1.在计划的第一剂研究治疗前21天内接受任何常规或研究性抗癌治疗或14天内接受姑息性放疗。2.事先接受过任何与免疫相关的治疗。另一项治疗性临床研究的同期登记。将允许参加观察性研究。在过去3个月内有静脉血栓形成史的受试者在开始治疗前3个月内有心肌梗死、短暂性脑缺血发作或中风病史的受试者在开始治疗前的过去3年内，有活跃的或既往记录的自身免疫或炎症疾病。2年内有其他浸润性恶性肿瘤。 8. Any history of leptomeningeal disease or cord compression. 9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose
1.签署知情同意书。2.年龄大于或等于(>=)18岁和小于或等于(<=)75岁的参与者。3.根据公认的临床、内窥镜、组织学和/或放射学标准，在筛查来访前至少6个月诊断为乳糜泻的参与者。4.存在复杂的肛周瘘，根据临床评估，最多有2个内瘘口和最多3个外瘘口;进行局部造影增强(钆)盆腔MRI中心读数，以确认瘘管的位置和潜在的相关肛周脓肿。瘘管必须在筛查到访前至少引流6周。 Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are not allowed in this study. A complex perianal fistula is defined as a fistula that meets one or more of the following criteria : •括约肌间高，括约肌外高，括约肌外高或括约肌上高 •>=2个外部开口。 •相关肛周脓肿。注意:MRI上大于2cm(至少二维)的脓肿必须由外科医生确认在准备刮除术时已充分引流。5.临床对照、非活动性或轻度活动性乳糜泻，在筛查来访前的最后6个月内: •患者报告筛查时预后(PRO-2)评分<14，且 结肠镜检查显示结肠黏膜没有大于0.5 cm的溃疡: •如果筛查前6个月内没有结肠镜检查数据: •随机分组前，在筛查时进行的结肠镜检查中，克罗恩病(SES-CD) <=6且无大于0.5 cm的直肠溃疡的简单内镜评分必须记录。 •如果在筛查前6个月内获得结肠镜检查数据，必须记录以下信息，否则必须进行新的结肠镜检查(如上所述): •结肠黏膜无大于0.5 cm的溃疡 •自临床记录中最后一次结肠镜检查以来，腹痛和/或腹泻持续一周或更长时间无恶化或改善，直到筛查来访。与筛查来访期间的结果相比，自最后一次结肠镜检查以来，血红蛋白没有降低>=2.0克/分升(g/dL)或无法解释的c反应蛋白(CRP)升高，> 5.0毫克/升(mg/L)，浓度高于参考正常上限(ULN)(除非升高是由于管腔克罗恩病以外的已知过程)。从最后一次内镜检查到筛查随访以来，没有开始或加强使用皮质类固醇、免疫抑制剂或单克隆抗体(mAbs)剂量方案的治疗。6.既往接受过肛周瘘管治疗的参与者，在接受免疫抑制剂或肿瘤坏死因子(TNF)- α拮抗剂或维多珠单抗或乌斯特金单抗时，表现出反应不充分或反应丧失，或在上述最短时间内对至少批准或推荐剂量的上述治疗有耐受记录的参与者: •免疫抑制剂:在本研究筛查前，至少接受3个月的硫唑嘌呤(2-3毫克/公斤/天[mg/kg/天])、6-巯基嘌呤(1-1.5毫克/公斤/天)或皮下/肌肉注射甲氨蝶呤(25毫克/周)治疗。 TNFalpha拮抗剂: •英夫利昔单抗:在本研究筛查前，以批准的剂量对克罗恩病进行诱导和/或维持治疗至少14周。诱导:1次静脉注射，每公斤5毫克(mg/kg)，然后在2周和6周后进行同样的剂量。维持:静脉注射5-10毫克/公斤每8周，或更频繁。 •阿达木单抗:在本研究筛查前，以批准的剂量对克罗恩病进行诱导和/或维持治疗至少14周。诱导:1次皮下剂量160毫克(mg)，然后在2周后80毫克。保养:每隔一周或每周皮下注射40毫克。 •Certolizumab l:在本研究筛查前，以批准的剂量对克罗恩病进行诱导和/或维持治疗至少14周。诱导:皮下注射1次400 mg, 2周和4周后分别注射相同剂量。保养:每2 - 4周皮下注射400毫克。 •抗整合素:在本研究筛查前，对克罗恩病的诱导和/或维持至少进行14周的批准剂量治疗。用于诱导:Vedolizumab 300 mg。维持:Vedolizumab 300mg每4 - 8周。 •抗白介素(IL)-12/23:在本研究筛查前，对克罗恩病进行至少16周的批准剂量治疗。诱导:Ustekinumab，最初静脉注射约6mg/kg，然后每8周皮下注射90mg。7.有生育潜力(WCBP)的妇女在筛查时必须血清妊娠试验阴性(对25国际单位[IU]人绒毛膜促性腺激素[hCG]敏感)。WCBP或参与本研究的男性参与者，有WCBP作为伴侣，必须同意在整个研究期间使用适当的避孕方法。适当的避孕方法被定义为完全的、非周期性的节欲(避免异性性交)、单一屏障法、输精管结扎法、充分的激素避孕(至少在筛查来访前7天开始)或子宫内节育器(在筛查来访前至少2个月已经就位)。
排除标准:
