肝病患者腹水中常见病原菌分布及其耐药性回顾分析

目的:分析632例肝病患者腹水中常见细菌的分布及其耐药性,指导临床合理使用抗菌药物.方法:药敏实验采用纸片扩散法,使用whonet 5.3软件进行数据分析,对湖北细菌耐药监测网中16家三级甲等医院肝病区632例患者腹水中分离的菌株进行研判.结果:共分离632株细菌,革兰氏阳性球菌(G+C) 297株(47％),分离量最多的依次是粪肠球菌、金黄色葡萄球菌、表皮葡萄球菌;革兰氏阴性杆菌(G-B) 335株(53％),分离最多的依次是大肠埃希菌、阴沟肠杆菌、肺炎克雷伯菌.G+C耐药率较高的前三位药物依次为红霉素、复方新诺明、青霉素.耐甲氧西林的葡萄球菌检出率为65.4％.G-B耐药率较高的前三位药物依次为氨苄西林、哌拉西林、阿莫西林/棒酸.超广谱β-内酰胺酶(ESBLs)检出率为55.1％.结论:对甲氧西林敏感的葡萄球菌则对各种抗生素敏感,对甲氧西林呈耐药性的葡萄球菌则呈现多重耐药性;ESBLs(-)的肠杆菌科细菌对各种抗生素敏感,ESBLs(+)的肠杆菌细菌呈现多重耐药性.肝病患者腹水中常见病原菌的分布、耐药牲具有以上特点,这可为临床合理用药提供依据.     

酒精性肝病的肠道作用机制新进展

酒精性肝病仍缺乏有效治疗药物。酒精代谢可直接引起肝细胞凋亡和肝组织炎性损伤。酒精引起肠道屏障受损,肠道菌群失调可改变肠道和肝脏的免疫微环境,肠道微生物及其衍生物移位可促进酒精性肝病进展。深入了解酒精性肝病不同阶段的肠道免疫特点、微生物组变化、屏障功能障碍,以及对肝损伤的影响和作用机制,对于酒精性肝病的诊疗研发具有重要价值。     

非酒精性脂肪性肝病大鼠系统免疫及肠道免疫的变化

目的 观察在肥胖导致的非酒精性脂肪性肝病的进展过程中系统免疫及肠道免疫屏障的变化.方法 90只雄性SD大鼠均分为3组,即为正常饮食组、高糖饮食组、高脂饮食组,建立非酒精性脂肪性肝病大鼠模型,并于4、8、12周各组分别处死10只.肝脏HE染色观察肝脏脂肪变程度.鲎试验终点显色法检测门静脉血中内毒素水平.流式细胞术检测外周血单个核细胞及小肠集合淋巴结(PP结)中淋巴细胞CD4-CD8比值.结果 高糖饮食组在所有时间点内毒素水平均无显著升高,与正常饮食组差异均无统计学意义(P值均＞0.05).而高脂饮食组在8周时内毒素水平显著上升,与正常饮食组差异有统计学意义(P＜0.05).高糖饮食组与高脂饮食组在4周时外周血单个核细胞CD4/CD8显著高于正常饮食组(P值均＜0.05),至8周、12周时均显著低于正常饮食组(P值均＜0.05).PP结中CD4/CD8,高糖饮食组与高脂饮食组4、8周与外周血单个核细胞CD4/CD8变化趋势一致,12周时CD4/CD8与正常饮食组差异无统计学意义(P值均＞0.05).结论 肥胖可以抑制系统免疫及肠道免疫,肝脏可能参与调节肠道免疫.

