肝硬化患者肠黏膜通透性与Child—Pugh分级的相关性研究

目的探讨肝硬化患者肠黏膜通透性（IP）与Child—Pugh分级的相关性及肠道去污剂对肝硬化患者肠道屏障功能及肝功能状态的影响。方法按Child—Pugh分级标准将76例肝硬化患者分为A、B、C3组,并选择30例体检者作为对照组,采用高压液相色谱法检测各组患者尿液乳果糖／甘露醇排出比（L／M）;给予76例肝硬化患者选择性肠道去污剂,比较用药前后各组患者肝功能Child—Pugh分级和肠黏膜通透性。结果肝硬化患者尿乳果N／甘露醇排出比明显高于对照组（0．208±0．025vs0．057±0．019）,肝硬化患者按Child。Pugh分级各组尿乳果糖／甘露醇排出比也均明显高于对照组,差异有显著性（P〈0．01）;采用Spearman等级相关分析发现,肝功能Child—Pu巾评分与乳果糖／甘露醇排出比呈正相关（r=0．658,P〈0．05）;给予肠道去污药物2周后肝硬化Child-Pugh分级各组患者尿液乳果糖／甘露醇排出比与治疗前比较均明显下降（P〈0．05）,各组Child—Pugh评分均有改善。结论肝硬化患者的肠黏膜通透性与肝功能Child—Pugh评分呈正相关,即肠道通透性随肝功能下降而升高,肠黏膜通透性对于肝硬化患者的诊断和治疗有临床意义。     

肝硬化腹水治疗进展

腹水是指超过正常生理范围（200ml）的液体在腹腔内积聚,是肝硬化最常见的并发症之一。腹水的出现预示着肝硬化进入失代偿期,提示预后不良,影响患者的生存质量。约50％代偿期肝硬化患者将在10年内发生腹水,约44%腹水患者于5年内死亡[1]。及时、规范的治疗可以有效提高患者生存率。近年来,国内外对腹水的控制和治疗有了不少被证明有效的新经验。     

肝硬化腹水发病机制研究现状

腹水是肝硬化常见的并发症,也是临床上腹水的常见原因[1,2]。新发肝硬化患者10年内腹水的发生率高达50%～70%,腹水的出现被视为肝硬化病程的一个重要转折点,是肝硬化疾病进展和肝功能失代偿的重要表现。肝硬化患者腹水的发生不但会导致患者生活质量的下降[3],而且与肝硬化的其他并发症如自发性细菌性腹膜炎、肝肾综合征等密切相关。肝硬化腹水还与不良预后相关,1a病死率约为15%,5a病死率则高达44%[4]。对肝硬化腹水发病机制的研究以及新的治疗方法的探索有助于改善患者的生活质量和预后。然而,目前肝硬化腹水发病机制仍未完全阐明。     

Increased intestinal permeability as a predictor of bacterial infections in patients with decompensated liver cirrhosis and hemorrhage

Background and Aim: There have been no trials comparing the prophylactic effect of oral quinolone and intravenous cephalosporin antibiotics and elucidating the predictive factors for the occurrence of bacterial infections in cirrhotic patients with gastrointestinal bleeding in Asian‐Pacific region. Methods: One hundred and thirteen patients with advanced liver cirrhosis and active gastrointestinal hemorrhage were enrolled in our study. The patients were randomly allocated into either the oral ciprofloxacin group (n = 50, 500 mg every 12 h) or the intravenous ceftriaxone group (n = 63, 2.0 g per day for 7 days). Results: Proven or possible infections were significantly more frequent in the patients in the oral ciprofloxacin group (34.0%) than the intravenous ceftriaxone group (14.3%, P = 0.002). The intestinal permeability index (IPI, mean [SD]) measured the day after admission was significantly higher in the patients with proven or possible infections (1.45 [0.96]) compared with the no infection group (0.46 [0.48], P < 0.01). By multivariate analysis, oral ciprofloxacin prophylaxis and higher IPI at the time of inclusion were independent and significant predictors for proven or possible infections. By receiver operating characteristic curve analysis, the best cutoff value of IPI for the prediction of the occurrence of bacterial infection was 0.62%. Conclusions: The frequency of proven or possible infections was significantly lower in the intravenous ceftriaxone group compared with the oral ciprofloxacin group. The IPI measured the day after admission is a good clinical parameter predicting the occurrence of infection in these patients.     

