目的 为中草药肝损伤(HILI)的临床诊断提供基于模块化证据链的路线图.方法 分析中草药应用与肝损伤发生的时序关系、中草药自身相关肝毒性信息、合并用药情况的评估及非药物性肝损伤因素的排查等4大模块信息,并进行证据链的逻辑组合.结果及结论 HILI的临床诊断原则与现代药(化学药和生物医药)相似,但具有自身的特点和难点.在阐述中草药与肝损伤时序关系多样性的基础上,对中草药相关肝毒性、合并用药肝毒性及其他肝损伤病因的存在情况进行了多维评估,构建了基于完整证据链的HILI临床诊断路线图.罗素优克福因果关系评估法(RUCAM)量表对HILI的诊断有参考价值,改良电子化因果关系评估法(RECAM)量表对HILI的诊断价值有待在真实世界临床进一步论证,必要时可借助结构化专家观点程序(SEOP)确认诊断;肝活检病理组织学的某些病变特点有助于明确HILI的诊断;HILI相关生物标志物有待深入探索.

In March 2022, EASL released a new version of the clinical practice guidelines on haemochromatosis. Haemochromatosis is characterized by elevated transferrin saturation (TSAT) and progressive iron overload mainly involving the liver, and early diagnosis and venesection can prevent liver cirrhosis, hepatocellular carcinoma, diabetes, arthritis, and other complications. For patients with p.Cys282Tyr homozygous mutation of the hemochromatosis gene HFE, haemochromatosis can be diagnosed if serum iron parameters show TSAT ＞45% and ferritin ＞200 μg/L in female patients, or TSAT ＞50% and ferritin ＞300 μg/L in male patients and postmenopausal female patients. If a patient has elevated TSAT and ferritin and belongs to other HFE genotypes, magnetic resonance or liver biopsy is needed to confirm iron overload in the liver. Liver fibrosis stage and damage to other organs should be carefully assessed at the time of diagnosis, which will help to determine management strategies. Hepatocellular carcinoma should be screened for patients with progressive liver fibrosis. The goal of venesection is to achieve ferritin ＜50 μg/L during the induction stage and ferritin ＜100 μg/L during the maintenance stage.

2022年6月美国肝病学会(AASLD)发布了关于药物及草药和膳食补充剂(HDS)所致肝损伤的实践指导(Practice Guidance),针对药物性肝损伤的分类(固有肝毒性、特异质肝毒性和间接肝毒性)、特异质性DILI的流行病学和风险因素、DILI的诊断和鉴别诊断、DILI患者肝活检的时机和价值、DILI的因果关系评估、HDS的肝毒性及易感因素和临床结局、特异质性DILI的自然史及治疗和预后、对乙酰氨基酚的肝毒性、临床实践中DILI的早期发现、DILI的未来研究方向等方面进行了详细阐述,并提出了64条指导说明(Guidance Statements),这对于临床上识别、治疗和预防DILI具有重要参考价值.

SARS冠状病毒2(SARS-CoV-2)奥密克戎(Omicron)变异株是继Alpha、Beta、Gamma及Delta变异株之后新出现的一种需关注的变异株,其抗原特别是刺突蛋白受体结合区(RBD)的氨基酸突变明显多于其他变异株,使得Omicron变异株的感染性、传播性及免疫逃逸性明显增强,疫苗接种的保护效果下降,感染潜伏期明显缩短,但致病力也明显下降,绝大多数感染者表现为无症状或轻症;重症患者的病情加重多与原有基础疾病的进展相关.及时筛查并医学隔离感染者,做好各项个人防护措施以切断传播途径,积极推进疫苗接种以保护易感人群,是控制疫情传播的重要举措.少部分患者可出现所谓长新型冠状病毒肺炎(COVID-19)、后COVID-19综合征或后COVID-19状态,应加强长期随访.有效的抗病毒治疗可以缩短感染进程及促进恢复,还有助于疫情控制,因此研发具有良好成本效益比且方便服用的抗病毒药物是今后重要的研究方向之一.

