与非HRS患者在性别、病程、BMI、糖尿病、血小板计数、血K⁺、平均动脉压方面比较无显著性差异（P>0.05）,两组在年龄、高血压、冠心病、白细胞计数、白蛋白、蛋白尿、血尿素氮、血Na⁺和Child-Pugh评分方面存在明显差异（P<0.05）;HRS患者NGAL、Cys-C、sCr、β2-MG、BUN水平分别为（64.1±18.4） ng/mL、（3.1±1.1） mg/L、（165.8±25.7） mol/L、（6.3±2.1） mg/L、（12.6±4.3） mmol/L,显著高于无HRS组【（11.5±2.3） ng/mL、（1.2±0.4） mg/L、（62.6±11.4） mol/L、（2.7±1.2） mg/L、（4.1±1.5） mmol/L,P<0.05】;HRS组患者肝损伤程度显著重于无HRS组（P<0.05）;血清 NGAL和Cys-C诊断ACLF并发HRS的敏感度和准确度分别为（89.6%）和（92.1%）,和85.9%和95.4%,显著高于血清sCr、β2-MG或BUN,而NGAL联合Cys-C检测诊断的敏感度和准确度分别为92.1%和96.2%,明显优于血清NGAL或Cys-C单独检测。结论 在ACLF患者中年龄越大,并发HRS的机会越大,病情重的患者血清NGAL和Cys-C水平升高,应用它们联合诊断ACLF患者并发HRS的效能较好,值得进一步研究。     

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bili     

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM:To investigate the protective effects of ethyl pyruvate(EP) on acute-on-chronic liver failure(ACLF) in rats.METHODS:An ACLF model was established in rats,and animals were randomly divided into normal,model and EP treatment groups.The rats in EP treatment group received EP(40 mg/kg) at 3 h,6 h,12 h and 24 h after induction of ACLF.Serum endotoxin,high mobility group box-1(HMGB1),alanine transaminase(ALT),tumor necrosis factor-(TNF-),interferon-(IFN-),interleukin(IL)-10 and IL-18 levels,changes of liver histology and HMGB1 expressions in liver tissues were detected at 48 h after induction of ACLF.The effects of EP on the survival of ACLF rats were also observed.RESULTS:Serum levels of endotoxin(0.394 ± 0.066 EU/mL vs 0.086 ± 0.017 EU/mL,P 0.001),HMGB1(35.42 ± 10.86 g/L vs 2.14 ± 0.27 g/L,P 0.001),ALT(8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L,P 0.001),TNF-(190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L,P 0.001),IFN-(715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L,P 0.001),IL-10(6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L,P 0.001) and IL-18(85.19 ± 3.49 ng/L vs 55.38 ± 1.25 ng/L,P 0.001) were significantly increased,and liver tissues presented severe pathological injury in the model group compared with the normal group.However,EP administration significantly improved hepatic histopathology and reduced the serum levels of endotoxin(0.155 ± 0.045 EU/mL vs 0.394 ± 0.066 EU/mL,P 0.001) and inflammatory cytokines(11.13 ± 2.58 g/L vs 35.42 ± 10.86 g/L for HMGB1,3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT,128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-,438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-,3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10,and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18,respectively,P 0.001),and the levels of HMGB1 in liver tissues regardless of treatment time after induction of ACLF.EP treatment at the four time points prolonged the median survival time of ACLF rats(60 h) to 162 h,120 h,102 h and 78 h,respectively(2 = 41.17,P 0.0001).CONCLUSION:EP administration can protect against ACLF in rats,and is a potential and novel therapeutic agent for severe liver injury.     

