Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury.
Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury.
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DOI：
10.1016/j.cgh.2016.05.043
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Drug-Induced Liver Injury Network
中科院分区：
文献类型：
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作者：
de Boer YS;Kosinski AS;Urban TJ;Zhao Z;Long N;Chalasani N;Kleiner DE;Hoofnagle JH;Drug-Induced Liver Injury Network
药物性肝损伤（DILI）具有与包括自身免疫性肝炎（AIH）在内的其他肝病相似的特征。我们的目的是描述由呋喃妥因、米诺环素、甲基多巴或肼苯哒嗪引起的肝损伤的临床和自身免疫特征。我们分析了2004年至2014年药物性肝损伤网络前瞻性研究中纳入的88例因呋喃妥因、米诺环素、甲基多巴或肼苯哒嗪引起的DILI病例的数据。在基线和随访检查时采集患者血清，检测免疫球蛋白G（IgG）、抗核抗原（ANA）抗体、平滑肌抗体（SMA）和可溶性肝抗原（SLA）水平。根据IgG、ANA、SMA和SLA水平的增加推导出自身免疫评分（指定值为0、1+或2+）。将AIH相关的HLA-DRB 1 *03：01和DRB 1 *04：01等位基因频率与普通人群（对照组）进行比较。在88例病例中，80例为女性（91%），74%有肝细胞损伤，25%有严重损伤。在DILI发作时，39%的病例IgG水平升高，72%的病例ANA水平升高，60%的病例SMA水平升高，无一例SLA升高。在呋喃妥因和米诺环素引起的82%和73%的病例（73%）中观察到自身免疫表型（自身免疫评分≥2），但只有55%的病例归因于甲基多巴和43%的病例归因于肼屈嗪（呋喃妥因和米诺环素与甲基多巴和肼屈嗪的P = 0.16）。我们观察到在DILI发作和随访期间，ANA（P = 0.01）或SMA（P <0.001）阳性的血清样本数量以及自身免疫评分（P <0.001）减少。与对照组（分别为12%和9%）相比，具有HLA-DRB 1 *03：01（15%）和HLA-DRB 1 *04：01（9%）的DILI患者百分比相似。在对DILIN数据的分析中，我们发现大多数DILI病例归因于呋喃妥因或米诺环素，约一半的病例归因于甲基多巴和肼苯哒嗪，具有与AIH相似的自身免疫表型。这些特征随着损伤的恢复而减少，并且与特发性AIH患者中发现的典型HLA等位基因无关。
Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine. We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA DRB1*03:01 and DRB1*04:01 allele frequencies were compared with those of the general population (controls). Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively). In analysis of data from the DILIN, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH.