肝性脑病10年国际研究热点与趋势

doi:10.3969/j.issn.1673-5374.2012.34.011

摘要/Abstract

摘要：

目的：分析肝性脑病的国际研究趋势，认识肝性脑病时神经电生理和神经影像评价的意义。
数据检索：检索Web of Science数据库2002-2011收录肝性脑病研究的文献数据。
选择标准：纳入标准：①在Web of Science数据库，经同行评审通过，并发表的关于肝性脑病研究的文献。②文献体例为研究原著、评论、会议摘要、会议论文或专籍。③出版时间在2002-2011年。排除标准：①需要手工检索或电话随访的文献。②未公开发表的文献。③更正内容的文献。
主要观察指标：该领域10年发表文献的特点：①文献数量。②文献类型。③学科分类。④来源出版物。⑤作者分析。⑥文献机构。⑦国家分布。⑧中国作者发表文献机构。⑨高被引文献。
结果：2002-2011年Web of Science数据库收录肝性脑病研究文献数量为3233篇，其中2010年发表文献数量最多为402篇，文献总体数量逐年上升。文献的研究领域为胃肠病学及肝脏病学；《肝脏病学》是收录肝性脑病研究文献最多的期刊，而且被收录文献的被引频次相对较高，是肝性脑病研究的经典期刊。收录的文献中，美国发表文献数量最多，中国排名第9位。加拿大的蒙特利尔大学发表文献数量最多为111篇，中国的浙江大学发表相关文献15篇。
结论：通过文献计量学方法分析2002-2011肝性脑病研究的文献，认识肝性脑病时神经损伤与再生的变化，提出了该领域的研究热点、突出机构和有成绩的专家，证实了神经电生理学和神经影像学检查对肝性脑病的临床分型和严重程度有较高的敏感性，为从事肝性脑病研究的临床医务工作者进一步确定科研思路提供有价值的参考。

关键词: 肝性脑病, 神经电生理, 神经影像, 诊断, 氨, 锰, 神经递质, 星形细胞, 氨基酸失衡, 文献计量学

Abstract:

Abstract
OBJECTIVE: To analyze international research trends in hepatic encephalopathy and examine the role of neuroelectrophysiology and neuroimaging in diagnosis of hepatic encephalopathy.
DATA RETRIEVAL: We performed a bibliometric analysis of studies on hepatic encephalopathy published during 2002–2011 retrieved from Web of Science.
SELECTION CRITERIA: Inclusion criteria: (1) peer-reviewed published articles on hepatic encephalopathy; (2) original article, review, meeting abstract, proceedings paper, book chapter, editorial material, news items, and (3) published during 2002–2011. Exclusion criteria: (1) articles that required manual searching or telephone access; (2) documents that were not published in the public domain; and (3) corrected papers from the total number of articles.
MAIN OUTCOME MEASURES: (1) Annual publication output; (2) type of publication; (3) publication by research field; (4) publication by journal; (5) publication by author; (6) publication by institution; (7) publication by country; (8) publication by institution in China; (9) most-cited papers.
RESULTS: A total of 3 233 papers regarding hepatic encephalopathy were retrieved during 2002–2011. The number of papers gradually increased over the 10-year study period and was highest in 2010. Most papers appeared in journals with a focus on gastroenterology and hepatology. Among the included journals, Hepatology published the greatest number of papers regarding hepatic encephalopathy, and the published studies were highly cited. Thus, Hepatology appears to represent a key journal publishing papers on hepatic encephalopathy. Regarding distribution by country for publications on hepatic encephalopathy indexed in Web of Science during 2002–2011, the United States published highest number of papers, with China ranked ninth. As per distribution by institute for publications, the University of Montreal in Canada published the highest number of papers (n = 111). Among the Chinese institutes, Zhejiang University in China was the most prolific institute with 15 papers.
CONCLUSION: The present bibliometric analysis on hepatic encephalopathy provides an overview of research progress, as well as identifying the most active institutes and experts in this research field during 2002–2011. Research into hepatic encephalopathy has revealed changes in neural injury and regeneration in hepatic encephalopathy. Neuroelectrophysiological and neuroimaging examinations are important for determining clinical classifications and disease severity of hepatic encephalopathy, providing a foundation for further research.

Key words: hepatic encephalopathy, neuroelectrophysiology, neuroimaging, diagnosis, ammonia, manganese, astrocyte, amino acids unbalance, bibliometrics, neural regeneration

. 肝性脑病10年国际研究热点与趋势[J]. 中国神经再生研究(英文版), 2012, 7(34): 2727-2733.

Nan Li. Research progress in hepatic encephalopathy in recent 10 years
A Web of Science-based literature analysis[J]. Neural Regeneration Research, 2012, 7(34): 2727-2733.

参考文献

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引言

材料方法

讨论

文章快阅

延伸阅读

肝性脑病
肝性脑病（hepatic encephalopathy, HE）是由于急、慢性肝病或各种原因的门－体分流（porto-systemicvenous shunting）所引起的，以代谢紊乱为基础的神经精神方面的异常。临床表现可以是仅仅用智力测验或电生理检测方法才能检测到的轻微异常，也可表现为行为异常、意识障碍，甚至昏迷。过去所称的肝性昏迷只是肝性脑病中程度严重的一期。仅用心理学检测方法才能检测到的轻微异常的肝性脑病又称为亚临床型肝性脑病（subclinical hepatic encephalopathy, SHE）或轻微肝性脑病（minimal hepatic encephalopathy, MHE）。

