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New Algorithm Rules Out Acute-on-chronic Liver Failure Development within 28 Days from Acute Decompensation of Cirrhosis

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 550-559页

作者： Xiaoting Tang Hai Li Guohong Deng Xin Zheng Xianbo Wang Yan Huang yanhang gao Zhongji Meng Zhiping Qian Feng Liu Xiaobo Lu Yu Shi Beiling Li Wenyi Gu Xiaomei Xiang Yan Xiong Yixin Hou Jun Chen Na gao Sen Luo Liujuan Ji Jing Li Rongjiong Zheng Haotang Ren Jinjun Chen Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Department of Gastroenterology Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShang-haiChina Shanghai Institute of Digestive Disease Key Laboratory of Gastroenterology and HepatologyChinese Ministry of Health(Shanghai Jiao Tong University)ShanghaiChina Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijingChina Department of Infectious Diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangshaHunanChina Department of Hepatology The First Hospital of Jilin UniversityChangchunJilinChina Department of Infectious Diseases Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver CancerTaihe HospitalHubei University of MedicineShiyanHubeiChina Department of Liver Intensive Care Unit Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Hepatology The Second Hospital of Shandong Univer-sityJinanShandongChina Infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityXinjiangChina The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhouZhejiangChina Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease HangzhouZhejiangChina National Clinical Research Center of Infectious Disease HangzhouZhejiangChina Hepatology Unit Zengcheng BranchNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina.

Background and Aims:Approximately 10%of patients with acute decompensated(AD)cirrhosis develop acute-on-chronic liver failure(ACLF)within 28 days.Such cases have high mortality and are difficult to predict.Therefore,we aimed to establish and validate an algorithm to identify these patients on hospitalization.Methods:Hospitalized patients with AD who developed ACLF within 28 days were considered pre-ACLF.Organ dysfunction was defined accord-ing to the chronic liver failure-sequential organ failure as-sessment(CLIF-SOFA)criteria,and proven bacterial infec-tion was taken to indicate immune system dysfunction.A retrospective multicenter cohort and prospective one were used to derive and to validate the potential algorithm,re-spectively.A miss rate of<5%was acceptable for the calcu-lating algorithm to rule out pre-ACLF.Results:In the deri-vation cohort(n=673),46 patients developed ACLF within 28 days.Serum total bilirubin,creatinine,international normalized ratio,and present proven bacterial infection at admission were associated with the development of ACLF.AD patients with≥2 organ dysfunctions had a higher risk for pre-ACLF patients[odds ratio=16.58195%confidence interval:(4.271-64.363),p<0.001].In the derivation co-hort,67.5%of patients(454/673)had≤1 organ dysfunction and two patients(0.4%)were pre-ACLF,with a miss rate of 4.3%(missed/total,2/46).In the validation cohort,65.9%of patients(914/1388)had≤1 organ dysfunction,and four(0.3%)of them were pre-ACLF,with a miss rate of 3.4%(missed/total,4/117).Conclusions:AD patients with≤1 organ dysfunction had a significantly lower risk of developing ACLF within 28 days of admission and could be safely ruled out with a pre-ACLF miss rate of<5%.

关键词： Liver cirrhosis Prognosis Liver failure End-stage liver disease Organ dysfunction scores.

Inhibition of the Neddylation Pathway Suppresses Enterovirus Replication

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Virologica Sinica 2021年第6期36卷 1664-1667页

作者： Zhe Zhang Haoran Guo Jing Wang Yan Li yanhang gao Quan Liu Junqi Niu Wei Wei Institute of Virology and AIDS Research First HospitalJilin UniversityChangchun 130021China Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of Translational MedicineFirst HospitalJilin UniversityChangchun 130021China Department of Hepatology First HospitalJilin UniversityChangchun 130021China Department of Emerging Infectious Diseases Institute of Translational MedicineFirst HospitalJilin UniversityChangchun 130021China

Dear Editor,Human enteroviruses(HEVs)comprise polioviruses,coxsackieviruses,echoviruses,rhinoviruses,and the enterovirus subgroups and belong to the genus Enterovirus in the family Picornaviridae(Baggen et al.2018).The HEV genome was thought to contain a single open reading frame(ORF)encoding one polyprotein,which was post-translationally processed into structural capsid proteins(VP1-4)and non-structural accessory proteins(2A,2B,2C,3A,3B,3C,3D)(Baggen et al.2018).Recently,we and others,have identified an additional upstream ORF(Guo et al.2019a;Lulla et al.2019)(ORF2/uORF).

