Drug-induced liver injury in children: A nationwide cohort study from China

Rongtao Lai; Xinjie Li; Jie Zhang; Jun Chen; Changqing Yang; Wen Xie; Yuecheng Yu; Xiaoyan Guo; Xinrong Zhang; Guoliang Lu; Xi’an Han; Qing Xie; Chengwei Chen; Tao Shen; Yimin Mao

JHEP Reports (Aug 2024)

Drug-induced liver injury in children: A nationwide cohort study from China

Rongtao Lai,
Xinjie Li,
Jie Zhang,
Jun Chen,
Changqing Yang,
Wen Xie,
Yuecheng Yu,
Xiaoyan Guo,
Xinrong Zhang,
Guoliang Lu,
Xi’an Han,
Qing Xie,
Chengwei Chen,
Tao Shen,
Yimin Mao

Affiliations

Rongtao Lai: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Xinjie Li: Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
Jie Zhang: Department of Pediatrics, Shanghai General Hospital, Shanghai, China
Jun Chen: Department of Liver Diseases, the Third People’s Hospital of Shenzhen, the Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
Changqing Yang: Department of Gastroenterology and Hepatology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China
Wen Xie: Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
Yuecheng Yu: Department of Infectious Diseases and Center of Hepatology, General Hospital of Eastern Theater Command, Jinling Hospital Affiliated to School of Medicine, Nanjing University, Nanjing, China
Xiaoyan Guo: Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Shanxi, China
Xinrong Zhang: Division of Gastroenterology and Hepatology, Stanford University, School of Medicine, Palo Alto, CA, United States
Guoliang Lu: Department of Neonatology, People’s Hospital of Anshun City, Guizhou, China
Xi’an Han: Unimed Scientific, Wuxi, China
Qing Xie: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Corresponding authors. Addresses: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China. (Y. Mao), or Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. (T. Shen), or Liver Disease Center of Naval 905 Hospital, Shanghai, 200235, China; (C. Chen), or Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; (Q. Xie).
Chengwei Chen: Liver Disease Center of No. 905 Hospital, Shanghai, 200235, China; Corresponding authors. Addresses: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China. (Y. Mao), or Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. (T. Shen), or Liver Disease Center of Naval 905 Hospital, Shanghai, 200235, China; (C. Chen), or Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; (Q. Xie).
Tao Shen: Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; Corresponding authors. Addresses: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China. (Y. Mao), or Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. (T. Shen), or Liver Disease Center of Naval 905 Hospital, Shanghai, 200235, China; (C. Chen), or Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; (Q. Xie).
Yimin Mao: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China. Clinical Research Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authors. Addresses: Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China. (Y. Mao), or Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. (T. Shen), or Liver Disease Center of Naval 905 Hospital, Shanghai, 200235, China; (C. Chen), or Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; (Q. Xie).

Journal volume & issue: Vol. 6, no. 8
p. 101102

Abstract

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Background & Aims: Currently, there is limited knowledge on the clinical profile of drug-induced liver injury (DILI) in Chinese children. We aimed to assess the clinical characteristics, suspected drugs, and outcomes associated with pediatric DILI in China. Methods: This nationwide, multicenter, retrospective study, conducted between 2012 and 2014, analyzed 25,927 cases of suspected DILI at 308 medical centers using the inpatient medical register system. Utilizing the Roussel Uclaf causality assessment method score, only patients with scores ≥6 or diagnosed with DILI by three experts after scoring <6 were included in the analysis. Among them, 460 cases met the EASL biochemical criteria. The study categorized children into three age groups: toddlers (≥30 days to <6 years old), school-age children (6 to <12 years old), and adolescents (12 to <18 years old). Results: Hepatocellular injury was the predominant clinical classification, accounting for 63% of cases, with 34% of these cases meeting Hy's law criteria. Adolescents comprised the majority of children with moderate/severe DILI (65%). Similarly, adolescents faced a significantly higher risk of severe liver injury compared to younger children (adjusted odd ratios 4.75, p = 0.002). The top three most frequently prescribed drug classes across all age groups were antineoplastic agents (25.9%), antimicrobials (21.5%), and traditional Chinese medicine (13.7%). For adolescents, the most commonly suspected drugs were antitubercular drugs (22%) and traditional Chinese medicine (23%). Conclusion: Adolescents are at a greater risk of severe and potentially fatal liver injury compared to younger children. Recognizing the risk of pediatric DILI is crucial for ensuring safe medical practices. Impact and implications:: Drug-induced liver injury, a poorly understood yet serious cause of pediatric liver disease, encompasses a spectrum of clinical presentations, ranging from asymptomatic liver enzyme elevation to acute liver failure. This retrospective study, utilizing a large Chinese cohort of pediatric liver injury cases from 308 centers nationwide, characterized the major clinical patterns and suspected drugs in detail, revealing that adolescents are at a greater risk of severe liver injury compared to younger children. Vigilant care and careful surveillance of at-risk pediatric patients are crucial for physicians, researchers, patients, caregivers, and policymakers. Additional multicenter prospective studies are needed to evaluate the risk of hepatotoxicity in outpatients and hospitalized pediatric patients.

Published in JHEP Reports

ISSN: 2589-5559 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/jhep-reports

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