铁死亡调控慢性肝病的研究进展

铁死亡(iron death)是一种铁依赖的非凋亡性的新程序性死亡方式,其是因铁代谢异常导致细胞内大量活性氧与脂质过氧化物堆积造成的。铁死亡对慢性肝病的发生发展起着重要的调控作用,是治疗慢性肝病的潜在靶点。本文对近年来铁死亡在非酒精性脂肪性肝病、酒精性肝病、药物性肝损伤、肝纤维化和肝细胞癌发病中作用的最新研究进展进行总结,希冀为慢性肝病的预防和治疗提供新思路。     

质子泵抑制剂对慢性肝病患者肠道微生态的影响

目的探究质子泵抑制剂(PPIs)对慢性肝病患者肠道微生态的影响。方法选取郑州市第六人民医院2018年12月至2019年3月诊断及拟行PPIs治疗的慢性肝病患者31名,使用奥美拉唑进行治疗,20 mg/次,2次/d,疗程4周,检测治疗前后肠道菌群的构成。结果治疗前后患者肠道菌群构成差异显著:治疗后患者肠道菌群在Shannon指数(4.61±0.62 vs 5.01±0.83;t=2.889,P=0.005)、Simpson指数(0.89±0.09 vs 0.95±0.11;t=3.159,P=0.002)显著低于治疗前;治疗前患者肠道菌群中Coriobacteriaceae、Eggerthella、Ruminococcus、Anaerotruncus、Dorea、Turicibacter、Paraprevotella的相对丰度显著高于治疗后,治疗后肠道菌群中Veillonellaceae、Campylobacter、Haemophilus、Streptococcus、Streptococcaceae、Lactobacillus、Lactobacillaceae的相对丰度显著高于治疗前(均P<0.05)。结论PPIs可改变慢性肝病患者肠道菌群的构成。     

乳酸菌素治疗HBV感染与肠源性内毒素血症的临床观察

目的 研究慢性肝病的内毒素血症发生率以及乳酸菌素治疗的效果。方法 用鲎试验（ＬＬＴ）检测。结果 检测１１７例临床各类型慢性肝病的肠源性内毒素血症阳性率,结果为４０％～８０％,以重症肝炎最高。内毒素与肿瘤坏死因子互为因果对肝病发生发展产生重要影响。检测结果显示慢性肝病ＬＬＴ阳性病人ＴＮＦ－α较ＬＬＴ阴性及正常人明显提高,差别有显著性（Ｐ〈０．０５）,应用乳酸菌素治疗肝病肠源性内毒血症３０例,鲎试验转阴率为７０．６％,显著高于对照组的６．６％,Ｐ〈０．０１。结论 乳酸菌素可作为肝病的辅助治疗的有效药物之一。     

复合益生菌活菌制对慢性肝病患者血内毒素的影响

探讨复合益生菌活菌制剂对慢性肝病患者血内毒素 (ＥＴ)的影响 ,明确此类药物在慢性肝病治疗中的应用价值 ,我们选择了 6 0例住院慢性肝病患者随机分组作对照观察 ,现报告如下。1　材料与方法1 1　临床资料和方法　按照Ｃｈｉｌｄ分级标准 ,1999年 1月— 2 0 0 1年 6月选择ＣｈｉｌｄＢ级和Ｃ级慢性肝病病人 6 0例 ,随机分为 3组 :Ⅰ组为一般治疗组 ,ＣｈｉｌｄＢ级 4例 ,Ｃ级 16例 ,男 14例 ,女 6例 ,年龄 4～6 0岁 ;Ⅱ组为益生菌组 ,其中ＣｈｉｌｄＢ级 4例 ,Ｃ级 16例 ,男 13例 ,女 7例 ,年龄 4 0～ 6 8岁 ;Ⅲ组为乳果糖组 ,其中Ｃｈｉｌ…     

高原地区慢性肝病肠道微生态结构的变化

目的 分析高原地区慢性肝病患者肠道菌群物种多样性及菌群丰度结构变化,探讨肠道微生态失衡与慢性肝病的关联。方法 收集高原地区90例慢性肝病（慢性乙型病毒性肝炎30例、乙肝后肝硬化30例、原发性肝癌30例）及25例健康人的粪便,利用高通量基因测序及生物信息学分析技术,探讨慢性肝病患者与健康人之间物种多样性以及不同分类水平上肠道菌群组成是否存在差异。结果 慢性肝病患者肠道菌群多样性较健康人显著降低（Z=1.462,P=0.005）,Beta多样性分析发现慢性肝病患者与健康人肠道菌群组成上差异存在统计学意义（r=0.122,P=0.020）;对慢性肝病组与健康组进行组间肠道菌群差异性分析,发现在门水平上,拟杆菌门在慢性肝病组中富集（Z=1.065,P=0.043）,慢性肝病组内比较发现拟杆菌门在慢性乙型病毒性肝炎、乙肝后肝硬化、原发性肝癌患者中的相对丰度呈逐渐减少的趋势,但差异无统计学意义（P>0.050）;属水平上,粪杆菌属在慢性肝病组中富集（Z=1.092,P=0.032）,而肠球菌属分布减少（Z=1.398,P=0.036）,同时慢性肝病患者肠道菌群中一些潜在致病菌如链球菌属、韦荣...     

