药物性肝损伤的免疫遗传学机制研究进展

doi:10.12092/j.issn.1009-2501.2025.08.016

中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (8): 1133-1146.doi: 10.12092/j.issn.1009-2501.2025.08.016

药物性肝损伤的免疫遗传学机制研究进展

曾祥昌^1,2,3,4,5,7, 饶泰^1,3,4,5, 陈露露², 李超鹏², 曾贵荣⁶, 陈军⁷, 欧阳冬生^1,2,3,4,5

¹中南大学湘雅医院临床药理研究所,长沙 410008,湖南;
²长沙都正生物科技股份有限公司,复杂基质样本生物分析湖南省重点实验室,长沙 410205,湖南;
³中南大学临床药理研究所,遗传药理学湖南省重点实验室,长沙 410078,湖南;
⁴药物基因组应用技术教育部工程研究中心,长沙 410078,湖南;
⁵国家老年疾病临床医学研究中心,长沙 410008,湖南;
⁶湖南普瑞玛药物研究中心有限公司,新药药效与安全性评价湖南省重点实验室,长沙 410329,湖南;
⁷深圳市第三人民医院,南方科技大学第二附属医院疑难重症肝病科,深圳 518055,广东

收稿日期:2024-06-05 修回日期:2025-04-28 发布日期:2025-08-12
通讯作者: 欧阳冬生,男,博士,教授,研究方向：临床药理学、药物基因组学。E-mail： 801940@csu.edu.cn;饶泰,共同通信作者,男,博士,副研究员,研究方向：药物基因组学。E-mail： raotai9298@csu.edu.cn
作者简介:曾祥昌,男,博士,研究方向：药物基因组学。E-mail： zxchang45168@163.com
基金资助:
国家自然科学基金（82073942; 82274032）; 湖南省重点领域研发计划（2022SK2022）; 复杂基质样本生物分析湖南省重点实验室（2017TP1037）; 长沙市科技计划重大专项（kh2401014）; 中南大学中央高校基本科研业务费专项资金资助（2020zzts262）

Advances in immunogenetic mechanisms of drug-induced liver injury

ZENG Xiangchang, RAO Tai, CHEN Lulu, LI Chaopeng, ZENG Guirong, CHEN Jun, OUYANG Dongsheng

¹Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China;
²Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha 410205, Hunan, China;
³Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, Hunan, China;
⁴Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha 410078, Hunan, China;
⁵National Clinical Research Center for Geriatric Disorders, Changsha 410008;
⁶Hunan Prima Drug Research Center Co., Ltd. & Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha 410329, Hunan, China;
⁷Department of Liver Diseases, the Third People's Hospital of Shenzhen, the Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518055, Guangdong, China

Received:2024-06-05 Revised:2025-04-28 Published:2025-08-12

摘要/Abstract

摘要： 药物性肝损伤是药物研发和临床实践中面临的重要挑战之一,缺乏有效的防控措施。研究表明,药物性肝损伤主要由免疫反应介导。人类白细胞抗原（HLA）等位基因是目前报道与药物性肝损伤相关性最强的遗传因素。由于HLA等位基因的阳性预测值低,给药前HLA基因筛查对预防药物性肝损伤的临床转化价值有限;但其阴性预测值较高,在药物性肝损伤诊断和因果关系评估中具有重要的价值。近年来,抗原加工呈递通路、T细胞受体、免疫刺激分子、细胞因子等免疫相关基因多态性被发现与药物性肝损伤有关;未来将这些基因与HLA联合分析或许可加深药物性肝损伤机制的理解,同时推动其转化应用于临床来改善人类用药安全。

关键词: 药物性肝损伤, 人类白细胞抗原, 免疫遗传, 药物基因组学

Abstract: Drug-induced liver injury (DILI) is one of the major challenges in drug development and clinical practice, and effective prevention and control measures remain lacking. Research has shown that DILI is primarily mediated by immune responses. Human leukocyte antigen (HLA) alleles are currently the strongest genetic factors reported to be associated with DILI. Due to the low positive predictive value of HLA alleles, preemptive HLA genetic screening has limited clinical utility in preventing DILI. However, its high negative predictive value makes it valuable for DILI diagnosis and causality assessment. In recent years, polymorphisms in immune-related genes-such as those involved in antigen processing and presentation pathways, T-cell receptors, immunostimulatory molecules, and cytokines-have been found to be associated with DILI. Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational application in clinical practice, ultimately improving drug safety.

