核苷类药物治疗乙型肝炎肝硬化患者IL-6、TNF-α及TGF-β1的变化研究

目的 观察乙型肝炎（乙肝,HBV）相关失代偿期肝硬化患者接受核苷类药物治疗后细胞因子白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、转化生长因子β1（TGF-β1）水平的变化及意义.方法 应用ELISA法对52例HBV相关失代偿期肝硬化患者进行血清IL-6、TNF-α及TGF-β1的水平含量进行测定,并与28例健康对照组进行比较;对接受核苷类药物抗病毒治疗患者与未接受抗病毒治疗的患者以上细胞因子的变化进行比较.结果 HBV相关失代偿期肝硬化患者血清IL-6、TNF-α及TGF-β1的含量显著高于健康对照组（P〈0.01）,接受核苷类药物抗病毒治疗1年后,抗病毒治疗组的细胞因子水平较治疗前明显降低（P〈0.01）,且优于未抗病毒治疗组（P〈0.05）.结论 HBV相关失代偿期肝硬化患者血清IL-6、TNF-α及TGF-β1的含量变化对了解核苷类药物抗病毒治疗临床疗效及明确机体免疫状态有重要意义.     

肝炎肝硬化患者血清内毒素和肿瘤坏死因子-α水平检测意义

目的探讨肝炎肝硬化患者血清内毒素（LPS）、肿瘤坏死因子-α（TNF-α）水平的检测意义。方法选择46例肝炎肝硬化患者,分为代偿组、失代偿组;22例轻度慢性肝炎患者作为对照组。采用鲎试验定量检测血浆LPS,双抗体夹心ELISA法检测TNF-α。结果对照组、肝硬化代偿组,失代偿组血清LPS与TNF-α依次明显升高。3组之间差异有统计学意义（P〈0．01或P〈0．05）。结论肝硬化失代偿期患者肠道内内毒素生成和吸收增多,其血清LPS、TNF-α生成和吸收增多,细菌易位的发生率增加,可促使病情进一步加重。     

乙型肝炎肝硬化并发腹膜炎患者血清及腹腔积液TNF-α、IL-8、IL-18水平临床意义的探讨

目的：探讨乙型肝炎肝硬化并发自发性腹膜炎（SBP）患者血清和腹腔积液中肿瘤坏死因子（TNF-α）、白细胞介素-8（IL-8）、白细胞介素-18（IL-18）的水平,及其在疾病发生发展中的作用。方法：应用双单克隆抗体夹心法酶联免疫吸附测定（ELISA）法检测48例乙型肝炎肝硬化并发腹腔积液患者血清和腹腔积液中TNF-α、IL-8、IL-18的水平,其中肝炎肝硬化并发SBP患者24例,肝硬化腹腔积液未合并自发性腹膜炎患者24例,并与24例正常人比较。结果：乙型肝炎肝硬化合并SBP患者的血清和腹腔积液中的TNF-α、IL-8、IL-18的水平明显高于未合并SBP者及对照组,未合并SBP者亦明显高于对照组（P〈0.05）。结论：乙型肝炎后肝硬化并发SBP患者血清和腹腔积液中的TNF-α、IL-8、IL-18明显升高,TNF-α、IL-8、IL-18参与了肝硬化腹腔积液并发SBP的发生与发展,检测乙型肝炎后肝硬化自发性腹膜炎患者血清及腹腔积液的TNF-α、IL-8、IL-18水平对SBP的早期诊断有重要的临床意义。     

肝炎后肝硬化血清TNF-α、IL-6和IL-8检测的临床意义

目的探讨肝炎后肝硬化患者血清TNF-α、IL-6和IL-8的临床意义。方法 85例肝炎后肝硬化患者采用ELISA双抗体夹心法检测血清TNF-α、IL-6及IL-8水平,根据Child分级分为A(35例)、B(30例)、C(20例)3组,并与正常组(56例)相对照。结果肝炎后肝硬化组血清TNF-α、IL-6和IL-8水平较正常组明显升高(P<0.01),A、B、C三组各项指标比较差异显著(P<0.01)。结论血清TNF-α、IL-6和IL-8水平是反映肝炎后肝硬化肝功损害程度及判断病情预后的重要指标。     

