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- 腺苷蛋氨酸在肝病患者中抗抑郁作用的研究进展

S-腺苷蛋氨酸(S-adenosyl-L-methionine,SAMe)是一种天然分子存在于人体所有细胞中,在肝脏、肾上腺以及松果体中具有较高浓度,在大脑中亦均匀分布。S-腺苷蛋氨酸通过抗氧化自由基及促进肝细胞再生等机制对肝细胞具有多重保护作用长久以来被广泛应用于肝病所致的肝内胆汁淤积、抗肝纤维化等治疗。近年来,研究亦发现S-腺苷蛋氨酸可增加患者脑中神经元膜的流动性及促进兴奋性神经递质的产生等对改善肝病患者情绪、治疗肝病患者抑郁症等方面具有重要的双重作用。通过静脉或口服用药,均可提高患者脑脊液中SAMe浓度,对于轻、中度抑郁患者的辅助治疗,更具安全性、有效性,这为人类的"生理-心理"疾病的治疗带来更广阔的应用前景。现将其对肝病患者抗抑郁的作用机制及临床应用综述如下。     

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,     

丹参在肝脏疾病防治中的应用及作用机制研究进展

丹参为唇形科多年生草本丹参Salvia miltiorrhiza Beg.的干燥根及根茎。临床与药理学研究发现丹参对胆汁淤积性肝损害、免疫性肝损害、肝纤维化、肝癌、药物性肝损伤等多种肝病具有防治作用。本文对丹参在肝脏疾病防治中的应用及作用机制进行了全面综述,以期为丹参相关保肝药物的开发及临床合理用药提供理论指导。     

肠道菌群与肝脏疾病相关性

肠道菌群是一个复杂的微生态系统,其种类、数量、比例、定位等要素的平衡对宿主健康产生重大影响,尤其与消化系统关系紧密。肝脏是身体内以代谢功能为主的器官,大量研究显示,肠道菌群可对酒精性肝病、非酒精性肝病、肝性脑病、肝硬化、肝癌以及自身自身免疫性肝炎等肝病的发生发展产生重要影响。本文从肠道菌群与肝脏疾病的相关性,肠道菌群影响肝脏疾病的可能机制等方面进行综述,为以肠道菌群为靶点的肝病临床治疗研究提供借鉴。     

乙肝病毒感染与抗中性粒细胞胞浆抗体相关性分析

目的 探讨乙肝患者病毒复制活动情况与血清抗中性粒细胞胞浆抗体(ANCA)的相关性.方法 回顾性分析浙江大学医学院附属第一医院近三年来慢乙肝患者临床资料,排除并发自身免疫性肝病、酒精性肝病、药物性肝病等其他肝病和并发其他病毒感染,完善ANCA检测,共有21例患者纳入.根据乙肝患者入院后检测HBV DNA的拷贝水平,将患者分为HBV复制活动组和合HBV复制非活动组,根据ANCA检出情况又可分为ANCA阳性组和阴性组.采用实时荧光定量PCR检测HBVDNA拷贝水平,间接免疫荧光方法检测血清ANCA水平.结果 21例患者中,HBV复制活动组(11例)中pANCA阳性患者6例(55.5％),而HBV复制非活动组(10例)中pANCA阳性患者0例(0％)(x2=5.198,P=0.023).pANCA阳性组(6例)中HBV复制活动患者6例(100％),而pANCA阴性组(15例)中HBV复制活动患者5例(33.3％)(x2=5.198,P=0.023).而两组患者中肝硬化患者、原发性肝癌患者和ABO血型检测差异无统计学意义(P＞0.05).结论 乙肝病毒活动可能引起血管损害,同时乙型肝炎病毒引起的血管损害并不一定增加肝硬化和肝癌的发生.     

124例慢性肝硬化失代偿期患者感染病原菌特点及危险因素

正肝硬化为常见的慢性进行性肝病,乙型、丙型病毒性肝炎是引起肝硬化的主要原因,少部分患者为酒精性肝硬化、血吸虫性肝硬化所致,表现为弥漫性肝损害,肝脏功能严重下降,最终进入失代偿期[1]。临床报道[2-3]显示在肝炎肝硬化失代偿期时,大部分患者免疫功能严重受损,枯否氏细胞杀伤力急剧下降,对内源性、外源性病原体抵抗能力显著减弱,此时在医院病原体聚集区域极易发生院内感染。因此,慢性肝硬化失代偿期患者被认为是     

