Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis

OBJECTIVES: The significance of small intestinal bacterial overgrowth in patients with cirrhosis is not fully understood and its diagnostic criteria are not uniform. We examined the association of small intestinal bacterial overgrowth with spontaneous bacterial peritonitis and compared various microbiological criteria. METHODS: Jejunal secretions from 70 patients with cirrhosis were cultivated quantitatively and classified according to various definitions. Clinical characteristics of patients were evaluated and the incidence of spontaneous bacterial peritonitis was monitored during a 1-yr follow-up. RESULTS: Small intestinal bacterial overgrowth, defined as > or = 10(5) total colony-forming units/ml jejunal secretions, was present in 61% of patients. Small intestinal bacterial overgrowth was associated with acid-suppressive therapy (p = 0.01) and hypochlorhydria (p < 0.001). Twenty-nine patients with persistent ascites were observed. Six episodes of spontaneous bacterial peritonitis occurred after an average 12.8 wk. Occurence of spontaneous bacterial peritonitis correlated with ascitic fluid protein concentration (p = 0.01) and serum bilirubin (p = 0.04) but not with small intestinal bacterial overgrowth (p = 0.39). Its association with acid-suppressive therapy was of borderline significance (hazard ratio = 7.0, p = 0.08). CONCLUSIONS: Small intestinal bacterial overgrowth in cirrhotic patients is associated with acid-suppressive therapy and hypochlorhydria, but not with spontaneous bacterial peritonitis. The potential role of acid-suppressive therapy in the pathogenesis of spontaneous bacterial peritonitis merits further studies.     

Diagnosis of small intestinal bacterial overgrowth in patients with cirrhosis of the liver: poor performance of the glucose breath hydrogen test

BACKGROUND/AIMS: Small intestinal bacterial overgrowth is known to occur in association with cirrhosis of the liver and studies are needed to assess its pathophysiological role. The glucose breath hydrogen test as an indirect test for small intestinal bacterial overgrowth has been applied to patients with cirrhosis but has not yet been validated against quantitative culture of jejunal secretion in this particular patient population. METHODS: Forty patients with cirrhosis underwent glucose breath hydrogen test and jejunoscopy. Jejunal secretions were cultivated quantitatively for aerobe and anaerobe microorganisms. RESULTS: Small intestinal bacterial overgrowth was detected by culture of jejunal aspirates in 73% of patients, being associated with age and the administration of acid-suppressive therapy. The glucose breath hydrogen test correlated poorly with culture results, sensitivity and specificity ranging from 27%-52% and 36%-80%, respectively. CONCLUSIONS: In patients with cirrhosis, the glucose breath hydrogen test correlates poorly with the diagnostic gold standard for small intestinal bacterial overgrowth. Until other non-invasive tests have been validated, studies addressing the role of small intestinal bacterial overgrowth in patients with cirrhosis should resort to microbiological culture of jejunal secretions.     

The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis

BACKGROUND: Small intestinal bacterial overgrowth may contribute to the development of non-alcoholic steatohepatitis, perhaps by increasing intestinal permeability and promoting the absorption of endotoxin or other enteric bacterial products. AIMS: To investigate the prevalence of small intestinal bacterial overgrowth, increased intestinal permeability, elevated endotoxin, and tumour necrosis factor alpha (TNF-alpha) levels in patients with non-alcoholic steatohepatitis and in control subjects. PATIENTS AND METHODS: Twenty two patients with non-alcoholic steatohepatitis and 23 control subjects were studied. Small intestinal bacterial overgrowth was assessed by a combined (14)C-D-xylose and lactulose breath test. Intestinal permeability was assessed by a dual lactulose-rhamnose sugar test. Serum endotoxin levels were determined using the limulus amoebocyte lysate assay and TNF-alpha levels using an ELISA. RESULTS: Small intestinal bacterial overgrowth was present in 50% of patients with non-alcoholic steatosis and 22% of control subjects (p=0.048). Mean TNF-alpha levels in non-alcoholic steatohepatitis patients and control subjects were 14.2 and 7.5 pg/ml, respectively (p=0.001). Intestinal permeability and serum endotoxin levels were similar in the two groups. CONCLUSIONS: Patients with non-alcoholic steatohepatitis have a higher prevalence of small intestinal bacterial overgrowth, as assessed by the (14)C-D-xylose-lactulose breath test, and higher TNF-alpha levels in comparison with control subjects. This is not accompanied by increased intestinal permeability or elevated endotoxin levels.     