肝炎后肝硬化患者血清血管活性物质及细胞因子测定的临床意义

目的:探讨肝炎后肝硬化血浆活性物质ET-1、CGRP和血清TNF-α、IL-8的联合检测在肝炎后肝硬化诊断中的应用价值.方法:87例肝炎后肝硬化患者,根据Child Pugh分级分为A级27例,B级29例,C级31例.采用放射免疫(RIA)方法联合检测ET-1、CCRP、TNF-α和IL-8水平,并与40例健康组相对照.结果:肝炎后肝硬化组ET-1、CGRP、TNF-α、和IL-8水平较健康组明显升高(均P＜0.01),且A、B、C三级中ET-1、CCRP、TNF-α和IL-8水平比较差异有极显著性(均P＜0.01)C级＞B级＞A级.结论:联合检测ET-1、CGRP、TNF-α和IL-8水平对估测肝硬化肝脏损害程度及预后判断具有十分重要的临床价值.     

肝硬化患者血清HA、PCⅢ水平与部分肝功能指标的关系研究

目的 探讨肝硬化患者血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)水平与部分肝功能指标的关系。方法 检测81例乙肝后肝硬化患者血清HA、PCⅢ水平及部分肝功能指标(ALT、AST、TBIL、DBIL、ALB、GLO)。结果 失代偿期肝硬化组血清HA含量明显高于代偿期肝硬化组；而失代偿期肝硬化组血清PCⅢ与代偿期肝硬化组无明显差异。失代偿期肝硬化组血清TBIL、DBIL明显高于代偿期肝硬化组。失代偿期肝硬化组血清ALB明显低于代偿期肝硬化组。失代偿期肝硬化组血清ALT、AST、GLO与代偿期肝硬化组之间无明显差异。血清HA与血清TBIL、DBIL、AST呈正相关，与血清ALB呈负相关；血清PCⅢ与血清TBIL、DBIL呈正相关，与血清GLO呈正相关。结论 肝硬化患者血清纤维化指标血清HA与血清TBIL、DBIL、AST呈正相关，与血清ALB呈负相关；血清PCⅢ与血清TBIL、DBIL、GLO呈正相关。     

肺癌患者血清IL-6、IL-8及TNF-α的表达及临床意义

目的 研究肺癌患者血清白介素-6(IL-6)、IL-8及肿瘤坏死因子-α(TNF-α)的表达,并探讨其在肺癌发病中的作用.方法 用ELISA法检测45例肺癌患者血清IL-6、IL-8及TNF-α的水平,并与30例健康人做比较.结果 肺癌患者血清中IL-6、IL-8及TNF-α的表达水平明显高于健康对照组(P＜0.01),肺癌患者血清中IL-6、IL-8及TNF-α的表达水平随着临床分期的进展而升高.结论 IL-6、IL-8及TNF-α参与了肺癌的发生、发展,检测其血清含量对了解肺癌患者体内免疫状态和预后判断有重要意义.     