认知干预对肝癌介入患者焦虑和抑郁情绪的影响

目的:探讨认知干预对肝癌介入患者焦虑和抑郁情绪的影响。方法:选取我院2013年01月-2014年06月于中心导管室行肝癌介入术患者86例,按随机数字表法分为对照组和实验组。对照组实施常规护理;干预组在常见护理基础上实施认知干预行为。采用焦虑自测评量表(SAS)、抑郁自量评量表(SDS)对两组患者于入院时、术前1天及术后1天和1周时进行焦虑状和抑郁态评估。结果:两组患者入院时SAS和SDS评分比较无显著性差异(t=0.24、-0.08,P0.05),与国内常模相比有明显差异(t=16.63、15.87、9.64、11.31,P0.05);与入院时比较,两组患者术前、术后1天和术后1周SAS和SDS评分明显下降(F=10.37、42.07、4.76、29.68,P0.05);与对照组同时段比较,认知干预后SAS和SDS评分相比均有明显降低(t=1.97、4.58、5.29、1.83、3.85、5.20,P0.05)。结论:积极有效的认知干预行为对肝癌介入患者的焦虑、抑郁情绪障碍具有明显的缓解和减轻作用。     

综合性心理干预对冠心病介入治疗患者抑郁焦虑及生活质量的影响

目的:探究综合性心理干预对冠心病介入治疗患者焦虑、抑郁及生活质量的影响。方法:选择2014年6月~2015年6月期间我院收治冠心病性介入治疗患者3280例为研究对象,采用随机数字法将其分为观察组(1648例)和对照组(1632例),观察组患者给予常规治疗、抗抑郁治疗及综合心理干预,对照组给予常规治疗、抗抑郁治疗;采用焦虑自评量表(SAS)、抑郁自评量表(SDS)评价患者治疗前后焦虑、抑郁状态,生活质量评价量表QLQ-C30量表评价患者治疗前后生活质量的变化情况。结果:两组患者在入院时SAS和SDS得分不存在差异(P0.05);干预1月后两组组患者的SAS和SDS得分均出现显著降低(P0.05),且观察组患者的SAS和SDS评分均明显低于对照组(P0.05);干预前两组患者生存质量各维度的评分均不存在显著差异(P0.05);干预1个月后两组患者躯体功能、角色功能、社会功能、情绪功能及总体症状较干预前均出现明显改善(P0.05),且干预后观察组患者躯体功能、角色功能、社会功能、情绪功能及总体症状均显著优于对照组(P0.05)。结论:冠心病介入治疗患者进行综合性心理干预能够改善患者心理状态,降低患者焦虑、抑郁情绪,提高生活质量,对临床冠心病的治疗有重要的意义。     

运动疗法对慢性阻塞性肺疾病患者抑郁状态的效果观察

目的:探讨运动疗法对慢性阻塞性肺疾病(COPD)患者抑郁状态的临床效果。方法:选取52例COPD患者,随机分为试验组和对照组,各26例。对照组给予支气管扩张、健康教育、氧疗,试验组在对照组的基础上实施运动疗法,采用焦虑自评量表(SAS)、抑郁自评量表(SDS)、ADL生活质量量表对两组患者治疗前后进行评估。结果:对照组患者SAS、SDS评分治疗前后无明显变化,试验患者SAS、SDS评分均明显低于治疗前(P0.05),两组治疗后组间比较,差异亦有统计学意义(P0.05);试验组生活质量的改善优于对照组(P0.05)。结论:运动疗法能有效的改善COPD患者焦虑、抑郁负性情绪,提高患者的生存质量。     

病毒性肝病抗病毒治疗期间新发肝癌7例临床分析

目的:探讨病毒性肝炎肝硬化患者经抗病毒治疗仍发生原发性肝癌的原因。方法:回顾性分析兰州大学第一医院东岗院区肝病中心在2012年10月-2013年6月收治的7例病毒性肝炎肝硬化患者在规范抗病毒治疗期间新发原发性肝癌的临床资料、抗病毒治疗情况。结果:7例患者中有HBV感染6例,HCV感染1例;慢性肝炎2例,肝硬化5例;HBeAg阴性5例;3例合并糖尿病;经抗病毒治疗后病毒载量均处于低度复制或不可测状态。结论:病毒性肝炎肝硬化患者经抗病毒治疗不能完全消除原发性肝癌发生的风险,病毒载量、HBeAg阴性、糖尿病、肝硬化等可能是肝癌发生的危险因素。     