关键词： ORF2 Replication upstream

nterferon alpha （IFNα）-induced TRIM22 interrupts HCV ＇eplication by ubiquitinating NS5A

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Cellular & Molecular Immunology 2016年第1期13卷 94-102页

作者： Chen Yang Xinhao Zhao Dakang Sun Leilei Yang Chang Chong Yu Pan Xiumei Chi yanhang gao Moli Wang Xiaodong Shi Haibo Sun Juan Lv Yuanda gao Jin Zhong Junqi Niu Bing Sun State Key Laboratory of Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Key Laboratory of Molecular Virology and Immunology Institut Pasteur of Shanghai Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China Hepatology Section First Hospital University of Jilin Changchun China Infectious Diseases Department Fourth Hospital University of Jilin Changchun China Experiment Center of Clinical Medicine Affiliated Hospital of Binzhou Medical University Binzhou China

TRIM22, a tripartite-motif （TRIM） protein, is upregulated upon interferon alpha （IFNa） administration to hepatitis C virus （HCV）-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRI M22＇s targeting of the HCV NSSA protein. NS5A is important for HCV replication and for resistance to I FNa therapy. During the first 24 h following the initiation of I FNa treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells （PBMCs） of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA （siRNA）-mediated knockdown of TRIM22 diminished IFNα-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNα treatment and Dlavs an important role in controlling HCV replication in vitro.

关键词： HCV IFNα NS5A TRIM22 ubiquitin

凌风踏浪续写荣光——《临床肝胆病杂志》2024年主编致辞

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临床肝胆病杂志 2024年第1期40卷 9-9页

作者：贾继东牛俊奇高沿航《临床肝胆病杂志》

百舸争流,奋楫者先。2023年,《临床肝胆病杂志》12期重点号专刊权威引领,树立学科发展风向标,奏响学术前沿最强音;创办“柳荫医学峰会”“柳芽医学论坛”“柳荫访谈”系列活动,打造我国医学学术活动品牌新IP;获准加入国际管理与技术编... 详细信息

百舸争流,奋楫者先。2023年,《临床肝胆病杂志》12期重点号专刊权威引领,树立学科发展风向标,奏响学术前沿最强音;创办“柳荫医学峰会”“柳芽医学论坛”“柳荫访谈”系列活动,打造我国医学学术活动品牌新IP;获准加入国际管理与技术编辑学会(ISMTE)和国际医学期刊编辑委员会(ICMJE),接轨国际学术出版规范之路取得新突破;数字出版矩阵建设从“相融”迈向“深融”,实现全媒体、全形态、全流程传播体系高速发展,官方网站年度访问量超236万次,21个新媒体平台年度受众超3000万人次,79场学术直播参会观众超100万人。

关键词：编辑学会新媒体平台数字出版医学论坛传播体系肝胆病官方网站学术前沿

Aldehyde dehydrogenase 2 suppresses cirrhosis and alcohol-induced hepatocellular carcinoma via the inhibition of acetaldehyde-derived DNA damage and multiple oncogenic signaling pathways

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Cancer Biology & Medicine 2018年第S1期15卷 14-14页

作者： Bin gao Wonhyo Seo yanhang gao Tianyi Ren Seungjin Kim Yong He Dechun Feng Junqi Niu Laboratory of Liver Diseases National Institute on Alcohol Abuse and AlcoholismNational Institute of HealthBethesdaMarylandUSA