肝硬化患者血IL-1β、TNF-α及尿crosslaps水平与骨密度关系

目的探讨血清IL-1β、TNF-α及尿Crosslaps变化对肝硬化患者骨密度变化的影响。方法测定46例肝硬化患者血清IL-1β、TNF-α及尿Crosslaps水平及骨密度,并与25例健康者对照。结果 :肝硬化组血清IL-1β、TNF-α及尿Crosslaps水平显著升高(P<0.05),骨质疏松组(OP)较非骨质疏松(NOP)升高更显著(P<0.05),OP组IL-1β、TNF-α及尿Crosslaps水平与骨密度呈负相关。结论 IL-1β、TNF-α及尿Crosslaps水平升高导致骨吸收增强,参与了肝性骨病的发生,降低体内IL-1β、TNF-α及尿Crosslaps水平对HBD防治有一定作用。     

原发性高血压病患者血清细胞因子水平变化及贝那普利对其影响的意义分析

目的探讨原发性高血压病患者细胞因子IL-8、TNF-α及IL-10的变化及临床意义。方法采用酶联免疫吸附法（ELISA法）检测52例原发性高血压病患者及30例正常人血清细胞因子水平并进行比较。结果与正常对照组相比,原发性高血压病患者血清IL-8及TNF-α水平明显升高（P〈0.01）,IL-10明显降低（P〈0.01）;贝那普利治疗后患者血清IL-8和TNF-α水平明显下降（P〈0.01）,血清IL-10明显升高（P〈0.01）。结论原发性高血压患者血清细胞因子水平出现明显变化,并在疾病的发生发展过程中起重要作用。     

血清IL-8、TNF-α在AECOPD机械通气中的变化及意义

目的探讨IL-8、TNF-α在COPD急性加重期患者机械通气过程中的变化及临床意义。方法 43例COPD急性加重期机械通气患者经治疗后分为顺利脱机组、脱机困难组,分别检测治疗前后血清IL-8、TNF-α浓度并进行比较分析。结果顺利脱机组血清IL-8、TNF-α浓度较COPD急性发作期明显下降。脱机困难组血清IL-8、TNF-α浓度较COPD急性发作期明显上升。结论检测COPD急性加重期患者血清IL-8、TNF-α水平能够间接反映AECOPD机械通气患者病情的严重程度及转归情况,为监测AECOPD患者肺部感染疗效提供新的临床指标。     

ENDOGENOUS NITRIC OXIDE PRODUCTION IS AUGMENTED AS THE SEVERITY ADVANCES IN PATIENTS WITH LIVER CIRRHOSIS

• 1 Since endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitrous ions, we measured the serum nitrate ion (NO₃^?) and the amount of urinary excretions of NO₃^? as an index for endogenous NO to ascertain whether NO formation is augmented in patients with chronic liver diseases.
• 2 Using inpatients suffering from chronic liver diseases, serum levels and urinary excretions of NO₃^? were measured by using high-performance liquid chromatography with an anion exchange column.
• 3 Among the four patient groups of normal controls, and those with chronic liver diseases such as chronic active hepatitis, compensated cirrhosis, and decompensated cirrhosis the serum level of NO₃^? showed the highest level in a patient group with decompensated cirrhosis. The amount of urinary excretion of NO₃^? was significantly increased in both groups of patients with liver cirrhosis compared with the control group and patients with chronic active hepatitis. Patients with chronic active hepatitis did not show any difference between the normal control group. The amount of urinary excretion of NO₃^? correlated significantly and negatively with the level of serum albumin (P<0.05) and counts of platelets (P< 0.01) in patients with compensated cirrhosis.
• 4 These findings suggest that the production of endogenous NO is augmented in patients with liver cirrhosis, particularly in a decompensated subgroup. Increases in the production of endogenous NO correspond to the progress of liver cirrhosis, but not in patients with chronic hepatitis.

