El-Naggar Moustafa Hm, Helmy Ahmed, Moawad Mahmoud, Al-Omary Mohamed, Al-Kadhi Yusuf, Habib Bassil
Section of Internal Medicine, Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Ann Pharmacother. 2008 May;42(5):713-8. doi: 10.1345/aph.1K543. Epub 2008 Apr 8.
To report a case of rosiglitazone-associated hepatotoxicity in a patient with Hodgkin's lymphoma.
A 52-year-old man presented with low-grade fever and fatigue that had been present for 4 months. He had been receiving insulin for 5 years and rosiglitazone 4 mg/day for 11 months for control of type 2 diabetes; he was receiving no other drug therapy. During hospitalization, hepatotoxicity was shown, with abnormal liver function test results including alanine aminotransferase 488 U/L, aspartate aminotransferase 344 U/L, alkaline phosphatase 832 U/L, total bilirubin 4.61 mg/dL, and direct bilirubin 3.63 mg/dL. Rosiglitazone was discontinued after further elevation of bilirubin (total 14.67 mg/dL, direct 12.10 mg/dL) occurred. Other causes for hepatotoxicity were ruled out. Hodgkin's lymphoma was diagnosed during the workup; however, liver imaging and biopsy also excluded this as the direct cause of acute liver failure. Despite discontinuation of rosiglitazone, the bilirubin level continued to increase to 49.29 mg/dL (direct > 20 mg/dL). The patient died 3 months after admission.
Rosiglitazone maleate is a thiazolidinedione approved for treatment of type 2 diabetes mellitus. The first member of this drug class, troglitazone, was withdrawn from the market due to reports of acute liver failure. Rosiglitazone has been shown to be much safer than troglitazone, despite some reported cases of early-onset nonfatal hepatotoxicity. Use of the Naranjo probability scale indicated that rosiglitazone was the probable cause of acute liver failure in our patient.
We conclude that rosiglitazone may be associated with late-onset acute liver failure. Clinicians should be aware of such a complication and monitor liver function in patients receiving the drug.
报告1例霍奇金淋巴瘤患者发生的罗格列酮相关性肝毒性。
一名52岁男性，出现低热和乏力4个月。他已接受胰岛素治疗5年，罗格列酮4毫克/天治疗11个月，用于控制2型糖尿病；未接受其他药物治疗。住院期间，出现肝毒性，肝功能检查结果异常，包括丙氨酸氨基转移酶488 U/L、天冬氨酸氨基转移酶344 U/L、碱性磷酸酶832 U/L、总胆红素4.61毫克/分升和直接胆红素3.63毫克/分升。胆红素进一步升高（总胆红素14.67毫克/分升，直接胆红素12.10毫克/分升）后停用罗格列酮。排除了肝毒性的其他原因。检查期间诊断为霍奇金淋巴瘤；然而，肝脏影像学检查和活检也排除了其为急性肝衰竭的直接原因。尽管停用了罗格列酮，胆红素水平仍继续升高至49.29毫克/分升（直接胆红素>20毫克/分升）。患者入院3个月后死亡。
马来酸罗格列酮是一种被批准用于治疗2型糖尿病的噻唑烷二酮类药物。该药物类别的首个成员曲格列酮因急性肝衰竭报告而退出市场。尽管有一些早期非致命性肝毒性报告，但罗格列酮已被证明比曲格列酮安全得多。使用纳伦霍概率量表表明罗格列酮是我们患者急性肝衰竭的可能原因。
我们得出结论，罗格列酮可能与迟发性急性肝衰竭有关。临床医生应意识到这种并发症，并在接受该药物治疗的患者中监测肝功能。
