Hartl Johannes, Miquel Rosa, Zachou Kalliopi, Wong Guan-Wee, Asghar Asma, Pape Simon, Sebode Marcial, Peiseler Moritz, Zenouzi Roman, Ehlken Hanno, Krech Till, Weiler-Normann Christina, Drenth Joost P H, Oo Ye H, Dalekos George Nikolaos, Heneghan Michael, Schramm Christoph, Lohse Ansgar Wilhelm
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
European Reference Network on Hepatological Diseases.
JHEP Rep. 2020 Feb 29;2(3):100094. doi: 10.1016/j.jhepr.2020.100094. eCollection 2020 Jun.
BACKGROUND & AIMS: High IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored.
In a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up.
Out of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 8%; = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 12.5 ± 3.2 g/L; <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 5.4 ± 2.4; <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 5.5 ± 2.2; = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels.
Compared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal.
A characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.
高IgG水平被认为是自身免疫性肝炎（AIH）的一个标志。尽管有临床疾病活动的证据，但有一小部分AIH患者的IgG在正常范围内。这种生物标志物的临床意义尚未得到探索。
在一项欧洲多中心研究中，我们将诊断时IgG值正常的AIH患者的生化、临床和组织学特征与年龄和性别匹配的典型AIH且IgG升高的对照组患者进行了比较。在诊断时、治疗12个月后和最后一次随访时评估数据。
在1318例AIH患者中，130例（10%）就诊时IgG正常。诊断时的组织学和生化参数以及治疗反应在两组之间没有差异。正常IgG组比典型AIH组更常见地实现了停药后的稳定缓解（24对8%；P = 0.0012）。对照组患者不仅在诊断时IgG水平更高（29.5±5.8对12.5±3.2 g/L；P<0.0001），而且IgG/IgA比值也更高（9.3±6.9对5.4±2.4；P<0.0001）。IgG/IgA比值仅在典型AIH患者中下降，12个月后两组之间不再有差异（6.3±4.3对5.5±2.2；P = 0.1），表明典型AIH中IgG选择性升高并被免疫抑制所抑制。典型AIH组自身抗体滴度更高，但在控制IgG水平后则不然。
与具有典型生化特征的AIH相比，诊断时IgG水平正常（i）的患者表现出相似的生化、血清学和组织学特征以及相当的治疗反应，（ii）似乎缺乏典型活动性AIH疾病中观察到的血清IgG水平的选择性升高，（iii）可能代表一个成功停药机会更高的亚组。
自身免疫性肝炎（AIH）的一个特征是免疫球蛋白G（IgG）升高，因此它被用作主要诊断标准以及监测治疗反应。然而，正常IgG并不能排除AIH的诊断。因此，我们在一项大型多中心研究中评估了AIH且IgG正常的患者的特征。这项研究表明，所有AIH患者中约10%的患者IgG正常；这些患者在生化标志物、肝脏组织学、疾病严重程度和治疗反应方面与其他AIH患者没有区别，但可能代表一个停药后缓解机会更高的亚组。