1.并发直肠阴道瘘或直肠膀胱瘘。2.参与者naïve之前接受过复杂肛周瘘的特殊治疗，包括免疫抑制剂(IS)或抗tnfs。3.筛查时，MRI中心读数显示肛周有至少两个维度的> 2cm的收集物，在准备过程中(第3周至第0天)经外科医生证实未充分引流。严重的直肠和/或肛门狭窄和/或严重的直肠炎(定义为直肠内存在0.5 cm的大溃疡)，导致无法遵循手术操作手册。5.有分流气孔的参与者。6. Active, uncontrolled infection requiring parenteral antibiotics. 7. Participant with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to the Preparation visit. 8. Participants with major alteration on any of the following laboratory tests or increased risk for the surgical procedure: •血清肌酐水平>是ULN的1.5倍 •总胆红素>1.5 ULN •天冬氨酸转氨酶(AST)/丙氨酸转氨酶(ALT) >3倍ULN •血红蛋白<10.0 g/dL •血小板<75.0*10^9/L •白蛋白血症<3.0 g/dL筛查来访前两周内疑似或有记录的传染性小肠结肠炎。10.筛查来访前5年内确诊的任何浸润性恶性肿瘤。在会阴部外完全切除的基底细胞癌的参与者可以被包括在内。11.当前或近期(筛查来访前6个月内)有严重、进展和/或无法控制的肝脏、血液、胃肠(GI)(乳糜泻除外)、肾脏、内分泌、肺、心脏、神经或精神疾病史，这些疾病可能导致参与者参与研究和/或不遵守研究程序的风险增加。12.原发性硬化性胆管炎的参与者。13. Participants with known chronically active hepatopathy of any origin, including cirrhosis and participants with persistent positive Hepatitis B Virus (HBV) surface antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive serology for Hepatitis C Virus (HCV) and quantitative HCV PCR within 6 months prior to Screening. 14. Congenital or acquired immunodeficiencies, including participants known to be HIV carriers 15. Known allergies or hypersensitivity to penicillin or aminoglycosides; Dulbecco Modified Eagle's Medium (DMEM); bovine serum; local anaesthetics or gadolinium (MRI contrast). 16. Contraindication to MRI scan (example, due to the presence of pacemakers, hip replacements or severe claustrophobia). 17. Severe trauma within 6 months prior to Screening visit. 18. Pregnant or breastfeeding women. 19. Participants who do not wish to or cannot comply with study procedures. 20. Participants currently receiving, or having received any investigational drug within 3 months prior to Screening visit. 21. Participants previously treated with Cx601 or other allogeneic stem-cell therapy cannot be enrolled into this clinical study. 22. Any major surgery of the GI tract (including one or more segments of the colon or terminal ileum) within 6 months prior the screening or any minor surgery of the GI tract within 3 months prior to screening. 23. Participants who had local perianal surgery other than drainage for the fistula within 6 months prior to the Screening visit, or those who may need surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study. 24. Contraindication to the anaesthetic procedure.