     

Entecavir: a review of its use in the treatment of chronic hepatitis B in patients with decompensated liver disease

The oral deoxyguanosine nucleoside analogue entecavir (Baraclude?) has potent activity against hepatitis B virus (HBV) and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of entecavir in the treatment of chronic hepatitis B in patients with decompensated liver disease, as well as summarizing its pharmacological properties. Entecavir 1?mg/day was more effective than adefovir dipivoxil 10?mg/day in the treatment of patients with chronic hepatitis B and decompensated liver disease, according to the results of a randomized, open-label, multicentre trial. Patients were either nucleos(t)ide naive or lamivudine experienced. The reduction from baseline in HBV DNA levels at week 24 (primary endpoint) was significantly greater with entecavir than with adefovir dipivoxil. The proportion of patients with HBV DNA levels of <300 copies/mL was also significantly greater with entecavir than with adefovir dipivoxil at weeks 24, 48 and 96, as was the proportion of patients with ALT normalization. Entecavir 0.5 or 1?mg/day, tenofovir disoproxil fumarate 300?mg/day and a fixed-dose combination of emtricitabine/tenofovir disoproxil fumarate 200?mg/300?mg per day were effective in the treatment of chronic hepatitis B in patients with decompensated liver disease, according to the 48-week analysis of a randomized, double-blind, multicentre trial, primarily designed to examine tolerability endpoints. In this trial, over one-third of patients had received previous therapy with lamivudine for ≥6 months. The efficacy of entecavir in treatment-naive patients with HBV-related decompensated cirrhosis did not significantly differ from that seen in patients with chronic hepatitis B or compensated cirrhosis (compensated group), according to the results of a prospective, nonrandomized study. After 6 or 12 months of entecavir treatment, there were no significant differences between the decompensated and compensated groups in virological, biochemical or serological endpoints. In patients with decompensated cirrhosis, significant improvements from baseline in liver function were seen after 12 months of entecavir therapy. Oral entecavir was generally well tolerated in patients with chronic hepatitis B and decompensated liver disease, with most of the reported treatment-emergent adverse events consistent with decompensated liver disease. In the trial primarily designed to examine tolerability endpoints, there was no significant difference between patients receiving entecavir and those receiving tenofovir disoproxil fumarate with or without emtricitabine in terms of the proportion of patients experiencing tolerability failure or the proportion of patients with confirmed increases in serum creatinine levels of ≥0.5?mg/dL above baseline or confirmed serum phosphorus levels of <2.0?mg/dL at week 48 (co-primary endpoints). It has been suggested that the risk of lactic acidosis associated with oral nucleos(t)ide analogue therapy is increased in patients with highly impaired liver function. However, only one case of lactic acidosis was reported among entecavir recipients across two clinical trials in patients with chronic hepatitis B and decompensated liver disease. Moreover, small studies found that the risk of lactic acidosis was not increased in patients with chronic hepatitis B and decompensated liver disease who received entecavir, compared with patients with non-HBV decompensated liver disease. In conclusion, entecavir is a valuable agent for the first-line treatment of chronic hepatitis B in patients with decompensated liver disease.     

拉米夫定联合阿德福韦酯治疗失代偿期乙型肝炎肝硬化临床疗效观察

目的：观察拉米夫定联合阿德福韦酯治疗乙型肝炎肝硬化患者的临床疗效。方法：53例失代偿期乙型肝炎肝硬化患者在保肝、利尿和补充白蛋白等基础治疗的同时,给予拉米夫定100mg,1次/d口服,3个月后,加用阿德福韦酯10mg,1次/d口服,疗程48周。治疗结束时,观察血清ALT、HBVDNA及Child-Pugh评分变化。结果：治疗后HBVDNA阴转率为90.2%,肝功能指标即血清ALT水平及Child-Pugh评分明显改善。结论：拉米夫定联合阿德福韦酯治疗能明显改善乙型肝炎肝硬化患者的肝功能指标,不易产生耐药性,改善预后。     