Objective:Hepatocellular carcinoma(HCC)is the most common primary liver cancer,the fifth most common cancer and the third most common global cause of cancer related deaths.Chronic alcohol consumption is a well-known r... 详细信息

关键词： Aldehyde dehydrogenase suppresses

Investigation on the short-term outcome and prognostic impact of predisposition,and precipitants in inpatients with chronic liver disease from Chinese AcuTe on CHronic LIver FailurE(CATCH-LIFE)cohorts

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Portal Hypertension & Cirrhosis 2023年第3期2卷 115-126页

作者： Yan Zhang Wenting Tan Xiaobo Wang Xin Zheng Yan Huang Beiling Li Zhongji Meng yanhang gao Zhiping Qian Feng Liu Xiaobo Lu Jia Shang Yubao Zheng Weituo Zhang Shan Yin Wenyi Gu Tongyu Wang Jianyi Wei Zixuan Shen Guohong Deng Yi Zhou Yixin Hou Qun Zhang Shue Xiong Jing Liu Liyuan Long Ruochan Chen Jinjun Chen Xiuhua Jiang Sen Luo Yuanyuan Chen Chang Jiang Jinming Zhao Liujuan Ji Xue Mei Jing Li Tao Li Rongjiong Zheng Xinyi Zhou Haotang Ren Yu Shi Hai Li for the CATCH‐LIFE Study Investigators of Chinese(Acute‐on)Chronic Liver Failure(CLIF)Consortium(Ch‐CLIFC) Department of Gastroenterology Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Institute of Digestive Disease NHC Key Laboratory of Digestive DiseasesShanghaiChina Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijingChina Department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Hunan Key Laboratory of Viral Hepatitis Department of Infectious DiseasesXiangya HospitalCentral South UniversityChangshaHunanChina Department of Infectious Diseases Hepatology UnitNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Department of Infectious Disease Taihe HospitalHubei University of MedicineShiyanHubeiChina Department of Hepatology The First Hospital of Jilin UniversityJilinChangchunChina Department of Liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghaiChina Tianjin Institute of Hepatology Nankai University Second People's HospitalTianjinChina Department of Infectious Diseases and Hepatology The Second Hospital of Shandong UniversityJinanShandongChina Infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiangChina Department of Infectious Diseases Henan Provincial People's HospitalZhengzhouHenanChina Deparment of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou CityGuangdongChina Clinical Research Center Shanghai Jiao Tong University School of MedicineShanghaiChina The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhouZhejiangChina Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease HangzhouZhejiangChina Nati

Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.Methods:The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies(NCT02457637 and NCT03641872)conducted in highly endemic hepatitis B virus(HBV)areas.Competing risk analysis was used to evaluate the effect of predispositions,including the etiology and severity of CLDs and precipitants;on sequential 28,90,and 365-day liver transplantation(LT)-free mortality.Results:Among all enrolled patients,76.8%of adverse outcomes(including death and LT)within one year occurred within 90 days.Compared with alcoholic etiology,the association of HBV etiology with poorer outcomes was remarkably on the 28th day(hazard ratio[HR],1.81;95%confidence interval[CI],1.07-3.06;p=0.026);however,and dimin-ished or became insignificant at 90 days and 365 days.Cirrhosis increased the adjusted risk for 365-day(HR,1.50;CI,1.13-1.99;p=0.004)LT-free mortality when compared with noncirrhosis.In patients with cirrhosis,prior decompensation(PD)independently increased the adjusted risk of 365-day LT-free mortality by 1.25-fold(p=0.021);however,it did not increase the risk for 90-day mortality.Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90-day LT-free mortality.Conclusions:The 90-day outcome should be considered a significant endpoint for evaluating the short-term prognosis of hospitalized patients with CLD.Predisposing factors,other than etiology,mainly affected the delayed(365-day)outcome.Timely effective therapy for CLD etiology,especially antiviral treatments for HBV,and post-discharge long-term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.

