人工肝治疗的临床实践与研究进展

韩涛; 张倩

doi:10.12449/JCH240201

人工肝治疗的临床实践与研究进展

DOI: 10.12449/JCH240201

韩涛^, ,,
张倩

南开大学人民医院，天津市人民医院消化（肝病）科，天津 300121

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：韩涛负责构思与撰写文章并最终定稿；张倩协助撰写部分文稿。

详细信息

通信作者:
韩涛， hantaomd@126.com （ORCID： 0000-0003-4216-6968）

计量
- 文章访问数: 854
- HTML全文浏览量: 504
- PDF下载量: 216
- 被引次数: 0
出版历程
- 收稿日期: 2023-11-20
- 录用日期: 2023-12-20
- 出版日期: 2024-02-19

Clinical practice and research advances in artificial liver support therapy

Tao HAN^{,
,},
Qian ZHANG

Department of Gastroenterology and Hepatology，Tianjin People’s Hospital，Tianjin Union Medical Center Affiliated to Nankai University，Tianjin 300121，China

More Information

Corresponding author: HAN Tao， hantaomd@126.com （ORCID： 0000-0003-4216-6968）

摘要

摘要: 人工肝支持系统是治疗肝衰竭的重要方法之一，近年来非生物型人工肝在肝衰竭救治中的作用越来越受到认可，在非肝衰竭疾病中的应用也日益广泛。临床上需要综合多种因素，合理选择非生物型人工肝治疗的时机及模式，规范化、个体化、精准化治疗及不同模式的优化组合是人工肝临床应用的趋势。生物型人工肝有关种子细胞来源、生物反应器等关键技术不断完善，且部分已经进入临床试验阶段。尽管人工肝治疗的临床实践与研究已取得很大进展，但仍面临不少挑战。如何通过技术创新与优化组合进一步提高其疗效与安全性，如何通过高质量的临床试验获得更高级别循证医学证据，仍是目前亟需解决的难题。
- 肝，人工 /
- 肝功能衰竭 /
- 治疗学
Abstract: Artificial liver support system is one of the important therapies for liver failure， and in recent years， the role of non-bioartificial liver support system in the treatment of liver failure has been gradually recognized， with wide application in non-liver failure diseases. In clinical practice， various factors should be considered to reasonably select the timing and mode of non-bioartificial liver support therapy， and standardized， individualized， and precise treatment and optimal combination of different modes are the trend of the clinical application of artificial liver support therapy. There have been constant improvements in the key techniques of bioartificial liver support system such as seed cell source and bioreactor， and some of them have entered the stage of clinical trial. Although remarkable progress has been made in the clinical practice and research of artificial liver support therapy， there are still many challenges， and it is urgently needed to solve the problems of how to further improve its efficacy and safety through technological innovation and combination optimization and how to obtain higher-level evidence-based medical evidence through high-quality clinical trials.
- Liver， Artificial /
- Liver Failure /
- Therapeutics

HTML全文

越来越多的证据表明，肠道菌群与慢性HBV感染的病理生理学和疾病进展密切相关。肠道菌群通过其代谢产物作用于宿主。首都医科大学附属北京地坛医院的Sun等就肠道菌群代谢产物对HBV感染者疾病进展的影响进行综述。检索的数据库包括PubMed和Wiley Online Library数据库。使用预先设定的标准进行文献检索，经过专家讨论，从搜到的90篇文献中筛选出符合入选标准的80篇原始文献，提取相关内容进行了综述。