血清β2微球蛋白和胱抑素C检测对评估高胆红素血症新生儿肾损害的临床意义

目的 探讨血清β2微球蛋白（β2-MG）及胱抑素C（CysC）在评估高胆红素血症新生儿肾损害的临床意义。方法 2014年1月~2016年6月符合新生儿高胆红素血症诊断标准的新生儿128例,根据总胆红素（TBIL）水平分为轻度黄疸组（256.5 μmol/L>TBIL≥221 μmol/L）76例和中重度黄疸组（TBIL≥256.5 μmol/L）52例,另选年龄、性别相匹配的正常足月新生儿60例作为对照组,比较各组新生儿血清尿素氮（BUN）、肌酐（sCr）、CysC、β2-MG水平,观察治疗前后患儿TBIL、BUN、sCr、CysC、β2-MG的变化情况。结果 在128例高胆红素血症新生儿中,肾功能损伤25例,其中中重度黄疸组20例,轻度黄疸组5例;中重度组血清BUN、sCr、CysC、β2-MG水平分别为（5.76±1.45） mmol/L、（52.35±17.16） μmol/L、（2.68±0.45） mg/L、（4.25±1.52） mg/L,明显高于对照组的[（4.20±1.06） mmol/L、（38.65±14.23） μmol/L、（0.92±0.25） mg/L、（2.15±1.24） mg/L,均P<0.01]和轻度组的[（4.58±1.23） mmol/L、（43.76±15.75） μmol/L、（1.76±0.37） mg/L、（3.48±1.40） mg/L,均P<0.01];轻度组血清CysC、β2-MG分别为（1.76±0.37） mg/L、（3.48±1.40） mg/L,明显高于对照组的[（0.92±0.25）mg/L、（2.15±1.24）mg/L,均P<0.01],对照组和轻度组血清BUN和sCr水平差异无统计学意义（P>0.05）;治疗后患儿血TBIL、BUN、sCr、CysC、β2-MG水平分别为（182.42±45.25） μmol/L、（4.32±1.25） mmol/L、（45.24±14.35） μmol/L、（1.86±0.38）mg/L、（3.42±1.36） mg/L,明显低于治疗前的[（278.65±68.46） μmol/L、（5.35±1.30） mmol/L、（50.56±16.25）μmol/L、（2.25±0.41） mg/L、（3.96±1.45） mg/L,均P<0.01]。结论 高胆红素血症早期可导致新生儿不同程度的肾功能损害,及时治疗后可恢复。血β2-MG和CysC水平可作为判断高胆红素血症新生儿早期肾损害的敏感指标。     

HBV相关慢加急性肝衰竭患者血清角蛋白18水平及其与患者预后的关系探讨*

目的 探讨乙型肝炎病毒相关性慢加急性肝衰竭（HBV-ACLF）患者血清角蛋白18（K-18）水平变化及其对患者预后的预测价值。方法 2015年1月~2017年1月我院收治的HBV-ACLF患者100例,另选择性别和年龄相匹配的慢性乙型肝炎（CHB）患者30例和健康人30例。采用酶联免疫吸附试验法检测血清K18（M30和M65）水平。随访3 m。应用受试者工作特征曲线（ROC）分析M30/M65比值和终末期肝病模型（MELD）预测患者预后的效能。结果 ACLF患者血清M30、M65水平和M30/M65比值分别为（1.0±0.1） lg U/L、（3.4±0.3） lg U/L和（0.3±0.1）,与CHB患者【分别为（2.1±0.1） lg U/L、（3.3±0.2） lg U/L和（0.6±0.0）】或者健康人【分别为（2.1±0.1） lg U/L、（2.1±0.1） lg U/L和（1.0±0.2）】比,有显著性统计学差异（P<0.05）;68例生存患者MELD评分为（18.2±.0）,显著低于32例死亡患者的【（26.1±3.3）,P<0.05】,血清M65水平为（2.9±0.2） lg U/L,显著低于死亡患者的【（4.1±0.5） lg U/L,P<0.05】,M30/M65比值为（0.4±0.1）,显著高于死亡患者的【（0.2±0.1）,P<0.05】;MELD评分预测ACLF患者死亡的截断点为23.21,其AUC为0.650,预测的灵敏度、特异度和正确性分别为85.5%、65.0%和72.0%,而M30/M65比值预测ACLF患者死亡的截断点为0.30,其AUC为0.875,预测的灵敏度、特异度和正确性分别为94.5%、85.0%和85.0%,显著优于MELD评分（P<0.05）。结论 K18（M30和M65）与肝脏疾病的严重程度有关。早期检测血清M30和M65水平可能有助于对HBV-ACLF患者预后的判断。     