The effect of probiotics on gut flora, level of endotoxin and Child-Pugh score in cirrhotic patients: results of a double-blind randomized study

OBJECTIVE: To determine the effect of Escherichia coli Nissle (Mutaflor, Ardeypharm GmbH, Herdecke, Germany) on the intestinal colonization, level of endotoxin and liver functions in patients with liver cirrhosis. METHODS: Thirty-nine patients with liver cirrhosis diagnosed by means of biopsy and clinical examinations were randomly allocated to treatment with E. coli Nissle or placebo for 42 days. Standard clinical examination, biochemical and hematological examinations, level of endotoxin and microbiological examination of the stool were performed before and after the treatment. RESULTS: In comparing the treatment of E. coli Nissle and placebo, significant improvement of the intestinal colonization (P<0.001) in the E. coli Nissle group was described. We found a trend of significant lowering of the endotoxemia (P=0.07) and improvement of liver functions evaluated by Child-Pugh score (P=0.06). CONCLUSION: E. coli Nissle seems to be effective in the restoration of normal colonic colonization and can probably lower endotoxemia in cirrhotic patients.     

枯草杆菌二联活菌肠溶胶囊联合枸橼酸莫沙必利治疗乙肝肝硬化合并小肠细菌过度生长疗效探究

目的:探究枯草杆菌二联活菌肠溶胶囊联合枸橼酸莫沙必利治疗乙肝肝硬化合并小肠细菌过度生长(SIBO)疗效。方法:选取潍坊市人民医院感染科2020年10月-2021年4月收治的68例失代偿期乙肝肝硬化患者,行葡萄糖甲烷氢呼气试验诊断乙肝肝硬化合并SIBO 48例,随机分为试验组(24例)和对照组(24例),对照组给予保肝、低蛋白饮食、抗病毒等常规治疗,试验组在常规治疗的基础上加用枯草杆菌二联活菌肠溶胶囊(500 mg/次,3次/饭后)联合枸橼酸莫沙必利(5 mg/次,3次/饭前)治疗,观察2组治疗前后葡萄糖甲烷氢呼气试验、血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、内毒素、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF-α)、肝功能Child-Pugh及腹部不适变化。结果:48例患者中有44例完成试验,有4例退组,其中试验组有1例出现消化道出血,1例未规律服药,对照组有2例出现肝性脑病(HE)。治疗后,试验组呼气试验转阴率为63.6%,明显高于对照组的9.1%(P<0.01);腹部不适减轻总有效率为100.0%,显著高于对照组68.5%(P<0.01);内毒素、TNF-α...     

肝炎肝硬化患者血浆D-乳酸、二胺氧化酶和内毒素的检测及其临床意义

目的　探讨血D 乳酸、二胺氧化酶 (DAO)和内毒素水平在肝炎肝硬化患者中的变化及其临床意义。方法　将 5 0例肝炎肝硬化患者和 3 0例健康体检者分为试验组和对照组 ,采用分光光度法检测外周血中D 乳酸、DAO和内毒素的活性。结果　肝炎肝硬化患者试验组D 乳酸活性明显高于对照组 (P <0 .0 1) ,试验组 3组间比较差异有显著性 (P <0 .0 1) ,治疗后显著低于治疗前 (P <0 .0 1) ;试验组DAO活性明显高于对照组 ,组间比较Child PughC级组活性明显低于Child PughB级组 (P <0 .0 1) ,治疗后A级组及B级组水平显著低于治疗前 (P <0 .0 5 ) ,C级组水平显著高于治疗前 (P <0 .0 5 ) ;Child PughA级组内毒素活性与对照组比较差异显著性 (P >0 .0 5 ) ,Child PughB、C级组明显高于对照组 (P <0 .0 1) ,治疗后A、B级组水平与治疗前比较差异无显著性 (P >0 .0 5 ) ,C级组水平显著降低 (P <0 .0 1)。相关分析显示 3者水平均相关。结论　血浆D 乳酸、DAO水平是肠粘膜损伤早期诊断的敏感指标 ,内毒素血症是肝硬化患者病情加重的重要因素     

肝硬化患者肠道菌群的研究

目的:研究肝硬化患者肠道菌群的变化、并分析血内毒素水平与肠道细菌的关系。方法:对37例肝硬化患者和18例健康者粪便中8种常见的厌氧菌及需氧菌进行定量研究,以偶氮基质显色法测外周血内毒素。结果:(1)肝硬化患者双歧杆菌、拟杆菌、真杆菌量明显低于正常组,而大肠杆菌、产气荚膜梭菌量高于正常组(P<0.05);(2)肝硬化患者肠菌失调程度与肝功能Child-Pugh分级有关;(3)肝硬化患者血内毒素水平与大肠杆菌量存在相关性。结论:肝硬化患者存在肠道菌群失调,具有代表性的厌氧菌减少,需氧菌增多。需氧革兰阴性杆菌大量繁殖可能是引起肝硬化肠源性内毒素血症的一个重要因素。     