核糖核酸治疗肝硬变重度腹水临床疗效观察

目的：观察核糖核酸（南京新白药业提供）治疗肝硬变重度腹水的疗效。方法：使用注射用核糖核酸治疗肝硬变重度腹水30例，疗程2月，并与综合治疗组对比分析。结果：治疗组症状、体征、肝功能及肝纤维化指标改善优于对照组。结论：核糖核酸治疗肝硬变腹水有良好的保护细胞、抗肝纤维化及促进腹水消退的作用。     

SAAG联合腹水总蛋白水平诊断肝硬化腹水的意义

回顾性调查我院120例肝硬化腹水患者SAAG及腹水总蛋白水平,并以30例结核性腹膜炎、40例癌性腹水作对照。结果发现,以SAAG≥11 g/L且腹水总蛋白〈25 g/L为标准,判断为肝硬化腹水,其准确率为98%,无假阳性,假阴性率为2%;结核性腹膜炎患者中无SAAG≥11 g/L且总蛋白〈25 g/L患者;癌性腹水SAAG≥11 g/L且总蛋白〈25 g/L占2.5%。我们认为,以SAAG≥11 g/L且腹水总蛋白〈25 g/L,可有效判断肝硬化腹水。     

重视肝硬化腹水及其并发症的防治研究

腹水是肝硬化最常见的失代偿期表现,并标志着不良转归。而自发性细菌性腹膜炎（SBP）系致病菌经肠道、血液或淋巴系统引起的腹腔感染,是肝硬化腹水患者的一种常见而严重的并发症,也是导致患者死亡的常见原因。有关其防治一直是临床研究的热点和难点,涉及肝硬化腹水的防治、SBP的防治及白蛋白在肝硬化腹水中的应用等方面。     

益生菌对肝硬化患者肠黏膜通透性的影响

目的:探讨肝硬化门脉高压患者肠黏膜屏障功能及双歧杆菌等三联活菌胶囊(培菲康)对肝硬化患者肠黏膜通透性的影响.方法:选择我院肝硬化门脉高压、肝功能Child-pugh分级为B级的患者34例,随机分为对照组和双歧杆菌等三联活菌胶囊(培菲康)治疗组,两组均给予常规对症治疗,治疗组加用培菲康,每次420 mg,每日3次,口服2 wk.所有患者均于治疗前后测定血清二胺氧化酶(DAO)及内毒素(ETX)含量.另选12例健康体检者作为正常对照组.结果:肝硬化患者治疗组及对照组血清DAO及ETX含量均高于正常对照组,差异有统计学意义(0.2502±0.0969 kU/L,0.2263±0.1145kU/L vs 0.1145±0.0680 kU/L,P<0.01;0.3801±0.1929 EU/mL,0.3283±0.1251 EU/mL vs0.2338±0.0843 EU/mL,均P<0.05);血清DAO及ETX两指标呈线性相关(r=0.800,P<0.01);培菲康组治疗后血清DAO及ETX水平较治疗前下降,差异均有统计学意义(0.1635±0.0592kU/L vs 0.2502±0.0969 kU/L,0.2445±0.1219EU/mL vs 0.3801±0.1929 EU/mL,P<0.05);对照组治疗后血清DAO及ETX水平较治疗前下降,但差异无统计学意义.结论:血清DAO及ETX水平可作为肝硬化Child-pugh分级B级患者肠黏膜屏障功能的监测指标;补充肠道益生菌可帮助改善肠黏膜屏障功能.     

