谷氨酰胺颗粒对重度慢性乙型病毒性肝炎患者肠道通透性、内毒素血症与肝功能的影响

目的: 研究谷氨酰胺颗粒对重度慢性乙型病毒性肝炎患者肠黏膜通透性异常、内毒素血症及肝功能的影响,并探讨其病理生理机制.方法: 60例重度慢性乙型病毒性肝炎患者随机分为对照组和实验组.每组各30例.对照组采用常规护肝,抗病毒治疗,而实验组在对照组治疗方案的基础上加用谷氨酰胺颗粒10 g,tid,疗程为2 wk.于治疗前后采用自动生化分析仪分别测定2组患者的肝功能,包含ALT、AST、TBIL、PT、ALB,胆碱酯酶(CHE) 等;同时于治疗前后采用鲎实验法测定血清内毒素(ET),高效液相色谱蒸发光散射器(HPLCELSD)法测定尿乳果糖和甘露醇排泄率的比值(L/M).并加以比较.结果: 2 wk治疗后,2组患者的肝功能、ET、L /M水平均较治疗前有不同程度的好转( P＜0.05或0.01).与对照组治疗前后ALT、TBIL、CHE、ET、L/M的差值比较,治疗组治疗前后各指标的差值更为显著(281.86±149.34 U vs 199.65±127.09 U,168.65±102.04μmol/L vs 94.13±172.67 μmol/L,-1301.04±662.78 U vs -892.23±861.41 U,0.0198±0.0128 vs 0.0089±0.0228,均P＜0.05).结论: 谷氨酰胺颗粒能够起到保护肠上皮细胞,纠正重度慢性乙型肝炎患者肠黏膜通透性异常,改善肠源性内毒素,加速肝功能恢复的作用.     

慢性肝病患者肠道通透性和炎症因子变化的研究

目的 探讨慢性肝病患者肠黏膜屏障及炎症细胞因子的变化.方法 收集各种慢性肝病患者和正常人的血清,统一采用酶联免疫吸附法和改良分光光度法检测血清D-乳酸(D-Lac)、二胺氧化酶(DAO)、内毒素(ET)、降钙素原(PCT)和肿瘤坏死因子(TNF)水平.结果 各组患者人口学特征无明显差别(P>0.05),从肝炎病毒携带者...     

肝衰竭肠源性内毒素血症的研究进展

肝衰竭的发生和发展与肠源性内毒素血症密切相关,本文从其生物特性、发病机制、诊断及防治等方面对肝衰竭肠源性内毒素血症作一综述。     

Identification of alcoholic liver disease or hidden alcohol abuse in patients with elevated liver enzymes

Abstract. The aim of this prospective study was to identify alcoholic liver disease or covert alcohol abuse in unselected consecutive patients referred to a gastroenterologic out-patient's clinic for elevated liver enzymes. One-hundred-and-thirteen patients were questioned about alcohol consumption, trauma history and loss of driver's licence. Laboratory tests claimed to reflect alcohol consumption and liver biopsy were taken. Using data from patients with the highest (26 patients) and lowest (29 patients) stated consumptions, logistic regression analysis identified violence score (trauma score + driver's licence score) and a laboratory index combining MCV, ASAT/ALAT ratio and IgA values as significant independent predictors of alcohol abuse (index = 2.3 × violence score + 1.08 × laboratory index— 3.19). Twenty-six patients openly admitted alcohol abuse (> 300 g week^?1) and 85% of these had alcoholic liver damage. The index identified a further 12 patients as abusers who stated an intermediate alcohol consumption (25–300 g week^?1). Half of these had alcoholic liver damage. Thus, a total of 34% of the patients were identified as abusers and in one-third of these the abuse was covert.     

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。     

HCV genotypes in patients with liver disease of different stages and severity

Aims/Material: Hepatitis C virus (HCV) genotyping was performed in 213 anti-HCV-positive patients with chronic liver disease ranging from minimal histological changes to hepatocellular carcinoma. One hundred and twenty-two patients had non-cirrhotic chronic active or persistent hepatitis (including 29 who were asymptomatic with persistently normal ALT levels) (chronic liver disease group). The other 91 had hepatocellular carcinoma and, in all but three cases, cirrhosis (hepatocellular carcinoma group).Results: The overall prevalence of HCV variants was: 54.9% type 1b, 37.8% type 2, 2.5% type 1a, 2.0% type 3a, 2.0% type 4a. The genotype distribution showed no relation to the stage (chronic liver disease vs. hepatocellular carcinoma) or severity (chronic active vs. chronic persistent hepatitis) of the liver disease, or to the duration of the disease (<10 years vs. >10 years). Within the hepatocellular carcinoma group, the duration of type-1b disease was similar to that of type-2 infections. Ages at the time of infection and genotype were both independently associated with progression to cirrhosis and hepatocellular carcinoma, but multivariate analysis revealed that the effect of age was much stronger than that of genotype 1b.Conclusions: The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our findings indicate that infections caused by each HCV genotype are capable of progressing to hepatocellular carcinoma.     

