肠道菌群调节对肝硬化患者血浆内毒素及肝功能的影响

目的探讨肠道菌群调节对肝硬化患者血浆内毒素及肝功能的影响。方法现选取我科室2017年6月至12月收治的80例肝硬化患者为研究对象,随机分为观察组和对照组,每组40例。对照组采用常规治疗,观察组在对照组的基础上采用益生菌进行肠道菌群调节。比较两组治疗前后的菌群变化、血浆内毒素、降钙素原(PCT)以及肝功能的变化。结果观察组治疗后的肠杆菌、肠球菌、双歧杆菌、乳杆菌均高于对照组,酵母样真菌低于对照组,差异有统计学意义(P0.05)。观察组治疗后的ALT、AST、TBil低于对照组,差异有统计学意义(P0.05)。观察组治疗后的血浆内毒素、PCT均低于对照组,差异有统计学意义(P0.05)。结论对肝硬化患者的菌群进行调节有利于降低患者的内毒素水平,改善肝功能。     

早期肠内营养联合微生态制剂治疗肝性脑病患者肠道菌群的改变

目的探讨早期给予肠内营养联合微生态制剂对肝性脑病(HE)患者肠道菌群的影响。方法将64例乙型肝炎肝硬化并发HE患者随机分成观察组32例和对照组32例。在抗昏迷治疗的基础上,给予对照组肠内营养治疗,观察组在对照组治疗的基础上给予双歧杆菌乳杆菌三联活菌片治疗。观察两组2 w。结果在观察2 w末,观察组和对照组分别死亡3例和4例;观察组生存患者粪便酵母样真菌为(3.2±0.4) CFU/g,显著低于对照组的[(3.9±0.5) CFU/g,P0.05],需氧肠球菌和厌氧乳杆菌水平分别为(12.3±1.2)CFU/g和(9.7±0.7)CFU/g,显著高于对照组的[(9.3±1.2) CFU/g和(8.2±0.8)CFU/g,P0.05];观察组血清内皮素、血氨、白介素-18和肿瘤坏死因子-α水平分别为(9.4±1.8) EU/mL、(75.4±10.2)μmol/L、(365.3±102.5) pg/mL和(26.3±10.7)n g/mL,显著低于对照组[(14.5±2.2) EU/mL、(109.3±5.5)μmol/L、(597.5±155.8) pg/mL和(42.8±11.2) ng/mL,P0.05];观察组血清白蛋白、血浆前白蛋白、转铁蛋白和视黄醇结合蛋白水平分别为(35.3±3.5) g/L、(341.1±35.2) mg/L、(2.5±0.4) g/L和(41.3±5.6)μg/L,显著高于对照组[(31.7±2.9) g/L、(310.1±33.4) mg/L、(2.2±0.4) g/L和(36.8±5.2)μg/L,P0.05]。结论早期给予肠内营养联合微生态制剂治疗可以有效改善HE患者肠道菌群失调症、抑制炎症应激反应,有利于营养的吸收和肝功能的恢复。     

肝硬化患者肠道菌群的研究

目的　观察肝硬化患者口服三联活菌和二联活菌前后肠道菌群、粪便pH、粪氨、血氨及血浆内毒素的变化。方法　选择肠道菌群中具有代表性的细菌共 7种进行培养和计数。 5 0例肝硬化患者随机分成 2组 ,分别予三联活菌及二联活菌治疗 14d。测定治疗前后肠道菌群菌落计数、粪便 pH值 ,粪氨、血氨 (干片法 ) ,血浆内毒素 (改良鲎试验法 )。结果　与正常对照组相比 ,肝硬化组患者存在不同程度的肠道菌群失调 ,主要表现为双歧杆菌减少 (10 .0 4± 0 .78比 9.4 8± 1.13,P <0 .0 5 )。治疗后 ,三联活菌组双歧杆菌由 9.4 6± 1.0 9增至 10 .30± 1.11;二联活菌组由 9.81± 0 .6 2增至 10 .4 4± 1.0 8,差异均有显著性 (P值均 <0 .0 5 )。且血氨、粪氨和粪便 pH值降低 (P <0 .0 5 )。二联活菌可降低合并内毒素血症的肝硬化患者血浆内毒素水平 [(0 .0 876± 0 .0 117Eu/ml比 (0 .0 6 85± 0 .0 2 4 6 )Eu/ml,P <0 .0 5 ]。结论　肝硬化患者存在肠道菌群失调。益生菌制剂可有效改善肝硬化患者肠道菌群失调 ,并降低血氨、粪氨和粪便 pH值。     

