肝纤维化过程中整合素α5β1动态变化与扶正化瘀方干预作用

目的探讨肝纤维化形成过程中整合素α5β1蛋白的变化特点,及其扶正化瘀方影响该蛋白表达的抗肝纤维化作用机制.方法四氯化碳(CCl4)皮下注射与高脂低蛋白饲料复合建立大鼠肝纤维化模型.135只大鼠分为正常组、模型组与扶正化瘀方药物干预组.模型组又分为2 d、1、2、3、4、5、6周共7个动态观察点.药物组自造模之日起以扶正化瘀方稀释液灌胃,共用药6周.其余大鼠灌以等量生理盐水.天狼猩红染色观察肝组织胶原沉积,盐酸水解法测定肝组织羟脯氨酸含量,Western印迹法分析肝组织纤维连接蛋白(FN)、α5β1与α-平滑肌肌动蛋白(α-SMA)表达量,并分析其相关性.结果随肝纤维化形成,模型组大鼠肝组织FN、α5β1与α-SMA蛋白表达量逐渐上升,早期以FN升高明显,而后以α5β1及α-SMA增加较为显著,三者之间呈明显正相关.与模型组比较,扶正化瘀方预防组大鼠肝脏胶原沉积减轻,肝羟脯氨酸含量下降,FN、α5β1与α-SMA蛋白表达减少.结论CCl4大鼠肝纤维化形成中肝脏整合素α5β1表达逐渐增加,肝损伤早期FN显著上升,并可通过α5β1促进肝星状细胞活化与肝纤维化.扶正化瘀方抑制肝纤维化大鼠肝脏FN与整合素α5β1表达,该作用为扶正化瘀方抗肝纤维化机制之一.     

原发性肝癌和慢性肝病患者血清肝纤维化指标的观察

为了解原发性肝癌和慢性肝病患者血清中肝纤维标志物ＨＡ、ＬＮ、Ⅳ．Ｃ的水平，用放射免疫方法检测１３８例患者血清３项指标的含量，并以２５例健康献血员作对照检查，结果显示；肝癌组与肝硬变组ＩＶ．Ｃ的数比较差异有显著性（Ｐ〈０．０１）；在慢性肝炎轻度组３项指标中Ⅳ．Ｃ的阳性率最高（Ｐ〈０．０１）。提示血清Ⅳ．Ｃ是反映早期肝纤维化的敏感指标，对肝癌与肝硬变的鉴别有一定参考价值。     

黄葵胶囊对慢性肾衰竭模型肾纤维化的影响

目的：本文拟探讨黄葵胶囊对慢性肾衰竭（chronic renal failure,CRF）肾纤维化的影响。方法：采用腺嘌呤制作大鼠慢性肾衰竭模型,本实验分为4组：正常组、模型组、黄葵胶囊组及苯那普利组,治疗4周后分别观察血清肌酐（Scr）、尿素氮（BUN）及血红蛋白（Hb）的改变,以及组织病理学改变。结果：在模型组中Scr及BUN水平明显高于正常组,其肾脏病理改变主要为小管间质纤维化;采用黄葵胶囊治疗后Scr及BUN水平明显降低,Hb改善,与模型组比较有统计学差异（P〈0.05）,且病理改变明显减轻。结论：黄葵胶囊可减轻CRF模型中肾纤维化程度。     