Abstract：

Objective To study the changes of system immune and intestinal immune in the progression of non-alcoholic fatty liver disease due to obesity. Methods Ninty male SD rats were divided into control, high-sucrose and high-fat diet groups. Non-alcoholic fatty liver disease models were established by feeding with high-sucrose diet or high-fat diet and were killed at the 4th,8th and 12th weeks with 10 each for each group. The extent of liver steatosis was observed with HE staining.Portal blood endotoxin level was assessed by limulus test. The percentage of CD4+ and CD8+ cells in peripheral blood mononuclear cells (PBMC) and lymphocytes in Peyer's patches (PP) were calculated by flowcytometry. Results In comparison with control group, the endotoxin level was not elevated from the 4th week to 12th week in high-sucrose diet group, (all P values＞0.05), but was increased in high-fat diet group at the 8th week (P＜0.05). CD4/CD8 ratio in PBMC was higher in high-sucrose and higt-fat diet groups than that in control group at the 4th week (P＜0. 05) ,but was lower than that in control group at the 8th and 12th weeks (P＜0. 05). Whereas the variation of CD4/CD8 ratio in PP was consisted with that in PBMC between the high-sucrose and high-fat diet groups at the 4 th and 8 th weeks, but there was no difference when compared with control group at the 12 th week (P＞0.05).Conclusion Obesity can inhibit systematic immune and intestinal immune. The intestinal immune may be regulated by the liver.     

酪酸梭菌对非酒精性脂肪性肝病患者肠道菌群的影响研究

目的 通过比较酪酸梭菌用药前后NAFLD患者的生化指标、B超结果及肠道菌群构成等,评价酪酸梭菌对NAFLD的疗效及对肠道菌群的影响。方法 选择在我院消化内科就诊的NAFLD患者100例,另选50名健康对照者,分别用16S rDNA高通量测序检测两组的肠道菌群含量。所有NAFLD患者随机分为两组,对照组予以低脂饮食+有氧运动(如存在转氨酶升高,予以双环醇1粒tid po),观察组在此基础上联用酪酸梭菌(2粒tid po),3个月后通过Illumina NovaSeq平台对样本粪便DNA进行测序,观察肠道菌群变化,同时复查腹部B超、血脂(TG、CHOL)、肝功能(ALT、AST)、炎症因子(IL-6、TNF-α)、肠屏障指标(血清内毒素、DAO、D-乳酸活性水平)等。结果 NAFLD患者较健康人群的厚壁菌减少,肠杆菌增多;肠屏障指标血清内毒素、DAO、D-乳酸活性水平升高。用药后观察组肠道有益菌较治疗前增多。两组的内毒素、DAO、D-乳酸水平均较治疗前下降(P<0.05),观察组下降较对照组更明显,差异有统计学意义(P<0.05)。观察组的治疗有效率(86.0%)高于对照组(7...     

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...     

肠道微生态变化与非酒精性脂肪性肝病研究进展

由定植于肠道的大量固有菌群、肠道上皮细胞及肠道局部粘膜免疫系统组成了肠道微生态系统。"肝-肠轴"概念的提出为从肠道微生态角度寻找非酒精性脂肪性肝病(NAFLD)的诊疗措施提供了依据。肠道微生态失衡所致的肠道菌群过度生长、肠黏膜通透性改变、免疫功能紊乱、肠源性内毒素血症、效应细胞激活及炎症因子生成等在NAFLD发生发展中发挥了不容忽视的作用。深入研究肠道菌群与NAFLD之间的关系将为NAFLD的预防和治疗提供新靶点。     

肠道菌群失调与慢性肝病

正常肠道菌群是人体的一道天然屏障,对维持机体健康起着重要作用.当机体内、外环境发生变化时,便会造成肠道菌群失调.肠道菌群失调会引发或加重很多疾病,尤其是慢性肝病,而慢性肝病也可反过来加重肠道菌群失调,两者相互影响、互为因果.因此,临床上需关注肠道菌群与慢性肝病之间的特殊关系.     

肠道菌群及其代谢物与非酒精性脂肪性肝病

总结相关的实验研究发现,人体肠道菌群是非酒精性脂肪性肝病(NAFLD)发生发展的关键因素,除了人体肠道菌群组成的变化外,肠道菌群的代谢物也成为调节NAFLD病理过程的关键因素;有研究发现,肠道菌群的代谢物如短链脂肪酸、胆汁酸、三甲胺和乙醇等通过肠-肝轴途径影响肝脏代谢功能,从而导致疾病发生。现从NAFLD患者肠道菌群和代谢物的变化及发病机制,总结并探讨通过调节肠道菌群及其代谢物来治疗NAFLD,期望这些治疗策略会成为未来优化治疗NAFLD等代谢性肝病的有效方法。     

肠道菌群与脂肪性肝病研究新进展

目前,肠道菌群已成为一个当今研究的热点问题之一.脂肪性肝病是指由于各种原因引起的肝细胞内脂肪堆积过多的病变,引起肝的正常结构、生理及生化功能受损,最终出现临床症状的一类疾病总称,一般包括非酒精性脂肪性肝病和酒精性肝病两大类.肠道菌群和肠道通透性的变化可以通过肠-肝轴进一步影响脂肪性肝病的发展.同样,在脂肪性肝病的发生发...     