1.至少18岁。男女和所有种族和民族的成员都将被包括在内。2.愿意并能够提供书面知情同意。直肠腺癌的病理诊断T3-4和/或N+疾病根据AJCC第8版5。既往无直肠腺癌治疗6。东部合作集团(ECOG)业绩状态为0-2。7. Laboratory values supporting acceptable organ and marrow function within 30 days of eligibility confirmation. Defined as follows: •WBC≥3000 /mL; •ANC WBC≥1000 /mL; •PLT≥75,000/mL; •T Bili≤1.5 x正常上限(ULN); •AST/ALT≤2.5 x ULN; •肌酐不高于ULN，或肌酐清除率>50 mL/min/1.73 m2的肌酐水平高于机构正常水平的参与者。8.所有男性以及有生育潜力的女性必须同意使用充分的避孕措施(激素或屏障避孕法;禁欲)从第一剂研究治疗开始，直到最后一剂研究药物后90天。如果妇女在参与本研究期间怀孕或怀疑自己怀孕，她应立即通知她的主治医生。有生育潜力的女性是指符合下列标准的任何女性(不论性取向、婚姻状况、是否接受过输卵管结扎或选择保持独身): •未做过子宫切除术或双侧卵巢切除术;或 •至少连续12个月没有自然绝经(即在之前连续12个月的任何时间都有月经)。
1.签署知情同意书时年龄≥18岁。70岁的患者>必须具有G8健康状态筛查工具(老年筛查工具)评分>。2.完全错配修复/微卫星稳定(pMMR/MSS)，组织学或细胞学证实的结肠或直肠腺癌。任何BRAF或KRAS突变状态的患者都符合条件。3.根据RECIST v1.1，不可切除和可测量或可评估的疾病ECOG性能状态为0 ~ 1 5。必须确认福尔马林固定的石蜡包埋(FFPE)肿瘤标本(来自档案或新鲜活检)和记录pMMR/MSS mCRC的相关病理报告，以便发送给主办方进行计划的回顾性生物标志物分析。 6. Adequate organ function Selected
排除标准:
1.既往mCRC的系统治疗。接受结肠直肠癌辅助/新辅助治疗(即有治疗目的的治疗)的患者，如果从最后一次全身化疗剂量到知情同意之日已≥6个月，则符合条件。2.在第一剂trilaciclib/安慰剂前3周内，任何用于癌症治疗的放疗、化疗、免疫疗法、生物疗法、研究疗法或激素疗法(定义为M0疾病或PSA持续/复发而无转移性疾病的乳腺癌或前列腺癌的辅助激素疗法除外)。3.在第一剂trilaciclib/安慰剂前3周内接受任何非肿瘤目的的低剂量全身化疗药物(例如，小剂量甲氨蝶呤治疗类风湿关节炎)。4.存在中枢神经系统(CNS)转移/轻脑膜疾病，需要立即用放射疗法或类固醇治疗5。筛查时QTcF间隔> 450 msec(男性)或> 470 msec(女性)。 For patients with ventricular pacemakers, QTcF > 500 msec. 6. Personal or family history of long QT syndrome 7. Symptomatic peripheral neuropathy 8. History of interstitial lung disease (ILD) 9. Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation
1.在进入研究前签署并注明日期的书面知情同意书;2.组织学或细胞学证实的胰腺转移性或局部晚期腺癌;3.根据实体瘤反应评价标准(RECIST, 1.1版)，至少有一个可测量的病变;4.年龄≥18岁;5.既往不超过一个非吉西他滨/nab-紫杉醇含系统性治疗转移性/局部晚期胰腺癌的药物系列; 6. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1; 7. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration; (Note: contraception in patients with reproductive capacity will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.) 8. Adequate biological parameters at baseline (obtained within 14 days prior to registration). 9. If elevated liver function tests develop at the time of initial presentation or develop during workup and are the result of mechanical obstruction of the biliary drainage by tumor compression or invasion, a biliary drain may be placed. If drainage allows the liver function tests to come within inclusion criteria, the patient may be enrolled.