肝络欣丸对酒精性肝纤维化动物肝功能和血清肝纤维化指标的影响

目的:研究肝络欣丸治疗肝纤维化(hepatic fibrosis HF)的效果及部分作用机制.方法:采用酒精诱导HF动物模型.68只大鼠随机分为6组:正常组,模型组,秋水仙碱阳性对照组(简称对照组)、肝络欣丸低、中、高剂量(剂量分别为2.5、5和10g/kg)治疗组.模型组和肝络欣丸治疗组造模4周后,模型组和正常组0.85%氯化钠灌胃,治疗组大鼠予肝络欣治疗,低、中、高剂量组(剂量分别为2.5、5和lOg/kg),灌胃,每日2次,对照组试验时用生理盐水配制成浓度为1.25mg/ml的混悬液使用.实验8周后结束,检测各组大鼠血清丙氨酸氨基转移酶(ALT),天冬氨酸转氨酶(AST),透明质酸(HA),层黏连蛋白(LN),Ⅳ型胶原(1V-C).结果:与正常组比较:模型组大鼠血清ALT、AST、HA、LN、Ⅳ-C水平明显升高(P<0.01);肝络欣丸低、中、高剂量治疗组与对照组均可降低血清ALT、AST水平与模型组比较均有统计学意义(P<0.01).肝络欣丸低、中、高剂量治疗组与对照组均可降低HA、LN、Ⅳ-C水平与模型组比较差异有统计学意义(P<0.01);肝络欣丸低剂量治疗组与模型组比较LN、HA变化无统计学意义(P>0.05).结论:肝络欣丸能有效改善酒精诱导的HF大鼠肝组织损伤程度,可以有效降低模型大鼠血清ALT、AST等酶学指标和HA、LN、Ⅳ-C肝纤维化指标的含量水平.其机制可能是通过保护肝细胞,减轻肝脏炎症,抑制星状细胞活化和胶原合成,减轻肝细胞纤维增生以及肝细胞脂肪样变,促进肝脏代谢和肝细胞再生来实现的.     

慢性乙型肝炎患者肝细胞HBV ccc DNA与血清HBV DNA及肝纤维化程度的相关性

目的探讨慢性乙型肝炎（CHB）患者肝细胞HBV ccc DNA含量与血清HBV DNA、肝组织纤维化程度的相关性及在抗病毒治疗中的临床意义。方法对48例未接受抗病毒治疗CHB患者（A组）和6例经聚乙二醇化干扰素α-2a规律抗病毒治疗48周CHB患者（B组）进行肝组织活检以检测肝纤维化分期,并应用real time-PCR检测肝细胞HBV ccc DNA含量。分析A组患者肝细胞HBV ccc DNA与肝纤维化程度以及两组患者肝细胞HBV ccc DNA与血清HBV DNA相关性,分析B组患者HBV ccc DNA变化。结果肝细胞cccDNA及血清DNA水平均与肝组织纤维化程度呈负相关,但HBV ccc DNA相关性更强（r=-0.465,P=0.008）。肝细胞HBV ccc DNA与血清HBV DNA不存在相关性（r =0.057, P =0.418）。B组患者肝细胞HBV ccc DNA较对照组（自A组中选取性别、年龄及HBV DNA无差异患者共12例）显著下降,其中3例患者血清HBV DNA载量低于检测下限,但肝细胞仍可检出HBV ccc DNA。结论肝细胞HBV ccc DNA与肝纤维程度呈负相关,而血清HBV DNA水平不能反映肝内病毒复制的程度。CHB患者抗病毒治疗需要长期进行才可能完全清除肝细胞内HBV ccc DNA。     

血清补体C3和C4在预测慢性乙型肝炎肝纤维化程度中的价值

目的 探讨血清补体C3和C4预测慢性乙型肝炎肝纤维化程度的价值.方法 选择442例经肝组织病理学检查的慢性乙型肝炎患者.血清补体C3和C4采用Beckman-Coulter Immage 800免疫化学系统及其配套试剂测定.血清补体C3和C4预测肝纤维化程度的评价采用ROC曲线法.结果 血清补体C3和C4预测显著肝纤维...     