慢性肝病与肠道菌群的研究进展

肝脏与肠道微生态可谓息息相关,互为影响。慢性肝病患者均存在不同程度的菌群失调,而菌群失调与血内毒素水平升高相关,且可诱发肝性脑病、二重感染的发生。肠道菌群失调促进了慢性肝病并发症的发生、发展,增加了患者的死亡率,且菌群失调与肝功能损害程度成正比。微生态制剂可通过恢复肠道菌群平衡,维持肠道屏障的完整性,抑制产生内毒素的G-数量,减少肠氨的产生,辅助治疗慢性肝病。     

多元化管理模式对急诊肝病患者的效果观察

目的:近年来,急诊收治的不同病症的肝病患者越来越多,给医护人员带来很大的工作压力,以致工作频频出错,影响护理质量和患者的临床疗效。本文针对急诊肝病患者采取多元化管理模式进行护理,探讨该模式的特点及作用,为肝病的临床护理工作提供可借鉴的方法。方法:选取2011年10月-2012年12月我院急诊科收治的160例肝病患者,分为常规组和管理组。常规组采取基础护理,观察组采取多元化管理模式进行护理,包括人性化管理、分层级管理、情绪管理及环境管理。观察并比较两组患者对护理工作的满意度、护理工作的落实情况及患者的依从性。结果:管理组患者对护理服务的满意度为98.7%,护理工作落实率为97.62%,患者依从性为90.46%;常规组患者对护理服务的满意度为77.5%,护理工作落实率为94.58%,患者依从性为87.82%;管理组的患者满意度、护理工作落实情况及患者依从性均优于对照组,差异显著且具有统计学意义(P0.05)。结论:采取多元化管理模式进行护理有助于提高护理质量,推进急诊工作顺利进行,更有利于提高肝病患者的临床疗效及对护理工作的满意度,该模式对临床护理工作有重要的指导意义,值得推广。     

干细胞移植规范化治疗失代偿期肝硬化的专家共识

一、概述失代偿期肝硬化是指各种慢性肝脏损害所导致的肝病晚期阶段,主要表现为门脉高压、肝功能减退和不能满足人体的生理需求。肝硬化最常见的病因为慢性病毒性肝炎。我国是一个肝炎大国,人群乙型肝炎病毒携带率高达7.18﹪,丙型肝炎病毒感染率达3.2﹪。此外,酒精性肝病、药物性肝病、自身免疫性肝病、遗传代谢性肝病等多种肝病的发病率逐年升高。我国每年新增肝硬化病例数超过600万。代偿期肝硬化患者多无临床症状,     

重视肠道微生态变化在慢性肝病中作用的研究

病毒、酗酒等引起的慢性肝病是世界性的问题。我国是世界上病毒性肝炎的高发地区 ,乙型肝炎病毒携带者达 1.3亿 ,每年乙型肝炎的发病人数达 1千 3百万。由于病毒性肝炎发病机制极为复杂 ,尚未阐明 ,尽管目前干扰素、拉米夫定等抗病毒药物在临床已得到广泛的应用 ,但慢性病毒性肝炎进展为肝硬化、慢性重型肝炎的势头并未因此得到有效的遏制。肝移植、人工肝脏治疗可显著降低肝硬化、慢性重型肝炎患者的病死率 ,但由于经济、技术等诸多因素的限制 ,慢性肝病总体病死率仍居高不下。己知内毒素及内毒素—肿瘤坏死因子细胞因子网络作用通过致肝细…     

当前消化系统疾病的临床进展

本文通过对当前消化系统疾病的临床进展研究,分别从消化系肿瘤,小肠疾病和慢性肝病三个方面的进展进行总结阐述,旨在推动消化系统疾病的诊疗,为消化领域的医学研究提供参考借鉴。     