慢性病毒性肝炎研究进展

近年,慢性病毒性肝炎研究领域有较大进展,慢性乙型肝炎病毒（HBV）感染,虽然有了应用广泛、历史较久、且效果较好的疫苗,但迄今仍是世界范围肝硬化和肝癌的主要诱因。传染途径可经产道、性接触和非肠道途径（包括静脉吸毒、血制品等）。成年病人有少有变慢性,但一岁以下患儿90％变成慢性肝炎。慢性肝损伤的临床表现可以是轻微的炎症重到晚期肝硬化,程度不等。α干扰素（IFNα）是治疗活动性肝炎的产宰药物,单核苷酸类药物（lamivudine和adefovir）也具有同样的疗效。晚期肝病和肝癌患者可进行移植,但异常伴发移植物的感染。乙型肝炎免疫球蛋白和新型抗病毒药物联合应用,可降低移植物感染的严重性。丙型肝炎病毒（HCV）在20世纪后期感染了大约1％的世界人口。这中RNA病毒非经口传播,绝大多数病人变成慢性肝炎,约20％逐渐演变成肝硬化或肝癌。用IFNα和病毒唑（Ribavirin）联合治疗,约40％病人的病理表现有所改善。肝移植对某些病例是适宜的,但移植物感染仍是悬而未决的问题,新发现的庚型肝炎病毒（HGV）和TT病毒目前认为并不引起严重的肝损害。     

Mechanisms of human hepatocarcinogenesis

The major risk factors and etiological agents responsible for development of hepatocellular carcinoma in humans have been identified and characterized. Among these are chronic infection with hepatitis B virus or hepatitis C virus, exposure to aflatoxin B1, and cirrhosis of any etiology (including alcoholic cirrhosis and cirrhosis associated with genetic liver diseases). Both chronic hepatitis and cirrhosis represent major preneoplastic conditions of the liver as the majority of hepatocellular carcinomas arise in these pathological settings. Hepatocarcinogenesis represents a linear and progressive process in which successively more aberrant monoclonal populations of hepatocytes evolve. Regenerative hepatocytes in focal lesions in the inflamed liver (chronic hepatitis or cirrhosis) give rise to hyperplastic hepatocyte nodules, and these progress to dysplastic nodules, which are thought to be the direct precursor of hepatocellular carcinoma. In most cases, the neoplastic transformation of hepatocytes results from accumulation of genetic damage during the repetitive cellular proliferation that occurs in the injured liver in response to paracrine growth factor and cytokine stimulation. Hepatocellular carcinomas exhibit numerous genetic abnormalities (including chromosomal deletions, rearrangements, aneuploidy, gene amplifications, and mutations), as well as epigenetic alterations (including modulation of DNA methylation). These genetic and epigenetic alterations combine to activate positive mediators of cellular proliferation (including cellular proto-oncogenes and their mitogenic signaling pathways) and inactivate negative mediators of cellular proliferation (including tumor suppressor genes), resulting in cells with autonomous growth potential. However, hepatocellular carcinomas exhibit a high degree of genetic heterogeneity, suggesting that multiple molecular pathways may be involved in the genesis of subsets of hepatocellular neoplasms. Continued investigation of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in liver, enabling the development of effective strategies for prevention and/or more effective treatment of hepatocellular carcinoma.     

Prognosis for the patients with alcoholic and nonalcoholic liver disease

The purpose of this investigation was to determine the role of alcohol in development of progressive liver disease. For this purpose, 41 alcoholic patients were followed up for 5 years. Criteria for alcohol abuse was that the patients were enjoying 20 g alcohol daily in a period of 5 years for females and respectively 60 g daily for males. In the same time a group of 51 nonalcoholic patients with histologically proven chronic liver disease were investigated. In all 92 patients chronic liver disease and progression of the disease was proven by liver biopsy during a 5-years follow-up. In sera of all patients the markers of hepatitis viruses B, D and C were continuously determined and chronic viral hepatitis was excluded. Also, autoimmune chronic hepatitis was excluded. The results of the investigation showed that alcoholics develop cirrhosis hepatitis, in most cases 78.04%. The most progressive chronic liver diseases--cirrhosis and hepatocellular carcinoma--are significantly present among nonalcoholics (p < or = 0.05). In the mentioned investigation a large group of 51 patients with severe chronic hepatitis without a proven etiology of disease was found and it deserves priority in future research.     

Proteome analysis of human hepatocellular carcinoma tissues by two-dimensional difference gel electrophoresis and mass spectrometry