Toll样受体7和9基因多态性与慢性丙型肝炎病毒感染的相关性

目的 分析慢性丙型肝炎病毒(HCV)感染与Toll样受体7(TLR7)和Toll样受体9(TLR9)单核苷酸多态性(SNP)的相关性.方法 选择2011年1月至2012年5月武汉大学人民医院150例慢性丙型肝炎(CHC)患者及同期体检的168名健康对照者.采用Sanger测序法检测TLR7IVS2-151(rs179009)基因型,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测TLR9T-1486C(rs187084)基因型.采用SPSS 15.0软件进行统计学分析,对基因型进行Hardy-Weinberg平衡吻合度检验.结果 TLR7 IVS2-151G频率在男性CHC患者中高于对照组男性(41.4％∶21.6％,x2=7.250,P=0.007,OR=0.389,95％ CI:0.194 ～0.781);TLR7 IVS2-151A的频率在女性CHC患者中显著高于对照组女性(76.9％∶63.1％,x2=7.202,P=0.007, OR=1.942,95％ CI:1.192 ～3.164).TLR9 T-1486C (rs187084)位点不同基因型和等位基因在CHC组和健康对照组间的分布频率差异均无统计学意义(P＞0.05).结论 TLR7 IVS2-151 (rs179009)位点与HCV感染存在相关性,其可能参与了CHC的发病.     

广州市慢性丙型肝炎医保策略改变对患者生活质量的影响

目的 研究聚乙二醇干扰素α-2a抗病毒治疗对慢性丙型肝炎患者生活质量的干预作用,并评估广州市慢性丙型肝炎医保策略对患者生活质量的影响.方法 应用生活质量评定问卷(gqoli-74),对102例慢性丙型肝炎患者生活质量进行评估,其中,42例为广州市医保缴费的聚乙二醇干扰素α-2a治疗组,30例为自费聚乙二醇干扰素α-2a治疗组,其余30例未进行干扰素治疗.三组患者均于治疗前、治疗结束时接受测评,每组治疗前后比较采用wilcoxon检验,并用kruskal-wallis检验对三组间的各维度及总分值进行比较.结果 治疗前,三组间躯体功能、心理功能、社会功能、物质生活维度及总分值比较(医保治疗组分别为55.3、58.8、61.9、60.6和58.5;自费治疗组分别为57.5、60.4、61.1、55.2和58.3;未治疗组分别为58.6、60.3、57.5、54.8和56.4),差异无统计学意义(z=-1.177、-0.846、-1.062、-0.377和-1.085,p值均＞0.05).治疗后,医保治疗组各维度(分别为67.1、76.4、68.1、70.1)及总分值(72.6)均高于未治疗组(分别为54.6、54.0、53.3、57.5和54.6,p＜0.01);自费治疗组除物质生活维度外(56.3),其余3个维度(65.1、65.0和69.6)及总分值(64.3)均高于未治疗组(p＜0.05);医保治疗组心理功能、物质生活维度及总分值高于自费治疗组(p＜0.05).结论聚乙二醇干扰素α-2a治疗可以提高慢性丙型肝炎患者生活质量.由广州市医保缴费的聚乙二醇干扰素α-2a治疗组患者生活质量改善水平高于自费治疗组. abstract： objective to investigate the effect of peg-interferon α-2a therapy on the quality of life (qol) of patients with chronic hepatitis c,and to evaluate the effect of healthcare insurance policy in guangzhou city on these patients.methods totally 102 patients with chronic hepatitis c were enrolled.forty-two patients (group a) were treated with peg-interferon α-2a plus ribavirin whose medical expenses were covered by medical insurance; 30 patients (group b ) received the same therapy but at their own expenses ; and the other 30 patients ( group c) were not treated with peg-interferon α-2a.qol of patients in three groups were investigated using the general quality of life inventory questionnaire (gqoli-74) before and after peg-interferon α-2a treatment.wilcoxon test was used to compare on all scales and total scores before and after treatment in each group,and kruskal-wallis test was performed to compare on all scales and total scores among three groups.results before treatment,the physical function,psychological function,social function,material life and total score of group a were 55.3,58.8,61.9,60.6 and 58.5 ; those of group b were 57.5,60.4,61.1,55.2 and 58.3; those of group c were 58.6,60.3,57.5,54.8 and 56.4.there was no statistic difference on all scales and total scores among three groups (z =- 1.177,- 0.846,- 1.062,-0.377 and - 1.085,p ＞ 0.05).after treatment,group a had higher qol on all scales (67.1,76.4,68.1,70.1) and total score (72.6) than group c (54.6,54.0,53.3,57.5 and 54.6,p ＜0.01) ; group b had higher qol (p ＜0.05) on three scales (65.1,65.0 and 69.6) and total score ( 64.3 ) except material life ( 56.3 ) than group c ; group a had higher qol on psychological function,material life and total score than group b ( p ＜ 0.05 ).conclusions qols of chronic hepatitis c patients treated with peg-interferon α-2a are higher than those without peg-interferon α-2a treatment.patients whose medical expenses are covered by medical insurance may have higher qols than those at their own expenses.     