红霉素辅助治疗对糖尿病胃轻瘫肠道菌群及转归的影响

目的观察红霉素辅助治疗对糖尿病胃轻瘫肠道菌群及转归的影响。方法纳入2012年5月至2016年5月于我院收治的94例糖尿病胃轻瘫患者为对象,按照抽签随机方法分为两组,各47例,均接受常规基础治疗,在此基础上对照组予以莫沙比利治疗,观察组予以红霉素辅助治疗。对比两组肠道菌群变化状况,观察住院期间胃轻瘫症状痊愈率,并分析随访期间症状反复发作率及多次住院、血糖控制不佳、抑郁发生情况和2年累积生存率。结果治疗后,观察组拟杆菌菌落数量为(8.94±0.18) lg CFU/g,显著高于治疗前[(8.48±0.20) lg CFU/g]及对照组[(8.21±0.21) lg CFU/g];观察组肠球菌菌落数数据为(6.25±0.31) lg CFU/g,显著低于治疗前[(6. 80±0. 23) lg CFU/g]及对照组[(6. 76±0.20) lg CFU/g],差异均有统计学意义(P 0.05)。观察组治疗后肠杆菌、乳酸杆菌、双歧杆菌与治疗前及对照组比较,差异均无统计学意义(P 0.05)。观察组胃轻瘫症状痊愈率为82.98%,显著高于对照组的59.57%(P 0.05)。观察组随访期间症状反复发作、多次住院发生率分别为6. 38%、8.51%,显著低于对照组的21.28%、25.53%,两组比较差异均有统计学意义(P 0.05)。观察组血糖控制不佳、抑郁状态发生率及2年累积生存率与对照组比较差异无统计学意义(P 0.05)。结论红霉素辅助治疗对糖尿病胃轻瘫肠道菌群及转归有一定影响,临床上应引起足够重视。     

肝硬化患者肠道菌群失调与Child-Pugh分级的关系

目的评估肝硬化患者与健康人相比肠道菌群分布状态;肠道菌群分布与肝功能Child-Pugh分级的关系;益生菌治疗对于肝硬化患者肠道菌群的改善情况及对患者肝脏生化指标的影响。方法随机选择2014年2月至2014年7月健康成人21例及孝感市中心医院就诊的肝硬化不伴腹水患者26例及肝硬化伴腹水患者22例,其中肝硬化组在常规治疗基础上给予益生菌(贝飞达),共治疗14 d进行比较研究。测定研究对象的肠道菌群、血氨及ALT,血清白蛋白水平及TBil值,计量资料组间比较采用t检验,多组间比较采用方差分析,计数资料采用非参数检验。结果肝硬化患者均存在程度不同的肠道菌群失调,主要表现为肠球菌、肠杆菌显著增多(P0.01),双歧杆菌减少(P0.01);菌群失调的严重程度与患者肝功能严重程度有关,肝功能Child-Pugh C级患者菌群失调较A级严重(P0.01);益生菌可改善肝硬化患者生化指标、降低血氨、提高肠道双歧杆菌数量(P0.01);益生菌亦可改善肝硬化患者肝功能Child-Pugh分级,其中肝硬化合并腹水患者效果更明显(P0.01)。结论肝硬化组患者存在不同程度肠道菌群失调,益生菌能有效改善肝硬化患者肠道菌群失调并可改善生化指标及降低血氨。     

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.     

益生菌干预对慢性乙肝患者肠道菌群、炎症因子及肝功能等的影响

目的探讨益生菌干预对慢性乙型肝炎(乙肝)患者肠道菌群、炎症因子、内毒素及肝功能的影响。方法将2010年3月至2015年12月在我院诊治的乙肝患者380例按照随机数表法分为观察组和对照组,每组190例。对照组患者给予常规治疗,观察组在常规治疗基础上联合益生菌干预治疗,比较两组患者治疗前后肠道菌群变化、血清内毒素水平、炎症因子水平和肝功能的变化。结果观察组患者治疗后肠球菌、双歧杆菌和乳酸杆菌均显著增加(P0.05),肠杆菌和梭菌无显著变化(P0.05);对照组患者治疗前后肠道菌群无显著变化(P0.05)。两组患者治疗后内毒素、肝功能、炎症因子水平均显著降低(P0.05);观察组患者内毒素、ALT、AST、TBIL、IL-6、TNF-α水平均显著低于对照组(P0.01)。结论在常规治疗的基础上联合益生菌干预治疗慢性乙肝患者,能有效改善肠道菌群失调,降低炎症反应,改善肝功能,可作为乙肝患者的辅助治疗。     

