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开拓创新、协同攻关，助力人血白蛋白的迭代研发及临床研究
DOI: 10.12449/JCH250301
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：贾继东负责拟定选题，撰写稿件；牛俊奇负责审定终稿。
Driving innovation and fostering collaboration to advance the development and clinical research of next-generation human serum albumin
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摘要: 白蛋白是人血浆中含量最高的蛋白质，除维持血浆胶体渗透压外，还有物质转运、解毒、维持血管完整性、抗氧化、抗炎及免疫调控等功能。在肝病领域，目前白蛋白主要用于预防大量放腹水后循环功能障碍和治疗肝硬化低白蛋白血症和腹水、自发性腹膜炎以及肝肾综合征。研发重组人血白蛋白有助于降低人血白蛋白制品的潜在生物安全风险和大量依赖进口的弊端。由于缺乏对已上市人血白蛋白关键注册临床试验结果的借鉴，人血白蛋白的临床试验设计、实施和审评均面临诸多挑战。因此需要制药企业、临床医学、方法学以及评审监管等方面的专家，求真务实、锐意创新、协同攻关。Abstract: Albumin is the most abundant protein in human plasma， and in addition to the function of maintaining plasma colloid osmotic pressure， it also has the functions of material transport， detoxification， maintaining vascular integrity， antioxidation， anti-inflammation， and immune modulation. In the field of liver disease， albumin is mainly used to prevent circulatory dysfunction after large-volume paracentesis and treat cirrhotic hypoalbuminemia and ascites， spontaneous bacterial peritonitis， and hepatorenal syndrome. The development of recombinant human serum albumin helps to reduce the potential biosafety risks of human serum albumin products and the disadvantages of relying heavily on import. Due to the lack of reference to the results of pivotal clinical trials of marketed human albumin products， there are still various challenges in the design， implementation， and evaluation of clinical trials of human albumin. Therefore， experts in pharmaceutical enterprises， clinical medicine， methodology， and evaluation/supervision are needed to be pragmatic， innovative and collaborative.
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Key words:
- Albumins /
- Recombinant Human Serum Albumin /
- Liver Cirrhosis /
- Clinical Trial
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【据Hepatology international 2021年1月报道】题：低剂量利福昔明可预防肝硬化失代偿期患者的并发症并提高生存率(作者Zeng X等)
利福昔明已被推荐作为肝性脑病(HE)和自发性细菌性腹膜炎(SBP)的预防药物。该研究旨在探讨低剂量利福昔明是否能预防肝硬化患者的整体并发症和延长生存期。
在这项多中心随机开放标签的前瞻性研究中，200例失代偿期肝硬化患者按1∶1的比例随机分配。利福昔明组患者给予利福昔明400 mg，每日2次，疗程6个月，其余治疗策略在两组患者中尽量保持不变。主要疗效终点是总并发症发生率和无肝移植生存率。次要终点是各种主要肝硬化相关并发症的发生率，以及Child-Pugh评分和分级。
除HE外，两组主要的基线特征相似。利福昔明组总并发症的累积发生率明显低于对照组(P＜0.001)。虽然两组间无肝移植生存率无显著差异，但亚组分析显示，利福昔明显著延长Child-Pugh评分≥9的患者无肝移植生存率(P=0.007)。此外，利福昔明显著减少腹水加重(P＜0.001)、HE (P＜0.001)和胃静脉曲张出血(P=0.031)的发生。两组不良事件发生率相似。
在该研究中，低剂量利福昔明显著降低了总体并发症的发生，延长了晚期肝硬化患者的生存期。低剂量利福昔明与正常剂量(1200 mg/d)利福昔明在预防肝硬化相关并发症方面的效果有待进一步研究。
摘译自ZENG X, SHENG X, WANG PQ, et al. Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis[J]. Hepatol Int, 2021, 15(1): 155-165.