Key words: drug-induced liver injury, human leukocyte antigen, immunogenetics, pharmacogenomics

中图分类号:

R968

曾祥昌, 饶泰, 陈露露, 李超鹏, 曾贵荣, 陈军, 欧阳冬生. 药物性肝损伤的免疫遗传学机制研究进展[J]. 中国临床药理学与治疗学, 2025, 30(8): 1133-1146.

ZENG Xiangchang^{1, 2, 3, 4, 5, 7}, RAO Tai^{1, 3, 4, 5}, CHEN Lulu², LI Chaopeng², ZENG Guirong⁶, CHEN Jun⁷, OUYANG Dongsheng^{1, 2, 3, 4, 5}. Advances in immunogenetic mechanisms of drug-induced liver injury[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(8): 1133-1146.

参考文献

[1] Hoofnagle JH, Bjornsson ES.Drug-induced liver injury-types and phenotypes[J]. N Engl J Med, 2019, 381(3): 264-273.
[2] Stravitz RT, Lee WM.Acute liver failure[J]. Lancet, 2019, 394(10201): 869-881.
[3] Wang Y, Zou C, Wee A, et al.Comparison of the prognostic models for mortality in idiosyncratic drug-induced liver injury[J]. Hepatol Int, 2023, 17(2): 488-498.
[4] Uetrecht J.Mechanistic studies of idiosyncratic DILI: Clinical Implications[J]. Front Pharmacol, 2019, 10: 837.
[5] Daly AK, Donaldson PT, Bhatnagar P, et al.HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin[J]. Nat Genet, 2009, 41(7): 816-819.
[6] Nicoletti P, Aithal GP, Chamberlain TC, et al.Drug-induced liver injury due to flucloxacillin: Relevance of multiple human leukocyte antigen alleles[J]. Clin Pharmacol Ther, 2019, 106(1): 245-253.
[7] Clare KE, Miller MH, Dillon JF.Genetic factors influencing drug-induced liver injury: Do they have a role in prevention and diagnosis ?[J]. Curr Hepatol Rep, 2017, 16(3): 258-264.
[8] Donaldson PT, Daly AK, Henderson J, et al.Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury[J]. J Hepatol, 2010,53(6): 1049-1053.
[9] Lucena MI, Molokhia M, Shen Y, et al.Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles[J]. Gastroenterology, 2011, 141(1): 338-347.
[10] Nicoletti P, Dellinger A, Li YJ, et al.Identification of reduced ERAP2 expression and a novel HLA allele as components of a risk score for susceptibility to liver injury due to amoxicillin-clavulanate[J]. Gastroenterology, 2023, 164(3): 454-466.
[11] Singer JB, Lewitzky S, Leroy E, et al.A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury[J]. Nat Genet, 2010, 42(8): 711-714.
[12] Kindmark A, Jawaid A, Harbron CG, et al.Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis[J]. Pharmacogenomics J, 2008, 8(3): 186-195.
[13] Bessone F, Bjornsson ES.Drug-induced liver injury due to biologics and immune check point inhibitors[J]. Med Clin North Am, 2023, 107(3): 623-640.
[14] Fontana RJ, Bjornsson ES, Reddy R, et al.The evolving profile of idiosyncratic drug-induced liver injury[J]. Clin Gastroenterol Hepatol, 2023, 21(8): 2088-2099.
[15] Bjornsson ES, Gunnarsson BI, Grondal G, et al.Risk of drug-induced liver injury from tumor necrosis factor antagonists[J]. Clin Gastroenterol Hepatol, 2015, 13(3): 602-608.
[16] Bruno CD, Fremd B, Church RJ, et al.HLA associations with infliximab-induced liver injury[J]. Pharmacogenomics J, 2020, 20(5): 681-686.
[17] Bjornsson HK, Gudbjornsson B, Bjornsson ES.Infliximab-induced liver injury: Clinical phenotypes, autoimmunity and the role of corticosteroid treatment[J]. J Hepatol, 2022, 76(1): 86-92.
[18] de Joode K, Heersche N, Basak EA, et al. Review-The impact of pharmacogenetics on the outcome of immune checkpoint inhibitors[J]. Cancer Treat Rev, 2024, 122: 102662.
[19] Sung C, An J, Lee S, et al.Integrative analysis of risk factors for immune-related adverse events of checkpoint blockade therapy in cancer[J]. Nat Cancer, 2023, 4(6): 844-859.
[20] Navarro VJ, Barnhart H, Bonkovsky HL, et al.Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network[J]. Hepatology, 2014, 60(4): 1399-1408.