肝硬化患者肠道菌群的研究

目的研究肝硬化患者肠道菌群的变化，并分析血浆内毒素水平与肠道细菌的关系。方法对３７例肝硬化患者和１８例健康者粪便中８种常见的厌氧菌及需氧菌进行定量研究，以偶氮基质显色法测外周血内毒素。结果（１）肝硬化患者双歧杆菌、拟杆菌、真杆菌量明显低于正常组，而大肠杆菌、产气荚膜杆菌量高于正常组（Ｐ＜０．０５）：（２）肠菌失调程度与肝功能Ｃｈｉｌｄ－Ｐｕｇｈ分级有关；（３）内毒素水平与大肠杆菌量存在相关性。结论肝硬化患者存在肠道菌群失调，具有代表性的厌氧菌减少，需氧菌增多。需氧革兰氏阴性杆菌大量繁殖可能是引起肝硬化肠源性内毒素血症的一个重要因素。     

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.     

Leaky Gut and Gut-Liver Axis in Liver Cirrhosis: Clinical Studies Update

Portal blood flows into the liver containing the gut microbiome and its products such as endotoxin and bacterial DNA. The cirrhotic liver acts and detoxifies as the initial site of microbial products. In so-called “leaky gut,” the increased intestinal permeability for bacteria and their products constitutes an important pathogenetic factor for major complications in patients with liver cirrhosis. Prolonged gastric and small intestinal transit may induce intestinal bacterial overgrowth, a condition in which colonic bacteria translocate into the small gut. Cirrhotic patients further show gut dysbiosis characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous nonpathogenic bacteria. Pathological bacterial translocation (BT) is a contributing factor in the development of various severe complications. Bile acids (BAs) undergo extensive enterohepatic circulation and play important roles in the gut-liver axis. BT-induced inflammation prevents synthesis of BAs in the liver through inhibition of BA-synthesizing enzyme CYP7A1. A lower abundance of 7α-dehydroxylating gut bacteria leads to decreased conversion of primary to secondary BAs. Decreases in total and secondary BAs may play an important role in the gut dysbiosis characterized by a proinflammatory and toxic gut microbiome inducing BT and endotoxemia, as addressed in my previous reviews. Selective intestinal decontamination by the use of various antimicrobial drugs for management of complications has a long history. Lactobacillus GG decreasing endotoxemia is reported to improve the microbiome with beneficial changes in amino acid, vitamin and secondary BA metabolism. Current approaches for hepatic encephalopathy are the use of nonabsorbable antibiotics and disaccharides. Probiotics may become an additional therapeutic option for advanced liver cirrhosis. (Gut Liver 2021;15:-676)     

Intestinal mucosal proliferation,apoptosis and oxidative stress in patients with liver cirrhosis

Background. Intestinal mucosal barrier dysfunction in liver cirrhosis and its implicated mechanisms is of great clinical importance because it is associated with the development of serious complications from diverse organs through promotion of systemic endotoxemia.Aim. The present study was designed to investigate whether enterocytes’ proliferation, apoptosis and intestinal oxidative stress are altered in the intestinal mucosa of patients with compensated and decompensated liver cirrhosis.Material and methods. Twelve healthy controls (group A) and twenty four cirrhotic patients at a compensated (n = 12, group B) or decompensated condition (n = 12, group C) were subjected to duodenal biopsy. In intestinal specimens mucosal apoptotic and mitotic activity and their ratio were recorded by means of morphological assessment and mucosal lipid hydroperoxides were measured. Plasma endotoxin concentration, an index of gut barrier function, was also determined.Results. Cirrhotic patients presented significantly higher serum endotoxin concentrations as compared to healthy controls (P < 0.001), whilst endotoxemia was higher in decompensated disease (P < 0.05 vs. compensated cirrhosis). Intestinal mucosal mitotic count was significantly lower in patients with compensated and decompensated cirrhosis compared to controls (P < 0.01, respectively), whilst a trend towards increased apoptosis was recorded. The mitotic/apoptotic ratio was significantly reduced in groups B (P < 0.05) and C (P < 0.01) as compared to controls. Intestinal lipid peroxidation was significantly increased in decompensated cirrhotics (P < 0.001 vs. groups A and B).Conclusions. The present study demonstrates for the first time that human liver cirrhosis is associated with decreased intestinal mucosal proliferation and proliferation/apoptosis ratio even at early stages of cirrhosis and increased intestinal oxidative stress in advanced liver disease.     

