Drug-induced Liver Injury Due to Medications for Alcohol Use Disorder: Results From the DILIN Prospective Study.

IF 4.2 3区医学 Q1 SUBSTANCE ABUSE

Journal of Addiction Medicine Pub Date : 2024-12-09 DOI:10.1097/ADM.0000000000001421

Harish Gopalakrishna, Marwan Ghabril, Jiezhun Gu, Yi Ju Li, Robert J Fontana, David E Kleiner, Christopher Koh, Naga Chalasani

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引用次数: 0

Abstract

Objectives: Concerns about drug-induced liver injury (DILI) may deter physicians from prescribing medications for alcohol use disorder (MAUD). We aim to explore DILI due to MAUD in Drug-Induced Liver Injury Network (DILIN) prospective study.

Methods: High-confidence DILI cases (ie, definite, highly likely, or probable) due to MAUD in DILIN prospective study (2004-2024) were included. Demographic, clinical, laboratory data, and 6-month outcomes were analyzed. HLA allele frequency (AF) of disulfiram cases was compared to matched controls with DILI due to non-MAUD (DILI controls).

Results: Among 1975 high-confidence cases, 13 were attributed to MAUD (11 disulfiram; 1 naltrexone and 1 baclofen; and none from acamprosate). Median age was 45 years, with 77% female and 85% White. All had hepatocellular injury. In disulfiram group, the median time for DILI occurrence was 34 days. Eight patients developed jaundice, with 3 fatal or near-fatal cases (2 liver transplantation and 1 liver-related death). Five (71%) patients with severe or fatal disulfiram DILI had underlying liver disease. AF for HLA-C*01:02 (OR, 6.29; P = 0.02) and DRB1*09:01 (OR, 10.16; P = 0.02) were significantly higher in disulfiram cases than in DILI controls. DILI from baclofen and naltrexone was mild and self-limited with no chronic DILI.

Conclusions: Disulfiram is the leading cause of DILI among MAUD and is most common in women. Disulfiram can cause severe DILI and is associated with HLA-C*01:02 and DRB1*09:01. Baclofen and naltrexone can cause mild to moderate self-limited DILI. There were no cases of acamprosate. These findings suggest DILI due to MAUD are less frequent.

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来源期刊

Journal of Addiction Medicine 医学-药物滥用

CiteScore

6.10

自引率

9.10%

发文量

260

审稿时长

>12 weeks

期刊介绍： The mission of Journal of Addiction Medicine, the official peer-reviewed journal of the American Society of Addiction Medicine, is to promote excellence in the practice of addiction medicine and in clinical research as well as to support Addiction Medicine as a mainstream medical sub-specialty. Under the guidance of an esteemed Editorial Board, peer-reviewed articles published in the Journal focus on developments in addiction medicine as well as on treatment innovations and ethical, economic, forensic, and social topics including: •addiction and substance use in pregnancy •adolescent addiction and at-risk use •the drug-exposed neonate •pharmacology •all psychoactive substances relevant to addiction, including alcohol, nicotine, caffeine, marijuana, opioids, stimulants and other prescription and illicit substances •diagnosis •neuroimaging techniques •treatment of special populations •treatment, early intervention and prevention of alcohol and drug use disorders •methodological issues in addiction research •pain and addiction, prescription drug use disorder •co-occurring addiction, medical and psychiatric disorders •pathological gambling disorder, sexual and other behavioral addictions •pathophysiology of addiction •behavioral and pharmacological treatments •issues in graduate medical education •recovery •health services delivery •ethical, legal and liability issues in addiction medicine practice •drug testing •self- and mutual-help.