Antiviral Treatment for HCV Recurrence After Liver Transplantation
直接抗病毒药物治疗肝移植术后HCV感染复发的有效性和安全性分析
直接抗病毒药物治疗肝移植术后HCV感染复发的有效性和安全性分析孙力波;鲁俊锋;张海涛;赵晓飞;栗光明【期刊名称】《传染病信息》【年(卷),期】2022(35)3【摘要】目的评估直接抗病毒药物(direct antivirus agent, DAA)治疗肝移植术后HCV感染复发的有效性和安全性。
方法回顾性分析首都医科大学附属北京佑安医院2011年2月—2018年12月收治的14例肝移植术后HCV感染复发患者的DAA治疗临床数据,比较患者基线与治疗结束后肝肾功能、血常规、凝血功能、病毒学水平以及无创纤维化评分天冬氨酸转氨酶血小板比率指数(aspartate aminotransferase-platelet ratio index, APRI)的差异。
利用电子病历系统和电话随访收集患者治疗期间不良反应发生情况。
结果所有患者均在治疗结束时达到病毒学清除,12周、24周持续病毒学应答率均为100%,DAA治疗后随访17~44个月,期间均未见病毒学复发。
与基线水平相比,治疗终点时ALT、AST、TBIL、γ-谷氨酰转移酶以及无创纤维化评分APRI显著下降,WBC、HGB、PLT、CRE、肾小球滤过率和血糖等指标均未见显著变化。
DAA治疗期间共3例患者发生不良反应,均为轻度,可自然缓解。
结论肝移植术后HCV感染复发的DAA治疗是安全有效的。
【总页数】4页(P228-231)【作者】孙力波;鲁俊锋;张海涛;赵晓飞;栗光明【作者单位】首都医科大学附属北京佑安医院普通外科中心器官移植科;首都医科大学附属北京佑安医院普通外科中心肝病内科【正文语种】中文【中图分类】R512.63;R978.7【相关文献】1.直接作用抗病毒药物治疗丙型肝炎肝硬化和肝移植术后丙型肝炎复发的初步临床观察2.直接抗病毒药物治疗肝移植术后丙型肝炎复发患者的临床分析3.直接作用抗病毒药物治疗慢性HCV感染者的初步临床分析4.直接抗病毒药物治疗HCV相关肝细胞癌肝移植受者的研究进展5.索非布韦/雷迪帕韦联合治疗肝移植术后HCV 再感染患者的有效性及安全性因版权原因，仅展示原文概要，查看原文内容请购买。
关于乙肝英语
关于乙肝英语作为医学英语词汇专家，我能够为你提供与乙肝相关的常见英语词汇和信息。
以下是与乙肝相关的专业术语和常用表达，包括定义、症状、诊断、治疗等方面的内容：乙肝定义相关词汇：Hepatitis B：乙型肝炎，是由乙型肝炎病毒（HBV）引起的肝炎。
HBV (Hepatitis B Virus)：乙型肝炎病毒，是导致乙型肝炎的病原体。
乙肝症状相关词汇：Jaundice：黄疸，乙肝患者常见的症状之一，表现为皮肤和眼白发黄。
Fatigue：疲劳，乙肝患者常感到的非特异性症状。
Abdominal pain：腹痛，可能是乙肝引起的肝脏肿大或炎症导致的。
Nausea and Vomiting：恶心和呕吐，乙肝患者可能出现的消化系统症状。
Dark urine and light-colored stools：尿液深黄、大便颜色变浅，与黄疸有关的症状。
乙肝诊断相关词汇：HBsAg (Hepatitis B Surface Antigen)：乙型肝炎表面抗原，血液检测中用于诊断乙肝感染的标志物。
Anti-HBs (Hepatitis B Surface Antibody)：乙型肝炎表面抗体，表明机体对HBV有免疫力或感染过HBV。
HBV DNA test：乙型肝炎病毒DNA检测，用于确定病毒载量和监测治疗效果。
Liver function tests (LFTs)：肝功能测试，包括转氨酶等指标，用于评估肝脏损伤程度。
Liver biopsy：肝活检，通过取小块肝组织进行显微镜检查以确诊和评估肝炎的严重程度。
乙肝治疗相关词汇：Antiviral therapy：抗病毒治疗，使用抗病毒药物抑制HBV复制。
Interferon：干扰素，一种用于乙肝治疗的免疫调节剂。
Nucleos(t)ide analogues：核苷（酸）类似物，一类抗病毒药物，如拉米夫定、恩替卡韦等。
Liver transplantation：肝移植，对于终末期肝病患者的一种治疗方法。
慢加急性肝衰竭
GUIDELINESAcute-on-chronic liver failure:consensus recommendationsof the Asian Pacific Association for the Study of the Liver (APASL)2014Shiv Kumar Sarin•Chandan Kumar Kedarisetty•Zaigham Abbas•Deepak Amarapurkar•Chhagan Bihari•Albert C.Chan•Yogesh Kumar Chawla•A.Kadir Dokmeci•Hitendra Garg•Hasmik Ghazinyan•Saeed Hamid•Dong Joon Kim•Piyawat Komolmit•Suman Lata•Guan Huei Lee•Laurentius A.Lesmana•Mamun Mahtab•Rakhi Maiwall•Richard Moreau•Qin Ning•Viniyendra Pamecha•Diana Alcantara Payawal•Archana Rastogi•Salimur Rahman•Mohamed Rela•Anoop Saraya•Didier Samuel•Vivek Saraswat•Samir Shah•Gamal Shiha•Brajesh Chander Sharma•Manoj Kumar Sharma•Kapil Sharma•Amna Subhan Butt•Soek Siam Tan•Chitranshu Vashishtha•Zeeshan Ahmed Wani•Man-Fung Yuen•Osamu Yokosuka•the APASL ACLF Working PartyReceived:4April2014/Accepted:25August2014/Published online:26September2014ÓAsian Pacific Association for the Study of the Liver2014Abstract Thefirst consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL)set up in2004on acute-on-chronic liver failure (ACLF)was published in2009.Due to the rapid advancements in the knowledge and available information, a consortium of members from countries across Asia Pacific,‘‘APASL ACLF Research Consortium(AARC),’’was formed in2012.A large cohort of retrospective and prospective data of ACLF patients was collated and fol-lowed up in this data base.The current ACLF definition was reassessed based on the new AARC data base.These initiatives were concluded on a2-day meeting in February 2014at New Delhi and led to the development of thefinal AARC consensus.Only those statements which were based on the evidence and were unanimously recommended were accepted.These statements were circulated again to all the experts and subsequently presented at the annual confer-ence of the APASL at Brisbane,on March14,2014.The suggestions from the delegates were analyzed by the expert panel,and the modifications in the consensus were made. Thefinal consensus and guidelines document was pre-pared.After detailed deliberations and data analysis,theS.K.Sarin(&)ÁC.K.KedarisettyÁH.GargÁR.MaiwallÁM.K.SharmaÁK.SharmaÁC.VashishthaÁZ.A.Wani Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi110070,Indiae-mail:shivsarin@Z.AbbasDepartment of Hepatogastroenterology,Sindh Institute of Urology and Transplantation,Karachi,PakistanD.AmarapurkarDepartment of Gastroenterology and Hepatology,Bombay Hospital and Medical Research,Mumbai,IndiaC.BihariÁA.RastogiDepartment of Pathology,Institute of Liver and Biliary Sciences, New Delhi110070,IndiaA.C.ChanDivision of Hepatobiliary and Pancreatic Surgery,and Liver Transplantation,Department