在慢性HBV感染的肝病不同阶段，肠道菌群构成及丰度会发生变化，这会影响细菌代谢产物的产生。短链脂肪酸如丁酸盐通过促进紧密连接、细胞增殖和增加杯状细胞的黏蛋白产生来改善肠道上皮细胞的完整性。在慢性HBV感染者中，产生短链脂肪酸如丁酸盐的细菌数量减少，与细菌移位和肝病进展相关。肠道菌群-胆汁酸-宿主轴的破坏也会影响肝病的进展。必需氨基酸色氨酸摄入后在多种肠道细菌的参与下，通过3条主要代谢途径影响肠-肝轴，其中犬尿氨酸途径与乙型肝炎的免疫反应密切相关。HBV感染的肝癌中三甲胺-N-氧化物水平(由胆碱转化而来)降低，并被用作肝癌的潜在生物标志物。肝病时维生素缺乏症包括与肠道菌群相关的维生素D和维生素A缺乏症是常见的情况，并与患者生存率相关。由肠道菌群调节的硫化氢也与肠-肝轴的平衡密切相关。在伴有HBV感染的肝病中，肠道菌群失衡影响到多种肠道菌群代谢产物的产生及功能，参与了疾病的发生和发展。该综述对于认识肠道菌群及其代谢产物在慢性HBV感染者疾病进展中的作用有重要的帮助。

摘译自SUN X, PAN CQ, XING H. Effect of microbiota metabolites on the progression of chronic hepatitis B virus infection[J]. Hepatol Int, 2021, 15(5): 1053-1067. DOI: 10.1007/s12072-021-10230-6.

(首都医科大学附属北京地坛医院邢卉春报道)

参考文献(22)