慢性乙型肝炎患者血清脂肪细胞因子水平变化及其临床意义*

目的 研究慢性乙型肝炎（CHB）患者血清脂肪细胞因子水平及其临床意义。方法 2014年11月~2018年4月我院收治的154例CHB患者和同期来我院体检的健康人154例,采用ELISA法检测血清内脏脂肪素、瘦素、脂联素和网膜素水平。所有患者接受肝活检,将肝组织炎症活动度评分为G3或G4者,判定为肝组织严重炎症活动,将肝纤维化S3期和S4期视为严重肝纤维化或肝硬化。结果 CHB患者血清内脏脂肪素、瘦素和脂联素水平健康人比较,差异无统计学意义（P>0.05）,而CHB患者血清网膜素水平为（361.0±132.4） μg/L,显著高于健康人的（300.9±110.5） μg/L（P<0.05）;89例肝组织严重炎症活动与65例轻度炎症活动患者血清内脏脂肪素、瘦素、脂联素和网膜素水平比较差异无统计学意义（P>0.05）;96例肝组织严重纤维化患者与58例轻度纤维化患者血清内脏脂肪素、瘦素和脂联素水平比较差异无统计学意义（P>0.05）,而肝组织严重纤维化患者血清网膜素水平为（397.8±150.4） μg/L,显著高于肝组织轻度纤维化患者的（316.7±118.5） μg/L（P<0.05）。结论 CHB患者血清网膜素水平显著升高,且肝组织严重纤维化患者血清网膜素水平显著升高,或许可以用来帮助评估肝内病变。     

血浆置换联合连续性血浆透析滤过治疗慢加急性肝衰竭患者临床疗效及其对血浆细胞因子水平的影响

目的 研究使用连续性血浆透析滤过（CPDF）和血浆置换（PE）治疗慢加急性肝衰竭（ACLF）患者的临床疗效及其对血浆细胞因子水平的影响。方法 2012年3月~2017年4月西京医院收治的ACLF患者92例,其中46例接受常规护肝和支持治疗,另46例观察组在常规治疗的基础上联合使用CPDF和PE治疗。采用ELISA法检测血清细胞因子水平,采用脂多糖法测定血清内毒素水平,使用L-8800氨基酸自动检测仪测定血清芳香族和支链氨基酸水平。结果 在治疗后,观察组血清凝血酶原时间国际标准化比值（INR）和总胆红素（TBIL）水平显著低于,而血清白蛋白（ALB）水平显著高于对照组（P<0.05）;观察组血清肿瘤坏死因子（TNF-α）、白介素（IL）-6和IL-8水平显著低于对照组[分别为（68.9±43.3） pg/ml对（89.7±39.5） pg/ml、（53.3±39.7） pg/ml 对（69.4±41.2） pg/ml和（271.7±135.4） pg/ml 对 （307.6±147.2） pg/ml,P<0.05];观察组血清内毒素水平为0.2（0.2,0.4） EU/ml,显著低于对照组【1.1（0.8,1.7） EU/mL,P<0.05】,血氨水平为（64.8±19.4） μg/L,显著低于对照组【（80.3±31.1） μg/L,P<0.05】,芳香氨基酸水平为2.1（1.5,2.7） mg/dL,显著低于对照组【（2.3（1.8,2.5） mg/dL,P<0.05】,而支链氨基酸水平为（2.6±0.5）mg/dL,显著高于对照组【（2.1±0.1） mg/dL,P<0.05】;在治疗6个月末,观察组死亡15例（32.6%）,而对照组死亡20例（43.5%,P>0.05）。结论 使用PE联合CPDF治疗ACLF患者能降低血清毒素和细胞因子水平,短期改善肝功能指标,但是否能提高患者生存率,还需要继续研究。     

