Clinical manifestations and typing of drug-induced liver injury
-
摘要: 药物性肝损伤是人体最常见和最严重的药物不良反应之一,部分严重者会出现肝衰竭甚至死亡。不同药物所致肝损伤的临床表现各异,严重程度不尽相同,大多数药物性肝损伤患者没有症状或症状较轻。根据临床表现、病程和发病机制,可将药物性肝损伤进行多种分型。根据R值,可进行如下临床分型:肝细胞损伤型(R≥5);胆汁淤积型(R≤2);混合型(2<R<5)。根据病程,药物性肝损伤可分为急性药物性肝损伤和慢性药物性肝损伤。根据发病机制,药物性肝损伤可分为固有型、特异质型和间接损伤型。全面了解药物性肝损伤的临床表现和分型方式,有助于揭示其发病机制,以及时诊断和治疗药物性肝损伤。
-
关键词:
- 化学性与药物性肝损伤 /
- 临床特征 /
- 发病机制 /
- 分型
Abstract: Drug-induced liver injury (DILI) is one of the most common and severe adverse drug reactions in humans, which may lead to liver failure and even death in some patients. Liver injury caused by different drugs has various clinical manifestations and severities, and most patients with DILI have no symptoms or have mild symptoms. There are various typing methods for DILI based on clinical features, course of disease, and pathogenesis. According to the R value, DILI can be classified into hepatocellular injury type (R ≥5), cholestasis type (R ≤2), and mixed type (2 < R < 5); according to the course of the disease, DILI can be classified into acute DILI and chronic DILI; according to the pathogenesis, DILI can be classified into intrinsic DILI, idiosyncratic DILI, and indirect DILI. A comprehensive understanding of the clinical manifestations and typing methods of DILI helps to reveal its pathogenesis and perform diagnosis and treatment in a timely manner.-
Key words:
- Chemical and Drug-Induced Liver Injury /
- Clinical Feature /
- Pathogenesis /
- Phenotypes
-
[1] Drug-induced Liver Disease Study Group, Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the management of drug-induced liver injury[J]. J Clin Hepatol, 2015, 31(11): 1752-1769. DOI: 10.3969/j.issn.1001-5256.2015.11.002.中华医学会肝病学分会药物性肝病学组. 药物性肝损伤诊治指南[J]. 临床肝胆病杂志, 2015, 31(11): 1752-1769. DOI: 10.3969/j.issn.1001-5256.2015.11.002. [2] OSTAPOWICZ G, FONTANA RJ, SCHIØDT FV, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States[J]. Ann Intern Med, 2002, 137(12): 947-954. DOI: 10.7326/0003-4819-137-12-200212170-00007. [3] DAVERN TJ. Drug-induced liver disease[J]. Clin Liver Dis, 2012, 16(2): 231-245. DOI: 10.1016/j.cld.2012.03.002. [4] CHALASANI NP, HAYASHI PH, BONKOVSKY HL, et al. ACG Clinical Guideline: The diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2014, 109(7): 950-966; quiz 967. DOI: 10.1038/ajg.2014.131. [5] CHALASANI N, BONKOVSKY HL, FONTANA R, et al. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN prospective study[J]. Gastroenterology, 2015, 148(7): 1340-1352. e7. DOI: 10.1053/j.gastro.2015.03.006. [6] KLEINER DE, CHALASANI NP, LEE WM, et al. Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations[J]. Hepatology, 2014, 59(2): 661-670. DOI: 10.1002/hep.26709. [7] AITHAL PG, DAY CP. The natural history of histologically proved drug induced liver disease[J]. Gut, 1999, 44(5): 731-735. DOI: 10.1136/gut.44.5.731. [8] ANDRADE RJ, LUCENA MI, KAPLOWITZ N, et al. Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry[J]. Hepatology, 2006, 44(6): 1581-1588. DOI: 10.1002/hep.21424. [9] AITHAL GP, WATKINS PB, ANDRADE RJ, et al. Case definition and phenotype standardization in drug-induced liver injury[J]. Clin Pharmacol Ther, 2011, 89(6): 806-815. DOI: 10.1038/clpt.2011.58. [10] MEDINA-CALIZ I, ROBLES-DIAZ M, GARCIA-MUÑOZ B, et al. Definition and risk factors for chronicity following acute idiosyncratic drug-induced liver injury[J]. J Hepatol, 2016, 65(3): 532-542. DOI: 10.1016/j.jhep.2016.05.003. [11] EASL Clinical Practice Guidelines: Drug-induced liver injury[J]. J Hepatol, 2019, 70(6): 1222-1261. DOI: 10.1016/j.jhep.2019.02.014. [12] LARSON AM, POLSON J, FONTANA RJ, et al. Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study[J]. Hepatology, 2005, 42(6): 1364-1372. DOI: 10.1002/hep.20948. [13] PYE M, NORTHCOTE RJ, COBBE SM. Acute hepatitis after parenteral amiodarone administration[J]. Br Heart J, 1988, 59(6): 690-691. DOI: 10.1136/hrt.59.6.690. [14] DALTON TA, BERRY RS. Hepatotoxicity associated with sustained-release niacin[J]. Am J Med, 1992, 93(1): 102-104. DOI: 10.1016/0002-9343(92)90689-9. [15] SUÁREZ FERRER C, LLOP HERRERA E, CALVO MOYA M, et al. Idiopathic portal hypertension regarding thiopurine treatment in patients with inflammatory bowel disease[J]. Rev Esp Enferm Dig, 2016, 108(2): 79-83. DOI: 10.17235/reed.2015.3954/2015. [16] COTTE L, BÉNET T, BILLIOUD C, et al. The role of nucleoside and nucleotide analogues in nodular regenerative hyperplasia in HIV-infected patients: A case control study[J]. J Hepatol, 2011, 54(3): 489-496. DOI: 10.1016/j.jhep.2010.07.030. [17] MALLET V, BLANCHARD P, VERKARRE V, et al. Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV-infected patients[J]. AIDS, 2007, 21(2): 187-192. DOI: 10.1097/QAD.0b013e3280119e47. [18] WANG JJ, CHENG C, XIE W, et al. Analysis on the clinical characteristics of hepatic veno-occlusive disease caused by gynurasegetum for 8 cases[J]. Chin Med Modern Distance Educ of China, 2021, 19(7): 139-142. DOI: 10.3969/j.issn.1672-2779.2021.07.053.王京京, 程澄, 谢雯, 等. 土三七致肝窦阻塞综合征8例临床特点分析及文献复习[J]. 中国中医药现代远程教育, 2021, 19(7): 139-142. DOI: 10.3969/j.issn.1672-2779.2021.07.053. [19] BATTIPAGLIA G, LABOPIN M, CANDONI A, et al. Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: A retrospective study from the Acute Leukemia Working Party of the EBMT[J]. Bone Marrow Transplant, 2017, 52(4): 592-599. DOI: 10.1038/bmt.2016.302. [20] KUMAR S, DELEVE LD, KAMATH PS, et al. Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation[J]. Mayo Clin Proc, 2003, 78(5): 589-598. DOI: 10.4065/78.5.589. [21] DELEVE LD, SHULMAN HM, MCDONALD GB. Toxic injury to hepatic sinusoids: Sinusoidal obstruction syndrome (veno-occlusive disease)[J]. Semin Liver Dis, 2002, 22(1): 27-42. DOI: 10.1055/s-2002-23204. [22] STEWART JD, HORVATH R, BARUFFINI E, et al. Polymerase γ gene POLG determines the risk of sodium valproate-induced liver toxicity[J]. Hepatology, 2010, 52(5): 1791-1796. DOI: 10.1002/hep.23891. [23] MARGOLIS AM, HEVERLING H, PHAM PA, et al. A review of the toxicity of HIV medications[J]. J Med Toxicol, 2014, 10(1): 26-39. DOI: 10.1007/s13181-013-0325-8. [24] JONES DB, MULLICK FG, HOOFNAGLE JH, et al. Reye's syndrome-like illness in a patient receiving amiodarone[J]. Am J Gastroenterol, 1988, 83(9): 967-969. [25] CULLEN JM. Mechanistic classification of liver injury[J]. Toxicol Pathol, 2005, 33(1): 6-8. DOI: 10.1080/01926230590522428. [26] MCKENZIE R, FRIED MW, SALLIE R, et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B[J]. N Engl J Med, 1995, 333(17): 1099-1105. DOI: 10.1056/NEJM199510263331702. [27] WEI CM, CHEN HL, LEE PI, et al. Reye's syndrome developing in an infant on treatment of Kawasaki syndrome[J]. J Paediatr Child Health, 2005, 41(5-6): 303-304. DOI: 10.1111/j.1440-1754.2005.00617.x. [28] ZHANG X, OUYANG J, THUNG SN. Histopathologic manifestations of drug-induced hepatotoxicity[J]. Clin Liver Dis, 2013, 17(4): 547-564, vii-viii. DOI: 10.1016/j.cld.2013.07.004. [29] RAMACHANDRAN R, KAKAR S. Histological patterns in drug-induced liver disease[J]. J Clin Pathol, 2009, 62(6): 481-492. DOI: 10.1136/jcp.2008.058248. [30] SHEN T, LIU Y, SHANG J, et al. Incidence and etiology of drug-induced liver injury in Mainland China[J]. Gastroenterology, 2019, 156(8): 2230-2241. e11. DOI: 10.1053/j.gastro.2019.02.002. [31] CAO XY, XUE M, WEN Y, et al. Research progress on susceptibility genes of anti-tuberculous drug-induced liver injury[J]. Chin J Antituberc, 2021, 43(2): 190-193. DOI: 10.3969/j.issn.1000-6621.2021.02.016.