目的 评估牛磺熊去氧胆酸联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝病(NAFLD)的疗效和安全性.方法 186例N A FLD患者分为两组,A组患者给予口服牛磺熊去氧胆酸、多烯磷脂酰胆碱治疗,B组给与口服谷胱甘肽、多烯磷脂酰胆碱治疗,疗程24周,比较两组患者肝功能、血脂、CAP值.结果 A组ALT、AST、GGT、ALP、TC、TG、CAP值基线水平分别为:(102.5±28.5)U/L、(80.1±22.4)U/L、(148.2±36.9)U/L、(151.3±32.5)U/L、(7.6±1.9)mmol/L、(3.4±1.3)mmol/L、(288.7±35.4)dB/m,治疗12周为(74.4±24.6)U/L、(61.6±19.5)U/L、(97.4±29.5)U/L、(110.6±25.3)U/L、(6.2±1.7)mmol/L、(2.5±1.1)mmol/L、(259.4±32.2)dB/m,治疗24周为(46.3±19.7)U/L、(42.2±16.7)U/L、(63.7±21.8)U/L、(82.4±19.7)U/L、(5.0±1.4)mmol/L、(1.7±0.9)mmol/L、(241.7±29.4)dB/m,治疗12、24周,ALT、AST、GGT、ALP、TC、TG、CAP值均低于基线水平(P<0.05).治疗12周,A组ALT、AST、GGT、ALP、CAP值低于B组(P<0.05),TC、TG值差异无统计学意义;治疗24周,A组ALT、AST、GGT、ALP、TC、TG、CAP值低于B组(P<0.05).治疗过程中,A组患者有4例在治疗初期出现轻微胃部隐痛、恶心不适,B组有3例出现稀便、轻微纳差症状.结论 牛磺熊去氧胆酸联合多烯磷脂酰胆碱可有效改善NAFLD患者的肝功,降低血脂和CAP值,安全性良好.

目的 了解Crigler-Najjar综合征Ⅱ型的遗传特点及诊断方法.方法 收集1例Crigler-Najjar综合征Ⅱ型患者的病史资料、肝脏生化、影像学结果、肝脏病理资料及本人与父母的UGT1A1的基因测序结果.结果 Crigler-Najjar综合征Ⅱ型患者的胆红素升高通常大于5倍正常值上限,为间接胆红素明显升高,ALT、AST均正常,病理未见肝细胞炎症坏死,患者为UGT1A1的基因检测示第5外显子c.1456T>G(p.Tyr486Asp)的纯合突变,其父母均为该突变的杂合子.苯巴比妥诱导治疗有效.结论 c.1456T>G(p.Tyr486Asp)的基因突变为本例患者及其家系的致病基因,患者为常染色体隐性遗传性疾病,表现为间接胆红素明显升高,肝脏无炎症损伤,苯巴比妥诱导有效.

新型冠状病毒肺炎(COVID-19)大流行严重威胁着人类的生命健康和社会发展.为应对这一公共卫生事件,全球各国迅速研发了多种COVID-19疫苗.迄今为止,已有41项疫苗获得紧急使用批准,疫苗的使用显著降低了COVID-19的发病率和病死率.然而,随着病毒不断变异,尤其奥密克戎变异株的出现,疫苗产生的免疫保护作用受到了挑战,COVID-19疫苗的持续研发工作还任重道远.本文就目前COVID-19疫苗的研究情况,以及突变病毒株对疫苗研究带来的挑战进行综述.

随着人类生活方式、疾病谱和发病率的改变,加之健康保健需求,新的药物和保健品不断开发和上市,与药物相关的肝损伤以惊人速度增长,因肝损伤而增加黑框警示或被撤销的药物时有所闻.在病毒性肝炎的预防和诊治问题得到长足进展的新态势下,药物性肝损伤(DILI)已成为临床急性肝损伤的常见原因,其在临床急性肝损伤病因中的占比不断上升,且一部分急性DILI还可能转为慢性DILI.因此,DILI绝不仅仅是临床肝病专业医生,而是全体临床医生都无法避免和必须加以重视的问题.

