Liaw Y F, Huang M J, Fan K D, Li K L, Wu S S, Chen T J
Chang Gung Memorial Hospital, Taipei, Taiwan.
Ann Intern Med. 1993 Mar 15;118(6):424-8. doi: 10.7326/0003-4819-118-6-199303150-00005.
To evaluate the incidence, severity, and course of propylthiouracil-induced hepatic injury in patients with hyperthyroidism.
Cohort study.
Outpatient clinic of a university-based hospital.
Fifty-four patients with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values and a definite diagnosis of hyperthyroidism.
Treatment with propylthiouracil, 300 mg/d for 2 months followed by 100 to 150 mg/d for 3 months and a subsequent maintenance dose of 100 mg/d.
Liver biochemical tests were studied before therapy and 2 months and 5 months after starting propylthiouracil therapy. The patients were monitored with clinical evaluation and weekly liver biochemical tests after AST or ALT levels became abnormal. Serologic markers of hepatitis A, B, C, and delta virus infection were also studied when appropriate.
Fifteen (28%; 95% CI, 16% to 42%) of the 54 patients showed ALT elevations 2 months after propylthiouracil therapy. The mean peak ALT level for these patients was 1.35 mu kat/L (range, 0.65 3.85 mu kat/L). None of these patients had symptoms or hyperbilirubinemia. Liver biopsy in three patients showed mild perivenular focal necrosis or ill-defined granuloma composed of foamy histiocytes with ceroid pigment and mild fatty metamorphosis. Despite continued propylthiouracil therapy at a reduced dose, ALT levels returned to normal in 13 of 15 patients in the following 3 months. None of these ALT elevations resulted from hepatitis A, B, C, or delta virus infection. No statistical difference was seen in the pretreatment characteristics between patients with and those without ALT elevation, except that the former had a higher pretreatment T4 level (270 +/- 12.9 compared with 237 +/- 7.72 nmol/L, P = 0.027) and T3 level (7.22 +/- 0.72 compared with 5.85 +/- 0.39 nmol/L, P = 0.048).
Propylthiouracil-induced subclinical liver injury is common and is usually transient and asymptomatic. Therapy with propylthiouracil may be continued with caution in the absence of symptoms and hyperbilirubinemia.
评估丙硫氧嘧啶所致甲状腺功能亢进症患者肝损伤的发生率、严重程度及病程。
队列研究。
一所大学附属医院的门诊。
54例天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）值正常且确诊为甲状腺功能亢进症的患者。
给予丙硫氧嘧啶治疗，300mg/d，持续2个月，随后100～150mg/d，持续3个月，后续维持剂量为100mg/d。
在治疗前以及开始丙硫氧嘧啶治疗后2个月和5个月时进行肝脏生化检查。在AST或ALT水平异常后，通过临床评估和每周的肝脏生化检查对患者进行监测。必要时还研究甲型、乙型、丙型和丁型肝炎病毒感染的血清学标志物。
54例患者中有15例（28%；95%可信区间，16%～42%）在丙硫氧嘧啶治疗2个月后出现ALT升高。这些患者的平均ALT峰值水平为1.35μkat/L（范围为0.65～3.85μkat/L）。这些患者均无症状或高胆红素血症。3例患者的肝脏活检显示轻度小叶中央静脉周围局灶性坏死或由含类蜡质色素的泡沫组织细胞组成的边界不清的肉芽肿以及轻度脂肪变性。尽管以较低剂量继续使用丙硫氧嘧啶治疗，但15例患者中有13例在接下来的3个月内ALT水平恢复正常。这些ALT升高均非由甲型、乙型、丙型或丁型肝炎病毒感染所致。ALT升高患者与未升高患者的治疗前特征无统计学差异，只是前者治疗前的T4水平较高（270±12.9与237±7.72nmol/L，P = 0.027），T3水平较高（7.22±0.72与5.85±0.39nmol/L，P = 0.048）。
丙硫氧嘧啶所致亚临床肝损伤常见，通常为一过性且无症状。在无症状和无高胆红素血症的情况下，可谨慎继续使用丙硫氧嘧啶治疗。