不同调整肠道菌群治疗方案对慢性乙型重型肝炎肠道菌群和血浆内毒素的影响

目的研究不同调整肠道菌群治疗方案对慢性乙型重型肝炎患者肠道菌群和血浆内毒素的影响。方法纳入慢性乙型重型肝炎患者127例,分为A、B、C 3组,A组63例,B组32例,C组32例。A组患者口服金双歧,B组患者金双歧口服+乳果糖口服,C组患者金双歧口服+乳果糖灌肠。在治疗前和治疗第5、10、15以及20 d,分别检测3组患者大便肠球菌、酵母菌、双歧杆菌数量以及血浆内毒素水平。结果治疗10 d时A、B和C组患者双歧杆菌数量分别为8.58±1.84、8.21±1.82和8.43±1.94 l gn/g,均较治疗前升高,差异有统计学意义(P均0.01);治疗20 d时3组患者双歧杆菌数量分别为8.80±1.67、7.82±1.70和7.58±1.85l gn/g,与治疗10 d时比较,A组患者双歧杆菌数量无明显变化,B组和C组均明显减少,差异有统计学意义(P均0.01)。治疗20 d时3组患者肠球菌数量分别为7.83±1.66、8.17±1.78和8.85±2.03lgn/g,酵母菌数量分别为4.77±1.38、5.38±1.29和5.89±1.45lgn/g,与治疗前比较,A、B组肠球菌无明显变化,C组患者肠球菌明显升高,差异有统计学意义(Pc0.01);A组酵母菌无明显变化,B、C组患者酵母菌均升高,差异有统计学意义(PB0.05,PC0.01)。A组患者在第15天,B、C组患者在第10天血浆内毒素下降至最低值,分别为184.48±69.56、152.71±32.44和122.71±32.61 EU/L,较治疗前下降,差异有统计学意义(P均0.05);3组最低值比较,C组明显低于A、B组。治疗20d时3组患者血浆内毒素分别为187.62±80.73、265.62±90.55和328.62±101.43 EU/L,与治疗最低值比较,A组无明显变化,B组和C组患者血浆内毒素均明显升高,差异有统计学意义(P均0.05)。结论单用金双歧口服可以调节肠道菌群、降低血浆内毒素,但作用轻微。金双歧口服联合乳果糖口服或灌肠可以显著降低血浆内毒素水平,但在治疗第5~15 d可能出现新的菌群失调,加重内毒素血症。乳果糖灌肠方式使药物作用更直接,对肠道菌群及内毒素水平影响更明显、迅速。     

熊去氧胆酸联合微生态制剂治疗原发性胆汁性胆管炎患者对肠道菌群的影响*

目的 研究熊去氧胆酸(UDCA)联合微生态制剂治疗原发性胆汁性胆管炎(PBC)患者对粪肠道菌群的影响。方法 2017年6月～2019年6月我院收治的128例PBC患者被随机分为两组,每组64例,分别给予UDCA和UDCA联合双歧杆菌三联活菌肠溶胶囊治疗24周。采用实时荧光定量PCR法检测粪肠道菌群,采用放射免疫分析法测定血清肿瘤坏死因子-α(TNF-α),采用ELISA法测定血清白介素2(IL-2)、IL-6、IL-17和IL-22水平。结果 治疗后,观察组粪双歧杆菌和拟杆菌菌落数分别为(8.7±0.9)lg CFU/g和(8.9±0.9 lg CFU/g,显著高于对照组【分别为(8.0±0.6)lg CFU/g和(8.1±0.6)lg CFU/g,P＜0.05】,而酵母样真菌和大肠埃希菌菌落数分别为(4.3±0.7)lg CFU/g和(8.7±0.6)lg CFU/g,显著低于对照组【分别为(5.1±0.7)lg CFU/g和(9.2±0.7)lg CFU/g,P＜0.05】;治疗后,观察组血清TNF-α、IL-2、IL-6、IL-17和IL-22水平分别为(5.9±1.6)pg/ml、(65.5±12.6)pg/ml、(5.6±1.1)pg/ml、(7.6±2.3)pg/ml和(17.5±2.7)pg/ml,显著低于对照组【分别为(7.0±2.1)pg/ml、(85.7±20.1)pg/ml、(6.7±1.5)pg/ml、(9.2±3.2)pg/ml和(23.3±4.4)pg/ml,P＜0.05】;治疗后,观察组血清HA、Ⅳ-C和PⅢP水平分别为(113.2±24.1)μg/L、(145.5±19.8)μg/L和(134.6±21.5)μg/L,显著低于对照组【分别为(168.4±47.2)μg/L、(178.4±51.7)μg/L和(170.5±48.2)μg/L,P＜0.05】。结论 应用UDCA联合微生态制剂能有效纠正PBC患者肠道菌群失调,调节血清细胞因子水平,缓解肝纤维化程度。     

双歧三联活菌对肝硬化患者肠道菌群的调节作用及其对内毒素血症的影响

肝硬化患者存在肠道菌群失调,并与肠源性内毒素血症(enterotoxemia,ETM)有密切关系.目前对ETM的治疗仍无特效的方法.使用活菌制剂,调节患者肠道菌群,抑制肠道中革兰氏阴性杆菌的生长,减少内毒素的产生,可能是有效方法之一.本研究,旨在观察双歧三联活菌制剂对肝硬化患者肠道菌群的调节作用及其对血浆内毒素水平的影响,初步探讨其作用机制,为应用提供可靠的理论依据.     