间充质干细胞的来源及其对肝脏损伤及修复的研究进展

全球终末期肝病、肝衰竭的发病率和死亡率逐年升高,且目前肝移植是唯一疗效确切的治疗选择,但是,肝移植的使用受到肝源供体严重不足,长期存活率低,医疗费用昂贵等缺点使得原位肝移植的应用受限,绝大多数患者无法受益。为了克服肝脏器官短缺,干细胞替代治疗策略逐渐成为另一个肝病治疗的重要选择,干细胞治疗,特别是间充质干细胞（MSC）提供了一个新的肝病治疗选择。MSC是一群贴壁生长的成纤维细胞样细胞,由于MSC能够分化为多种类型的细胞,能够产生多种的细胞因子和生长因子,具有造血支持和免疫调节和抗炎功能,MSC被认为在再生医学领域具有重大的科学和实用价值。另外,由于MSC应用于治疗实验性肝损伤能明显提高动物存活率,明显改善肝功能。此外,一些临床前研究和临床研究也表明MSC对肝损伤性疾病具有显著地疗效。因此MSC在损伤性和退行性肝脏疾病的治疗具有广阔的应用前景。本文综述了MSC在肝损伤疾病治疗应用的进展,并对MSC在肝病治疗中的应用前景进行了展望。     

慢性病轨迹模式在射血分数保留型心力衰竭患者中的应用研究进展

近年来,射血分数保留型心力衰竭(HFpEF)的防治进展已成为国内外心血管医生关注的热点。HFpEF的防治是一个长期、综合的过程,虽然在规范化药物治疗方面有所进步,但是HFpEF患者的症状仍未得到理想控制。因此,以合理防治为主的全周期健康管理模式对HFpEF患者具有极其重要的意义。随着对HFpEF患者长期随访管理及预后相关研究的深入,慢性病轨迹模式逐步成为具有良好前景的规范化管理模式。科学、合理的慢性病轨迹模式管理可以更好地控制HFpEF患者症状,持续改善其生活质量。本文就慢性病轨迹模式管理在HFpEF患者中的最新进展做一综述。     

Liver and bone

Osteoporosis is a frequent complication in patients with chronic liver disease, especially in end-stages and in cases with chronic cholestasis, hemochromatosis and alcohol abuse. The problem is more critical in transplant patients when bone loss is accelerated during the period immediately after transplantation, leading to a greater incidence of fractures. Advanced age, low body mass index and severity of the liver disease are the main risk factors for bone disease in patients with cholestasis. Mechanisms underlying osteoporosis in chronic liver disease are complex and poorly understood, but osteoporosis mainly results from low bone formation, related to the effects of retained substances of cholestasis, such as bilirubin and bile acids, or to the effects of alcohol on osteoblastic cells. Increased bone resorption has also been described in cholestatic women with advanced disease. Although there is no specific treatment, bisphosphonates associated with supplements of calcium and vitamin D are effective for increasing bone mass in patients with chronic cholestasis and after liver transplantation. The outcome in reducing the incidence of fractures has not been adequately demonstrated essentially because of the low number of patients included in the therapeutic trials. Randomized studies assessing bisphosphonates in larger series of patients, the development of new drugs for osteoporosis and the improvement in the management of liver transplant recipients may change the future.     

Dealing With Obesity as a Chronic Disease

There are major efforts underway to educate the primary care physician about the health risks of obesity. Obesity is a chronic disease that requires chronic management. We must establish models that allow primary care physicians to participate in the chronic management of obesity, while recognizing that the interest and ability of primary care physicians to participate in obesity management will vary. Three general models of obesity management are proposed for the primary care physician, ranging from minimal evaluation to complete evaluation and treatment. In order for the models to be implemented, we must consider establishing a category of obesity specialists who can develop comprehensive treatment programs to which patients with obesity can be referred, and who can provide leadership and guidance for primary care physicians who are involved in obesity management. The North American Association for the Study of Obesity (NAASO) could help establish obesity specialists and provide a structure to allow them to provide leadership for obesity treatment.     

S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁／焦虑的临床效果研究

目的：研究s-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁／焦虑患者的临床效果。方法：选择2011年3月-2013年3月我院收治的51例不同病因的胆汁淤积性肝病（药物性肝损害13例、慢性乙型肝硬化14例、酒精性肝硬化11例、自身免疫性肝病6例、肝癌5例、胆管癌2例）并抑郁／焦虑的患者,予s-腺苷蛋氨酸1．0g治疗2周,应用SDS／SAS量表分别评估和比较治疗前后各组患者抑郁／焦虑程度的评分情况。结果：S-腺苷蛋氨酸治疗后,所有组别胆汁淤积性肝病肝病改善的临床总有效率94．12％,其中药物性肝损害、慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝硬化总有效率均为100．00％,肝癌的有效率为60．00％,胆管癌的有效率为50．00％,药物性肝损害患者临床疗效与其他各组有差异（P〈0．05）;药物性肝病患者SDS和SAS评分均较治疗前显著降低（P〈0．05）。而慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝病、肝癌、胆管癌患者SDS和SAS评分与治疗前相比均无统计学差异（P〉0．05）。结论：S-腺苷蛋氨酸可改善药物性胆汁淤积性肝病并轻、中度抑郁／焦虑患者的肝功能,并有效减轻其抑郁／焦虑情绪。     