of Surgery,The University of Hong Kong,Hong Kong,China Y.K.ChawlaDepartment of Hepatology,Post Graduate Institute of Medical Education and Research,Chandigarh,IndiaA.K.DokmeciDepartment of Gastroenterology,Ankara University School of Medicine,Ankara,TurkeyH.GhazinyanDepartment of Hepatology,Nork Clinical Hospital of Infectious Diseases,Yerevan,ArmeniaS.HamidÁA.S.ButtDepartment of Medicine,Aga Khan University Hospital, Karachi,PakistanD.J.KimCenter for Liver and Digestive Diseases,Hallym University Chuncheon Sacred Heart Hospital,Chuncheon,Gangwon-Do, Republic of KoreaHepatol Int(2014)8:453–471 DOI10.1007/s12072-014-9580-2original proposed definition was found to withstand the test of time and identify a homogenous group of patients pre-senting with liver failure.Based on the AARC data,liver failure grading,and its impact on the‘‘Golden therapeutic Window,’’extra-hepatic organ failure and development of sepsis were analyzed.New management options including the algorithms for the management of coagulation disor-ders,renal replacement therapy,sepsis,variceal bleed, antivirals,and criteria for liver transplantation for ACLF patients were proposed.Thefinal consensus statements along with the relevant background information are pre-sented here.Keywords Liver failureÁChronic liver diseaseÁCirrhosisÁAscitesÁAcute liver failure and Scute liver failureIntroductionLiver failure is a common medical ailment,and its inci-dence is increasing with the use of alcohol and growing epidemic of obesity and diabetes.It can present as acute liver failure(ALF)(in the absence of any preexisting liver disease),acute-on-chronic liver failure(ACLF)(an acute deterioration of known or unknown chronic liver disease), or an acute decompensation of an end-stage liver disease. Each of these is a well-defined disease entity with a homogenous population of patients with expected out-comes.Due to an overlap and lack of clarity of definitions and outcomes,entities like late-onset liver failure and subacute hepatic failure have become less relevant and are not often used.The growing interest in ACLF after thefirst consensus definition of ACLF from APASL[1]is evident by the fact that more than200publications as full paper have been published and the trend is surely increasing.A seminal paper from the EASL-CLIF consortium on the definition and out-come of ACLF has since appeared[2]based on the work of experts from several European and Western countries.The group of investigators working on liver failure in the Asia–Pacific region working for the past decade carefully analyzed the patient characteristics,natural history,and outcome over the years.The group met on yearly basis and collated data on Web site(www.aclf.in)since2009.The data were analyzed at meeting in China and Dhaka in2012,with the setting up of the APASL ACLF Research Consortium(AARC).The ret-rospective and prospective data of patients from different centers were analyzed,and the completed patient records were utilized for defining predictors of mortality and grades of liver failure and incidence of other organ failures.Experts from all over the globe,especially from the Asia–Pacific region,and members of thefirst consensus group were requested to identify pertinent and contentious issues in ACLF.Six major contentious issues and unmet needs in the management of ACLF were approached for the update:(1)what constitutes an acute insult;(2)whether chronic liver disease should be included or only cirrhosis of the liver in defining underlying liver disease;(3)the role of SIRS and sepsis as a cause or consequence of liver failure;(4)the incidence and impact of non-hepatic organ failures;(5)the relevance and grades of liver failure,the urgency, and outcome of liver transplant;and(6)an AARC pre-diction model of outcome of ACLF.The process for the development of the recommendations and guidelines included review of all available published literature onP.KomolmitDivision of Gastroenterology and Hepatology,Department of Medicine,Chulalongkorn University,Bangkok,ThailandtaDepartment of Nephrology,Institute of Liver and Biliary Sciences,New Delhi110070,IndiaG.H.LeeDepartment of Gastroenterology and Hepatology,National University Health System,Singapore,SingaporeL.A.LesmanaDivision of Hepatology,University of Indonesia,Jakarta, IndonesiaM.MahtabÁS.RahmanDepartment of Hepatology,Bangabandhu Sheikh Mujib Medical University,Dhaka,BangladeshR.MoreauInserm,U1149,Centre de recherche sur