Proteome analysis of human hepatocellular carcinoma tissues was conducted using two-dimensional difference gel electrophoresis coupled with mass spectrometry. Paired samples from the normal and tumor region of resected human liver were labeled with Cy3 and Cy5, respectively while the pooled standard sample was labeled with Cy2. After analysis by the DeCyder software, protein spots that exhibited at least a two-fold difference in intensity were excised for in-gel tryptic digestion and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A total of 6 and 42 proteins were successfully identified from the well- and poorly-differentiated samples, respectively. The majority of these proteins are related to detoxification/oxidative stress and metabolism. Three down-regulated metabolic enzymes, methionine adenosyltransferase, glycine N-methyltransferase, and betaine-homocysteine S-methyltransferase that are involved in the methylation cycle in the liver are of special interest. Their expression levels, especially, methionine adenosyltransferase, seemed to have a major influence on the level of S-adenosylmethionine (AdoMet), a vital intermediate metabolite required for the proper functioning of the liver. Recent work has shown that chronic deficiency in AdoMet in the liver results in spontaneous development of steatohepatitis and hepatocellular carcinoma, and hence the down-regulation of hepatic methionine adenosyltransferase in our hepatocellular carcinoma samples is in line with this observation. Moreover, when a comparison is made between the differentially expressed proteins from our human hepatocellular carcinoma samples and from the liver tissues of knockout mice deficient in methionine adenosyltransferase, there is a fairly good correlation between them.     

Aflatoxin-induced TP53 R249S mutation in hepatocellular carcinoma in Thailand: association with tumors developing in the absence of liver cirrhosis

Primary Liver Cancer (PLC) is the leading cause of death by cancer among males in Thailand and the 3(rd) among females. Most cases are hepatocellular carcinoma (HCC) but cholangiocarcinomas represent between 4 and 80% of liver cancers depending upon geographic area. Most HCC are associated with chronic infection by Hepatitis B Virus while a G → T mutation at codon 249 of the TP53 gene, R249S, specific for exposure to aflatoxin, is detected in tumors for up to 30% of cases. We have used Short Oligonucleotide Mass Analysis (SOMA) to quantify free circulating R249S-mutated DNA in plasma using blood specimens collected in a hospital case:control study. Plasma R249S-mutated DNA was detectable at low concentrations (≥ 67 copies/mL) in 53 to 64% of patients with primary liver cancer or chronic liver disease and in 19% of controls. 44% of patients with HCC and no evidence of cirrhosis had plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL, compared to 21% in patients with both HCC and cirrhosis, 22% in patients with cholangiocarcinoma, 12% in patients with non-cancer chronic liver disease and 3% of subjects in the reference group. Thus, plasma concentrations of R249S-mutated DNA ≥ 150 copies/mL tended to be more common in patients with HCC developing without pre-existing cirrhosis (p = 0.027). Overall, these results support the preferential occurrence of R249S-mutated DNA in HCC developing in the absence of cirrhosis in a context of HBV chronic infection.     

Human livers with cirrhosis and hepatocellular carcinoma have less mitochondrial DNA deletion than normal human livers.

We measured the populations of mutated mitochondrial DNAs with the 7,436 bp or the 4,977 bp deletion from apparently normal human liver and human livers with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The amount of the mutated mitochondrial DNA was at the same level between normal and chronically hepatitic livers but was significantly lower in human livers with cirrhosis and hepatocellular carcinoma, especially the latter, suggesting that the mutated mitochondrial DNAs may be decreased with the progress of liver disease from chronic hepatitis to cirrhosis and hepatocellular carcinoma. This phenomenon is opposite to that occuring in the ageing process.     

黛力新联合中药熏香治疗慢性肾衰竭伴发抑郁焦虑的效果研究

目的:探讨黛力新联合中药熏香治疗慢性肾衰竭伴发抑郁焦虑的临床效果。方法:将我院自2017年10月至2018年9月收治的慢性肾衰竭伴发抑郁焦虑患者65例作为研究对象,按照随机数字表法将其分为研究组33例和对照组32例,研究组患者给予黛力新联合中药熏香进行治疗,对照组患者给予黛力新进行治疗,观察和比较两组患者抑郁自评量表(Self-rating depression scale,SDS)、焦虑自评量表(Self-Rating Anxiety Scale,SAS)及社会支持评定量表(social support rate scale,SSRS)量表评分的变化情况。结果:治疗前,两组患者SAS、SDS、SSRS评分比较差异均无统计学意义(P0.05)。治疗后,两组患者的SAS和SDS情绪评分均较治疗前明显降低,SSRS评分均较治疗前明显升高,且研究组SAS和SDS情绪评分明显低于对照组,而SSRS评分显著高于对照组(P0.05)。研究组患者治疗依从率为96.97%,口干、恶心、头晕、纳差等轻度不良反应发生率为30.30%,均明显高于对照组(84.38%和12.50%,P0.05),两组患者在治疗过程中均未出现明显的恶性不良反应,研究组患者上述不良反应在停止熏香治疗后自行缓解。结论:黛力新联合中药熏香梅花香和安神香用于治疗慢性肾衰竭伴发抑郁焦虑患者能够有效的缓解患者抑郁、焦虑的不良情绪,提高社会支持和治疗依从率。