在患有脂肪肝疾病的痛风患者中，非布司他的肝脏安全性优于别嘌醇。
Hepatic Safety of Febuxostat Compared with Allopurinol in Gout Patients with Fatty Liver Disease.
机构信息
From the Department of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center; Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
J.S. Lee, MD, Department of Rheumatology, Asan Medical Center; J. Won, MD, Department of Rheumatology, Asan Medical Center; O.C. Kwon, MD, Department of Rheumatology, Asan Medical Center; S.S. Lee, MD, PhD, Department of Radiology, Asan Medical Center; J.S. Oh, MD, PhD, Clinical Research Center, University of Ulsan College of Medicine, Asan Medical Center; Y.G. Kim, MD, PhD, Department of Rheumatology, Asan Medical Center; C.K. Lee, MD, PhD, Department of Rheumatology, Asan Medical Center; B. Yoo, MD, PhD, Department of Rheumatology, Asan Medical Center; S. Hong, MD, PhD, Department of Rheumatology, Asan Medical Center.
出版信息
J Rheumatol. 2019 May;46(5):527-531. doi: 10.3899/jrheum.180761. Epub 2018 Nov 15.
OBJECTIVE
Febuxostat has superior renal safety to allopurinol, but data on its hepatic safety are limited. Thus we compared the hepatotoxicity of febuxostat and allopurinol, and the clinical factors associated with hepatotoxicity, in patients with gout and fatty liver disease (FLD).
METHODS
We included gout patients treated with allopurinol or febuxostat who were diagnosed with fatty liver based on ultrasonography or computed tomography. Hepatotoxicity was defined as follows: (1) elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) at least 3× the upper limit of normal, when the baseline AST/ALT was normal; or (2) doubling of the baseline AST/ALT, when the baseline AST/ALT was elevated. The factors associated with hepatotoxicity were evaluated by Cox regression analysis.
RESULTS
Of 134 patients identified with gout and FLD, 32 (23.9%) received febuxostat and 102 (76.1%) received allopurinol. There were no significant differences in age, body mass index, comorbidity, or disease severity between the groups; however, the incidence of hepatotoxicity was significantly lower in the febuxostat group (3/32, 9.4%) than in the allopurinol group (36/102, 35.3%, p = 0.005). Diabetes (HR 3.549, 95% CI 1.374-9.165, p = 0.009) and colchicine use (HR 11.518, 95% CI 5.515-24.054, p < 0.001) were associated with a higher risk of hepatotoxicity, whereas febuxostat use was associated with a lower risk of hepatotoxicity (HR 0.282, 95% CI 0.086-0.926, p = 0.037).
CONCLUSION
In the 32 patients studied, febuxostat was well tolerated in patients with gout and FLD. However, the presence of diabetes and colchicine use may increase the risk of hepatotoxicity.
目的
非布司他的肾安全性优于别嘌醇，但关于其肝安全性的数据有限。因此，我们比较了痛风和脂肪肝（FLD）患者中，非布司他和别嘌醇的肝毒性，以及与肝毒性相关的临床因素。
方法
我们纳入了根据超声或 CT 诊断为脂肪肝的接受别嘌醇或非布司他治疗的痛风患者。肝毒性定义为：（1）当基线 AST/ALT 正常时，AST/ALT 至少升高至正常上限的 3 倍；或（2）当基线 AST/ALT 升高时，AST/ALT 加倍。采用 Cox 回归分析评估与肝毒性相关的因素。
结果
在确定的 134 例痛风合并 FLD 患者中，32 例（23.9%）接受非布司他治疗，102 例（76.1%）接受别嘌醇治疗。两组患者的年龄、体重指数、合并症或疾病严重程度无显著差异；然而，非布司他组的肝毒性发生率明显低于别嘌醇组（3/32，9.4% vs. 36/102，35.3%，p = 0.005）。糖尿病（HR 3.549，95%CI 1.374-9.165，p = 0.009）和秋水仙碱使用（HR 11.518，95%CI 5.515-24.054，p<0.001）与肝毒性风险增加相关，而非布司他使用与肝毒性风险降低相关（HR 0.282，95%CI 0.086-0.926，p = 0.037）。
结论
在研究的 32 例患者中，非布司他在痛风合并 FLD 患者中耐受良好。然而，糖尿病和秋水仙碱的使用可能会增加肝毒性的风险。
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