S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁/焦虑的临床效果研究

目的:研究S-腺苷蛋氨酸治疗胆汁淤积性肝病伴抑郁/焦虑患者的临床效果。方法:选择2011年3月~2013年3月我院收治的51例不同病因的胆汁淤积性肝病(药物性肝损害13例、慢性乙型肝硬化14例、酒精性肝硬化11例、自身免疫性肝病6例、肝癌5例、胆管癌2例)并抑郁/焦虑的患者,予S-腺苷蛋氨酸1.0 g治疗2周,应用SDS/SAS量表分别评估和比较治疗前后各组患者抑郁/焦虑程度的评分情况。结果:S-腺苷蛋氨酸治疗后,所有组别胆汁淤积性肝病肝病改善的临床总有效率94.12%,其中药物性肝损害、慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝硬化总有效率均为100.00%,肝癌的有效率为60.00%,胆管癌的有效率为50.00%,药物性肝损害患者临床疗效与其他各组有差异(P0.05);药物性肝病患者SDS和SAS评分均较治疗前显著降低(P0.05)。而慢性乙型肝硬化、酒精性肝硬化、自身免疫性肝病、肝癌、胆管癌患者SDS和SAS评分与治疗前相比均无统计学差异(P0.05)。结论:S-腺苷蛋氨酸可改善药物性胆汁淤积性肝病并轻、中度抑郁/焦虑患者的肝功能,并有效减轻其抑郁/焦虑情绪。     

What fires prometheus? The link between inflammation and regeneration following chronic liver injury

Liver progenitor cells (LPCs) play a major role in the regeneration process after chronic liver damage, giving rise to hepatocytes and cholangiocytes. Thus, they provide a cell-based therapeutic alternative to organ transplant, the current treatment of choice for end-stage liver disease. In recent years, much attention has focused on unravelling the cytokines and growth factors that underlie this response. Liver regeneration following acute damage is achieved by proliferation of mature hepatocytes; yet similar cytokines, most related to the inflammatory process, are implicated in both acute and chronic liver regeneration. Thus, many recent studies represent attempts to identify LPC-specific factors. This review summarises our current understanding of LPC biology with a particular focus on the liver inflammatory response being associated with the induction of LPCs in the liver. We will describe: (i) the pathways of liver regeneration following acute and chronic damage; (ii) the similarities and differences between the two pathways; (iii) the liver inflammatory environment; (iv) the unique features of liver immunology as well as (v) the interactions between liver immune cells and LPCs. Combining data from studies on the LPC-driven regeneration process with the knowledge in the field of liver immunology will improve our understanding of the LPC response and allow us to regulate these cells in vivo and in vitro for future therapeutic strategies to treat chronic liver disease.     

Controversies in patient selection for liver transplantation.

A variety of specific conditions often stimulate controversy regarding candidacy for liver transplantation. We review the published experience with liver transplantation for alcoholic liver disease, fulminant and chronic hepatitis B, and hepatocellular carcinoma and transplantation in older subjects. Liver transplantation for alcoholic liver disease and in subjects older than 60 years is becoming less controversial because recent data demonstrate that these patients have excellent survival and good quality of life after transplantation. Only 10% to 15% of persons with alcoholism return to drinking after transplantation, and most do so only transiently. Liver transplantation for patients with hepatitis B virus infection or primary liver cancer is more problematic because recurrent disease is common in both conditions. After transplantation for chronic hepatitis B, 80% to 90% of patients have reinfection of the allograft and long-term survival is 45% to 50%. Patients receiving transplants for hepatocellular carcinoma have only 20% to 30% long-term survival, but these survivors are cured of malignancy. Data are presented to support continued liver transplantation for chronic hepatitis B and hepatocellular carcinoma; however, patients must be selected based on factors that predict a favorable outcome, and experimental therapies should be employed to explore ways to improve the existing survival rates.     

Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy

A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease, treatment decisions, and assessing drug efficacy. This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging. Pooled plasma from different liver fibrosis stages, which were assessed in advance by the current gold-standard of liver biopsy, was quantitatively analyzed. A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process, and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis. Validation results of fibronectin by Western blotting reconfirmed the mass-based data. Ingenuity Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B patients. Consequently, quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver fibrosis. We quantitatively monitored the fibrogenesis process in CHB patients. We discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis disease. These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.