Roussel Uclaf因果关系评估量表(RUCAM)量表是近30年来最受临床欢迎和肯定的药物性损伤(DILI)评估量表,其参数相对全面,操作界面相对友好,但也存在主观性较大、操作说明不够详细、与专家观点一致性不够高、某些参数的设置和评分标准缺乏循证医学证据、存在观察偏差等不足.新近欧美部分学者提出了基于美国DILIN研究和西班牙DILI注册研究数据设计的"改良电子化因果关系评估量表"(RECAM),其保留了RUCAM的基本逻辑,但对具体内容和结构做了大幅改进,特别是将RUCAM的7类参数整合为RECAM的5个区块,剔除了RUCAM第3项(危险因素)和第4项(同时使用的药物),对第6项(药物既往肝毒性信息)采用LiverTox网站分类标准进行评分,对常见肝损伤病因的分层评估更详细,将再激发和肝活检等列为附加评估项.RECAM评分等级:≥8分,极可能(highly likely/highly probable);7～4分,很可能(probable);3～-3分,可能(possible);≤-4分,不可能或排除(unlikely/excluded).初步研究显示,RECAM与RUCAM对诊断DILI至少一样有效,但RECAM在判断两极值方面优于RUCAM.RECAM在临床上的适用性,以及是否可用于HDS所致肝损伤的评估,尚待论证.

2022年3月,以奥密克戎BA.2和BA.2.2变异株为主要流行株的新型冠状病毒(简称"新冠病毒")肺炎疫情在上海蔓延.为彻底、快速阻断疫情传播,上海市建造市区两级方舱医院,用于隔离收治轻型确诊患者及无症状感染者.文章回顾了国内外方舱医院的发展沿革,进而结合上海新冠病毒肺炎疫情的特点,着重介绍上海国家会展中心方舱医院第四分院的救治实践,分析救治中存在的床位规模大、收治任务重、老年患者疫苗接种率低、疫情初期防护物资紧缺、心理问题突出、医院感染风险高等主要问题,并介绍针对上述问题采取的主要应对措施,为当前及今后新冠病毒肺炎疫情防控提供宝贵经验,并对未来方舱医院的建设提出展望.

The risk factors for drug-induced liver injury (DILI) involve host factors (including general non-genetic factors and idiosyncratic genetic and immune factors), drug-related factors, and environmental factors. The pathogenesis of DILI can be classified as intrinsic (or direct) hepatotoxicity, idiosyncratic hepatotoxicity, and indirect hepatotoxicity, as well as tumorigenicity and carcinogenicity of some drugs to the liver. The pathogenesis of different types of hepatotoxicity not only has significant differences, but also has internal correlation at multiple links. The three-step model centered on mitochondrial permeability transition (MPT) and a two-stage model with liver cell regeneration and liver tissue repair capacity as the determinants of different outcomes display the mechanism progress of DILI from different perspectives. Clarification of the complex pathogenesis of DILI needs long-term collection of clinical cases and systematic studies, which is of great significance for the scientific prevention, diagnosis, and treatment of DILI.

2019年以来,严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的冠状病毒病-2019(coronavirus disease 2019,COVID-19;国内习惯称为新型冠状病毒肺炎)疫情肆虐全球.据世界卫生组织(WHO)评估,截至2021年1月,全球已有近1亿人感染SARS-CoV-2.有慢性肝病(chronic liver diseases,CLD)的人群,尤其是肝硬化、肝胆恶性肿瘤、等待肝移植以及肝移植后处于免疫抑制状态的患者,发生各种感染的风险较高,感染后病死率也较高.同理,肝硬化患者感染SARS-CoV-2后出现严重临床过程的风险很高.因此,CLD患者尽早接种包括 SARS -Cov-2疫苗在内的相关病原体疫苗是一种重要的保护措施.然而,由于CLD患者的免疫功能受损,接种疫苗后的免疫应答可能不够充分.