曹鑫宇, 薛秒, 文艳, 等. 抗结核药物性肝损伤易感基因研究进展[J]. 中国防痨杂志, 2021, 43(2): 190-193. DOI: 10.3969/j.issn.1000-6621.2021.02.016. [32] 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. DOI: 10.1053/j.gastro.2011.04.001. [33] 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. DOI: 10.1038/ng.379. [34] 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. DOI: 10.3748/wjg.v26.i12.1329. [35] KARDAUN SH, SIDOROFF A, VALEYRIE-ALLANORE L, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: Does a DRESS syndrome really exist?[J]. Br J Dermatol, 2007, 156(3): 609-611. DOI: 10.1111/j.1365-2133.2006.07704.x. [36] BJÖRNSSON ES, BERGMANN OM, BJÖRNSSON HK, et al. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland[J]. Gastroenterology, 2013, 144(7): 1419-1425. e1-e3; quiz e19-e20. DOI: 10.1053/j.gastro.2013.02.006. [37] ZIMMERMAN HJ. Drug-induced liver disease[J]. Clin Liver Dis, 2000, 4(1): 73-96, vi. DOI: 10.1016/s1089-3261(05)70097-0. [38] SPEEG KV, BAY MK. Prevention and treatment of drug-induced liver disease[J]. Gastroenterol Clin North Am, 1995, 24(4): 1047-1064. [39] GORDON V, ADHIKARY R, APPLEBY V, et al. Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK[J]. Liver Int, 2018, 38(9): 1686-1695. DOI: 10.1111/liv.13724. [40] BJÖRNSSON E, TALWALKAR J, TREEPRASERTSUK S, et al. Drug-induced autoimmune hepatitis: Clinical characteristics and prognosis[J]. Hepatology, 2010, 51(6): 2040-2048. DOI: 10.1002/hep.23588. [41] LICATA A, MAIDA M, CABIBI D, et al. Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: A retrospective cohort study[J]. Dig Liver Dis, 2014, 46(12): 1116-1120. DOI: 10.1016/j.dld.2014.08.040. [42] BJÖRNSSON ES, BERGMANN O, JONASSON JG, et al. Drug-induced autoimmune hepatitis: Response to corticosteroids and lack of relapse after cessation of steroids[J]. Clin Gastroenterol Hepatol, 2017, 15(10): 1635-1636. DOI: 10.1016/j.cgh.2017.05.027. [43] CZAJA AJ. Difficult treatment decisions in autoimmune hepatitis[J]. World J Gastroenterol, 2010, 16(8): 934-947. DOI: 10.3748/wjg.v16.i8.934. [44] HOOFNAGLE JH, BJÖRNSSON ES. Drug-induced liver injury - types and phenotypes[J]. N Engl J Med, 2019, 381(3): 264-273. DOI: 10.1056/NEJMra1816149. [45] PEERAPHATDIT TB, WANG J, ODENWALD MA, et al. Hepatotoxicity from immune checkpoint inhibitors: A systematic review and management recommendation[J]. Hepatology, 2020, 72(1): 315-329. DOI: 10.1002/hep.31227. [46] AFFOLTER T, LLEWELLYN HP, BARTLETT DW, et al. Inhibition of immune checkpoints PD-1, CTLA-4, and IDO1 coordinately induces immune-mediated liver injury in mice[J]. PLoS One, 2019, 14(5): e0217276. DOI: 10.1371/journal.pone.0217276. [47] 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. DOI: 10.1016/j.jhep.2018.01.033. [48] INAMORI O, MIYAGAWA-HAYASHINO A, UENO A, et al. Fulminant hepatitis as an immune-related adverse event after nivolumab treatment[J]. Pathol Int, 2019, 69(7): 434-436. DOI: 10.1111/pin.12812. [49] ROOKS JB, ORY HW, ISHAK KG, et al. Epidemiology of hepatocellular adenoma. The role of oral contraceptive use[J]. JAMA, 1979, 242(7): 644-648. [50] BARTHELMES L, TAIT IS. Liver cell adenoma and liver cell adenomatosis[J]. HPB (Oxford), 2005, 7(3): 186-196. DOI: 10.1080/13651820510028954. [51] VELAZQUEZ I, ALTER BP. Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions[J]. Am J Hematol, 2004, 77(3): 257-267. DOI: 10.1002/ajh.20183.
本文二维码
计量
- 文章访问数: 1905
- HTML全文浏览量: 431
- PDF下载量: 311
- 被引次数: 0