Gopalakrishna Harish, Ghabril Marwan, Gu Jiezhun, Li Yi Ju, Fontana Robert J, Kleiner David E, Koh Christopher, Chalasani Naga
From the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (HG, CK); Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN (MG, NC); Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Duke University, Durham, NC (JG, YJL); Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI (RJF); and Laboratory of Pathology, Intramural Division, National Cancer Institute, National Institutes of Health, Bethesda, MD (DEK).
J Addict Med. 2024 Dec 9. doi: 10.1097/ADM.0000000000001421.
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.
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).
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-C01:02 (OR, 6.29; P = 0.02) and DRB109:01 (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.
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-C01:02 and DRB109:01. 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.
对药物性肝损伤（DILI）的担忧可能会使医生不愿为酒精使用障碍（MAUD）患者开具药物。我们旨在通过药物性肝损伤网络（DILIN）前瞻性研究探讨MAUD所致的DILI。
纳入DILIN前瞻性研究（2004 - 2024年）中因MAUD导致的高可信度DILI病例（即确诊、极有可能或很可能）。分析人口统计学、临床、实验室数据以及6个月的结局。将双硫仑病例的人类白细胞抗原（HLA）等位基因频率（AF）与因非MAUD导致DILI的匹配对照（DILI对照）进行比较。
在1975例高可信度病例中，13例归因于MAUD（11例双硫仑；1例纳曲酮和1例巴氯芬；无来自阿坎酸的病例）。中位年龄为45岁，77%为女性，85%为白人。所有病例均为肝细胞损伤。在双硫仑组中，发生DILI的中位时间为34天。8例患者出现黄疸，3例为致命或近乎致命病例（2例肝移植和1例与肝脏相关的死亡）。5例（71%）发生严重或致命双硫仑DILI的患者有潜在肝脏疾病。双硫仑病例中HLA - C01:02（比值比[OR]，6.29；P = 0.02）和DRB109:01（OR，10.16；P = 0.02）的AF显著高于DILI对照。巴氯芬和纳曲酮所致的DILI为轻度且自限性，无慢性DILI。
双硫仑是MAUD中导致DILI的主要原因，在女性中最为常见。双硫仑可导致严重DILI，并与HLA - C01:02和DRB109:01相关。巴氯芬和纳曲酮可导致轻度至中度自限性DILI。未发现阿坎酸导致DILI的病例。这些发现表明MAUD所致的DILI较为少见。