l’Inflammation(CRI), Paris,France R.MoreauUMR_S1149,Labex INFLAMEX,Universite´Paris Diderot Paris7,Paris,FranceR.MoreauDe´partement Hospitalo-Universitaire(DHU)UNITY,Service d’He´patologie,Hoˆpital Beaujon,APHP,Clichy,FranceQ.NingDepartment of Infectious Disease,Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan,ChinaV.PamechaDepartment of Hepatobiliary Surgery,Institute of Liver and Biliary Sciences,New Delhi110070,IndiaD.A.PayawalDepartment of Hepatology,Cardinal Santos Medical Center, Manila,PhilippinesACLF by individual and group of experts;preparation of a review manuscript and consensus statements based on Oxford system of evidence-based approach[3]for devel-oping the consensus statements,circulation of all consen-sus statements to all experts,an effort to define the acute hepatic insults;the underlying chronic liver disease,a survey of the current approaches for the diagnosis and management of ACLF;discussion on contentious issues; and deliberations to prepare the consensus statement by the experts of the working party.A2-day meeting was held on February22–23,2014,at New Delhi,India,to discuss and finalize the recommendations and guidelines.These state-ments were circulated to all the experts,posted on the AARC Web site(www.aclf.in),and subsequentlyfinalized. These consensus statements and guidelines for the man-agement of such patients are included in this review.A brief background is included providing the available data and published information on each issue.Statements from thefirst consensus have been reproduced at places to give a background and continuity.The concept of ACLF and need for a definitionAcute liver failure is a well-defined medical emergency which is defined as a severe liver injury,leading to coag-ulation abnormality usually with an INR C1.5,and any degree of mental alteration(encephalopathy)in a patient without pre-existing liver disease and with an illness of up to4weeks duration[4].A proportion of patients who present with features mimicking ALF,however,have an underlying chronic liver disease or cirrhosis of the liver. These patients grouped together as acute-on-chronic liver failure(ACLF)also have a poor outcome.These patients are distinctly different from a group of cirrhotic patients who are already decompensated and have a sudden worsening of their condition due to an acute event as liver failure is central.The ACLF is a clinical syndrome manifesting as acute and severe hepatic derangements resulting from varied insults.This term wasfirst used in1995to describe a condition in which two insults to liver are operating simultaneously,one of them being ongoing and chronic, and the other acute[5].Over the years,nearly thirteen different definitions have been proposed,creating confu-sion in thefield[6].Any patient who has an underlying chronic liver disease with superimposed acute insult is being labeled as having ACLF,irrespective of evidence of liver failure per se or evidence of preexisting cirrhotic decompensation.Several investigators were concerned that this would lead to overlap with decompensated liver dis-ease.The main emphasis of the third consensus meeting of the APASL working party was to identify from this large group of patients,a subset of patients who have a relatively homogenous presentation and potentially similar outcome and restrict the use of the term‘‘acute-on-chronic liver failure’’to this subset.The2009APASL definition had provided a basis to select patients presenting with a distinct syndrome.To cover the entire spectrum of these patients, from mild to most severe,patients with chronic liver dis-ease with or without cirrhosis of the liver were included and carefully analyzed.It is understandable,though not well defined,that the nature and degree acute insult and the status of the underlying chronic liver disease would determine the outcome of the patient(Fig.1).To give clarity to the primary event,a hepatic insult, jaundice and coagulopathy,which defined liver failure was considered essential.In acute liver failure,though hepatic encephalopathy is part of the definition,it follows liver failure.Encephalopathy in the absence of overt jaundice or liver failure is separately categorized as due to by-pass[7]. Should one wait for defining the outcome of‘‘liver failure’’M.RelaInstitute of Liver Diseases and Transplantation,Global Health City,Chennai,IndiaA.SarayaDepartment of Gastroenterology,All India Institute of Medical Sciences,New Delhi,IndiaD.SamuelINSERM,Centre He´patobiliarie,Hoˆpital Paul Brousse,Villejuif, FranceV.SaraswatDepartment of Gastroenterology,Sanjay Gandhi Post Graduate Institute of Medical Sciences,Lucknow,IndiaS.ShahDepartment of Gastroenterology and Hepatology,Global Hospitals,Mumbai,India G.ShihaDepartment of Internal Medicine,Egyptian Liver Research Institute and Hospital,Cairo,EgyptB.C.SharmaDepartment of Gastroenterology,GB Pant Hospital,New Delhi, IndiaS.S.TanDepartment of Gastroenterology and Hepatology,Selayang Hospital,Kepong,MalaysiaM.