Increased urinary endothelin excretion in patients with liver cirrhosis

The urinary endothelin level in patients with chronic liver disease was determined in order to explore its possible involvement in renal function. The plasma endothelin level was significantly higher in patients with liver cirrhosis (LC) than in those with chronic hepatitis (CH) or in control patients (C). Similarly, urinary endothelin excretion in LC was significantly increased, compared with CH and C. Urinary endothelin demonstrated a significant positive correlation with creatinine clearance. The ratio of endothelin clearance/creatinine clearance did not differ statistically among the three groups. Urinary sodium excretion in LC was positively correlated with plasma endothelin, but not with urinary endothelin. Urinary endothelin excretion demonstrated a significant negative correlation with urinary kallikrein in LC. The present data suggest that increased urinary endothelin excretion in cirrhotic patients primarily depends upon elevated plasma levels of endothelin, but not renal production. Also, a possible link between endothelin and the kallikrein-kinin system in liver cirrhosis is indicated.     

肝硬化腹水和肝性胸水的治疗

腹水和肝性胸水是肝硬化失代偿期的并发症,其产生主要是由于门脉压升高、激活交感神经系统、肾素-血管紧张素-醛固酮系统、血浆胶体渗透压降低等因素有关,肝性胸水还有膈肌破裂形成裂孔等有关。治疗上多采用利尿剂、排放腹腔积液、输注白蛋白、腹水浓缩静脉回输、外科手术,甚至肝移植等综合治疗措施。     

二乙烯三胺戊乙酸(99Tc-DTPA)测定肝硬化大鼠小肠通透性及其临床意义

目的　应用二乙烯三胺戊乙酸 (99Tc-DTPA )测定肝硬化大鼠小肠通透性 ,并探讨其影响因素。方法　肝硬化模型采用CCl4皮下诱导。小肠通透性测定应用 5 μCi99Tc-DTPA溶于 1ml水中灌胃并收集 5h及 2 4h尿待测。通过测定尿排出的99Tc-DTPA比率来反映肠粘膜对DTPA的通透状态 ,尿中排出越多反映肠道的通透性越大。结果　肝硬化腹水大鼠的 5h及 2 4h99Tc-DTPA尿排出率分别为 (8.43± 0 .91) %及 (16.3± 8.9% ) ,明显高于正常大鼠的排出率 ,也高于肝纤维化大鼠的DTPA排出率。吗叮啉组的 5h尿DTPA的排出率高于阿托品组 (P <0 .0 1) ,而 12h尿两组则无差异。结论　肝硬化大鼠99Tc-DTPA尿排出率明显高于正常对照组 ,而肝纤维化大鼠的排出率则与正常组大鼠无差异 ,提示只有严重肝病时小肠通透性才有改变 ,同时也提示 2 4h尿的DTPA排出率不受胃排空及肠转运的影响     

酒精性肝病与肠道通透性

近年研究发现乙醇及其代谢衍生物乙醛,通过改变细胞内信号传导通道,进而破坏上皮细胞紧密连接,增加肠道细胞侧壁对大分子物质的通透性,促进内毒素血症与ALD的发生发展。此文就乙醇及乙醛介导的肠道通透性改变与ALD发生发展的关系作一综述。     