肝硬化患者血浆二胺氧化酶及内毒素检测的临床意义

探讨肝硬化患者血浆二胺氧化酶(DAO)和内毒素水平的临床意义.方法:以50例肝硬化患者和30例健康体检者为试验组和对照组,用分光光度法检测其外周血中DAO和内毒素的活性.结果:Child-Pugh A、B、C 3组肝硬化患者DAO活性均升高,与对照组比较差异有显著性意义(P＜0.01);Child-Pugh C级组DAO活性低于Child-Pugh B级,两者差异有显著性意义(P＜0.01).Child-Pugh A级组内毒素活性与对照组比较,差异无显著性意义(P＞0.05),Child-Pugh B、C级组与对照组比较,差异有显著性意义(P＜0.01).结论:血浆DAO水平是肠粘膜损伤早期诊断的敏感指标,内毒素血症、肠粘膜屏障衰竭是肝硬化患者病情加重的重要因素,也是治疗的关键之一.     

肝硬化患者腹水中细菌DNA与相关因素的关系

目的 探讨肝硬化患者腹水中细菌DNA与血浆内毒素、肠通透性、肠道菌群等因素的关系. 方法 选取失代偿期肝硬化伴腹水患者55例,于入院当日或次日抽取腹水行腹水中细菌DNA的提取及PCR扩增,同时行腹水常规、需氧菌及厌氧菌培养检查,于入院次日测定血浆内毒素、肠通透性并进行肠道菌群分析,同时测定血常规、肝肾功能、凝血功能等生物化学指标.30例健康成年人作为正常对照,行除腹水之外的上述检查. 结果 55例肝硬化患者腹水细菌培养均为阴性,其中19例(34.55%)患者腹水中检测到细菌DNA.与细菌DNA阴性组比较,细菌DNA阳性组患者的凝血酶原活动度明显降低(t=-3.184,P=0.002),而肝功能Child-Pugh评分(t=3.224,P=0.002)和腹水白细胞计数(t'=4.088,P=0.001)明显升高.与正常对照组比较,肝硬化患者血浆内毒素水平(t=13.705,P=0.000)、尿中乳果糖/甘露醇(L/M,t'=28.568,P=0.000)和肠道肠杆菌数量(t=2.912,P=0.005)明显升高,而肠道双歧杆菌数量明显减少(t=-3.669,P=0.000).与腹水中细菌DNA相关的指标为肠道肠杆菌数量(P=0.007)和凝血酶原活动度(P=0.011).结论 肝硬化患者发生腹水细菌移位的关键因素是肠腔细菌过度生长,并与肝病的严重程度相关.     

内毒素受体、内毒素血症与肝硬化

内毒素在肝脏内可激活Kupffer细胞,合成和释放多种细胞因子和炎症介质,使肝细胞受损,其作用机制主要是通过Kupffer细胞上的内毒素受体启动宿主免疫反应和效应功能。肝硬化患者因多种原因引起肠道菌群生长过度和菌群易位,可导致内毒素血症;反之,内毒素本身又可加重肝脏损伤。因此,通过改变肝硬化患者的肠道微生态,调节肠道菌群,可减少肠道内毒素的产生,防止内毒素血症的发生,减轻肝脏损伤,延缓肝硬化的进程。     

慢性肝病与小肠细菌过度生长--氢呼气试验的结果

背景：慢性肝病时胃肠道局部的免疫防御机制受损,肠道的微环境遭到破坏,有利于细菌的生长。小肠液细菌培养为诊断的“金标准”。但此法操作复杂,技术要求高。以碳水化合物为基质的氢呼气试验则相对简单。目的：观察慢性乙型肝炎和肝炎后肝硬化患者是否存在小肠细菌过度生长。方法：38例慢性乙型病毒性肝炎、26例乙型肝炎后肝硬化患者和40名正常对照者行乳果糖氢呼气试验（LHBT）,检测小肠细菌过度生长的情况。结果：64例慢性肝病患者中LHBT阳性者22例（34．4％）,40名正常对照者LHBT均阴性。LHBT阳性组3h累积平均氢呼出量、平均氢浓度峰值显著高于LHBT阴性组和正常对照组（P均〈0．01）;其峰值出现时间显著早于LHBT阴性组和正常对照组（P均〈0．01）。结论：部分慢性肝病患者LHBT阳性,提示存在小肠细菌过度生长;乳果糖氢呼气试验检测小肠细菌过度生长具有快速、较准确、患者易于接受等特点。     