-F.YuenDepartment of Medicine,The University of Hong Kong, Hong Kong,ChinaO.YokosukaDepartment of Gastroenterology and Nephrology,Graduate School of Medicine,Chiba University,Chiba,Japantill the time extra-hepatic organ failures set in or not remain contentious.For definition,the event must be universally present in all patients.From the point of view of intensi-vists,it is well known that with increasing number of organ dysfunction or failure,the mortality would cumulatively increase.Undoubtedly,these events are predictive of the outcome,the basis of SOFA score.It is therefore not sur-prising;the same has been reported in the CANONIC study [2].However,should organ failure be included in defining the clinical syndrome of liver failure needs a thorough analysis.As a corollary,despite decades of extensive experience,renal or circulatory dysfunction has not been included in the definition of ALF.The issue whether sepsis per se could lead to liver failure or is a result of liver failure had been debated for many years and was again revisited. However,sepsis is an integral part of development of multi-organ failure in any patient,be it of renal,pancreatic, or cardiac origin.The differences between the current definitions of CLIF consortium and APASL have been recently published[8].While thefirst APASL consensus was based on the data of only about200patients,the data of1700patients are now available from14countries.Records of1,363ACLF patients were analyzed.This formed the basis of re-eval-uating the validity of the APASL2009consensus.It was decided that,like in other studies,the analysis of the original data should be sent for separate publications and only the conclusions and recommendations based on these data can be used for the purpose of the consensus.To improve our understanding of the West,Prof Richard Moreau,thefirst author of the CANONIC study,kindly consented to join the consensus meeting.The6major issues as mentioned above,and28sub-issues,were defined,and systematic reviews were made available to all participants.These were addressed at length in the meeting.What constitutes an acute insultThis issue was divided into two parts:first,what is the time frame for the term‘‘acute,’’and second,what are the cri-teria to define the nature of an‘‘insult.’’A review of the different published definitions of acute liver failure and ACLF was done,and the current APASL definition of ACLF was reassessed.It was clear that the event must be new and acute,and its impact on the patient’s condition should be observable as liver failure within a given time frame.The EASL-AASLD consortium had initially kept the assessment of outcomes at3months[9],but subse-quently revised it to28days in the recent CANONIC study [2].The AARC data were carefully analyzed,and themortality rates were at different time points.A mortality rate of more than33%at4weeks was considered to be significant allowing recovery to less than two-thirds of the ing these criteria,the data showed that more than50%patients of ACLF die by week 4.It was, therefore,unanimously agreed that the4-week(28days) period should be maintained as per the initial definition for defining the impact of an acute event.Efforts were made in light of all the available data on defining the nature of acute event.The acute insult could vary depending on the geographic region and the popu-lation under study.These include both infectious and non-infectious causes.These were well characterized in the past.While Hepatitis B reactivation remains the pre-dominant cause of acute hepatic insult in the East,from the global perspective,the major etiologic agent was alcohol,both in the West and the East.This was a bit unexpected for the Asian countries where alcoholic hep-atitis is emerging as a major acute insult and shows the growing westernization of Asia.The predominant causes of acute hepatic insults are shown in Fig.2.A review of the recent CANONIC study data showed that in the West, the term