白蛋白和Ⅳ型胶原及脾长径评分系统对慢性乙型肝炎肝纤维化分期的诊断意义

目的从常用的非创伤性指标中筛选出与肝纤维化分期相关的指标,并进一步建立评分系统用于慢性乙型肝炎肝纤维化的诊断。方法收集208例慢性乙型肝炎患者的33项非创伤性指标值,分析这些指标与纤维化分期的关系,筛选与肝纤维化分期相关的指标,继续用Bayes逐步判别并分析筛选出具有判别作用的指标,从中选取代表性较强的指标以建立评分系统用于肝纤维化分期的诊断,并验证此评分系统的敏感性及特异性。结果通过相关分析,共筛选出20项与肝纤维化分期相关的指标,继续用Bayes逐步判别分析并筛选出白蛋白、Ⅳ型胶原及脾长径建立评分系统,取总分4分为诊断截断值,以该评分系统区分S0～2及S3～4纤维化的符合率为70.9%,诊断S3～4纤维化组的灵敏度和特异度分别为69.7%和71.7%。结论白蛋白、Ⅳ型胶原及脾长径3项指标组成的评分系统可以较好地区分S1～2及S3～4肝纤维化,符合率为70.9%。     

慢性丙型肝炎患者血清白细胞介素-8表达水平及抗病毒治疗后变化

目的探讨慢性丙型肝炎患者血清趋化因子白细胞介素-8(IL-8)的表达水平及抗病毒治疗后的动态变化。方法对74例慢性丙型肝炎患者及30例健康对照的血清标本,应用双抗体夹心ABC-ELISA法进行IL-8检测,并观察了36例聚乙二醇化干扰素联合利巴韦林抗病毒治疗12周后血清IL-8水平的变化。结果慢性丙型肝炎患者血清IL-8水平较健康对照组明显升高,分别为(42.95±50.00)pg/ml及(11.06±1.39)pg/ml(t=3.4831,P=0.0007)。抗病毒12周治疗后,26例HCVRNA低于检测下限者的血清IL-8水平较治疗前明显下降,由(41.29±28.65)pg/ml降至(23.15±10.58)pg/ml(t=3.76,P=0.001);10例HCVRNA仍阳性者血清IL-8水平无明显下降,治疗前后水平分别为(43.79±18.60)pg/ml及(42.38±18.00)pg/ml(t=1.04,P=0.32)。结论慢性丙型肝炎患者血清IL-8表达水平显著升高,提示IL-8参与了慢性丙型肝炎的致病过程,干扰素治疗抑制病毒复制,显著降低了血清IL-8的表达水平。     

海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响

目的 观察海昆肾喜胶囊对慢性肾脏病患者血清胱抑素C的影响.方法 20例明确诊断慢性肾脏病患者,在基础治疗上给予海昆肾喜胶囊每天6粒口服,于治疗前和治疗后8周分别检测血清胱抑素C、尿素氮、肌酐的变化.结果 海昆肾喜胶囊可明显降低慢性肾脏病患者的血清胱抑素C水平(P < 0.05);治疗前、后血清胱抑素C、血肌酐比较差异具有统计学意义(P < 0.05).结论 海昆肾喜胶囊可改善早期慢性肾脏病患者的肾功能,早期应用海昆肾喜胶囊有利于延缓慢性肾脏病的进展,具有一定临床意义.     

