程序性死亡蛋白-1抑制剂致肝损伤研究进展

闫琪; 宋立莎; 辛桂杰

doi:10.3969/j.issn.1001-5256.2019.09.051

程序性死亡蛋白-1抑制剂致肝损伤研究进展

DOI: 10.3969/j.issn.1001-5256.2019.09.051

1. 吉林大学第一医院肝胆胰内科
2. 吉林大学第一医院二部急救科

详细信息

中图分类号: R575
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出版历程
- 收稿日期: 2019-03-28
- 出版日期: 2019-09-20

Research advances in liver injury induced by programmed death protein-1 inhibitors

Department of Hepatology, The First Hospital of Jilin University

摘要

摘要: 随着程序性死亡蛋白-1抑制剂在肿瘤治疗中的应用,其带来的副反应——免疫相关不良反应（irAEs）也在全身发生,然而对irAEs中的肝损伤研究较少。主要阐述了程序性死亡蛋白-1抑制剂致肝损伤的分子机制、疾病分级、发病率、发病时间、血清学、组织学、影像学、生物标志物方面的特征以及治疗手段,进而全面认识irAEs中的肝损伤。认为其所致的肝损伤发病率虽低,但高级别肝损伤危险度较高,医务人员应引起注意,对其尽早识别并正确应对。
- 药物性肝损伤 /
- 程序性死亡蛋白-1抑制剂
Abstract: With the application of programmed cell death-1 ( PD-1) inhibitors in tumor treatment, related side effects and immune-related adverse events ( irAEs) are observed in the whole body; however, there are few studies on liver injury in irAEs. This article elaborates on the features of liver injury induced by PD-1 inhibitors from the aspects of molecular mechanism, disease grade, incidence rate, onset time, serology, histology, imaging, and biomarkers and related treatment methods, so as to provide a comprehensive understanding of liver injury in irAEs. It is believed that although there is a low incidence rate of liver injury caused by PD-1 inhibitors, high-grade liver injury has a high level of risk. Such liver injury should be taken seriously by the medical staff, and early identification and proper treatment should be performed.
- drug-induced liver injury /
- programmed cell death-1 inhibitors

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参考文献(30)

[1] PARRY RV, CHEMNITZ JM, FRAUWIRTH KA, et al. CTLA-4and PD-1 receptors inhibit T-cell activation by distinct mechanisms[J]. Mol Cell Biol, 2005, 25 (21) :9543-9553.

[2] WEI F, ZHONG S, MA Z, et al. Strength of PD-1 signaling differentially affects T-cell effector functions[J]. Proc Natl Acad Sci U S A, 2013, 110 (27) :e2480-e2489.

[3] WEI SC, LEVINE JH, COGDILL AP, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade[J]. Cell, 2017, 170 (6) :1120-1133.

[4] AHN E, ARAKI K, HASHIMOTO M, et al. Role of PD-1 during effector CD8 T cell differentiation[J]. Proc Natl Acad Sci U S A, 2018, 115 (18) :4749-4754.

[5] CHIU YM, TSAI CL, KAO JT, et al. PD-1 and PD-L1 upregulation promotes T-cell apoptosis in gastric adenocarcinoma[J]. Anticancer Res, 2018, 38 (4) :2069-2078.

[6] PARDOLL DM. The blockade of immune checkpoints in cancer immunotherapy[J]. Nat Rev Cancer, 2012, 12 (4) :252-264.

[7] DONG H, ZHU G, TAMADA K, et al. B7-H1 determines accumulation and deletion of intrahepatic CD8 (+) T lymphocytes[J]. Immunity, 2004, 20 (3) :327-336.

[8] GAO WJ, LIU YY, YUAN CR. International evaluation system for adverse events of chemotherapeutic drugs in cancer treatment:CTCAE v4. 0[J]. Tumor, 2012, 32 (2) :142-144. (in Chinese) 皋文君, 刘砚燕, 袁长蓉.国际肿瘤化疗药物不良反应评价系统———通用不良反应术语标准4. 0版[J].肿瘤, 2012, 32 (2) :142-144.

[9] NAIDOO J, PAGE DB, LI BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies[J]. Ann Oncol, 2015, 26 (12) :2375-2391.