[21] Li C, Rao T, Chen X, et al.HLA-B*35:01 Allele is a potential biomarker for predicting polygonum multiflorum-induced liver injury in humans[J]. Hepatology, 2019, 70(1): 346-357.
[22] Yang WN, Pang LL, Zhou JY, et al.Single-nucleotide polymorphisms of HLA and Polygonum multiflorum-induced liver injury in the Han Chinese population[J]. World J Gastroenterol, 2020, 26(12): 1329-1339.
[23] Hoofnagle JH, Bonkovsky HL, Phillips EJ, et al.HLA-B*35:01 and green tea-induced liver injury[J]. Hepatology, 2021,73(6): 2484-2493.
[24] Line J, Ali SE, Grice S, et al.Investigating the immune basis of green tea extract induced liver injury in healthy donors expressing HLA-B*35:01[J]. Chem Res Toxicol, 2023, 36(12): 1872-1875.
[25] Halegoua-demarzio D, Navarro V, Ahmad J, et al. Liver injury associated with turmeric-a growing problem: Ten cases from the drug-induced liver injury network [DILIN][J]. Am J Med, 2023, 136(2): 200-206.
[26] Vuppalanchi R, Bonkovsky HL, Ahmad J, et al.Garcinia cambogia, either alone or in combination with green tea, causes moderate to severe liver injury[J]. Clin Gastroenterol Hepatol, 2022, 20(6): e1416-e1425.
[27] Nakamura R, Arakawa N, Tanaka Y, et al.Significant association between HLA-B*35:01 and onset of drug-induced liver injury caused by Kampo medicines in Japanese patients[J]. Hepatol Res, 2023, 53(5): 440-449.
[28] Mosedale M, Watkins PB.Understanding idiosyncratic toxicity: lessons learned from drug-induced liver injury[J]. J Med Chem, 2020, 63(12): 6436-6461.
[29] Kim SH, Saide K, Farrell J, et al.Characterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induced liver injury[J]. Hepatology, 2015, 62(3): 887-899.
[30] Monshi MM, Faulkner L, Gibson A, et al.Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T cells provides the immunological basis for flucloxacillin-induced liver injury[J]. Hepatology, 2013, 57(2): 727-739.
[31] Wuillemin N, Adam J, Fontana S, et al.HLA haplotype determines hapten or p-i T cell reactivity to flucloxacillin[J]. J Immunol, 2013, 190(10): 4956-4964.
[32] Illing PT, Vivian JP, Dudek NL, et al.Immune self-reactivity triggered by drug-modified HLA-peptide repertoire[J]. Nature, 2012, 486(7404): 554-558.
[33] Ahmad J, Dellinger A, Nicoletti P, et al.Clinical and HLA associations of fluoroquinolone induced liver injury: results from the Drug-Induced Liver Injury Network[J]. Am J Gastroenterol, 2025, doi: 10.14309/ ajg.0000000000003457.
[34] Conlon C, Li YJ, Ahmad J, et al.Clinical characteristics and HLA associations of azithromycin-induced liver injury[J]. Aliment Pharmacol Ther, 2024, 60(6): 787-795.
[35] Bonkovsky HL, Ghabril M, Nicoletti P, et al.Drug-induced liver injury (DILI) ascribed to non-steroidal anti-inflammatory drugs (NSAIDs) in the USA-Update with genetic correlations[J]. Liver Int, 2024, 44(6): 1409-1421.
[36] Asif BA, Koh C, Phillips EJ, et al.Vancomycin-induced liver injury, DRESS, and HLA-A *32:01[J]. J Allergy Clin Immunol Pract, 2024, 12(1): 168-174.
[37] Nicoletti P, Dellinger A, Li YJ, et al.HLA-B*53:01 is a significant risk factor of liver injury due to phenytoin and other antiepileptic drugs in African Americans[J]. Am J Gastroenterol, 2024, 119(1): 200-202.
[38] Chalasani N, Li YJ, Dellinger A, et al.Clinical features, outcomes, and HLA risk factors associated with nitrofurantoin-induced liver injury[J]. J Hepatol, 2023, 78(2): 293-300.
[39] Devarbhavi H, Patil M, Menon M.Association of human leukocyte antigen-B*13:01 with dapsone-induced liver injury[J]. Br J Clin Pharmacol, 2022, 88(3): 1369-1372.
[40] Fontana RJ, Li YJ, Phillips E, et al.Allopurinol hepatotoxicity is associated with human leukocyte antigen Class I alleles[J]. Liver Int, 2021, 41(8): 1884-1893.