干扰素治疗慢性丙型肝炎患者所致视网膜病变的特征性分析

目的观察使用干扰素治疗的慢性丙型肝炎（HCV）患者出现视网膜病变的特征。方法接受干扰素治疗后出现视网膜病变的患者共24例纳入研究。所有患者均进行矫正视力、裂隙灯显微镜、散瞳间接检眼镜、眼底彩色照相检查。眼底检查由具有丰富经验的眼底病医生完成。观察所有患者的眼底病变特征。结果本研究24例患者中男性16例,女性8例,男女比例为2：1;年龄21～78岁,平均年龄（48士14）岁。24例患者中有35只眼眼底异常,双眼发病13例,单眼发病11例。12例患者使用后出现视物模糊。眼底检查中：35只患眼中17例23只眼,占患眼的65．7％;眼底表现为单纯棉绒斑,单纯视网膜出血2例2只眼,占忠眼的5．7％;棉绒斑合并视网膜出血8例10只眼,占患眼的28．6％。棉绒斑及出血多位于视盘旁颞上或颞下血管附近,少数可散布于全后极部血管旁;其出血部位多位于棉绒斑旁,表现为后极部火焰状、点状出血或Roth斑。结论干扰素所致眼底视网膜病变最常见的特征为棉绒斑,使用后建议定期随访。     

慢性乙型病毒性肝炎肝纤维化无创性血清诊断指标研究进展

我国乙型肝炎病毒（HBV）感染相关的肝硬化和肝细胞肝癌是引起肝病患者死亡的主要原因。有效的抗病毒治疗能够延缓患者肝纤维化的进展,肝纤维化分期对治疗方案的制定至关重要。肝组织活检仍是诊断肝纤维化的金标准,但其为有创性操作,应用受限。用可靠的无创性血清标志物来评估肝纤维化程度能降低肝组织活检的需求,本文就无创性血清标志物作一综述。     

Treatment of chronic hepatitis C in Europe

The lifetime cumulative risk of developing cirrhosis and hepatocellular carcinoma is the rationale for treating patients with chronic hepatitis C with antivirals. The standard treatment is combination therapy with interferon-alfa and ribavirin. In patients with high transaminases and histologic signs of chronic hepatitis, 6- to 12-month therapy with 3 mega units (MU) interferon-alfa thrice weekly, combined with ribavirin, yielded up to 30% sustained responders, and this was increased to 50% with pegylated interferon combined with ribavirin. Favorable predictors of response to the former treatment were genotype 2 or 3, less than 2 million copies of hepatitis C virus (HCV), no portal fibrosis at biopsy, age less than 40 years, and female sex. The same was true for the latter treatment; however, with body weight less than 82kg replacing female sex. A 98% cure of community-acquired acute hepatitis C was achieved with early treatment with daily doses of 5MU interferon, compared with a calculated 30% HCV-RNA clearance in untreated patients. More cost-effective strategies for ceasing treatment, based upon early clearance of HCV, are under investigation, with cutoff equal to or more than a 2log decrease in serum HCV-RNA at week 12. This approach has 100% negative predictive value and 80% positive predictive value. Treatment can also be optimized by combination retreatment of relapsers and nonresponders to monotherapy, which yielded sustained responses of 50% and 25%, respectively. There are difficult-to-treat patients who have high viremia, genotype 1 and 4, or coinfection with HIV or HBV, or carry an organ graft, and those who did not respond to combination therapy. Extended treatment of the latter patients with pegylated interferon might slow down the progression of fibrosis.     