排除标准:
1.对于转移性或局部晚期疾病，有一种以上任何类型的全身治疗方案。在确诊复发性疾病后6个月以上结束的辅助吉西他滨不被认为是一种方案;2.既往使用nintedanib或任何其他VEGFR抑制剂;3.已知对nintedanib、吉西他滨和nab-紫杉醇花生或大豆或任何其他试验药物、其赋形剂或造影剂过敏;4.在使用试验药物治疗前4周内，化疗、激素、放射治疗(脑和四肢除外)或免疫治疗或单克隆抗体或小酪氨酸激酶抑制剂治疗;5. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging 6. Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy; 7. Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomization); 8. Leptomeningeal disease; 9. Radiographic evidence of cavitary or necrotic tumors; 10. Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial; 11. Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day); 12. Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period; 13. History of clinically significant hemorrhagic or thromboembolic event in the past 6 months; 14. Known inherited predisposition to bleeding or thrombosis; 15. Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion); 16. Proteinuria CTCAE grade 2 or greater; 17. Creatinine > 1.5 x ULN or GFR < 45 mL/min; 18. Hepatic function: total bilirubin outside of normal limits; ALT or AST > 1.5 ULN in pts without liver metastasis. For Pts with liver metastasis: total bilirubin outside of normal limits, ALT or AST > 2.5 ULN; 19. Coagulation parameters: International Normalized Ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN; 20. Absolute neutrophil count (ANC) < 1500/mL, platelets < 100,000/mL, Hemoglobin < 9.0 g/dl; 21. Any known active cancer other than pancreatic primary; 22. Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy; 23. Active or chronic hepatitis C and/or B infection; 24. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug; 25. Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study; 26. Pregnancy or breast feeding female; 27. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; 28. Active alcohol or drug abuse; 29. Significant weight loss (> 20% of BW) within past 6 months prior to inclusion into the trial or actual body weight of less than 50 kg; 30. Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectable, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner for participating females, condoms for participating males) during the trial and for at least three months after end of active therapy.
1.≥18岁签署并注明日期的书面知情同意书。组织学或细胞学证实不可切除的局部晚期或转移性肝细胞癌。按RECIST 1.1标准可测量或评价的疾病。患者要么不治疗，要么服用贝伐珠单抗和阿特佐珠单抗进展。4.Child-Pugh a班ECOG性能状态≤1(见附录A)，预期寿命≥3个月。6. Body weight > 30 kg. 7. Measured creatinine clearance (crCL) >40 mL/min or calculated crCL >40 mL/min as determined by Cockcroft-Gault (using actual body weight). 8. Sexually active pre-menopausal female subjects (and female partners of male subjects) must use highly effective contraceptive measures, while on study and for at least 90 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study and for at least 90 days after the last dose of study drug. All fertile male and female subjects and their partners must agree to use a highly effective method of contraception.