[10] WANG PF, CHEN Y, SONG SY, et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies:A Meta-analysis[J]. Front Pharmacol, 2017, 8:730.

[11] LARKIN J, CHIARION-SILENI V, GONZALEZ R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma[J]. N Engl J Med, 2015, 373 (1) :23-34.

[12] WANG DY, SALEM JE, COHEN JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors:A systematic review and meta-analysis[J]. JAMA oncology, 2018, 4 (12) :1721-1728.

[13] PUZANOV I, DIAB A, ABDALLAH K, et al. Managing toxicities associated with immune checkpoint inhibitors:Consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group[J]. J Immunother Cancer, 2017, 5 (1) :95.

[14] EIGENTLER TK, HASSEL JC, BERKING C, et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy[J]. Cancer Treat Rev, 2016, 45 (2016) :7-18.

[15] CRAMER P, BRESALIER RS. Gastrointestinal and hepatic complications of immune checkpoint inhibitors[J]. Curr Gastroenterol Rep, 2017, 19 (1) :3.

[16] SUZMAN DL, PELOSOF L, ROSENBERG A, et al. Hepatotoxicity of immune checkpoint inhibitors:An evolving picture of risk associated with a vital class of immunotherapy agents[J].Liver Int, 2018, 38 (6) :976-987.

[17] MCGUIRE HM, SHKLOVSKAYA E, EDWARDS J, et al. AntiPD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells:A case report[J]. Cancer Immunol Immunother, 2017, 67 (4) :563-573.

[18] de VELASCO G, JE Y, BOSSE D, et al. Comprehensive Metaanalysis of key immune-related adverse events from CTLA-4and PD-1/PD-L1 inhibitors in cancer patients[J]. Cancer Immunol Res, 2017, 5 (4) :312-318.

[19] REUBEN A. Hy’s law[J]. Hepatology, 2004, 39 (2) :574-578.

[20] ZEN Y, YEH MM. Hepatotoxicity of immune checkpoint inhibitors:A histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury[J]. Mod Pathol, 2018, 31 (6) :965-973.

[21] de MARTIN E, MICHOT JM, PAPOUIN B, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors[J]. J Hepatol, 2018, 68 (6) :1181-1190.

[22] REDDY HG, SCHNEIDER BJ, TAI AW. Immune checkpoint inhibitor-associated colits and hepatitis[J]. Clin Transl Gastroenterol, 2018, 9 (9) :180.

[23] NADEAU BA, FECHER LA, OWENS SR, et al. Liver toxicity with cancer checkpoint inhibitor therapy[J]. Semin Liver Dis, 2018, 38 (4) :366-378.

[24] TIRUMANI SH, RAMAIYA NH, KERALIYA A, et al. Radiographic profiling of immune-related adverse events in advanced melanoma patients treated with ipilimumab[J]. Cancer Immunol Res, 2015, 3 (10) :1185-1192.

[25] HOFMANN L, FORSCHNER A, LOQUAI C, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy[J]. Eur J Cancer, 2016, 60:190-209.

[26] MEKKI A, DERCLE L, LICHTENSTEIN P, et al. Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1[J]. Eur J Cancer, 2018, 96 (2018) :91-104.

[27] OKADA N, KAWAZOE H, TAKECHI K, et al. Association between immune-related adverse events and clinical efficacy in patients with melanoma treated with nivolumab:A multicenter retrospective study[J]. Clin Ther, 2018, 41 (1) :59-67.

[28] FUJIMURA T, SATO Y, TANITA K, et al. Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab:A pilot study[J]. Oncotarge, 2018, 9 (21) :15542-15551.

[29] LIM SY, LEE JH, GIDE TN, et al. Circulating cytokines predict immune-related toxicity in melanoma patients receiving antiPD-1-based immunotherapy[J]. Clin Cancer Res, 2019, 25 (5) :1557-1563.

[30] WEBER JS, HODI FS, WOLCHOK JD, et al. Safety profile of nivolumab monotherapy:A pooled analysis of patients with advanced melanoma[J]. J Clin Oncol, 2017, 35 (7) :785-792.

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