慢性丙型肝炎合并2型糖尿病患者基因型特征分析

目的：了解慢性丙型肝炎并2型糖尿病患者基因型及相应的临床特征。方法检测88例慢性丙型肝炎并2型糖尿病患者与770例慢性丙型肝炎患者基因分型,分析88例慢性丙型肝炎并2型糖尿病患者的糖化血红蛋白、空腹血糖、空腹胰岛素、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、γ-谷氨酰转肽酶（GGT）、总胆红素（TBil）、HCV RNA病毒载量及血甘油三酯等临床相关指标,并调查患者糖尿病确诊时间及抗病毒治疗情况。结果慢性丙型肝炎并2型糖尿病患者3a基因型占11.36%（10/88）,高于未合并2型糖尿病者3a基因型3.38%（26/770）,差异具有统计学意义（χ2=7.248,P=0.002）;并2型糖尿病的3a基因型患者的甘油三酯高于其他基因型（t=2.271,P =0.028）;糖尿病诊断时间多在抗病毒治疗前,部分患者控制血糖同时抗病毒治疗。结论感染丙型肝炎病毒3a基因型的患者更易并2型糖尿病,应监测血糖情况,尽早筛查糖尿病,早期诊治。     

慢性丙型肝炎干扰素个体化治疗的临床观察

目的：观察不能耐受标准剂量干扰素治疗方案的部分丙型肝炎患者干扰素个体化给药的疗效,探索不同剂量干扰素治疗丙型肝炎的方法。方法收集多种原因不能耐受标准剂量干扰素治疗方案的丙型肝炎患者共28例,给予个体化低剂量干扰素（普通干扰素0.8～3 MIU/d,隔日1次）联合利巴韦林0.6～0.9 g/d治疗,疗程48周。结果89.29%（25/28）患者可耐受低剂量干扰素联合利巴韦林长期治疗。不同时间节点的病毒学应答率为：4周病毒学应答率（RVR）为7.04%,12周病毒学应答率（EVR）为17.85%、24周病毒学应答率53.85%、48周病毒学应答率为60.00%。停药后24周病毒学应答率（SVR）为48.00%。结论抗丙型肝炎病毒治疗可以改善肝功能,从而提高患者对高效抗逆转录病毒治疗的耐受性。     

阿德福韦酯对慢性乙型肝炎患者血清cccDNA的影响

目的探讨阿德福韦酯对慢性乙型肝炎患者血清HBVCCCDNA的影响。方法40例慢性乙型肝炎患者，按1：1随机分配接受阿德福韦酯或安慰剂治疗，所有患者均治疗52周并在停药后随访52周；应用实时荧光定量聚合酶链反应技术检测慢性乙型肝炎患者0周、26周、52周、78周、104周血清HBVCCCDNA及HBVDNA含量。结果治疗组20例患者治疗前（0周）血清HBVCCCDNA中位数水平为8．29×10^6拷贝／ml（与对照组相比P〉0．05）；接受阿德福韦酯治疗半年（26周）及1年（52周）血清HBVCCCDNA中位数水平分别为2．61×10^4拷贝／ml、7．78×10^3拷贝／ml（与治疗前相比两者P〈0．05），停药半年（78周）及1年（104周）血清HBVCCCDNA中位数水平分别为3．38×10^4拷贝／ml、3．60×10^4拷贝／ml（与治疗前相比两者P〈0．05）；接受阿德福韦酯治疗半年及1年血清HBVCCCDNA分别下降2．502log10、3．028log10（与对照组相比两者P〈0．05），停药半年及1年血清HBVCCCDNA较停药时上升0．638log10、0．665log10（与对照组相比两者P〈0．05）。结论阿德福韦酯对血清HBVCCCDNA有明显抑制作用；血清HBVCCCDNA可作为阿德福韦酯抗病毒治疗的重要监测指标。     

Long-term results of treatment of chronic hepatitis B, C and D with interferon-α in renal allograft recipients

Abstract The aim of this study was to evaluate the efficacy and safety of interferon-a (IFN-α) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-α three times weekly for 6 months. After IFN-α therapy, 18 patients (43 %) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-α therapy. Repeated liver biopsy was performed in 16 patients after 6–24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-α therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-α therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0–84 months). IFN-α seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.