乙型肝炎肝硬化患者肠道菌群变化研究*

目的 分析乙型肝炎肝硬化患者肠道菌群的分布情况及其临床意义。方法 2018年 7月～2019年4月我院收治的乙型肝炎肝硬化患者103例(代偿期肝硬化41例和失代偿期肝硬化62例)和同期健康人群20例,采集粪便,采用Illumina Miseq测序法分析肠道菌群结构差异和物种多样性。结果 在健康人,巨单胞菌属、拟杆菌属和粪杆菌属分别为14.8%、11.4%和9.8%,在代偿期肝硬化组,拟杆菌属、粪杆菌属和巨单胞菌属比例分别为15.2%、11.5%和11.2%,在失代偿期肝硬化组,拟杆菌属、粪杆菌属和韦荣球菌属比例分别为16.9%、9.6%和9.2%;健康人Chao指数为(1250.5±283.7),显著高于代偿期肝硬化组【(1111.5±277.1),P＜0.05】或失代偿期肝硬化组【(910.2±369.6),P＜0.05】,健康人Shannon指数为(3.7±0.6),显著高于代偿期肝硬化组【(3.5±0.1),P＜0.05】或失代偿期肝硬化组【(3.3±0.4),P＜0.05】,健康人Simpson指数为(0.3±0.1),显著高于代偿期肝硬化组【(0.2±0.1),P＜0.05】或失代偿期肝硬化组【(0.1±0.4),P＜0.05】。结论 乙型肝炎肝硬化患者肠道菌群丰度和多样性降低,失代偿期肝硬化患者肠道菌群变化更为明显,即存在随着病情进展肠道菌群多样性减少现象,其临床意义值得探讨。     

肝硬化患者血清可溶性热休克蛋白水平与肠壁通透性的关系研究*

目的 检测肝硬化患者可溶性热休克蛋白（sHSP25和sHSP72）水平,探讨其与肠道通透性的关系。方法 采用ELISA 法检测55例肝硬化患者和19例健康人血浆sHSP25和sHSP72水平。以血二胺氧化酶（DAO）为肠道通透性的评价指标,使用分光光度法检测肝硬化患者血二胺氧化酶水平,采用改良鲎试验法测定肝硬化患者血清内毒素水平。结果 肝硬化患者血sHSP25水平[（205.8±52.2） μg/L]和sHSP72[（190.0±45.2） μg/L]水平显著高于健康人[分别为 （89.1±29.2） μg/L和（65.5±20.2） μg/L,P<0.001];肝硬化患者血内毒素水平显著高于健康人[（0.35±0.11） Eu/ml 对（0.04±0.02） Eu/ml,P<0.001];肝硬化患者血浆sHSP25和sHSP72水平与DAO或内毒素呈正相关（sHSP25：DAO,r2=0.479,P<0.01;内毒素：DAO,r2=0.573,P<0.01;sHSP72：DAO,r2=0.35,P<0.05;内毒素：DAO,r2=0.24,P<0.01）。结论 肝硬化患者血浆sHSP25和sHSP72水平升高,其与肠道通透性有一定的相关性。热休克蛋白表达增加可能为机体对内毒素血症的保护性反应。     

201O年欧洲肝硬化腹水临床实践指南介绍

欧洲肝病研究会(European Association for the Study of the Liver,EASL)肝硬化腹水临床实践指南[1]依据GRADE系统(Grading of Recommendations Assessment Development and Evaluation)将证据按强度分为三个级别:A(高)、B(中)、C(低);推荐分为两个级别:1(强)、2(弱),见表1.     

酒精性肝硬化患者常见血清学指标分析

目的 分析酒精性肝硬化（AC）患者常见临床检测指标的特点。方法 我科自2012年1月～2016年9月收治住院的AC患者103例,其中无腹水患者33例,有腹水患者70例。收集临床常规检测的血清学、血常规和肿瘤标志物结果,采用t检验或Mann-Whitney U检验。结果 AC患者以男性为主,40～60岁为好发年龄;无腹水的AC患者血清PT-S、APTT、TT、INR、D-h分别为（17.5±3.5） s、（33.3±4.6） s、（17.0±1.9） s、（1.3±0.3）和（749.8±1246.9）μg/L,显著低于有腹水的AC患者[分别为（22.3±7.2） s、（39.2±10.5） s、（19.1±4.7） s、（1.7±0.7）和（1330.4±1402.4）μg/L,P<0.05];无腹水组血清ALB、RBC、HGB分别为（35.1±5.2） g/L、（3.6±0.9）×1012/L和（120.7±30.0） g/L,显著高于有腹水组[分别为（30.6±6.2） g/L、（3.0±0.8）×1012/L和（101.7±30.1） g/L,P<0.05];无腹水组血清肿瘤标志物CA125为（93.4±128.4） U/ml,显著低于有腹水组[（468.1±498.4） U/ml,P<0.05]。结论 有无腹水的AC患者血常规、生化和肿瘤标志物可能存在差异,定期对PT-S、APTT、TT、INR、D-h、ALB、RBC、HGB及肿瘤标志物等指标进行检测,或许能帮助监测病情变化。     

Diagnosis and therapy of ascites in liver cirrhosis

Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, ...     