precipitating event is generally used and proba-bly details of events such as Hepatitis B or superadded Hepatitis A and E are rarely encountered or recorded[2]. However,it was a bit surprising that active alcohol abuse and alcoholic hepatitis were also not the predominant causes.A plausible explanation could be that since the CANONIC study only recorded the acute decompensation of cirrhosis and not the hepatic insults,the major events recorded were only non-hepatic,such as bacterial infec-tions or sepsis.Acute decompensation of cirrhosis is a different entity than ACLF.As the core premise of ACLF is presented as liver failure,the acute insults should be hepatic insults.Both,hepatotropic or non-hepatotropic insults,should manifest in the patientfirst with liver failure.Acute hepatic insults of infectious etiology included reactivation of Hepatitis B virus(HBV)as the leading cause of ACLF in the Asian region[10–19].Reactivation of HBV could be either spontaneous or due to intensive chemotherapy or immunosuppressive therapy[10,11], immune restoration after highly active antiretroviral ther-apy for HIV[12,13],treatment-related[14],or reactivation of the occult HBV infection by rituximab(anti-CD20)-based chemotherapy[15–17].Similarly,reactivation of Hepatitis C virus infection has also been reported,espe-cially after immune suppressive therapy[18,19].The other very important infectious etiology of the acute event is super-infection with Hepatitis E virus,predominantly in patients in the Indian subcontinent[20–23].Various bac-terial,parasitic,and fungal infections may affect the liver.Spirochetal,protozoal,helminthic,or fungal organisms may directly infect the liver,whereas bacterial or parasitic infection may spread to the liver from other sites[24]. These infections may lead to liver failure in patients with underlying chronic liver disease.Among the non-infectious etiologies,alcoholic hepatitis is the major cause of acute deterioration in stable known or unknown chronic liver diseases,more often in the western countries[25,26].It was not clear what should be the interval from the last alcoholic drink to be included as acute insult.Since,after the direct hepatic injury,the immunologic injury starts to decline[27],a period of28days was considered adequate for inclusion as the last drink.The issue which remains to be addressed was of binge drinking in patients with ACLF due to recent alcohol intake.It was appreciated that a prospective data collection including the drinking behavior especially in the past6months would help decide the influence of drinking behavior on the clinical outcome and help in defining the time frame of what should be consid-ered as an acute insult.Hepatotoxic drugs and complimentary and alternative medicines(CAM)are important causes for acute and acute-on-chronic liver failure in the Asia–Pacific region[28]. Hepatitis following the use of anti-tubercular drugs was considered to be an important cause of acute insult leading to ACLF.In a proportion of patients,despite a history of use of CAM,the precise nature and injurious influence of the agent cannot be determined.The need for further data on the hepatic injury caused by different herbal prepara-tions needs to be studied.Acute variceal bleeding has been included as one of the events to define hepatic decompensation in the natural history of cirrhosis[29].Variceal bleeding has also been taken as an acute insult for ACLF in some western trials of ACLF.It was extensively debated whether to consider variceal bleed as an acute event of ACLF.Since the defi-nition of ACLF includes liver failure,jaundice,and coag-ulopathy,the variceal bleed should result in liver failure. The liver failure in such patients is mainly due to hepatic ischemia[30]and subsequent bacterial infections[31].It was discussed that for a patient with portal hypertension and cirrhosis of the liver who presents for thefirst time with variceal bleed without any previous or present signs or symptoms of chronic liver disease,it would not constitute an acute insult.This is especially relevant if such a patient does not develop any jaundice.The experts discussed the stratification of patients based on the stage of underlying liver disease and the severity of variceal bleed.However, since patients with ACLF never decompensated before and are distinct from patients with decompensated cirrhosis,it is unlikely that a variceal bleed would per se lead to sig-nificant liver failure manifesting