Ultrasound liver elastography beyond liver fibrosis assessment

Several guidelines have indicated that liver stiffness(LS) assessed by means of shear wave elastography(SWE) can safely replace liver biopsy in several clinical scenarios, particularly in patients with chronic viral hepatitis. However, an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation, acute hepatitis, obstructive cholestasis, liver congestion, infiltrative liver diseases. This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure, congenital heart diseases or valvular diseases. In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events. The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS) and in the Budd-Chiari syndrome. In the hepatic SOS, an increase of LS is observed some days before the clinical manifestations;therefore, it could allow an early diagnosis to timely start an effective treatment.Moreover, it has been reported that patients that were successfully treated showed a LS decrease, that reached pre-transplantation value within two to four weeks. It has been reported that, in patients with Budd-Chiari syndrome, LS values can be used to monitor short and long-term outcome after angioplasty.     

Recurrent nonviral liver disease following liver transplantation

Recurrent disease after liver transplantation is well recognized and remains a potential cause of premature graft loss. The rates of recurrence are difficult to establish because of the lack of consistency in diagnostic criteria and approaches to diagnosis. Owing to the fact that recurrent parenchymal disease may occur in the presence of normal liver tests, those centers that use protocol biopsies will report greater rates of recurrence. It is important to recognize that rates of recurrence vary according to indication and show little correlation with rates of graft loss from recurrent disease. Recurrance rates are greatest for primary sclerosing cholangitis and autoimmune hepatitis, and low reccurrance rates are reported for alcoholic liver disease and recurrent primary biliary cirrhosis. The impact of recurrent nonalcoholic fatty liver disease is not yet clear. Patients and clinicians need to be aware of the possibility of recurrent disease in the differential diagnosis of abnormal liver tests, and management stategies may require alteration to reduce the impact of disease recurrence on outcome. Finally, an understanding of which diseases do recur after transplantation and identification of the risk factors may lead to a better understanding of the pathogenetic mechanisms of these conditions.     

中国肝癌肝移植的现状与展望

肝癌行肝移植治疗的指征、效果和相关问题一直存在争论,国际上已经有数个通用的肝癌肝移植标准,如Milan标准、Pittsburgh标准、UCSF标准等等,中国的移植学家们也在纷纷探讨适合中国的肝癌肝移植标准.本文收集并分析近年来国内外的文献,结合本移植中心460例肝移植的病例,对肝癌的分期标准、晚期肝癌行肝移植的指征进行了探讨,笔者认为影响我国肝癌肝移植的主要因素有:供肝的来源、术后乙肝及肿瘤的复发及相关社会因素等.     

Chronic liver diseases as liver tumor precursors

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence increased over the past 4 decades in some Western countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most common cause of cancer mortality (behind only lung and colorectal cancer) with approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC almost entirely develops in the context of inflammation and organ injury and is related to cirrhosis in about 85% of the cases. Among underlying etiologies of liver cirrhosis, most frequent are viral infection and toxic substances, mostly alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus infection. Hepatitis C virus infection is the main risk factor in Western countries. Hereditary hemochromatosis is not a very frequent cause of liver cirrhosis, but these patients are at higher risk for HCC compared with other etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of plant mold, can play a role in some countries in Asia and Africa, and can have a synergistic effect with hepatitis B infection.     

Fatty liver in liver transplantation and surgery

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (> 60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (< 30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.     

非酒精性脂肪性肝病与肝移植

随着生活水平的提高,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)在人群中的发病率越来越高.非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是NAFLD的最严重类型,在发达国家已成为临床上最常见的慢性肝病类型.     

药物性肝损伤合并肝脓肿

1病例捅要患者王某,男,39岁,汉族,已婚,河北省唐山市人,职业为建筑工程承包商。于2010年6月无明显诱因自觉乏力、纳差、食量减半、恶心、厌油、呕吐（非喷射样,呕吐物为胃内容物）,无发热、腹痛、腹泻、尿黄等。于当地医院查ALTl81U／L、AST109U／L、GGT386U／L,HBsAg阴性,抗HAV阴性,抗HCV阴性。腹部B超提示肝脏实质密度增高。