Vuppalanchi Raj, Li Yi-Ju, Rockey Don C, Halegoua-DeMarzio Dina, Fontana Robert J, Bonkovsky Herbert L, Koh Christopher, Odin Joseph, Barnhart Huiman, Hoofnagle Jay H
Indiana University School of Medicine, Indianapolis, Indiana, USA.
Duke University School of Medicine, Durham, North Carolina, USA.
Aliment Pharmacol Ther. 2025 Jul 20. doi: 10.1111/apt.70284.
Cephalosporins are widely prescribed antibiotics due to their efficacy and safety. Although rare, idiosyncratic drug-induced liver injury (DILI) has been reported with their use. Here, we characterise the clinical features and HLA associations of cephalosporin-related liver injury.
Between Jan 1, 2004, and Nov 2, 2022, a total of 2347 cases of DILI were enrolled in the DILIN study, of which 1854 were adjudicated as probable, highly likely, or definite. HLA sequencing was performed, and association with the risk of DILI was examined.
58 cases (3%) were attributed to different cephalosporins, including cefazolin (n = 40), cephalexin (n = 4), ceftriaxone (n = 3), cefdinir (n = 3), cefuroxime (n = 3), and five other individual agents. Clinical features included a self-limited course with a mixed or cholestatic biochemical pattern without hypersensitivity features occuring in 1 to 4 weeks. Most striking was the phenotype of cefazolin and other parenteral cephalosporins given as a single dose with the onset of jaundice, fatigue, and itching 1 to 3 weeks later. In the total cohort, HLA-A*02:01 was significantly associated with an increased risk of cephalosporin-induced liver injury (OR: ~2.5-2.7, P < 0.0001). The association was strongest with cefazolin, with carrier frequencies of 85% vs. 38% in those with DILI from other drugs.
Cephalosporins can cause self-limited, mixed/cholestatic hepatitis that arises after a short course of therapy with a latency of up to 3 weeks with cefazolin. Cephalosporin-induced liver injury is associated with the HLA-A*02:01 allele, which is linked to more severe liver injury at the onset of illness.
头孢菌素因其疗效和安全性而被广泛使用。虽然罕见，但已有使用头孢菌素后发生特异质性药物性肝损伤（DILI）的报道。在此，我们描述头孢菌素相关肝损伤的临床特征和HLA相关性。
在2004年1月1日至2022年11月2日期间，共有2347例DILI病例纳入DILIN研究，其中1854例被判定为可能、很可能或确诊。进行了HLA测序，并检查了与DILI风险的相关性。
58例（3%）归因于不同的头孢菌素，包括头孢唑林（n = 40）、头孢氨苄（n = 4）、头孢曲松（n = 3）、头孢地尼（n = 3）、头孢呋辛（n = 3）以及其他五种单一药物。临床特征包括病程自限，生化模式为混合型或胆汁淤积型，无超敏反应特征，在1至4周内出现。最显著的是单次给予头孢唑林和其他胃肠外头孢菌素后的表型，1至3周后出现黄疸、疲劳和瘙痒。在整个队列中，HLA-A02:01与头孢菌素所致肝损伤风险增加显著相关（OR：约2.5 - 2.7，P < 0.0001）。这种关联在头孢唑林方面最为强烈，在因其他药物导致DILI的患者中，HLA-A02:01的携带频率分别为85%和38%。
头孢菌素可导致自限性、混合型/胆汁淤积型肝炎，在短疗程治疗后出现，头孢唑林的潜伏期长达3周。头孢菌素所致肝损伤与HLA-A*02:01等位基因相关，该等位基因与疾病发作时更严重的肝损伤有关。
