Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity:: A prospective series from Spain
Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity:: A prospective series from Spain
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DOI：
10.1002/hep.21324
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发表时间：
2006-10-01
期刊：
影响因子：
13.5
通讯作者：
Avila, Susana
中科院分区：
文献类型：
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作者：
Isabel Lucena, M.;Andrade, Raul J.;Avila, Susana
据报告，阿莫西林-克拉维汀（AC）肝毒性以胆汁淤积型损伤为主，尤其是在雄性动物中。然而，其临床表现的决定因素是未知的。本研究前瞻性评价了AC肝毒性特征。整理了报告给西班牙登记处的所有AC所致肝毒性病例数据，并在国际医学科学组织理事会（CIOMS）量表上评估为明确或很可能相关，并与已发表的病例系列进行比较。在69例患者（36例男性;平均年龄56岁）中确定了与阿莫西林-克拉维汀相关的肝毒性，占提交登记研究的所有肝毒性病例的14%。总体上有性别分布，病变的主要模式是肝细胞（36%），发生在较短的治疗时间（P <0.03）。治疗开始和黄疸发作之间的平均时间间隔为16天。半数病例在治疗结束后出现迟发症状。多元逻辑回归分析确定年龄增长是胆汁淤积/混合型损伤发生的相关因素（1年年龄间隔的比值比：1.045 [95%CI = 1.013-1-078; P = .005）。在7%的患者中观察到不利的结局。总之，年龄是AC肝毒性生化表达的最重要决定因素，年龄较小与细胞溶解损伤和治疗持续时间较短相关，而胆汁淤积/混合型损伤与年龄较大和AC治疗时间延长相关。
Amoxicillin-clavulanate (AC) hepatotoxicity has been reported to exhibit a higher predominance of cholestatic types of damage, especially in males. However, the determinants of its clinical expression are unknown. This study prospectively evaluated the profile of AC hepatotoxicity. Data on all cases of hepatotoxicity reported to the Spanish Registry attributed to AC and assessed as definite or probable on the Council for International Organizations of Medical Sciences (CIOMS) scale were collated and compared to published case series. Hepatotoxicity related to amoxicillin-clavulanate was identified in 69 patients (36 males; mean age 56 years) representing 14% of all cases of hepatotoxicity submitted to the Registry. There was an overall sex distribution and the predominant pattern of lesion was hepatocellular (36%) which occurred at a shorter duration of treatment (P < .03). Mean time lapse between therapy initiation and jaundice onset was 16 days. Late onset of symptoms following end of treatment occurred in half the cases. Multiple logistic regression analysis identified advancing age as the factor associated with the development of cholestatic/mixed type of injury (odds ratio for an age interval for 1 year: 1.045 [95% CI = 1.013-1-078; P = .005). An unfavorable outcome was seen in 7% of patients. In conclusion, age is the most important determinant in the biochemical expression of AC hepatotoxicity, younger age is associated with cytolytic damage and shorter treatment duration, whereas cholestatic/mixed type of damage is related to older age and prolonged AC therapy.