Hydrogen-rich water protects against acetaminopheninduced hepatotoxicity in mice

AIM: To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water(HRW) in acetaminophen(APAP)-induced liver injury in mice.METHODS: Male mice were randomly divided into the following four groups: normal saline(NS) control group, mice received equivalent volumes of NS intraperitoneally(ip); HRW control group, mice were given HRW(same volume as the NS group); APAP + NS group, mice received NS ip for 3 d(5 mL /kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d(same as NS treatment) after APAP challenge.In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates.In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg.Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury.RESULTS :Treatment with HRW resulted ina significant increase in the 5-d survival rate compared with the APAP + NS treatment group(60% vs 26.67%, P 0.05).HRW could significantly decrease the serum alanine aminotransferase level(24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P 0.01; and3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P 0.05, respectively) and aspartate aminotransferase level(24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group.The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result.Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels.The liver index(5.16% ± 0.26% vs 5.88% ± 0.073%, P 0.05) and percentage of liver necrosis area(27.73% ± 0.58% vs 36.87% ± 0.49%, P 0.01) were significantly lower in the HRW-treated animals.The malonyldialdehyde(MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group(10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P 0.05).A decrease in superoxide dismutase(SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected(9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P 0.05).Furthermore, HRW could significantly increase the glutathione(GSH) contents(878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group.Meanwhile, HRW could reduce the inflammation level(serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P 0.01, respectively).In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502 E expression.Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration.CONCLUSION: HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.     

替比夫定联合阿德福韦酯治疗慢性乙型肝炎患者效果及其对肾功能的影响*

目的 探讨应用替比夫定（LDT）联合阿德福韦酯（ADV）治疗慢性乙型肝炎（CHB）患者的效果及其对肾功能的影响。方法 2014年4月~2016年7月我院诊治的178例CHB患者,其中接受LDT治疗1年以上发生耐药者59例,接受ADV治疗1年以上发生耐药者59例和初始治疗的CHB患者60例,给予LDT联合ADV治疗,观察48 w。检测血清肌酐（Cr）水平,并计算估算的肾小球滤过率（eGFR）的变化。结果 在治疗48 w末,初始治疗患者完全应答率为46.7%,显著高于LDT耐药组的28.8%或ADV耐药组27.1%,差异有统计学意义（P<0.05）;治疗前,三组血清Cr和eGFR水平无统计学差异（P>0.05）,在治疗48 w末,初始联合治疗患者血清Cr水平为（63.2±12.3） μmol/L,显著低于LDT耐药组患者的（71.2±14.3） μmol/L或ADV耐药组的（73.2±14.8） μmol/L（P<0.05）,而eGFR为（111.4±16.1） ml·min^-1·1.73m²,显著高于LDT耐药组的（99.7±13.4）ml·min^-1·1.73m² 或ADV耐药组的（99.3±13.1）ml·min^-1·1.73m²（P<0.05）。结论 对于LDT或ADV治疗耐药的CHB患者采用LDT联合ADV继续治疗有效,或许能改善肾功能损伤,而初始联合治疗也值得进一步观察。     

Serum vitamin D and vitamin-D-binding protein levels in children with chronic hepatitis B

BACKGROUND Vitamin D is an essential fat-soluble secosteroid hydroxylated by the liver to form the intermediate metabolite calcidiol{25-hydroxy vitamin D[25(OH)D]},which is a reliable indicator to investigate individual vitamin D status.Vitamin-D-binding protein(VDBP)is a multifunctional glycoprotein mainly synthesized in the liver and the major transport protein for vitamin D and its metabolites.Serum vitamin D and VDBP are both associated with hepatitis B.However,few studies have reported the relationship and clinical significance of vitamin D and VDBP with hepatitis B virus(HBV)replication and hepatic fibrosis in children with chronic hepatitis B(CHB).AIM To explore vitamin D and VDBP serum levels in children with CHB and the association of vitamin D and VDBP with HBV replication and hepatic fibrosis.METHODS We enrolled 204 children with CHB admitted to Hunan Children’Hospital in summer and autumn between 2018 and 2019 and 170 healthy controls.CHB patients included:164 hepatitis B e antigen(HBeAg)positive and 40 HBeAg negative;193 hepatitis B surface antigen(HBsAg)positive and 11 HBsAg negative;164 with detectable HBV deoxyribonucleic acid(DNA)and 40 with undetectable HBV DNA;131 with HBV genotype B and 23 with HBV genotype C;and 27 without hepatic fibrosis and 97 with hepatic fibrosis.Serum levels of 25(OH)D,VDBP,liver function markers,and other clinical parameters were collected to analyze their association with vitamin D and VDBP.Mann-Whitney U test,Kruskal-Wallis H test,or t test was used to analyze serum 25(OH)D and VDBP levels in different groups.Spearman rank correlation test was utilized to analyze the correlation of 25(OH)D and VDBP with other markers.Statistically significant factors determined by univariate analysis were further analyzed by binary multivariate logistic regression analysis.P<0.05 was considered statistically significant.RESULTS Children with CHB had lower serum 25(OH)D(56.64±17.89 nmoL/L)and VDBP[122.40(70.74-262.84μg/L)]levels than healthy controls had(P<0.001).Serum 25(OH)D and VDBP levels were significantly different among the different grades of hepatic fibrosis(P<0.05).VDBP levels in children with HBV genotype C,HBsAg,HBeAg,and detectable HBV DNA were significantly lower than those in children with HBV genotype B,no HBsAg,no HBeAg,and undetectable HBV DNA(P<0.05).Serum 25(OH)D level was negatively correlated with age and serum total bilirubin level(r=-0.396 and-0.280,respectively,P<0.001).Serum VDBP level was negatively correlated with HBV DNA(log10 IU/mL)(r=-0.272,P<0.001).Serum 25(OH)D level was not correlated with VDBP level(P>0.05).Univariate(P<0.05)and multivariate logistic regression analysis showed that low level of 25(OH)D(odds ratio=0.951,95%confidence interval:0.918-0.985)and high level of HBV DNA(odds ratio=1.445,95%confidence interval:1.163-1.794)were independently correlated with hepatic fibrosis(P<0.01).CONCLUSION Serum levels of 25(OH)D and VDBP are decreased in children with CHB.Serum VDBP level is negatively correlated with HBV replication.Low level of 25(OH)D is independently associated with hepatic fibrosis in children with CHB.There is no significant association between serum levels of 25(OH)D and VDBP.     