排除标准:
1.除贝伐珠单抗和阿特佐珠单抗外，既往接受过HCC全身治疗的受试者。2.怀孕或哺乳期的女性受试者，或有生育潜力但不愿意采取有效避孕措施的男性或女性受试者，从筛查到最后一剂研究药物后90天。3.脑转移或脊髓压迫。在研究开始前，筛查时疑似脑转移的受试者应进行MRI(首选)或CT扫描，并进行脑部静脉造影。基线时，脑转移不会被记录在RECIST靶病变上。4.以下任何血液学异常: •血红蛋白< 9.0 g/dL •绝对中性粒细胞计数(ANC) < 1500 / mm3 •血小板计数< 75000 / mm3以下任何血清化学或尿液分析异常: •总胆红素>2 × ULN(吉尔伯特综合征受试者>2.5 mg/dL) •AST或ALT > 5 × ULN •碱性磷酸酶> 2.5 × ULN(或> 5 × ULN用于肝或骨转移患者) •血清肌酐> 1.5 × ULN•> 2+蛋白尿过去12个月内有肝性脑病病史，或需要使用预防或控制脑病的药物(如用于肝性脑病，未使用乳果糖、利福昔明等)。7.12个月内消化道出血(如食管静脉曲张或溃疡出血)。(注:对于有胃肠道出血史超过12个月或被研究者评估为食管静脉曲张出血高危的患者，需要按照机构标准进行充分的内镜治疗)。8.临床意义腹水定义为需要非药物干预(如穿刺术)来维持症状控制的腹水，在第一次预定剂量前6个月内。接受稳定剂量利尿剂治疗腹水≥2个月的受试者符合条件。9.主要门静脉血栓形成(Vp4)影像学记录。 (VP4 is defined as portal vein thrombosis in the main trunk of the portal vein or a portal vein branch contralateral to the primarily involved lobe (or both). 10. For subjects who require ongoing therapeutic anti-coagulation or anti-platelet therapy; the subject must be off either therapy for at least 7 days prior to the first dose of investigational product. Low-dose aspirin for cardiac prophylaxis/protection is permitted per local institutional standards. 11. Patients co-infected with HBV and HCVHBV positive [presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10IU/ml)]; HCV positive (presence of anti-HCV antibodies). 12. Major surgery (as defined by the investigator) within 28 days prior to first dose of IP or still recovering from prior surgery. Local procedures (eg, core needle biopsy, and prostate biopsy) are allowed if completed at least 3 days prior to the administration of the first dose of study treatment. 13. Significant cardiovascular disease, including: •临床症状性心力衰竭。有心衰史的受试者在开始方案治疗前必须进行超声心动图或MUGA扫描，记录左心室射血分数(LVEF) > 45% •任何纽约心脏协会分级≥2级(最好是0级或1级) •过去3个月内的任何支架植入手术 •最近3个月内有静脉血栓栓塞或动脉血栓栓塞 •任何下腔静脉肿瘤血栓形成 •出血事件史(即6个月内消化道出血) •无控制的高血压:服用2种以上抗高血压药物后，至少间隔24小时进行两次连续测量，血压>150/95 mmHg。有高血压史的受试者必须在方案治疗开始前服用稳定剂量的降压药≥2周。 •方案治疗开始前3个月内的心肌梗死伤口、溃疡和/或骨折愈合延迟的受试者15。严重/活动性感染或需要注射非肠外抗生素的感染从以前的任何外科手术中恢复不足;在治疗方案开始前4周内进行重大手术。17.不能符合协议要求18。其他原发恶性肿瘤病史，除: •在第一剂研究药物前≥5年无已知活动性疾病且有治愈意图的恶性肿瘤，复发的潜在风险低 •在没有疾病证据的情况下，得到充分治疗的非恶性肿瘤皮肤癌19。活动性感染，包括结核病(临床评估，包括临床病史、体格检查和放射检查结果，以及符合当地惯例的结核病检测)、丙型肝炎或人类免疫缺陷病毒(HIV 1/2抗体阳性)。