as jaundice and coagu-lopathy.Based on the data,it was unanimously agreed that acute variceal bleeding is not an acute hepatic insult unless in the patients where it produces jaundice and coagulopa-thy defining ACLF.A scenario may exist that a patient who has already fulfilled the criteria of ACLF,and has been diagnosed ACLF,develops a variceal bleed.In such a patient,variceal bleed would be considered as a complication in the natural history of ACLF.The issue of other non-hepatotropic insults which have been considered in other studies such as surgery,trauma, insertion of transjugular intrahepatic porto-systemic shunt, transartrial chemoembolization,or radiofrequency ablation for hepatocellular carcinoma was discussed in detail.While there is an indirect connection with each of these,it was debated that a patient who already has cirrhosis with HCC or a cirrhotic who undergoes surgery,and separate risk scores are already in practice and being utilized.The likely potential for hepatic decompensation would vary depend-ing on the nature of intervention and underlying hepatic reserve.It was agreed that non-hepatotropic insults pro-ducing direct hepatic insult and ACLF in an otherwise compensated liver disease could be considered as acute hepatic insults(2b,C).In a proportion of patients in Asia or even in the west,the precise agent(s)leading to acute hepatic insult is not well recognized on routine assessment. In such patients,this should be recorded as such. RecommendationsDefining the acute event in ACLFThe ACLF can develop from one or more clearly defined acute hepatic insults,which can be due to hepatotropic or non-hepatotropic agents/causes.Acute insults vary depending on the geographic region and the population under study.Major etiologic agents responsible for pre-cipitating ACLF are as follows:1.1Hepatotropic viral infections(1a,A).1.1.1Among these,reactivation of Hepatitis Bvirus(HBV)infection and super-infectionwith HEV are the major causes of acuteinsult in ACLF(1a,A).1.1.2Among the non-infectious causes,activealcohol consumption(within the last28days)remains the commonest cause(1a,A).1.1.3Drug-induced liver injury,consumption ofcomplimentary and alternative medicines(CAM),severe autoimmune hepatitis,andflare of Wilson’s disease are other causesof acute insult in ACLF(1a,A).1.2Non-hepatotropic insults like surgery,trauma,andviral infections if producing direct hepatic insultcould lead to ACLF(2b,C).1.3Variceal bleed per se may not qualify as an acuteinsult for ACLF,and we need more data toascertain this(5,D).1.4In a proportion of patients,the acute hepatic insultmay not be identifiable by the current routineassessment(5,D).Defining the underlying chronic liver diseaseTwo aspects were carefully analyzed,what constitutes chronic liver disease,cirrhosis alone or non-cirrhotic chronic liver diseases,and the etiology of the chronic liver disease.The degree of hepaticfibrosis and the functional hepa-tocellular mass remains heterogeneous in patients with the chronic hepatitis[32,33].Even in patients with stage IV disease,critical mass varies according to the parenchymal reserves.Modified Laennec Scoring System divides stage IV further,according to the thickness of septa into three, ending up in six stages altogether[34,35].Moreover, ACLF is not equivalent to the acute decompensation of cirrhosis,which is the result of parenchymal extinction. Majority of the ACLF patients present with liver failure without any previous assessment of liver disease.It is not possible to distinguish accurately patients with different degree offibrosis at this point in time.The liver with any significant degree offibrosis,with activated stellate cells, and infiltrated by the inflammatory cells,is expected to respond in a different way to the acute insult compared to the liver without inflammatory infiltrate[36].The NAFLD is the leading cause of donor rejection in liver transplantation[37].Experience from liver trans-plantation centers shows that steatosis[30%in the donor liver is associated with a higher risk of primary non-function and graft initial poor function as compared to grafts with no or\30%steatosis[38].Patients with met-abolic syndrome and fatty liver,diabetics,male patients of age[45–50years,patients with obesity,and dyslipidemia have the increased risk offibrosis[39].While cirrhosis could be a late event,a large proportion of them may have stage2or3fibrosis.Hence,NASH is indeed an important cause of chronic liver