慢性乙型肝炎与慢性丙型肝炎患者临床和肝组织病理学特征分析

目的 分析慢性乙型肝炎（CHB）与慢性丙型肝炎（CHC）患者临床特征及肝组织病理学表现的差异。方法 2013年~2017年我院诊治的CHB患者300例和CHC患者100例,收集临床资料并行肝活检组织病理学检查。结果 本组资料显示,CHC患者年龄显著大于【（47.6±12.8）岁对（36.3±9.7）岁】、病程显著长于【（13.1±0.9）年对（6.2±1.8）年】、基础疾病显著多于（39.0%对18.7%）、经血感染显著多于（63.0%对36.7%）、母婴传播显著少于（3.0%对29.7%）、吸毒感染显著多于（40.0%对7.0%）和性传播显著少于（14.0%对26.7%）CHB患者（P<0.05）;CHB患者血清ALT水平为（76.5±10.8） U/L,AST水平为（111.2±21.3） U/L,与CHC患者的【（105.2±20.8） U/L和（98.3±20.1） U/L】比,差异显著（P<0.05）;CHC患者肝组织炎症分级>G2者为83.0%,显著高于CHB患者的48.7%（P<0.05）,而肝纤维化分期>S2者为65.0%,也显著高于CHB患者的28.3%（P<0.05）。结论 CHC患者由于病程长,发病隐匿,肝组织损伤更明显,需要积极的治疗。     

Long-Term Treatment Efficacy and Safety of Clevudine Therapy in Na?ve Patients with Chronic Hepatitis B

Background/Aims

Clevudine (CLV) has potent antiviral activity against chronic hepatitis B (CHB) virus infection. The long-term efficacy and safety of CLV therapy in naïve patients with CHB were investigated.

Methods

In this retrospective study, 152 naïve Korean patients with CHB who received 30 mg of CLV once daily for at least 12 months were investigated.

Results

The cumulative rates at months 12, 24, and 36, respectively, were 65.8%, 74.7%, and 74.7% for undetectable serum hepatitis B virus (HBV) DNA (<12 IU/mL); 77.6%, 86.2%, and 86.2% for normalization of serum alanine aminotransferase (<40 IU/L); 17.6%, 23.5%, and 23.5% for hepatitis B e antigen (HBeAg) loss or seroconversion; and 6.6%, 22.5%, and 30.0% for viral breakthrough. HBeAg positivity (p=0.010), baseline serum HBV DNA level ≥6 log₁₀ IU/mL (p=0.032) and detectable serum HBV DNA (≥12 IU/mL) at week 24 (p=0.023) were independently associated with the development of viral breakthrough. During follow-up, CLV-induced myopathy developed in 5.9% of patients.

