Threshold setting of biochemical indexes related to diagnosis of drug-induced liver injury

doi:10.19803/j.1672-8629.2022.03.03

Abstract

Abstract: Objective To investigate the currently-used biochemical thresholds related to the diagnosis of drug-induced liver injury (DILI) in order to provide reference for monitoring of adverse drug reactions. Methods Based on the newly released guidelines for clinical diagnosis and treatment, expert consensus and health industry standards of DILI at home and abroad, the latest classification of pathogenesis of DILI and the establishment of thresholds of biochemical indicators related to diagnosis were summarized. Results The current international biochemical diagnostic criteria for DILI were determined as follows: ①ALT≥5×ULN; ②ALT≥3×ULN, TBL > 2×ULN, without ALP elevation; ③ALP≥2×ULN, especially with 5'- nucleotide enzyme elevation, but without any bone disease (ALP elevation is caused by the liver). The reference intervals of biochemical test indexes related to the diagnosis of DILI were age-dependent in children. Conclusion In DILI-related studies, especially those for children, the thresholds of DILI-related biochemical indicators should be determined by the reference interval corresponding to each age group in order to make outcome judgment more accurate.

Key words: drug-induced liver injury, biochemical indices, diagnostic threshold, guidelines, reference interval, monitoring

CLC Number:

R944.1

NIE Xiaolu, PENG Yaguang, SUN Zimo, PENG Xiaoxia. Threshold setting of biochemical indexes related to diagnosis of drug-induced liver injury[J]. Chinese Journal of Pharmacovigilance, 2022, 19(3): 244-247.

References

[1] Durg-induced Liver Disease Group, Chinese Society of Hepatology, Chinese Medical Association. Guidelines of diagnosis and treatment for drug-induced liver injury: a 2015 update[J]. J Clin Hepatol(临床肝胆病杂志), 2015, 31(11): 1752-1768.
[2] CHALASANI NP, MADDUR H, RUSSO MW, et al.ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2021, 116(5): 878-898.
[3] KOIDO M, KAWAKAMI E, FUKUMURA J, et al.Polygenic architecture informs potential vulnerability to drug-induced liver injury[J]. Nature Medicine, 2020, 26(10): 1541-1548.
[4] MAO YM.Strengthening transformation research and promoting scientific supervision of drug induced liver injury[J]. Adverse Drug Reactions Journal(药物不良反应杂志), 2020, 22(2): 58-61.
[5] HOOFNAGLE JH, BJÖRNSSON ES. Drug-induced liver injury - types and phenotypes[J]. N Engl J Med, 2019, 381(3): 264-273.
[6] YU LC, CHEN CW.Pathogenesis of drug-induced liver injury: current understanding and future needs[J]. J Clin Hepatol(临床肝胆病杂志), 2021, 37(11): 2515-2524.
[7] SHI YP, WANG SB, LI D, et al.Research progress of drug-induced liver injury[J]. Journal of Pediatric Pharmacy(儿科药学杂志), 2018, 24(7): 58-61.
[8] ROSENZWEIG P, BROHIER S, ZIPFEL A.The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies[J]. Clin Pharmacol Ther, 1993, 54(5): 578-583.
[9] ROSENZWEIG P, BROHIER S, ZIPFEL A.Data on placebo in healthy volunteers: impact of experimental conditions on safety, and on laboratory and physiological variables during phase I trials[J]. Therapie, 1996, 51(4): 356-357.
[10] SIBILLE M, DEIGAT N, DURIEU I, et al.Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials[J]. Eur J Clin Pharmacol, 1999, 55(1): 13-19.
[11] PURKINS L, LOVE ER, EVE MD, et al.The influence of diet upon liver function tests and serum lipids in healthy male volunteers resident in a phase I unit[J]. Br J Clin Pharmacol, 2004, 57(2): 199-208.
[12] TEMPLE R.Hy's law: predicting serious hepatotoxicity[J]. Pharmacoepidemiol Drug Saf, 2006, 15(4): 241-243.
[13] BÉNICHOU C. Criteria of drug-induced liver disorders. Report of an international consensus meeting[J]. J Hepatol, 1990, 11(2): 272-276.
[14] NEUSCHWANDER-TETRI BA, CALDWELL SH.Nonalcoholic steatohepatitis: summary of an AASLD single topic conference[J]. Hepatology, 2003, 37(5): 1202-1219.
[15] MAKAR GA, WEINER MG, KIMMEL SE, et al.Incidence and prevalence of abnormal liver associated enzymes in patients with atrial fibrillation in a routine clinical care population[J]. Pharmacoepidemiol Drug Saf, 2008, 17(1): 43-51.
[16] WEIL JG, BAINS C, LINKE A, et al.Background incidence of liver chemistry abnormalities in a clinical trial population without underlying liver disease[J]. Regul Toxicol Pharmacol, 2008, 52(2): 85-88.
[17] SAUKKONEN JJ, COHN DL, JASMER RM, et al.An official ATS statement: hepatotoxicity of antituberculosis therapy[J]. Am J Respir Crit Care Med, 2006, 174(8): 935-952.
[18] 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.
[19] 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, 967.
[20] EASL clinical practice guidelines: drug-induced liver injury[J]. J Hepatol, 2019, 70(6): 1222-1261.
[21] Group AcbaCW. Drug-induced liver injury (DILI): current status and future directions for drug development and the post-market setting[R/OL]. Geneva, Switzerland: Council for International Organizations of Medical Sciences (CIOMS), 2020. https://cioms.ch/wp-content/uploads/2020/06/CIOMS_DILI_Web_16Jun2020.pdf.
[22] DEVARBHAVI H, AITHAL G, TREEPRASERTSUK S, et al.Drug-induced liver injury: Asia pacific association of study of liver consensus guidelines[J]. Hepatol Int, 2021, 15(2): 258-282.
[23] ZHANG HL, XU LL, XIE YJ, et al.201 Cases of drug-induced liver injury in children[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2020, 17(10): 715-719.
[24] LI J, HE LM, ZHANG HX, et al.Analysis of 70 cases of children with drug-induced liver injury[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2020, 17(7): 431-436.
[25] Professional Committee of clinical examination standards of the Ministry of health. WS/T 404.1-2012. Reference intervals of clinical biochemistry tests commonly used[S]. Ministry of Health of the People's Republic of China, 2021.
[26] Beijing Children's Hospital Affiliated to Capital Medical University, the First Affiliated Hospital of China Medical University, Clinical laboratory center of National Health Commission, et al. WS/T 780-2021. Reference intervals of clinical biochemistry tests commonly used for children[S]. State Health Commission of the People's Republic of China, 2021.
[27] NI X, SONG W, PENG X, et al.Pediatric reference intervals in China (PRINCE): design and rationale for a large, multicenter collaborative cross-sectional study[J]. Science Bulletin, 2018, 63(24): 1626-1634.