肝病患者血液流变学分析

目的　探讨多种肝病患者血液流变学的改变及其不同时期内机体微循环的变化。方法　检测 90例慢性肝病患者血液流变学指标、肝功能、乙型肝炎 (乙肝 )DNA、输血传播病毒 (TTVDNA) ,并做出相关分析。结果　乙型肝炎组与正常对照组比较 :全血低切粘度、红细胞聚集指数均有明显升高 (P <0 .0 5 ) ;乙肝HBVDNA与血液流变学指标间差别无显著性 (P >0 .0 5 ) ;肝硬化组与正常对照组比较 :失代偿期组红细胞压积、全血高切粘度、全血低切粘度明显降低 (P <0 .0 5 ) ;代偿期组全血低切粘度、血浆粘度、红细胞聚集指数明显升高(P <0 .0 5 ) ;TTV阳性组与正常对照组 :全血高切粘度、全血低切粘度明显升高 (P <0 .0 5 )。结论　乙肝患者体内有微循环障碍 ,肝硬化患者代偿期机体内呈高凝状态 ,失代偿期呈低凝状态。TTV阳性患者体内有微循环障碍 ,TTV对机体有一定的致病作用。血液流变学应作为肝病患者检查的指标。     

阿德福韦酯联合安络化纤丸治疗慢性乙肝失代偿期肝硬化疗效观察

目的研究阿德福韦酯联合安络化纤丸对慢性乙型肝炎引起的失代偿期肝硬化抗病毒及抗纤维化治疗的效果。方法50例患者按1：1的比例随机分配到治疗组及对照组,两组均给予支持治疗,治疗组加用阿德福韦酯和安络化纤丸口服,疗程52周。结果治疗52周末Child-Pugll评分治疗组由10．4±2．3下降为6．2±2．4,对照组由10．3±2．2上升为10．6±1．9,t=7．042 P〈0．01;HBVDNA转阴率比较,治疗组58．33％,对照组8．33％,Х^2=13．5,P〈0．01;均存在差异且有统计学意义。结论阿德福韦酯联合安络化纤丸对慢性乙型肝炎引起的失代偿期肝硬化能显著地控制病毒复制,改善肝功能,降低Child-Pugh评分。     

恩替卡韦治疗代偿期乙型肝炎肝硬化的疗效与安全性观察

目的观察恩替卡韦治疗代偿期乙型肝炎肝硬化患者的疗效与安全性。方法 60例乙型肝炎肝硬化代偿期患者接受恩替卡韦治疗72周,观察患者生化学指标、病毒学指标和组织学指标的变化情况。结果所有患者均没有发展到失代偿期,生化学指标、病毒学指标和组织学指标均有明显改善,差异有统计学意义(P<0.05)。结论代偿期乙型肝炎肝硬化患者选用恩替卡韦有良好的疗效及安全性。     

HBV慢性肝病尿酶活性检测的临床意义

目的探讨尿酶(LAP、NAG、GPDA)水平对HBV慢性肝病的临床意义。方法①将研究对象分为慢性肝炎组、代偿期肝炎肝硬化组、失代偿期肝炎肝硬化组以及正常对照组,测定其晨尿中LAP、NAG、GPDA水平的变化,分析各组间LAP、NAG、GPDA活性的差异;②根据肝功损害程度将所有研究对象分为轻度、中度和重度三组,比较三组间尿LAP、NAG、GPDA水平的差异;③根据HBV DNA复制的水平,将所有研究对象分为低度和高度复制两组,分析两组间尿LAP、NAG、GPDA水平的变化。结果①代偿期及失代偿期肝硬化尿NAG、LAP和GPDA水平均明显高于正常对照组及慢性肝炎组(P<0.05和P<0.01),肝硬化失代偿期尿NAG、LAP和GPDA水平均明显高于代偿期(P<0.05);②肝功损害程度与尿NAG、LAP和GPDA活性呈正相关(P<0.05和P<0.01);③HB VDNA高度复制组和低度复制组两组比较,尿NAG、LAP和GPDA水平无显著性差异(P>0.05)。结论尿LAP、NAG、GPDA活性测定可较灵敏地反映HBV慢性肝病出现的早期肾脏损害,并可间接判断慢性肝病肝功能的损害程度;尿酶(NAG、LAP和GPDA)活性与HBV DNA复制水平无明显相关性。