丙型肝炎(HCV)抗体阳性的受试者只有在聚合酶链反应HCV RNA阴性时才符合条件。20.既往或目前有HBV感染(HBV DNA可检测)的患者应接受抗病毒治疗，并在每个周期检测HBV DNA病毒载量。21.在第一剂研究干预前，2周内进行有限辐射范围的姑息性放疗或大范围辐射或超过30%的骨髓在4周内进行。22.在方案治疗开始前3周内进行全身激素治疗，但以下情况除外: •刺激食欲或避孕的激素疗法 •鼻用、眼用、吸入和外用类固醇制剂 •口服替代治疗肾上腺功能不全 •其他情况的低剂量维持类固醇治疗(相当于强的松10mg/天) •激素替代疗法，如睾酮。强烈的CYP3A4诱导剂(见附录B)在开始前2周内，或在方案治疗期间。24.既往使用过tivozanib或durvalumab。对于之前接受过atezolizumab治疗的受试者: •必须没有经历过导致既往免疫治疗永久停止的毒性。 •所有接受免疫治疗的ae在本研究筛查前必须完全消退或消退至基线水平。 •在接受免疫治疗之前，不得经历过≥3级免疫相关声发射或任何级别的免疫相关神经或眼部声发射。注:内分泌声发射等级≤2级的参与者，如果他们能够稳定地维持适当的替代治疗并无症状，就可以入选。 •必须不需要使用除皮质类固醇外的其他免疫抑制来管理声发射，如果再次挑战，没有经历过声发射复发，目前不需要每天> 10 mg强的松或同等剂量的维持剂量。25.异基因器官移植史活动性或既往有记录的自身免疫或炎症性疾病(包括炎症性肠病[如结肠炎或克罗恩病]、憩室炎[憩室病除外]、系统性红斑狼疮、结节病综合征或韦格纳综合征[肉芽肿伴多血管炎、格雷夫斯病、类风湿性关节炎、垂体炎、葡萄膜炎等])。以下是该标准的例外情况: •白癜风或脱发患者 •甲状腺功能减退的受试者(例如桥本综合征后)在激素替代后稳定 •任何不需要全身治疗的慢性皮肤病 •在过去5年内没有活动性疾病的受试者可以纳入，但只有在与Medical Monitor咨询后才能纳入 •仅靠饮食控制的乳糜泻患者27例。无法控制的并发疾病，包括但不限于持续或活动性感染、症状性充血性心力衰竭、无法控制的高血压、不稳定型心绞痛、无法控制的心律失常、活动性间质性肺病、与腹泻相关的严重慢性胃肠疾病，或限制遵守研究要求的精神疾病/社会状况，大幅增加发生意外事件的风险或损害受试者给予书面知情同意的能力28。轻脑膜癌病史活动性原发性免疫缺陷病史用弗里德里克公式(QTcF)校正心率的平均QT间期≥470 ms，由3个心电图计算(15分钟内，间隔5分钟)31。已知对任何研究药物或任何研究药物赋形剂过敏或超敏32。同时参加另一项临床研究，除非是观察性(非介入性)临床研究或介入性研究的随访期33。在第一剂研究药物前30天内接受减毒活疫苗。注意:受试者，如果入选，在接受研究药物的同时和最后一剂研究药物后30天内不应接受活疫苗。 34. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: 鼻内、吸入、局部类固醇或局部类固醇注射(如关节内注射) •全身皮质激素生理剂量不超过10毫克/天的强的松或其等量物 •类固醇作为超敏反应的预用药(例如，CT扫描预用药)既往研究中药物分配在本研究中。
1.莱比锡标准>诊断WD2.筛查前用青霉胺、曲恩汀或锌连续治疗WD至少1年。3.体重指数< 30公斤/平方米。4.能够配合经皮肝活检。5.愿意并能够遵循协议规定的避孕要求。 6. Capable of giving signed informed consent.
排除标准:
1.失代偿性肝硬化或终末期肝病模型评分>2.修改Nazer评分> 7。3.在过去3个月内有临床意义的消化道出血。4.丙氨酸氨基转移酶> 2 ×正常上限。5.出血异常或已知凝血功能障碍史，包括血小板计数< 10万，凝血酶原时间国际标准化比值≥1.5。 6. Participant unwilling to accept blood products, if required. 7. Marked neurological disease requiring either nasogastric feeding tube or intensive inpatient medical care. 8. Hemoglobin less than lower limit of the reference range for age and sex. 9. Participants in renal failure, defined as in end-stage renal disease on dialysis (chronic kidney disease 5) or creatinine clearance < 30 milliliters/minute. 10. Lymphoma, leukemia, or any malignancy within the past 5 years. 11. Current or chronic history of liver disease not associated with WD.