目的研究慢性乙型肝炎（CHB）患者经核苷（酸）类似物（NUCs）治疗前后肝内T细胞受体（TCR）文库变化特征。方法选取10例接受替比夫定（LdT）治疗的CHB患者,根据治疗104周后是否发生HBeAg血清学转换分为两组。通过高通量测序分析LdT治疗前后肝穿刺组织中TCRβCDR3区,并分析TCR文库特征及其与血清学参数相关性。结果经过104周NUCs治疗,发生HBeAg血清学转换的CHB患者肝内TCR文库不重复VJ组合（151.0比71.0,P=0.043）、CDR3克隆型（223.0比109.0,P=0.043）,以及标准化香农熵（0.58比0.17,P=0.043）均表现为文库多样性显著下降,同时这些患者治疗前后HBsAg的变化程度与消失克隆型变化呈正相关（r=0.9,P=0.037）。结论 CHB患者口服NUCs治疗可引起肝内TCR文库发生有利于特定T细胞克隆增生的变化,这对于促进HBeAg血清学转换有重要意义,提示在NUCs抗病毒治疗的基础上联合免疫治疗可能会更有助于HBV的控制。

2021 年 5 月,美国胃肠病学会(American College of Gastroenterology,ACG)发布了新版《ACG临床指南:特异质性药物性肝损伤的诊断和处理》(简称《指南》)[1].这是该《指南》自2014年首次发布以来[2],时隔7 年进行的修订和更新.现对该《指南》进行介绍.

Objective:To explore the patterns and causes of occupational exposure to infectious diseases (OEID) among frontline medical staffs (FMS) in coronavirus disease 2019 (COVID-19) isolation wards (CIW), and the particularity of post-OEID management and the measures to prevent OEID.Methods:A total of 1 061 FMS of Wuhan Huoshenshan Hospital from February 4 to March 21, 2020 were enrolled. The OEID of FMS was investigated and analyzed from the perspectives of FMS physical and psychological conditions, protective equipment, infection-control related regulations and procedures, local air quality, exposure patterns, and the particularity of emergency treatment after exposure.Results:The incidence of OEID among FMS was 2.0%(21/1 061). The nurses and doctors accounted for 95.2%(20/21) and 4.8%(1/21), respectively. The incidences in 17 general wards and two intensive care units (ICU) were 71.4%(15/21) and 28.6%(6/21), respectively. Nearly 90.5%(19/21) and 9.5%(2/21) of the OEID events occurred in contaminated area and potential contaminated area, respectively. About 23.8%(5/21) of the OEID events were air exposure of oral-nasal skin, mucosa and respiratory tract, which was secondary to uncontrollable vomiting, and 76.2%(16/21) were pricking injuries. The inducement factors involved poor quality and inappropriate wearing of some goggles, atomization of the inside of goggles leading to blurring vision, chest distress and decreased sense of touch and operational flexibility related to level-3 protection equipment, poor air quality, FMS physical and psychological conditions, etc. Under the direction of "the Procedures for Handling OEID" , all incidents are properly handled and no FMS was infected by 2019 novel coronavirus and blood-borne pathogens. No new OEID event was found after the strict implement of set of preventive measures.Conclusions:The OEID among FMS in CIW is attributed to multiple causes. The optimized process that takes into account the specificity of OEID management for both COVID-19 and blood-borne infectious diseases can effectively prevent potential post-exposure infections. And reasonable precautions can fully reduce the risk of OEID of FMS in CIW.