[41] Nicoletti P, Devarbhavi H, Goel A, et al.Genetic risk factors in drug-induced liver injury due to isoniazid-containing antituberculosis drug regimens[J]. Clin Pharmacol Ther, 2021, 109(4): 1125-1135.
[42] Li YJ, Phillips EJ, Dellinger A, et al.Human leukocyte antigen B*14:01 and B*35:01 are associated with trimethoprim-sulfamethoxazole induced liver injury[J]. Hepatology, 2021, 73(1): 268-281.
[43] Li X, Jin S, Fan Y, et al.Association of HLA-C*03:02 with methimazole-induced liver injury in Graves' disease patients[J]. Biomed Pharmacother, 2019, 117: 109095.
[44] Fontana RJ, Cirulli ET, Gu J, et al.The role of HLA-A*33:01 in patients with cholestatic hepatitis attributed to terbinafine[J]. J Hepatol, 2018, 69(6): 1317-1325.
[45] Nicoletti P, Aithal GP, Bjornsson ES, et al.Association of liver injury from specific drugs, or groups of drugs, with polymorphisms in hla and other genes in a genome-wide association study[J]. Gastroenterology, 2017, 152(5): 1078-1089.
[46] Urban T J, Nicoletti P, Chalasani N, et al.Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B *35:02 as a risk factor[J]. J Hepatol, 2017, 67(1): 137-144.
[47] Nicoletti P, Werk AN, Sawle A, et al.HLA-DRB1*16: 01-DQB1*05: 02 is a novel genetic risk factor for flupirtine-induced liver injury[J]. Pharmacogenet Genomics, 2016, 26(5): 218-224.
[48] Xu CF, Johnson T, Wang X, et al.HLA-B*57:01 confers susceptibility to pazopanib-associated liver injury in patients with cancer[J]. Clin Cancer Res, 2016, 22(6): 1371-1377.
[49] Schaid DJ, Spraggs CF, Mcdonnell SK, et al.Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury[J]. J Clin Oncol, 2014, 32(22): 2296-2303.
[50] O'donohue J, Oien KA, Donaldson P, et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association[J]. Gut, 2000, 47(5): 717-720.
[51] Hirata K, Takagi H, Yamamoto M, et al.Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study[J]. Pharmacogenomics J, 2008, 8(1): 29-33.
[52] Dawes P, Moulder C.Perhexiline hepatitis and HLA-B8[J]. Lancet, 1982, 2(8289): 109.
[53] Carr DF, Bourgeois S, Chaponda M, et al.Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population[J]. J Antimicrob Chemother, 2017, 72(4): 1152-1162.
[54] Pavlos R, Deshpande P, Chopra A, et al.New genetic predictors for abacavir tolerance in HLA-B*57:01 positive individuals[J]. Hum Immunol, 2020, 81(6): 300-304.
[55] Fontana RJ, Li YJ, Vuppalanchi R, et al.ERAP-1 and ERAP-2 variants in liver injury following COVID-19 mRNA vaccination: A US multicenter study[J]. Am J Gastroenterol, 2024, 119(8): 1496-1505.
[56] Urrutia-maldonado E, Ales-palmer M, Munoz DRP, et al. The relation between activator and inhibitor killer-cell immunoglobulin-like receptors and hepatotoxicity in oncological treatment[J]. Minerva Pediatr (Torino), 2023, 75(5): 668-673.
[57] Puig M, Ananthula S, Venna R, et al.Alterations in the HLA-B*57:01 Immunopeptidome by Flucloxacillin and Immunogenicity of Drug-Haptenated Peptides[J]. Front Immunol, 2020, 11: 629399.
[58] Thomson P, Hammond S, Naisbitt DJ.Pathology of drug hypersensitivity reactions and mechanisms of immune tolerance[J]. Clin Exp Allergy, 2022, 52(12): 1379-1390.
[59] Tai Y, Wang Q, Korner H, et al.Molecular mechanisms of T cells activation by dendritic cells in autoimmune diseases[J]. Front Pharmacol, 2018, 9: 642.
[60] Gibson A, Faulkner L, Lichtenfels M, et al.The effect of inhibitory signals on the priming of drug hapten-specific T cells that express distinct vbeta receptors[J]. J Immunol, 2017, 199(4): 1223-1237.