脂肪性肝病形成中的免疫因素

脂肪性肝病是肝细胞发生脂肪变性的一类疾病的总称,可分为酒精性脂肪性肝病(AFLD)和非酒精性脂肪性肝病(NAFLD)两大类。脂肪性肝病的发生和发展影响因素较多,至今尚未完全阐明,目前认为肝源性及外源性(尤其是脂肪源性)的细胞因子与胰岛素抵抗、氧应激和脂质过氧化等共同促进了脂肪肝的发生发展。     

肠道寄生虫感染与黏膜局部的抗感染免疫

肠道是许多病原体入侵的门户，宿主对入侵肠道的病原体可产生不同程度的抵抗力，表现为肠道黏膜的屏障作用和肠黏膜细胞、黏膜相关淋巴组织产生的一系列特异性和非特异性免疫反应等。寄生虫是单细胞或多细胞病原生物，其抗原成分相当复杂，因此，寄生虫抗原诱发的免疫应答大都是由多种免疫细胞和免疫因子参与的复杂过程。该文就肠道寄生虫与宿主肠黏膜细胞之间的相互作用和宿主肠道黏膜局部抗寄生虫感染的非特异性免疫和特异性免疫机制等进行综述。     

Tissue inhibitor of metalloproteinase-1 in the liver of patients with chronic liver disease

Background/Aims: Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. The relationship between serum and liver levels of TIMP-1 was also examined in some patients.Methods: The subjects were 68 patients who underwent liver biopsy. The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidine.Results: As compared with the controls (n=10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A patients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1-fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease.Conclusion: Liver TIMP-1 concentration increases with progression of the liver disease, when the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis.     

Outcomes of COVID-19 among patients with liver disease

Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease with multi-organ involvement, including impaired liver function. It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction, especially those with a more severe disease course. The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2, a cell-surface receptor for cellular entry, that is expressed in the liver. According to previous research, liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients, and elevated liver transaminases were found in about 20% of these patients, alkaline phosphatase in 6.1%, and gamma-glutamyl transferase in 21.1%. COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic liver diseases (CLDs) and also in those without previous liver disorders. The majority of COVID-19 patients who develop liver injury are men, the elderly, and those with a higher body mass index. Compared to the general population, COVID-19 is associated with significant morbidity and mortality in patients with liver disease (cirrhosis and liver transplantation recipients). However, some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.     

肝病患者血浆输注的现状

肝脏疾病的患者往往会伴随不同程度的凝血功能障碍和出血。成分血液中的血浆中含有大量的各种凝血因子,故血浆在肝病患者的治疗过程中起着不可替代的作用。为了解血浆在肝病中应用动态,为血浆在肝病中的临床应用提供参考,本文就国内外血浆在肝病中的应用作一概述。     

Prevalence of coeliac disease in patients with non-alcoholic fatty liver disease

Background and study aimsCoeliac disease (CD) may be associated with several liver disorders including primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Furthermore preliminary data suggest a causative role of CD in steatosis and steatohepatitis. The aim of present study was to determine the prevalence of CD in a series of patients with non-alcoholic fatty liver disease (NAFLD).Patients and methodsIn a cross sectional study (2008–2010), 403 consecutive NAFLD patients (127 female and 276 male) referred to GI clinics of the Zahedan University of Medical Sciences were included. IgA anti-tissue transglutaminase (Anti-tTG) was used for screening of coeliac disease. In the patients with a positive serologic test, duodenal biopsies were taken to confirm the diagnosis.ResultsThe mean ± SD of the age and BMI of patients were 37.4 ± 12.4 years and 28.3 ± 4.15 kg/m² respectively. BMIs lower than 25 kg/m² were found in 58 subjects (14.5%). Furthermore diabetes mellitus and hyperlipidaemia were diagnosed in 48 (11.9%) and 84 (20.8%) individuals respectively. Positive Anti-tTGs were found in 14/403 (3.4%) and 13/403 (3.2%, 95% CI 1.5–4.9) had coeliac disease according to the modified Marsh classification; 8 had type I, 3 type II, 1 type IIIA and 1 type IIIB lesions.ConclusionAccording to our data, prevalence of CD in the subjects with NAFLD is higher than the rates reported in the general population. Therefore screening for CD in selected cases of NAFLD may be appropriate.     