目的 比较RACE法和Sansure法检测核苷(酸)类似物经治和初治慢性乙型肝炎患者HBV RNA定量值的相关性和一致性.方法 纳入南方医科大学南方医院门诊随访的慢性乙型肝炎患者并收集患者血清学、病毒学和生化数据.采集患者血清分别用RACE法和Sansure法检测HBV RNA水平,分析两者检测值的相关性和一致性.结果 共入组101例慢性乙型肝炎患者,其中接受核苷(酸)类似物治疗62例,未曾接受核苷(酸)类似物治疗39例.治疗和未治疗组的HBsAg和HBV DNA水平存在显著差异,HBV RNA水平差异有统计学意义.两种方法相比,RACE法比Sansure法检测到的阳性患者更多(60/101和56/101),平均检测值更高(3.16和2.53 lg拷贝/mL).HBV DNA水平与HBV RNA水平在治疗组没有相关性(RACE法R2=0.4406,Sansure法R2=0.5081),在未治疗组显著相关(RACE法R2=0.8448,Sansure法R2=0.8667).RACE法和Sansure法HBV RNA检测值显著相关(R2=0.8740);此外,两种HBV RNA检测方法Bland-Altman分析显示,95％ 一致性界限的范围较窄(在治疗组为-1.789～0.22 lg拷贝/mL,在未治疗组为-2.25～0.53 lg拷贝/mL);以RACE法为基准,Sansure法的偏差在治疗组为-0.78 lg拷贝/mL,在未治疗组为-0.86 lg拷贝/mL.两种方法线性回归后方程:Y(Sansure法)=0.9189X(RACE法)-0.3754.结论 两种HBV RNA检测方法的相关性显著,一致性较好,可用线性回归方程互算;两种HBV RNA检测方法均可有效弥补血清HBV DNA检测对指导慢性乙型肝炎临床诊治方面的不足.

目的 感染防控是遏制新型冠状病毒肺炎(COVID-19)传播的重要环节.武汉火神山医院作为专科医院,承担了大量COVID-19患者的救治任务,探讨一线救治中感染防控关键技术流程,提出针对性的防控措施,对于保障医患安全,提高救治成功率具有重要意义.方法 根据国家指南和感染控制目标要求,结合医院工作实际,从隔离技术、标准预防、清洁消毒和医疗废物处理等关键环节着手,制定具体技术流程,并应用于COVID-19医疗诊疗及防控工作实践.结果 从2月3日-4月3日,武汉火神山医院共收治患者3 059例,治愈出院2 806例,1 400名医务工作人员均未发生感染.结论 2个月的临床实践证明,以上关键技术流程实用、有效,可为制定和完善COVID-19的感染防控方案提供参考.

目的 探讨应急建设新型冠状病毒肺炎专科医院过程中的感染控制工作阶段与特点,为未来开展此类工作提供借鉴与参考.方法 以国家相关法律、法规为依据,分析总结在新型冠状病毒肺炎专科医院应急建设过程中感染控制工作主要特点和关键环节,提出感染控制工作策略.结果 应急建设新型冠状病毒肺炎专科医院的感染防控工作分为开局攻坚、持续改进和收尾总结三个阶段,在这三个不同时期感染防控工作各有侧重,第一阶段重点为组织指挥、流程改造和个人防护流程;第二阶段重点为感控制度完善、监测预警、应急响应等;第三阶段重点为制度总结和各类终末消毒方案的制定与落实.结论 新型冠状病毒肺炎专科医院应急建设过程中感染控制工作阶段性特点明显,应抓住重点并形成有效应急工作机制.

Drug-induced liver injury (DILI) with extrahepatic adverse drug reaction (EHADR) is the injury of extrahepatic organs which is caused by the same drug inducing liver injury and may occur simultaneously or successively with DILI, such as the skin, gastrointestinal tract, blood system, cardiovascular system, and bone and joint system, and it should be taken seriously in clinical practice. DILI with EHADR is not rare, and its pathogenesis may be associated with various factors including the physicochemical properties, distribution, metabolism, excretion, biological activity, and immunological properties of drugs, host genetic background, and underlying diseases. The diagnosis and treatment of DILI with EHADR is more challenging than that of DILI alone.

火神山医院作为一所收治新型冠状病毒肺炎确诊患者的新建专科传染病医院,为达到"零感染"的医院感控要求,从新型冠状病毒肺炎流行病学和临床特征出发,制定了多项感染控制与预防的制度和措施.该文对院内感染控制与预防的措施进行了总结和探讨.