High circulating D-dimers are associated with ascites and hepatocellular carcinoma in liver cirrhosis

AIM： To measure plasma D-dimer levels in cirrhotic patients with and without ascites, assessing the effect of ascites resolution in D-dimer concentration. METHODS： Seventy consecutive cirrhotic patients （M = 44, F = 26, mean age 65 years, SD ± 13）, observed from October 2005 to March 2006 were enrolled. Circulating D-dimer levels were measured using a latex-enhanced, immunoturbidimetric test. In patients with ascites （n = 42） the test was repeated after ascites resolution. RESULTS： Ascites was present in 42 patients （group A） and absent in 28 （group B）. Group A patients had more advanced liver disease. Hepatocellular carcinoma （HCC） was diagnosed in 14 patients and was more frequent in group B. Above normal range D-dimers were found in 45/70 patients. High D-dimers were more frequent in group A than in group B （P = 0.001）. High D-dimers were associated with presence of HCC （P = 0.048） only in group B. After ascites resolution, obtained in all patients, mean D-dimer values decreased in those 34 patients with high basal levels （P = 0.007）, returning to normal in 17. CONCLUSION： In patients with liver cirrhosis, ascites and HCC are the main factors associated with increased fibrinolytic activity.     

病毒性肝炎患者血浆一氧化氮和内皮素水平及意义

各型病毒性肝炎及活动性肝硬化患者共２１３例,采用镉柱还原法及重氮化法检测ＮＯ＾－２／ＮＯ＾－３水平,放免法检测了ＥＴ－１水平。急性肝为,慢性活动型肝炎,肝炎肝硬化等各型肝病患者血清ＮＯ＾－２／ＮＯ＾－３及ＥＴ－１水平均有不同程度的升高,肝炎急性期ＮＯ就有明显升高,慢性肝病ＮＯ与ＥＴ随病情进展水平升高,二者水平良好的相关性。     

Increased intestinal permeability as a risk factor for type 2 diabetes

AimRelationships between the intestinal microbiota, intestinal permeability and inflammation in the context of risk for obesity-associated disease continue to be of interest. The aim of the study was to examine the associations between intestinal permeability and type 2 diabetes (T2D).MethodsA total of 130 individuals with T2D (age: 57.5 ± 6.2 years (mean ± SD); BMI: 30.4 ± 3.2; 45% female) and 161 individuals without T2D (age: 37.4 ± 12.5 years; BMI: 25.1 ± 3.9; 65% female) were included in the study. Assessment of intestinal permeability included measurement of circulating lipopolysaccharide (LPS), LPS-binding protein (LBP) and intestinal fatty acid binding protein (iFABP) concentrations, which were used for calculation of a derived permeability risk score (PRS). Associations between permeability measures and T2D status were assessed using logistic regression models.ResultsLBP (∼34%, P < 0.001), iFABP (∼46%, P < 0.001) and the PRS (∼24% P < 0.001) were all significantly higher in the T2D affected individuals. Individuals with a PRS in the upper tertile were 5.07 times more likely (CI: 1.72–14.95; P = 0.003) to have T2D when models were adjusted for age, sex and BMI. There was a trend towards improved prediction when including the PRS in models containing age, sex and BMI (AUC: 0.954 versus 0.962; P = 0.06).ConclusionThese data demonstrate differences in measures of intestinal permeability between individuals with and without T2D. The utility of using intestinal permeability measures as a tool for predicting T2D risk in at risk individuals should be further investigated.