(吉林大学第一医院感染病中心肝病科 朱玉凡 牛俊奇 报道)
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[1] CARACENI P, O’BRIEN A, GINES P. Long-term albumin treatment in patients with cirrhosis and ascites[J]. J Hepatol, 2022, 76( 6): 1306- 1317. DOI: 10.1016/j.jhep.2022.03.005. [2] MURPHY G, BRAYDEN DJ, CHEUNG DL, et al. Albumin-based delivery systems: Recent advances, challenges, and opportunities[J]. J Control Release, 2025, 380: 375- 395. DOI: 10.1016/j.jconrel.2025.01.035. [3] FEATHERSTONE PJ, BALL CM. The development of albumin solutions in the second world war[J]. Anaesth Intensive Care, 2023, 51( 4): 236- 238. DOI: 10.1177/0310057X231174704. [4] FEATHERSTONE PJ, BALL CM. From conflict to controversy: The use and abuse of human albumin solutions after the Second World War[J]. Anaesth Intensive Care, 2023, 51( 6): 368- 371. DOI: 10.1177/0310057X231199368. [5] SANER FH, STUEBEN BO, HOYER DP, et al. Use or misuse of albumin in critical ill patients[J]. Diseases, 2023, 11( 2): 68. DOI: 10.3390/diseases11020068. [6] WIEDERMANN CJ, ZABOLI A, TURCATO G. Synthesis of expert opinions on fluid management in severe sepsis: A contextual review of human albumin and crystalloids[J]. Heart Lung, 2025, 70: 339- 359. DOI: 10.1016/j.hrtlng.2025.01.010. [7] GARCIA-TSAO G, ABRALDES JG, RICH NE, et al. AGA clinical practice update on the use of vasoactive drugs and intravenous albumin in cirrhosis: Expert review[J]. Gastroenterology, 2024, 166( 1): 202- 210. DOI: 10.1053/j.gastro.2023.10.016. [8] CARACENI P, RIGGIO O, ANGELI P, et al. Long-term albumin administration in decompensated cirrhosis(ANSWER): An open-label randomised trial[J]. Lancet, 2018, 391( 10138): 2417- 2429. DOI: 10.1016/S0140-6736(18)30840-7. [9] CHINA L, FREEMANTLE N, FORREST E, et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis[J]. N Engl J Med, 2021, 384( 9): 808- 817. DOI: 10.1056/NEJMoa2022166. [10] SOLÀ E, SOLÉ C, SIMÓN-TALERO M, et al. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial[J]. J Hepatol, 2018, 69( 6): 1250- 1259. DOI: 10.1016/j.jhep.2018.08.006. [11] CHRIS RUNKEN M, CARACENI P, FERNANDEZ J, et al. The cost-effectiveness of albumin in the treatment of decompensated cirrhosis in Germany, Italy, and Spain[J]. Health Econ Rev, 2019, 9( 1): 22. DOI: 10.1186/s13561-019-0237-7. [12] HASAN I, MURTI IS, BAYUPURNAMA P, et al. Cost-effectiveness of albumin in the treatment of decompensated cirrhosis in resource-limited healthcare settings[J]. Drugs Context, 2024, 13: 2024-2021- 1. DOI: 10.7573/dic.2024-1-1. [13] BALDASSARRE M, NALDI M, ZACCHERINI G, et al. Determination of effective albumin in patients with decompensated cirrhosis: Clinical and prognostic implications[J]. Hepatology, 2021, 74( 4): 2058- 2073. DOI: 10.1002/hep.31798. [14] ERSTAD BL. Introduction to the concept of effective albumin concentration[J]. Am J Health Syst Pharm, 2024, 82( 1): 5- 11. DOI: 10.1093/ajhp/zxae232. [15] CHEN Z, HE Y, SHI B, et al. Human serum albumin from recombinant DNA technology: Challenges and strategies[J]. Biochim Biophys Acta, 2013, 1830( 12): 5515- 5525. DOI: 10.1016/j.bbagen.2013.04.037. [16] ABRALDES JG, TREBICKA J, CHALASANI N, et al. Prioritization of therapeutic targets and trial design in cirrhotic portal hypertension[J]. Hepatology, 2019, 69( 3): 1287- 1299. DOI: 10.1002/hep.30314. [17] TORP N, ISRAELSEN M, COENRAAD M, et al. Personalised human albumin in patients with cirrhosis and ascites: Design and rationale for the ALB-TRIAL- a randomised clinical biomarker validation trial[J]. BMJ Open, 2024, 14( 2): e079309. DOI: 10.1136/bmjopen-2023-079309. [18] GENTILINI P, CASINI-RAGGI V, DI FIORE G, et al. Albumin improves the response to diuretics in patients with cirrhosis and ascites: Results of a randomized, controlled trial[J]. J Hepatol, 1999, 30( 4): 639- 645. DOI: 10.1016/s0168-8278(99)80194-9. [19] CARACENI P, ANGELI P, PRATI D, et al. AISF-SIMTI position paper on the appropriate use of albumin in patients with liver cirrhosis: A 2020 update[J]. Blood Transfus, 2021, 19( 1): 9- 13. DOI: 10.2450/2020.0414-20. [20] KALO E, READ S, BAIG A, et al. Efficacy of albumin use in decompensated cirrhosis and real-world adoption in Australia[J]. JGH Open, 2024, 8( 9): e70029. DOI: 10.1002/jgh3.70029. 期刊类型引用(2)
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