Conclusions

The results of long-term CLV therapy for the treatment of naïve patients with CHB showed a high frequency of antiviral resistance and substantial associated myopathy. Therefore, we advise that CLV should not be used as a first-line treatment for naïve patients given the availability of other more potent, safer antiviral agents.     

慢性乙型肝炎患者血清MMP-2和TIMP-2水平及超声检查指标评估肝纤维化分期意义探讨*

目的 探讨超声检查门静脉指标及血清基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制因子-2（TIMP-2）变化在慢性乙型肝炎（CHB）患者肝纤维化分期中的诊断价值。方法 2014年5月~2018年5月我院收治的CHB患者43例和同期健康体检者40例,使用超声B超检查测定门静脉宽度、脾静脉宽度和脾脏厚度,采用ELISA法检测血清MMP-2和TIMP-2水平,采用微孔板单光子计数仪检测血清透明质酸（HA）、层粘连蛋白（LN）、Ⅳ型胶原蛋白（IV-C）和III前胶原氨基端肽（P III P）水平。常规行肝穿刺活检。结果 肝穿组织病理学检查提示,S0~S1患者13例,S2患者11例,S3患者14例和S4患者5例;自S2期到S4期,随着肝纤维化程度的不断加重,患者门静脉宽度、脾静脉宽度和脾脏厚度不断增大,差异具有统计学意义（P<0.05）;S0~1、S2、S3和S4期患者血清MMP-2水平分别为（291.5±35.3） mg/L、（357.7±32.5） mg/L、（446.8±47.1） mg/L和（595.3±85.4） mg/L,血清TIMP-2水平分别为（154.3±28.6） mg/L、（210.7±24.1） mg/L、（255.7±31.9） mg/L和（302.5±74.3） mg/L,均显著高于健康人[分别为（246.5±32.1） mg/L和（126.5±20.1） mg/L,P<0.05];存在显著肝纤维化的CHB患者血清HA、LN、IV-C和P III P水平显著高于健康人（P<0.05）,且随着肝纤维化加重而逐渐升高。结论 超声检测门静脉指标联合血清指标检测将有助于对CHB患者肝纤维化程度的判断,对诊断和治疗疗效的判断可能具有指导意义。     

Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary bypass

Summary

Background and objectives

Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI.

Design, setting, participants, & measurements

A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50% from baseline, within 72 hours postoperatively.

Results

Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P < 0.0005) and was also significantly elevated in non-AKI versus AKI patients at POD 1 (P < 0.0005). Increased log₁₀ hepcidin-25/Cr ratio was strongly associated with avoidance of AKI on univariate analysis. On multivariate analysis, the log₁₀ hepcidin-25/Cr ratio (P < 0.0001) was associated with avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96.

Conclusions

Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1.     