Increased pulmonary and intestinal permeability in Crohn''s disease.

We tested the hypothesis that an increased epithelial permeability may affect sites other than the intestine in patients with Crohn's disease by simultaneously evaluating their pulmonary and intestinal permeability. Pulmonary and intestinal permeability were measured by clearance of inhaled technetium-99m diethylene triamine pentacetate (99mTc-DTPA) and by urinary recovery of chromium-51 ethylene diamine tetracetate respectively in 22 patients with Crohn's disease. The half time clearance of 99mTc-DTPA from lung to blood (t1/2LB) was decreased--that is pulmonary permeability increased--in the whole group of patients with Crohn's disease as compared with 13 controls (median 45.5 minutes (8-160) v 85 minutes (34-130) (p less than 0.003)). When analysed separately only patients with active Crohn's disease (n = 15) had a decreased t1/2 lung to blood v controls (42 minutes (8-160) v 85 minutes (34-130) (p less than 0.0025)). Among patients with active Crohn's disease, six were studied again when their disease was quiescent and their t1/2 lung to blood did not differ significantly. The intestinal permeability was increased in the whole group of Crohn's disease patients as compared with 15 controls (5.25% (1.2-24) v 1.7% (0.65-5.75) (p less than 0.0002)). When analysed separately both patients with active and inactive Crohn's disease had increased intestinal permeability v controls (8.1% (1.6-24) and 3.5% (1.2.9.2) v 1.7% (0.65-5.75)) (p less than 0.0001, p = 0.05 respectively). Six patients with active Crohn's disease were studied again when their disease was quiescent and their intestinal permeability decreased significantly p less than 0.04). Pulmonary permeability was increased in patients with Crohn's disease but was not greatly influenced by Crohn's disease activity as opposed to intestinal permeability. The mechanism of this increase is unknown, but may be related in some patients to the presence of an alveolitis.     

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.     

Increased intestinal permeability in rats with graft versus host disease.

BACKGROUND/AIMS: The study of graft versus host disease of the intestine has significant clinical relevance and may also be a model for other immune mediated intestinal diseases. There presently is no simple non-invasive test that can be used to evaluate graft versus host disease induced intestinal injury in humans or animal models. This study tested the hypothesis that graft versus host disease leads to an increase in host bowel permeability as assessed by the relative urinary excretion of orally administered lactulose and rhamnose. METHODS: The urinary excretion ratio of orally administered lactulose and rhamnose was determined daily for two weeks in (Lewis x Brown-Norway) F1 rats with graft versus host disease caused by either the transplantation of parental (Lewis) small bowel or the intraperitoneal injection of parental (Lewis) splenic lymphocytes. RESULTS: Significant twofold to fourfold increases in the lactulose to rhamnose ratio were seen in both small bowel transplant and splenic lymphocyte transfer animals suffering from graft versus host disease during the second postoperative week. This effect occurred sooner in small bowel transplant than in splenic lymphocyte transfer animals (postoperative day 7 versus 11, respectively). The signs of graft versus host disease, including splenomegaly and altered intestinal mucosal architecture, as well as the increased lactulose to rhamnose ratio were significantly attenuated in small bowel transplant animals treated with cyclosporine A (10 mg/kg/day). CONCLUSIONS: Graft versus host disease is associated with an increase in the lactulose to rhamnose clearance ratio reflecting an increase in host bowel permeability. This increase, along with the signs of systemic graft versus host disease, can be significantly ameliorated by cyclosporine A. The lactulose to rhamnose clearance ratio is a non-invasive technique that can be used to assess the intestinal effects of graft versus host disease and the associated increase in intestinal permeability.     