[1]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35( 1): 38- 44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35( 1): 38- 44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.
[2]	Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Expert consensus on clinical application of artificial liver and blood purification(2022 edition)[J]. J Clin Hepatol, 2022, 38( 4): 767- 775. DOI: 10.3969/j.issn.1001-5256.2022.04.007. 中华医学会肝病学分会重型肝病与人工肝学组. 人工肝血液净化技术临床应用专家共识(2022年版)[J]. 临床肝胆病杂志, 2022, 38( 4): 767- 775. DOI: 10.3969/j.issn.1001-5256.2022.04.007.
[3]	SALIBA F, BAÑARES R, LARSEN FS, et al. Artificial liver support in patients with liver failure: A modified DELPHI consensus of international experts[J]. Intensive Care Med, 2022, 48( 10): 1352- 1367. DOI: 10.1007/s00134-022-06802-1.
[4]	SARIN SK, CHOUDHURY A, SHARMA MK, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver(APASL): an update[J]. Hepatol Int, 2019, 13( 4): 353- 390. DOI: 10.1007/s12072-019-09946-3.
[5]	European Association for the Study of the Liver. EASL clinical practice guidelines on acute-on-chronic liver failure[J]. J Hepatol, 2023, 79( 2): 461- 491. DOI: 10.1016/j.jhep.2023.04.021.
[6]	BAJAJ JS, O’LEARY JG, LAI JC, et al. Acute-on-chronic liver failure clinical guidelines[J]. Am J Gastroenterol, 2022, 117( 2): 225- 252. DOI: 10.14309/ajg.0000000000001595.
[7]	European Association for the Study of the Liver. EASL clinical practical guidelines on the management of acute(fulminant) liver failure[J]. J Hepatol, 2017, 66( 5): 1047- 1081. DOI: 10.1016/j.jhep.2016.12.003. PMID: 28417882.
[8]	SHINGINA A, MUKHTAR N, WAKIM-FLEMING J, et al. Acute liver failure guidelines[J]. Am J Gastroenterol, 2023, 118( 7): 1128- 1153. DOI: 10.14309/ajg.0000000000002340.
[9]	Liver Failure and Artificial Liver Group, Branch of Infectious Diseases, Chinese Medical Association. Guideline for non-bioartificial liver support systems in treatment of liver failure: 2016 update[J]. Chin J Clin Infect Dis, 2016, 9( 2): 97- 103. DOI: 10.3760/cma.i.issn.1674-2397.2016.02.001. 中华医学会感染病学分会肝衰竭与人工肝学组. 非生物型人工肝治疗肝衰竭指南(2016年版)[J]. 中华临床感染病杂志, 2016, 9( 2): 97- 103. DOI: 10.3760/cma.j.issn.1674-2397.2016.02.001.
[10]	LIU L, HAN T. Advances in the application of non-bioartificial liver in treatment of non-liver failure diseases[J]. J Clin Hepatol, 2020, 36( 9): 2115- 2118. DOI: 10.3969/j.issn.1001-5256.2020.09.047. 刘磊, 韩涛. 非生物型人工肝在非肝衰竭疾病治疗中的应用进展[J]. 临床肝胆病杂志, 2020, 36( 9): 2115- 2118. DOI: 10.3969/j.issn.1001-5256.2020.09.047.
[11]	AGARWAL B, CAÑIZARES RB, SALIBA F, et al. Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure[J]. J Hepatol, 2023, 79( 1): 79- 92. DOI: 10.1016/j.jhep.2023.03.013.
[12]	BALLESTER MP, ELSHABRAWI A, JALAN R. Extracorporeal liver support and liver transplantation for acute-on-chronic liver failure[J]. Liver Int, 2023. DOI: 10.1111/liv.15647.[ Online ahead of print]
[13]	NICOLAS CT, HICKEY RD, CHEN HS, et al. Concise review: Liver regenerative medicine: From hepatocyte transplantation to bioartificial livers and bioengineered grafts[J]. Stem Cells, 2017, 35( 1): 42- 50. DOI: 10.1002/stem.2500.
[14]	DUAN ZP, XIN SJ, ZHANG J, et al. Comparison of extracorporeal cellular therapy(ELAD^®) vs standard of care in a randomized controlled clinical trial in treating Chinese subjects with acute-on-chronic liver failure[J]. Hepat Med, 2018, 10: 139- 152. DOI: 10.2147/HMER.S180246.
[15]	LI LJ, DU WB, ZHANG YM, et al. Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs[J]. J Hepatol, 2006, 44( 2): 317- 324. DOI: 10.1016/j.jhep.2005.08.006.
[16]	LI WJ, ZHU XJ, YUAN TJ, et al. An extracorporeal bioartificial liver embedded with 3D-layered human liver progenitor-like cells relieves acute liver failure in pigs[J]. Sci Transl Med, 2020, 12( 551): eaba5146. DOI: 10.1126/scitranslmed.aba5146.
[17]	SHI XL, GAO YM, YAN YP, et al. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes[J]. Cell Res, 2016, 26( 2): 206- 216. DOI: 10.1038/cr.2016.6.
[18]	WANG Y, ZHENG Q, SUN Z, et al. Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes[J]. Cell Stem Cell, 2023, 30( 5): 617- 631. DOI: 10.1016/j.stem.2023.03.013.
[19]	CHEN HS, JOO DJ, SHAHEEN M, et al. Randomized trial of spheroid reservoir bioartificial liver in porcine model of posthepatectomy liver failure[J]. Hepatology, 2019, 69( 1): 329- 342. DOI: 10.1002/hep.30184.
[20]	WENG J, HAN X, ZENG FH, et al. Fiber scaffold bioartificial liver therapy relieves acute liver failure and extrahepatic organ injury in pigs[J]. Theranostics, 2021, 11( 16): 7620- 7639. DOI: 10.7150/thno.58515.
[21]	FENG L, WANG Y, FU Y, et al. A simple and efficient strategy for cell-based and cell-free-based therapies in acute liver failure: hUCMSCs bioartificial liver[J]. Bioeng Transl Med, 2023, 8( 5): e10552. DOI: 10.1002/btm2.10552.
[22]	WANG J, REN H, LIU Y, et al. Bioinspired artificial liver system with hiPSC-derived hepatocytes for acute liver failure treatment[J]. Adv Healthc Mater, 2021, 10( 23): e2101580. DOI: 10.1002/adhm.202101580.