disease[40].Furthermore,in the East,a large proportion of patients do have reactivation of chronic Hepatitis B.In these patients,while liver failure and ACLF-like presentation does develop,cirrhosis is not necessarily present.The AARC data,based on the liver biopsy studies,corroborated the facts that a fair proportion of patients with ACLF do not have underlying cirrhosis, but still carry a poor prognosis,with mortality above33% at4weeks.Based on the available data,the published literature and the validity of the2009consensus on including the non-cirrhotic chronic liver disease were reaffirmed.Accurate and reliable assessment of underlying CLD in the setting of ACLF is important for the subsequent man-agement and need for liver transplant in these patients. Diagnosis of chronic liver disease in the setting of ACLF is made by history,physical examination,and previously available or recent laboratory,endoscopic or radiologic investigations[41].Ultrasound and CT abdomen may pick up CLD.However,to assess the degree offibrosis in an un-shrunken liver would require other radiologic modalities. The current noninvasive tests cannot clearly diagnose the presence of chronic liver disease in the presence of inflammation and liver failure.Hence,liver biopsy through the transjugular route remains an important tool to confirm the stage offibrosis and presence of cirrhotic or non-cir-rhotic liver disease.A liver biopsy through the transjugular route may be of help when the presence of already underlying CLD and the cause of liver disease are not clear.The liver biopsy may highlight the etiology,stage offibrosis and prognosis,and outcome in patients with ACLF[42].In addition,transju-gular access directly into the hepatic vein allows the hepatic venous pressure gradient to be measured(HVPG). There is a risk of bleeding leading to hemobilia,hemo-peritoneum,and hepatic hematoma in the setting of the deranged clotting profile[43].The need of liver biopsy in ACLF should therefore be individualized.Standardization of liver biopsy assessment would help a uniform approach to the diagnosis and treatment for CLD and the acute insult.There is a need to have reliable noninvasive tools to assess the severity offibrosis in a previously undiagnosed CLD.Ultrasound and CT abdomen may pick up CLD. However,to assess the degree offibrosis in an un-shrunken liver would require other radiologic modalities.Transient elastography(fibroscan)is a good modality to detect fibrosis radiologically[44].However,the liver tissue stiffness may also increase with hepatitis,steatosis,and inflammation present in the ACLF setting[45].The second issue was about the etiology of chronic liver disease and cirrhosis in the Asian–Pacific region.Experts reviewed the data from the AARC,and the etiologic profile of cirrhosis in ACLF was found to be similar to the etiol-ogy of cirrhosis in general in the respective countries[26, 46,47].With the rising incidence of obesity and NAFLD, proportion of burnt-out NASH presenting as cryptogenic cirrhosis is also increasing[48–50].Viral serology and nucleic acid testing are required to identify viral etiology.Specialized tests to rule to diagnose metabolic and autoimmune diseases would be needed as well. The presence of stigmata of liver disease on clinical exami-nation,low platelets,evidence of synthetic dysfunction in。
HCV感染-抗病毒治疗进展
2013EASL指南推荐的GT1,4型RGT策略
2014WHO指南推荐的GT1,4型RGT策略
2013EASL指南推荐的GT2,3,5,6型RGT策 略
2014WHO指南推荐的GT2,3,5,6型RGT策略
影响治疗应答的宿主因素：IFNL3和IFNL4, 等
干扰素λ3（IFNL3， 又称 IL28B）
NATURE| Vol 461| 17 September 2009
NATURE| Vol 461| 17 September 2009
影响治疗应答的宿主因素：IFNL3和IFNL4, 等
干扰素λ3（IFNL3，
又称 IL28B）
❖ IL28B基因编码IFN-λ3，为Ⅲ型干扰 素，位于19号染色体上，属于IFNλs家族
Hadziyannis S, et al. Ann Intern Med 2004; 140: 346-55.
抗病毒治疗方案的优 化
优化
•48W固定疗程
•基因型 •EVR
更优化
•基因型 •治疗期间的病 毒学应答 •HCV载量
2013EAபைடு நூலகம்L指南：
应HCV基因型检测，以确定治疗方案、RBV剂量和疗程 应用蛋白酶抑制剂的三联方案前，要明确HCV基因亚型1a/1b检测
❖ 乏力 ❖ 抑郁
流感样症状
抑郁/焦虑症状
❖ 自身0 免疫病2 及甲4状腺功6 能障碍8 。 10
12
干扰素治疗时间(周)
❖ 即使是控制很好的临床试验，也有 9-15%
HCV生命周期
HCV基因组、蛋白产物和抑制剂
❖ 在过去的 10-15 年
间，HCV 的体外培
养系统为发展直接
抗病DA毒A药：物丙提供肝了抗病毒治疗的春天
推荐-欧洲肝脏学会hcv感染治疗指南20XX年简介 精品
欧洲肝脏学会《HCV感染治疗指南（20XX年）》简介魏阳1,2史昌河3 闫杰1*1.首都医科大学附属北京地坛医院肝病中心，北京 100015，2.青岛大学医学院3.青岛市传染病医院，青岛 266033*通讯作者：闫杰，医学博士，副教授，副主任医师，e-mail：基金资助：北京市卫生系统高层次人才专项基金（项目编号20XX-3-025）欧洲肝脏学会（European Association for the Study of the Liver，EASL）新近发布了20XX年HCV感染治疗指南，并在线发表于《Journal of Hepatology》杂志。
本文对指南的推荐意见简介如下。
指南中提及的证据和推荐意见按照GRADE系统进行分级，证据强度分为高（A）、中（B）、低（C）3种水平，推荐意见分为强（1）、弱（2）两个级别。
1.丙型肝炎的诊断1.1抗-HCV是HCV感染的一线筛查指标（A1）。