慢性肝病小肠细菌过度生长与内毒素血症

目的观察慢性肝病患者小肠细菌过度生长(SIBO)的情况与内毒素、血小板源生长因子PDGF)水平及血清肝纤维化指标的关系。方法采用乳果糖氢呼气试验(LHBT)检测64例慢性肝病患者SIBO情况,鲎试验检测血浆内毒素,双抗体夹心ELISA检测PDGF,放免法检测透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽氨基末端肽(PⅢNP)、Ⅳ型胶原(Ⅳ.C)水平。分析SIBO与内毒素、血清肝纤维化指标之间的关系。结果64例慢性肝病患者中,LHBT阳性22例(34.4%),慢性肝病伴与不伴SIBO的血浆内毒素为(62±19)和(31±13)pg/ml;PDGF为(211±77)和(136±57)pg/ml;HA为649±189)和(394±210)ng/ml;LN为(139±24)和(110±35)μg/L;Ⅳ.C为(156±41)和(112±51)μg/L;PⅢNP为(32±10)和(21±12)μg/L(P值均<0.01)。慢性肝病患者血浆内毒素水平与PDGF水平呈直线正相关(r=0.803,P<0.01);血浆内毒素、PDGF水平与血清肝纤维化指标呈正相关。结论SIBO是慢性肝病患者出现高内毒素血症的原因之一,其引起的肠源性内毒素血症可能参与促进肝纤维化发生、发展的过程。     

Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor

The cause of Crohn's disease is unknown, although alterations in intestinal permeability may play a primary role. Because we were interested in permeability changes that occur before the onset of intestinal inflammation, we took advantage of the known genetic predisposition to this disease and studied not only patients with Crohn's disease, but their clinically unaffected relatives as well. Intestinal permeability was assessed using the marker polyethylene glycol-400 ingested with a standard meal. We found that 17 normal volunteers absorbed 215 +/- 29.6 mg (mean +/- SE), whereas 11 patients with Crohn's disease absorbed 514 +/- 94.7 mg and their 32 healthy relatives absorbed 566 +/- 62.4 mg. The twofold increase in permeability of patients and their relatives (p less than 0.005 compared with controls) indicates that the intestinal defect in the ability to exclude larger sized molecules is not secondary to clinically recognized intestinal inflammation, but is a primary defect that may be an etiologic factor in this disease.     

Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites

AIM： To determine intestinal permeability, the serum tumor necrosis factor （TNF）-α level and urine nitric oxide （NO） metabolites are altered in liver cirrhosis （LC） with or without ascites. METHODS： Fifty-three patients with LC and 26 healthy control subjects were enrolled in the study. The intestinal permeability value is expressed as the percentage of polyethylene glycol （PEG） 400 and 3350 retrieval in 8-h urine samples as determined by high performance liquid chromatography. Serum TNF-α concentrations and urine NO metabolites were determined using an enzyme-linked immunosorbent assay （ELISA） and Greiss reaction method, respectively. RESULTS： The intestinal permeability index wassignificantly higher in patients with LC with ascites than in healthy control subjects or patients with LC without ascites （0.88 ± 0.12 vs 0.52 ± 0.05 or 0.53 ± 0.03, P 〈 0.05） and correlated with urine nitrite excretion （r = 0.98）. Interestingly, the serum TNF-α concentration was significantly higher in LC without ascites than in control subjects or in LC with ascites （198.9 ± 55.8 pg/mL vs 40.9 ± 12.3 pg/mL or 32.1 ± 13.3 pg/mL, P 〈 0.05）. Urine nitrite excretion was significantly higher in LC with ascites than in the control subjects or in LC without ascites（ 1170.9± 28.7 μmol/L vs 903.1 ± 55.1 μmol/L or 956.7 ± 47.7 μmol/L, P 〈 0.05）. COMCLUSIOM： Increased intestinal macromolecular permeability and NO is probably of importance in the pathophysiology and progression of LC with ascites, but the serum TNF-α concentration was not related to LC with ascites.     

Increased susceptibility to liver disease in relation to alcohol consumption in women

Sex-related differences were prospectively studied in patients with the first presentation of alcoholic liver disease. Among 42 patients the diagnosis was cirrhosis in 8 women and 15 men, alcoholic hepatitis in 4 women and 1 man, steatosis in 6 women and 6 men, and no histologic changes were found in the liver biopsy specimens from 2 men (p greater than 0.1). The median (range) antipyrine clearance was 14.6 (1.0-64) versus 17.2 (3.0-83) ml/min and the clinical score in accordance with the Pugh modification of the Child-Turcotte classification was 8 (5-13) versus 8 (5-11) in the women and men, respectively (p greater than 0.05). In 5 women and only 1 man the antipyrine clearance was less than 5 ml/min, indicating an almost total loss of functional liver mass (p less than 0.05), whereas the Pugh score was above 11 in 6 women, but not in any of the men (p less than 0.05). On an average, the men estimated their total lifetime consumption of alcohol to be 2.1 times greater and the number of days they had consumed more than 5 drinks 2.9 times higher than the women (p less than 0.05). These ratios are reduced to 1.4 and 1.7, respectively (p greater than 0.05), if the female alcohol intake is adjusted to the average male volume of distribution. The results support the concept that women may develop similar, and sometimes even more severe, liver disease after consumption of less alcohol than men. The apparent difference in susceptibility to alcohol may be partly explained by differences in volume of distribution.     