乙型肝炎肝硬化患者血清IGF-Ⅰ水平与肠道屏障功能损害的关系分析

目的 研究乙型肝炎肝硬化患者血清胰岛素样生长因子Ⅰ（IGF-Ⅰ）水平与肠道屏障功能损害的关系。方法 2015年1月~2017年1月我院诊治的乙型肝炎肝硬化患者107例,其中Child-Pugh A级35例,Child-Pugh B级42例, Child-Pugh C级30例,另选同期健康志愿者40例。采用酶联免疫吸附法检测血清IGF-Ⅰ水平,采用化学比色法检测血清二胺氧化酶（DAO）,采用改良酶学分光光度法检测血清D-乳酸,采用显色基质鲎实验法检测血清内毒素,采用高压液相色谱分析法检测尿液乳果糖/甘露醇（L/M）排出比。结果 健康人血清IGF-Ⅰ水平为（217.1±40.2） ng/ml,显著高于Child-Pugh A级肝硬化患者的（180.3±33.4） ng/ml、B级的（152.4±26.5） ng/ml或C级的（126.9±21.8） ng/ml（P<0.05）;健康人血清DAO、D-乳酸、内毒素和尿液L/M比值分别为（2.5±0.5） U/ml、（7.1±1.3）μg/ml、（0.4±0.1） EU/ml和（6.3±1.1）%,显著低于Child-Pugh A级肝硬化患者的（3.3±0.7） U/ml、（9.0±1.6） μg/ml、（0.6±0.1） EU/ml和（9.2±1.7）%或B级的（4.6±0.9） U/ml、（11.2±1.9） μg/ml、（0.8±0.1） EU/ml和（12.6±2.3）%或C级的（5.8±1.0） U/ml、（13.4±2.4） μg/ml、（1.1±0.2） EU/ml和（15.7±2.8）%（P<0.05）;乙型肝炎肝硬化患者血清IGF-Ⅰ与DAO、D-乳酸、内毒素和尿液L/M比值均呈负相关（r=-0.845、r=-0.808、r=-0.867、r=-0.839,P<0.01）。结论 乙型肝炎肝硬化患者存在肠道屏障功能损害,检测血清IGF-Ⅰ水平有一定的判断意义。     

Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites

Circulating levels of endotoxin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α increase with intestinal bacterial overgrowth and translocation, and are believed to be involved in the pathogenesis of hyperdynamic circulatory syndrome and functional renal failure in patients with advanced cirrhosis. We investigated the effects of the antibiotic rifaximin on systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites. We measured mean arterial pressure, cardiac output (CO) by Doppler ultrasound, systemic vascular resistance (as the ratio of mean arterial pressure:CO), plasma renin activity, levels of plasma aldosterone, the glomerular filtration rate by plasma clearance of technetium-99m-DTPA, natriuresis, levels of plasma endotoxin, and serum levels of IL-6 and TNF-α in 13 patients at baseline and after 4 weeks of treatment with rifaximin. Rifaximin treatment significantly reduced CO and significantly increased systemic vascular resistance, in association with a significant decrease in plasma rennin activity. The therapy also significantly increased the glomerular filtration rate and natriuresis while reducing levels of endotoxin, IL-6, and TNF-α. Intestinal decontamination with rifaximin improved systemic hemodynamics and renal function in patients with advanced cirrhosis.     

Enteric coated polymyxin B in the treatment of hyperammonemia and endotoxemia in liver cirrhosis

Effects of enteric coated polymyxin B capsules on hyperammonemia and endotoxemia in liver cirrhosis were investigated. Six million units of polymyxin B were orally administered daily to 21 patients with liver cirrhosis and 3 patients with hepatoma cum liver cirrhosis, whose plasma ammonia was higher than normal limit and/or whose plasma endotoxin was positive, for 5-32 days, and serum polymyxin B concentration (in 5 cases), changes of plasma ammonia level (in 19 cases) and plasma endotoxin (in all cases) were observed. Serum polymyxin B concentration was below the detectable limit (0.5 unit/ml) in all cases observed. In the patients with liver cirrhosis, plasma endotoxin and ammonia levels decreased rapidly after polymyxin B treatment, and the decreases in endotoxin levels were kept throughout the treatment. Twelve patients with liver cirrhosis (10 among them were treated with lactulose) were served as controls. All patients who were treated with lactulose alone showed rapid decrease in plasma ammonia, but the decrease in endotoxin in these patients was slower than that in those treated with polymyxin B. From these results, oral administration of polymyxin B is concluded to be useful in the treatment of hyperammonemia and endotoxemia in liver cirrhosis, as a poorly absorbed antibiotic and as an antiendotoxin agent.     

Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.