1.2对于急性丙型肝炎或免疫功能不全的患者，HCV RNA检测应纳入初始评估（A1）。
1.3如果抗-HCV阳性，应通过敏感的分子生物学方法定量检测HCV RNA（A1）。
1.4抗-HCV阳性但HCV RNA阴性者，应在3个月后复查HCVRNA以明确感染是否痊愈(A1)。
2.HCV治疗的目标及终点2.1治疗目标是根除体内HCV以预防肝硬化（，LC）、肝硬化失代偿、肝细胞癌（Hepatocellular Carcinoma，HCC）和死亡。
治疗终点是治疗结束后12周及24周时敏感检测方法无法检出HCV RNA(<15 IU/ml)[即：持续病毒学应答(Sustained Virological Response，SVR)](A1)。
2.2对于肝硬化患者，清除HCV可降低肝硬化患者失代偿率，即使不能杜绝也可降低HCC风险。
对此类患者应继续监测HCC(A1)。
3.治疗前评估3.1应当证实HCV感染与肝病之间的因果关系(A1)。
扩大慢性乙型肝炎抗病毒治疗的专家意见
扩大慢性乙型肝炎抗病毒治疗的专家意见
慢性乙型肝炎病毒感染治疗的主要方法是抗病毒治疗，其常见的药物有以下几类：
一种是抗病毒核苷类似物，主要有里昂沙米特(Ribavirin)、米西泮(Micxonanabin) 、索拉司琼(Soravinson) 、寡聚核苷类似物(Pegiunavirin)；
第二类是抗病毒抗体，如特异性抗肝炎病毒抗体，能有效阻断肝炎病毒的感染;
第三类是其他抗病毒药，如伏立康(Virchlamycin)和索洛昔康(Solcoxan)及其它抗病毒药物；第四类是免疫抑制剂，如米非司韦(mefisenon)、硫利群素(suloidolin)、新可乐宁(tenokinol)等；
最后一类是免疫调节药，如利巴韦林(ribavirin)、环糠果(inolete)、氯胺酮(chloramphenicol)等，可以通过激活机体免疫力来促进肝脏修复。
因此，建议患者服用多种抗病毒药物，根据具体情况选取合适的抗病毒治疗方案，这样可以有效治疗慢性乙型肝炎病毒感染。
另外，为了更有效地治疗乙型肝炎，还可以考虑联合免疫抑制剂和免疫调节药。
医生还可以根据病情及时调整治疗方案，让患者的内科保健更加全面、有效。
儿童慢性HCV治疗2024课件
03
青少年儿童失代偿性肝硬化治 疗建议
针对失代偿性肝硬化的青 少年儿童患者提出。
感谢观看!
01
青少年儿童慢性HCV感染治疗 药格物卡组瑞合韦/哌仑他韦，索磷 布韦/维帕他韦或索磷布韦 /来迪派韦固定剂量联合。
02
资源有限地区青少年儿童慢性 HCV感染治疗药物组合 格卡瑞韦/哌仑他韦或索磷布 韦/维帕他韦固定剂量联合， 索磷布韦+达拉他韦。
03
青少年儿童失代偿性肝硬化慢性 HCV感染治疗 在经验丰富的儿科肝脏中心 接受治疗，遵循成人指南。
青少年儿童慢性HCV感染治疗 推荐使用固定剂量联合治疗方案。
有限资源下治疗
资源有限方案
资源有限地区青少年儿童慢
性HCV感染的治疗 建议采用格卡瑞韦/哌仑他韦或索
01
磷布韦/维帕他韦固定剂量组合治
疗。
无肝硬化或代偿性肝硬化患
者首选方案 推荐使用泛基因型、无利巴韦林
及最短治疗持续时间方案。
03
索磷布韦+达拉他韦联合用药 每日一次，用于资源有限情况下的青少年儿 童治疗。
儿童慢性HCV治疗
Contents 目 录
全球HCV概况 治疗目标与方案 无肝硬化治疗药物 有限资源下治疗
全球HCV概况
HCV感染现状
全球HCV感染情况 全球约300多万青少年儿童感 染丙型肝炎病毒。
ESPGHAN治疗建议
针对青少年儿童慢性HCV感染提 出最佳治疗管理方案。
成人HCV治疗进展
直接抗病毒治疗（DAA）方案安 全有效，但部分有年龄限制。
建议在资源有限的情况下，采用格卡瑞韦/哌仑他韦或索磷布韦/维帕他 韦固定剂量组合进行治疗。
消除病毒目标
HCV与HIV协同感染可缩短HCV相关性失代偿期肝硬化患者的存活期
HCV与HIV协同感染可缩短HCV相关性失代偿期肝硬化患者的存活期Pineda J.A.;Romero-Gómez M.;Daz-Garca F.;杨瑗【期刊名称】《世界核心医学期刊文摘：胃肠病学分册》【年(卷),期】2005(000)009【摘要】The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95%CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]);Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model forend-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compar- ed with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.【总页数】1页(P42-42)【作者】Pineda J.A.;Romero-Gómez M.;Daz-Garca F.;杨瑗【作者单位】Unidad de Enfermedades Infecciosas Servicio de Medicina Interna Hospital Universitario de Valme Carretera de Cádiz s/n 41014 Sevilla Spain Dr.【正文语种】中文【中图分类】R575.2【相关文献】1.HCV协同感染可能与HIV患者的身体构成变化有关 [J],2.HIV/HCV协同感染与HCV单独感染患者肝脂肪变性的患病率与意义 [J], Monto A.;Dove L.M.;Bostrom A.;徐瑞3.HBV和/或HCV协同感染与接受HAART治疗HIV/AIDS患者肝损害之间的关系研究 [J], 张彤;代丽丽;李侗曾;郭庆良;鲁俊峰;李在村;梁连春;陈新月;吴昊4.与单纯HCV感染者相比,HIV/HCV感染的肝硬化患者不再具有更高的肝癌或晚期肝病风险 [J], 李娜;胡玉琳5.协同感染HIV的HCV患者疾病复发率较高 [J], 相洪琴;寒冰因版权原因，仅展示原文概要，查看原文内容请购买。
肾移植前后丙型肝炎病毒感染的管理
·综述·肾移植前后丙型肝炎病毒感染的管理黄霞1，2，吉英杰2，程勇前1，2 （1.南方医科大学第二临床医学院， 广东 广州 510515；2.中国人民解放军总医院第五医学中心老年医学科，北京 100039） DOI ：10.3969/j.issn.2095-5332.2021.01.020 基金项目：首都卫生发展科研专项项目（2018-2-5034） 通讯作者：程勇前，Email ：******************丙型肝炎病毒（hepatitis C virus ， HCV ）除导致肝功能损伤外，约43%～85%的慢性丙型肝炎（chronic hepatitis C ，CHC ）患者可伴有多种肝外表现（extrahepatic manifestations ，EHM ）［1-4］，包括多种HCV 感染相关肾脏疾病［5-6］。
Ferri 等［2］研究表明，CHC 患者出现尿蛋白的风险增高51%， 慢性肾脏病（chronic kidney disease ，CKD ）发生率增高43%。
Park 等［7］通过回顾性队列纳入美国Truven Health MarketScan 数据库（2008 — 2015年）的56448例HCV 感染者和倾向评分（1：3）匹配的169344例非HCV 感染患者进行多变量Cox 回归模型分析，结果显示，HCV 感染患者发生CKD 的风险比增加27%（危险比为1.27；95%置信区间为 1.18 ~ 1.37）。
CKD 患者如进展至终末肾脏疾病（end stage renal disease ， ESRD ）则不可避免地接受规律性血液透析或肾移植治疗。
然而，ESRD 患者也可能因在治疗过程中感染HCV 导致肾损伤进一步加重。
相比透析治疗，肾移植治疗费用更低、生存质量更高和预期寿命更长，是ESRD 患者首选治疗 方式［8］。
直接抗病毒治疗药物（direct antiviral agents ， DAA ）的出现，使干扰素时代无法进行抗病毒治疗的CKD 合并HCV 感染者及肾移植术后患者的抗病毒治疗成为可能［9］，可在短期内（通常为12周）获得95%以上持续病毒学应答（sustained virologic response ，SVR ）。
2020年欧洲肝病学会丙型肝炎的治疗推荐意见更新(全文)
2020年欧洲肝病学会丙型肝炎的治疗推荐意见更新（全文）丙型肝炎是慢性肝病的一个主要病因，全世界范围内约有7100万丙型肝炎病毒（HCV）慢性感染者。
由于对该病病理生理的认识不断深入，诊断流程的优化以及治疗和预防的进步，HCV相关肝病的临床治疗取得了长足的进步，使世界卫生组织号召的“清除丙型肝炎”的目标成为可能。
本次为欧洲肝病学会对丙型肝炎治疗推荐意见的最终更新，提供了针对2020年及以后新发和慢性HCV感染者的最佳管理方案。
01方法学本建议采用的循证等级仍为GRADE系统，推荐强度反映相关证据的强度，证据等级分为高质量（Ａ）、中等质量（Ｂ）、低质量（Ｃ）；推荐强度分为：强推荐（１）和弱推荐（２）（表1）。
证据质量越高，推荐强度越高；价值和推荐的变异性越大或不确定性越高，推荐强度越低。
02欧洲地区可及的抗HCV药物见表2。
03新近HCV感染、慢性丙型肝炎和HCV的再感染推荐意见1：所有可疑新近再次感染HCV的患者应检测血清或血浆的抗-HCV抗体和HCV RNA或HCV核心抗原（A1）。
推荐意见2：可疑新近再次感染HCV的患者，若抗-HCV抗体阳性，HCV RNA或HCV 核心抗原阴性，应在12、24周后复查HCV RNA 确认病毒是否清除（A1）。
推荐意见3：血清或血浆抗-HCV抗体的检测应作为所有可疑慢性HCV 感染的一线检验手段（A1）。
推荐意见4：抗-HCV抗体阳性的可疑慢性HCV感染的患者应进一步检测HCV RNA或HCV核心抗原确诊（A1）。
推荐意见5：获得持续病毒学应答（SVR）后再次检出HCV RNA或HCV核心抗原，同时有感染危险因素的患者应警惕HCV再感染，通过证实感染是由不同基因型或与初始感染相同基因型的远亲系（应用系统进化分析测序）确诊（A1）。
推荐意见6：抗-HCV抗体应采用血浆或血清的标本，酶免疫分析法（EIA）检测（A1）。
推荐意见7：HCV RNA应采用血清或血浆标本，通过敏感、检测下限≤15 IU/ml的方法进行测定（A1）。