[61] Cardone M, Garcia K, Tilahun ME, et al.A transgenic mouse model for HLA-B*57:01-linked abacavir drug tolerance and reactivity[J]. J Clin Invest, 2018, 128(7): 2819-2832.
[62] Susukida T, Kuwahara S, Song B, et al.Regulation of the immune tolerance system determines the susceptibility to HLA-mediated abacavir-induced skin toxicity[J]. Commun Biol, 2021, 4(1): 1137.
[63] Song B, Aoki S, Liu C, et al.The PD1 inhibitory pathway and mature dendritic cells contribute to abacavir hypersensitivity in human leukocyte antigen transgenic PD1 knockout mice[J]. Toxicology, 2021, 463: 152971.
[64] Ananthula S, Krishnaveni SK, Cardone M, et al.Development of mouse models with restricted HLA-B *57:01 presentation for the study of flucloxacillin-driven T-cell activation and tolerance in liver injury[J]. J Allergy Clin Immunol, 2023, 152(2): 486-499.
[65] Guo Y, Fan Y, Qiu J, et al.Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients[J]. PLoS One, 2012, 7(12): e51723.
[66] Aithal GP, Ramsay L, Daly AK, et al.Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity[J]. Hepatology, 2004, 39(5): 1430-1440.
[67] Pachkoria K, Lucena MI, Crespo E, et al.Analysis of IL-10, IL-4 and TNF-alpha polymorphisms in drug-induced liver injury (DILI) and its outcome[J]. J Hepatol, 2008, 49(1): 107-114.
[68] Li Y, Tang H, Qi H, et al.rs1800796 of the IL6 gene is associated with increased risk for anti-tuberculosis drug-induced hepatotoxicity in Chinese Han children[J]. Tuberculosis (Edinb), 2018, 111: 71-77.
[69] Carr DF, Alfirevic A, Tugwood JD, et al.Molecular and genetic association of interleukin-6 in tacrine-induced hepatotoxicity[J]. Pharmacogenet Genomics, 2007, 17(11): 961-972.
[70] Kim SH, Kim SH, Yoon HJ, et al.TNF-alpha genetic polymorphism -308G/A and antituberculosis drug-induced hepatitis[J]. Liver Int, 2012, 32(5): 809-814.
[71] Liang X, Zhang J, Zhu Y, et al.Specific genetic polymorphisms of IL10-592 AA and IL10-819 TT genotypes lead to the key role for inducing docetaxel-induced liver injury in breast cancer patients[J]. Clin Transl Oncol, 2013, 15(4): 331-334.
[72] Mallal S, Phillips E, Carosi G, et al.HLA-B*5701 screening for hypersensitivity to abacavir[J]. N Engl J Med, 2008, 358(6): 568-579.
[73] Alfirevic A, Pirmohamed M.Predictive genetic testing for drug-induced liver injury: considerations of clinical utility[J]. Clin Pharmacol Ther, 2012, 92(3): 376-380.
[74] Aithal GP.Pharmacogenetic testing in idiosyncratic drug-induced liver injury: current role in clinical practice[J]. Liver Int, 2015, 35(7): 1801-1808.
[75] Swen JJ, van der Wouden CH, Manson LE, et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study[J]. Lancet, 2023, 401(10374): 347-356.
[76] Stephens C, Andrade RJ.Genetic predisposition to drug-induced liver injury[J]. Clin Liver Dis, 2020, 24(1): 11-23.
[77] Stephens C, Lucena MI, Andrade RJ.Genetic risk factors in the development of idiosyncratic drug-induced liver injury[J]. Expert Opin Drug Metab Toxicol, 2021, 17(2): 153-169.
[78] Kullak-ublick GA, Andrade RJ, Merz M, et al. Drug-induced liver injury: recent advances in diagnosis and risk assessment[J]. Gut, 2017, 66(6): 1154-1164.
[79] Ariyoshi N, Iga Y, Hirata K, et al.Enhanced susceptibility of HLA-mediated ticlopidine-induced idiosyncratic hepatotoxicity by CYP2B6 polymorphism in Japanese[J]. Drug Metab Pharmacokinet, 2010, 25(3): 298-306.
[80] Su SC, Chen CB, Chang WC, et al.HLA Alleles and CYP2C9*3 as Predictors of Phenytoin Hypersensitivity in East Asians[J]. Clin Pharmacol Ther, 2019, 105(2): 476-485.
[81] Chanhom N, Jittikoon J, Wattanapokayakit S, et al.The association of HLA-B*35 and GSTT1 genotypes and hepatotoxicity in Thai people living with HIV[J]. J Pers Med, 2022, 12(6): 940.