Assessment of liver disease in patients with chronic hepatitis C and unhealthy alcohol use

Hepatitis C virus (HCV) infection and unhealthy alcohol use are major drivers of the burden of liver disease worldwide and commonly co-occur. Assessment of underlying liver damage is a cornerstone of the clinical care of patients with chronic HCV infection and/or unhealthy alcohol use because many of them are diagnosed at advanced stages of disease. Early diagnosis of liver disease before decompensated liver cirrhosis becomes established is essential for treatment with direct acting antivirals and/or abstinence from alcohol consumption, which are the main therapeutic approaches for clinical management. In this review, we discuss current knowledge around the use of non-invasive methods to assess liver disease, such as abdominal ultrasound, controlled attenuation parameter, transient elastography, magnetic resonance imaging, and indices based on serum markers of liver injury.     

Effect of daily ethanol ingestion on intestinal permeability to macromolecules

The effects of regular ethyl alcohol ingestion on morphological and permeability characteristics of the small intestine were assessed in mature rats using the tracer protein, horseradish peroxidase. Thirty adult rats were divided into two groups and provided a standard commercial diet in pellet form. Each morning, after an overnight fast, every animal in the experimental group was administered by gavage an aliquot of 20% ethanol; animals in the control group were provided aliquots of 20% sucrose in water by the same method. After 4 and 8 weeks on the gavage routine (and 10 days and 4 weeks after gavage cessation), jejunal permeability to horseradish peroxidase was examined in animals from each group. Using a routine ligated-loop procedure and light and electron microscopy, ethanol-exposed rats demonstrated increased intestinal permeability to horseradish peroxidase by 4 weeks; sucrose-exposed animals revealed little alteration in mucosal integrity. It is proposed that regular ingestion of sizable amounts of alcohol alters morphological characteristics of the gut and increase the permeability of the mucosa to undigested macromolecules.     

Phagocytosis and production of reactive oxygen species by peripheral blood phagocytes in patients with different stages of alcohol-induced liver disease: effect of acute exposure to low ethanol concentrations

BACKGROUND: In rodents, the development of alcoholic liver disease (ALD) after chronic alcohol feeding was shown to depend on the activity of enzymes that are necessary for production of reactive oxygen species (ROS) in phagocytes. The aim of this study was to determine the formation of ROS by resting and challenged phagocytes of patients with different stages of ALD in the presence of ethanol concentrations commonly found in the blood of alcohol abusers. PATIENTS AND METHODS: The release of ROS and the phagocytosis of bacteria by neutrophils and monocytes obtained from 60 patients, who were categorized in three groups due to the severity of ALD, were compared to that of 28 healthy controls. ROS release by these phagocytes was measured after challenging with endotoxin and the addition of ethanol (22 and 44 mM). RESULTS: Resting neutrophils but not monocytes from patients with severe stages of ALD produced significantly more ROS than those of healthy controls. Basal values of ROS production from neutrophils correlated closely to markers of the severity of ALD. ROS formation was depressed dose-dependently by ethanol in the healthy controls but not in alcohol abusers. CONCLUSIONS: Changes in the ROS metabolism of phagocytes found in this study might contribute to both the development of ALD and the impaired immune response occurring in patients with severe ALD.     

Increased prevalence of intestinal inflammation in patients with liver cirrhosis

lNTRODUCTlONGastr0intestinalsympt0msarecomm0ninpatientswithlivercirrhosisandportalhypertensi0n.Theirpathophysiologyremains,f0rthem0stpart,obscure.Itiswellknownthates0phagealvaricesandportalhypertensiveg.,t,.p.thy[i'2jarec0mmoncausesofuppergastr0intestinal(GI)bleedinginpatientswithlivercirrh0sis.Recently,portalhypertensivecolopathy,suchascolonicvascularectasiaandrectalvarices,wererec0gnizedascausesoflowergastrointestinalbleedingincirrhoticpatients["'J.Otherthanbleeding,variouspathol0gical…     

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.