症状：HE的临床表现因基础病的性质、肝细胞损伤的程度、快慢及诱因的不同很不一致。且和其他代谢性脑病比并无特异性。A型HE发生在暴发性肝衰竭基础上，常在起病数日内由轻度的意识错乱迅速陷入深昏迷，甚至死亡，而无明确诱因，并伴有急性肝衰竭的表现，如黄疸、出血、凝血酶原活动度降低等。C型HE以慢性反复发作的性格、行为改变甚至木僵、昏迷为特征，常伴有肌张力增高、腱反射亢进、扑翼征、踝阵挛阳性，或巴彬斯基氏征阳性等神经系统异常。多数患者在初期为复发型，随后症状转为持续型。常有进食蛋白等诱因，亦可以是自发的或因停用治疗HE的药后发生。C型HE患者除脑病的表现外，还常伴有慢性肝损伤、肝硬化等表现。轻微型肝性脑病（MHE）常无明确的临床症状，只有通过神经精神或神经生理测试才能测出。

治疗：肝性脑病是严重肝病或门体分流时复杂代谢紊乱的结果，治疗需在多环节，采取综合性的措施。注要包括以下几方面：

(1)确认并去除诱因：在肝硬化基础上的急、慢性肝性脑多有各种各样的诱因。积极寻找诱因并及时排除可有效地制止肝性脑病的发展。例如食管曲张静脉破裂大出血后可发展成肝性脑病，积极止血、纠正贫血、清除肠道积血等可以制止肝性脑病的发生；其他如积极控制感染、纠正水电解质紊乱、消除便秘、限制蛋白饮食、改善肾功能等措施有利于控制肝性脑病的发展。

(2)减少或拮抗氨及其他有害物质，改善脑细胞功能：减少肠道内氨及其他有害物质的生成和吸收。可导泻或灌肠来清除肠道内的积血、积食及其他毒性物质。或用不吸收双糖的应用如乳果糖（lactulose）、乳山梨醇（lactitol）口服或灌肠，使肠腔pH降低，减少NH3的形成并抑制氨的吸收；有机微粒的增加使肠腔渗透压增加及酸性产物对肠壁的刺激作用可产生轻泻的效果，有利于肠道内氨及其他毒性物质的排出；同时还可不抑制产氨、产尿素酶的细菌的生长，减少氨的产生。副作用主要是腹部不适、腹胀、腹痛、食欲下降、恶心、呕吐、腹泻等，杂糖含量低（2%），对于有糖尿病或乳糖不耐症者亦可应用。但有肠梗阻时禁用。含双歧杆菌、乳酸杆菌的微生态制剂可通过调节肠道菌群结构，抑制产氨、产尿素酶细菌的生长。故可用益生菌制剂减少肠道氨及其他毒性物质的产生及吸收。与益生元制剂合用可增强其疗效。促进氨的代谢及清除、减少和拮抗假性神经递质，改善氨基酸平衡。

门冬氨酸－鸟氨酸是一种二肽，鸟氨酸可为体内鸟氨酸循环的底物，增加氨基甲酰磷酸合成酶及鸟氨酸氨基甲酰转移酶的活性，促进尿素的合成；门冬氨酸做为谷氨酰胺的合成的底物，与血中的氨结合转化为谷氨酰胺。因此门冬氨酸－鸟氨酸可促进脑、肝、肾消耗和利于氨合成尿素、谷氨酸、谷氨酰胺而降低血氨。在生理和病理条件下，尿素的合成及谷氨酰胺的合成会受到鸟氨酸、门冬氨酸和其他二羧基化合物的影响。鸟氨酸几乎涉及尿素循环的活化和氨的解毒的全过程；门冬氨酸还参与肝细胞内核酸的合成、间接促进肝细胞内三羧循环代谢过程，以利于被损伤肝细胞的修复。急慢性肝性脑病在24小时内给予至少40g，清醒后逐渐减量至20g/d。由于静脉耐受方面的原因，每500毫升溶液中不要溶解超过30g。输入速度最大不要超过每小时5克。

精氨酸：是肝脏合成尿素的鸟氨酸循环中的中间代谢产物，可促进尿素的合成而降低血氨。临床所用的制剂为其盐酸盐，呈酸性，可酸化血液，减少氨对中枢的毒性作用。可用25%的盐酸精氨酸40－80mg，加葡萄糖中静脉点滴，每日1次。谷氨酸钠、谷氨酸钾不能降低脑组织中的氨，且可诱发代谢性碱中毒，反而加重肝性脑病，因此，目前临床上已少用。影响神经递质及其受体的药疗效尚不确定，临床应用的也较少。

支链氨基酸可纠正氨基酸代谢的不平衡，抑制大脑中假神经递质的形成。摄入足量富含支链氨基酸的混合液对恢复患者的正氮平衡是有效和安全的。可以每日250－500ml，静脉点滴。

有脑水肿时，应予以脱水治疗；纠正水电解质及酸碱的失衡；保持呼吸道通畅；积极抗感染、控制内毒素血症；防治消化道出血与休克；预防和治疗肾功能、心功能及呼吸功能的衰竭。

（3）肝移植：对于肝硬化、慢性肝功能衰竭基础上反复发作的肝性脑病，肝移植可能是唯一有效的治疗方法。

（4）轻微肝性脑病的治疗：轻微肝性脑患者多无明显的症状及体征，但患者可能会有日常活动中操作能了的降低或睡眠障碍。治疗方案：调整饮食结构，适当减少蛋白的摄入量；可试验不吸收双糖如乳果糖、乳梨醇等；睡眠障碍者切忌用苯二氮卓类药物，以免诱发显性的肝性脑病。