药物性肝损伤的免疫遗传学机制研究进展

Advances in immunogenetic mechanisms of drug-induced liver injury

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王泉林, 孙树森, 张伟, 曹丹, 金一粟. 中美药物基因组学教育发展概况[J]. 中国临床药理学与治疗学, 2024, 29(9): 1076-1080.
[2]	李坤, 李璐璐, 李楠楠, 胡卫红, 周建超. 成人肾移植术后血糖控制和CYP3A5基因多态性对他克莫司谷浓度的影响[J]. 中国临床药理学与治疗学, 2023, 28(7): 767-774.
[3]	孙媛媛, 邓锟红, 王思懿, 况赟, 邹婵, 郭成贤, 何庆南, 刘和林, 阳国平. 个体化用药基因电子身份应用程序的设计与实现[J]. 中国临床药理学与治疗学, 2022, 27(3): 274-280.
[4]	宋如铮, 彭英, 王广基, 孙建国. 定量蛋白质组学常用研究技术及其在肝源性疾病发病机制中的应用进展[J]. 中国临床药理学与治疗学, 2021, 26(5): 570-578.
[5]	邢开, 龚金玉, 罗建权. 噻嗪类利尿剂相关不良反应的药物基因组学研究进展[J]. 中国临床药理学与治疗学, 2021, 26(2): 204-212.
[6]	梅笛, 沈纪中, 刘春妍, 陆程灿, 徐伟, 彭宇竹. 新型口服抗凝药的药物基因组学研究进展[J]. 中国临床药理学与治疗学, 2021, 26(10): 1200-1207.
[7]	许丽娜, 李月, 彭金咏. microRNA与药物性肝损伤[J]. 中国临床药理学与治疗学, 2020, 25(7): 803-809.
[8]	李红丽，文丹丹，贝承丽，高利臣，彭喜旭. 专项整治前后结核患者肝损伤及药物使用费用对比分析[J]. 中国临床药理学与治疗学, 2019, 24(9): 1030-1036.
[9]	周勇，应莉，徐佳佳，丁世雄，胡爱荣，高国生. 可溶性人类白细胞抗原G对丙型肝炎初治患者标准化治疗疗效的影响[J]. 中国临床药理学与治疗学, 2018, 23(7): 809-813.
[10]	谢商宸，李玮，廖萍，贺毅憬，Howard L. Mcleod. 全身麻醉药物遗传药理学研究进展[J]. 中国临床药理学与治疗学, 2018, 23(2): 217-222.
[11]	郭成贤，王晶，李金高，袁洪，周宏灏，阳国平. 临床药物基因组学应用现状[J]. 中国临床药理学与治疗学, 2016, 21(4): 458-462.
[12]	胡琴, 刘维, 邵宏. 药物性肝损伤的药物治疗研究进展[J]. 中国临床药理学与治疗学, 2016, 21(2): 231-236.
[13]	郭瑶雪, 邓晔, 李春, 贺蕾艳, 彭文兴. 异烟肼致线粒体损伤引起药物性肝损伤研究进展[J]. 中国临床药理学与治疗学, 2015, 20(3): 356-360.
[14]	赵德恒, 萧惠来. FDA对药物基因组学早期临床研究的建议[J]. 中国临床药理学与治疗学, 2015, 20(2): 208-212.
[15]	张月丽, 明英姿, 周宏灏, 张伟. 他克莫司:药代动力学,药效动力学和药物基因组学[J]. 中国临床药理学与治疗学, 2014, 19(9): 1042-1049.