关键词： cirrhosis precipitant prior decompensation short‐term mortality

《2022年亚太肝病学会临床实践指导:原发性胆汁性胆管炎的诊断与疾病管理》推荐意见

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临床肝胆病杂志 2022年第2期38卷 318-319页

作者：朱晶高沿航《临床肝胆病杂志》编辑部吉林大学第一医院感染病中心肝病科长春130021

原发性胆汁性胆管炎(PBC)是一种慢性肝内胆汁淤积性疾病,其发病机制尚未完全阐明。环境因素引发的免疫功能失调可能对遗传易感宿主的小叶间胆管产生自身免疫反应。PBC常见于中年女性,可表现为疲劳和瘙痒,或ALP/GGT无症状升高。病理特征... 详细信息

原发性胆汁性胆管炎(PBC)是一种慢性肝内胆汁淤积性疾病,其发病机制尚未完全阐明。环境因素引发的免疫功能失调可能对遗传易感宿主的小叶间胆管产生自身免疫反应。PBC常见于中年女性,可表现为疲劳和瘙痒,或ALP/GGT无症状升高。病理特征为进行性、非化脓性、破坏性肝内胆管炎,最终可形成肝硬化。抗线粒体抗体(AMA),尤其是其M2亚型(AMA-M2),对PBC诊断具有高度敏感性和特异性。

关键词：原发性胆汁性胆管炎诊断疾病管理诊疗准则(主题)

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铜代谢失调与细胞损伤及肝病的关系

临床肝胆病杂志 2023年第9期39卷 2244-2251页

作者：柳涛刘雅丽张飞宇高沿航吉林大学第一医院肝胆胰内科长春130021

铜是人体必需的微量元素,在维持人体健康方面起着至关重要的作用。铜参与人体许多代谢过程,铜代谢失调会导致糖耐量受损和血脂异常等代谢障碍。肝脏在维持体内铜的平衡中起着核心作用,铜缺乏或过量会导致细胞损伤和肝功能障碍。近期有... 详细信息

铜是人体必需的微量元素,在维持人体健康方面起着至关重要的作用。铜参与人体许多代谢过程,铜代谢失调会导致糖耐量受损和血脂异常等代谢障碍。肝脏在维持体内铜的平衡中起着核心作用,铜缺乏或过量会导致细胞损伤和肝功能障碍。近期有关铜代谢研究的最新进展揭示了铜代谢失调可通过影响氧化应激、蛋白酶体、铜死亡和血管生成引起细胞损伤,并有助于阐明由铜代谢失调引起的肝脏疾病和代谢障碍的假设机制。本文综述了近年来铜代谢失调在细胞损伤/死亡和慢性肝病(包括威尔逊氏病、非酒精性脂肪性肝病、肝细胞癌)中的研究进展,将有助于确定未来的研究重点。

关键词：肝疾病细胞死亡铜代谢

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乙醛脱氢酶与肝癌

中华肝脏病杂志 2020年第6期28卷 475-478页

作者：王文君高沿航吉林大学第一医院肝胆胰内科长春130021

乙醛脱氢酶2(ALDH2)是肝脏中乙醛(乙醇代谢产物)代谢的关键酶,全球约有8%、东亚有30%~40%的人口携带编码无/低活性ALDH2的缺陷基因。近期,诸多研究关注了ALDH与病毒性肝炎、酒精性肝病、肝纤维化以及肝癌的关系。尤其,ALDH2表达与肝癌... 详细信息

乙醛脱氢酶2(ALDH2)是肝脏中乙醛(乙醇代谢产物)代谢的关键酶,全球约有8%、东亚有30%~40%的人口携带编码无/低活性ALDH2的缺陷基因。近期,诸多研究关注了ALDH与病毒性肝炎、酒精性肝病、肝纤维化以及肝癌的关系。尤其,ALDH2表达与肝癌发病风险、发病机制及预后密切相关,并可作为潜在的治疗靶点。现就该领域新进展及新研究方向进行总结及评述。

关键词：缺陷基因乙醛脱氢酶酒精性肝病 ALDH2 乙醇代谢肝纤维化发病风险肝癌