终末期肝病并自发性腹膜炎109例临床分析

目的分析终末期肝病患者并自发性腹膜炎的临床特征。方法以重型肝炎、肝硬化及原发性肝癌患者为研究对象,详细记录其临床症状、体征及实验室检查,根据腹水培养及药敏试验结果选择合适的抗生素,观察其疗效及转归并判断其预后。结果终末期肝病并自发性腹膜炎(SBP)109例,占所观察532例肝病患者的20.49%,其中,重型肝炎占46.53%(47/101),肝硬化占14.61%(52/356),原发性肝癌占13.33%(10/75),分别死亡27例、4例和3例;外周血白细胞>10.0×109/L者29例(26.61%),中性粒细胞分类>0.7者62例(56.88%),体温>38℃者21例,腹水培养阳性率为19.26%,其中大肠埃希菌占培养阳性者占38.10%,治疗有效率为66.06%。结论终末期肝病并SBP临床表现不典型,存在脾功能亢进,白细胞减少,腹水培养阳性率低,因此以腹水白细胞、多形核细胞及血白细胞分类作为诊断SBP的主要依据。重型肝炎并SBP发生率高于肝硬化及肝癌,同时三者的病死率均高于不并发SBP者。因此,预防SBP的发生,给予敏感药物积极有效治疗SBP对提高终末期肝病患者疗效及改善预后有积极意义。     

The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease

Introduction and objectivesHepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis.Materials and methodsLiver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease.ResultsIn 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1–5×, 5–10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62–0.66), 0.72 (0.71–0.73), 0.80 (0.77–0.82) and 1.15 (1.0–1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1–5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93–1.63), 2.47 (2.13–2.70) and 4.57 (3.27–5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%).ConclusionsThese data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.     

肝病鼻出血500例临床分析

目的总结肝病鼻出血的临床特点、易发因素,探讨合适的临床处置及预防办法。方法回顾性分析500例肝病鼻出血病例,总结相关因素,提出注意事项,交流诊疗体会。结果 500例鼻出血患者中,出血部位以Little’s区多见者53.4%,合并肝硬化、肝癌者75%,多次反复出血者61%,70.6%合并血小板减少及凝血功能障碍。结论肝病患者鼻出血发生率高,与鼻腔黏膜干燥、血小板减少及凝血功能障碍密切相关,晚期肝病患者发生率明显增高。鼻腔保湿护理及鼻腔填塞仍为主要的防治手段。     

Gastrointestinal and liver disease in patients with schizophrenia: A narrative review

Schizophrenia is a severe mental illness which can have a devastating impact on an individual’s quality of life. Comorbidities are high amongst patients and life expectancy is approximately 15 years less than the general population. Despite the well-known increased mortality, little is known about the impact of gastrointestinal and liver disease on patients with schizophrenia. We aimed to review the literature and to make recommendations regarding future care. Literature searches were performed on PubMed to identify studies related to gastrointestinal and liver disease in patients with schizophrenia. High rates of chronic liver disease were reported, with Non-Alcoholic Fatty Liver Disease being of particular concern; antipsychotics and metabolic syndrome were contributing factors. Rates of acute liver failure were low but have been associated with antipsychotic use and paracetamol overdose. Coeliac disease has historically been linked to schizophrenia; however, recent research suggests that a causal link is yet to be proven. Evidence is emerging regarding the relationships between schizophrenia and peptic ulcer disease, inflammatory bowel disease and irritable bowel syndrome; clinical vigilance regarding these conditions should be high. Patients with schizophrenia poorly engage with bowel cancer screening programmes, leading to late diagnosis and increased mortality. Clozapine induced constipation is a significant issue for many patients and requires close monitoring. There is a significant burden of gastrointestinal and liver disease amongst patients with schizophrenia. Better levels of support from all members of the medical team are essential to ensure that appropriate, timely care is provided.