Plasma Cystatin C and Acute Kidney Injury after Cardiopulmonary Bypass

Background and objectives: Little is known about the performance of plasma cystatin C (CysC) in patients undergoing cardiopulmonary bypass (CPB) and its utility in the early diagnosis of acute kidney injury (AKI). In this post hoc analysis, the goal was to determine whether plasma cystatin C, measured 2 hours after the conclusion of CPB, is a reliable marker of AKI.Design, setting, participants, & measurements: Plasma CysC was measured in 150 patients undergoing CPB at the following times: preoperatively, 2 hours after the conclusion of CPB, postoperative day 1, and postoperative day 2. Plasma CysC levels were related to the development of AKI as defined by an increase in serum creatinine of ≥50% or ≥0.3 mg/dl from baseline up to 3 days postoperative. Mixed linear models were used to evaluate the relationship of serial plasma CysC values with AKI. The discriminatory capacity of plasma CysC was estimated using receiver operating characteristic curves. Logistic regression was utilized to assess the adjusted relationship between plasma CysC and subsequent AKI.Results: AKI developed in 47 (31.3%) patients. Plasma CysC was higher at all times among patients who developed AKI compared with those who did not (P < 0.0001). The discriminatory capacity of plasma CysC measured preoperatively and 2 hours after the conclusion of CPB was modest.Conclusions: Serial measures of plasma CysC are highly correlated with the development of AKI. However, the discriminatory capacity of plasma CysC as an early marker of AKI remains limited.Acute kidney injury (AKI) is a common and serious complication of cardiac surgery and cardiopulmonary bypass (CPB) (1,2). Current diagnostic criteria for AKI are based on the presence of relative or absolute increments in serum creatinine (sCr) (3). Although readily available and widely used, sCr is a suboptimal marker of AKI for several reasons: sCr concentration is affected by nonrenal factors (e.g., muscle mass and distribution volume); creatinine is secreted by the renal tubules and serum concentrations do not entirely reflect glomerular filtration; and in the setting of acute injury, elevations in sCr usually do not occur until well after the time of the actual insult. Discovery of an alternative marker that reliably reflects kidney function in the acute setting and enables the early detection of AKI would be very desirable.Cystatin C (CysC) is a 13-kD cysteine protease inhibitor that is synthesized in all nucleated cells at a steady state. It is freely filtered by the glomerulus, not secreted by renal tubules, and completely metabolized at the level of the renal tubules. These properties have made it an attractive marker of the GFR in chronic kidney disease (4,5). However, receipt of glucocorticoids, age, gender, and C-reactive protein are nonrenal factors that may affect the measurement of plasma CysC (6,7). There is a relative paucity of information on the plasma levels of CysC after acute kidney insults such as those associated with CPB. We therefore undertook a three-center cohort study that evaluated the performance of plasma CysC as an early diagnostic marker for AKI as compared with a reference standard based on sCr elevation from baseline. We also assessed the ability of plasma CysC to discern patients with AKI from those without AKI after cardiac surgery requiring CPB.     

Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats

AIM:To evaluate the ameliorative effect of naringenin(NG)during ulcerative colitis(UC)in rats.METHODS:Rats were treated with three different doses(25,50 and 100 mg/kg per day)of NG and a single dose of mesalazine(MES,300 mg/kg per day)for seven days prior to ulcerative colitis induction by4%acetic acid(AA).Twenty four hours after AA rectal administration,animals were scarified and the colonic tissues were dissected.Colonic mucus content was estimated using Alcian blue dye binding technique.In colon tissues,levels of total glutathione sulphadryls(T-GSH),non-protein sulphadryls(NP-SH)and thiobarbituric acid reactive substances(TBARS)were evaluated.The activities of the antioxidant enzymes,catalase(CAT)and superoxide dismutase(SOD)were measured.Concentrations of nucleic acids(DNA and RNA)and total protein were also estimated in colon tissues.Colonic levels of tumor necrosis factor-(TNF-),interleukin-1(IL-1),interleukin-6(IL-6),prostaglandin E2(PGE2)and nitric oxide(NO)were estimated.In cross section of colitis tissue the histopathological changes were observed.RESULTS:Colonic mucus content was decreased in AA compared to controls(587.09±65.59 mg/kg vs941.78±68.41 mg/kg,P<0.001).AA administration markedly reduced T-GSH(5.25±0.37 nmol/L vs 3.04±0.24 nmol/L,P<0.01),NP-SH(3.16±0.04 nmol/L vs 2.16±0.30 nmol/L,P<0.01),CAT(6.77±0.40 U/mg vs 3.04±0.2 U/mg,P<0.01)and SOD(3.10±0.11U/mg vs 1.77±0.18 U/mg,P<0.01)while TBARS,TNF-,IL-1,IL-6,PGE2 and NO levels(15.09±3.84nmol/L vs 59.90±16.34 nmol/L,P<0.01;113.56±1.91 pg/mg vs 134.24±4.77 pg/mg,P<0.01;209.20±36.38 pg/mg vs 422.19±31.47 pg/mg,P<0.01;250.83±25.09 pg/mg vs 638.58±115.9 pg/mg,P<0.01;248.19±36.98 pg/mg vs 541.74±58.34 pg/mg,P<0.01 and 81.26±2.98 mmol/g vs 101.90±10.73 mmol/g,P<0.001)were increased in colon of rats with UC compared controls respectively.Naringenin supplementation,significantly and dose dependently increased the colonic mucus content.The elevated TBARS levels were significantly decreased(39.35±5.86n