Background & aim

The diagnosis of primary biliary cholangitis (PBC), an uncommon immune-mediated cholestatic liver disease, is based on positive circulating anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA), coupled with elevated serum alkaline phopsphatase (ALP) levels. Timely initiation of treatment with ursodeoxycholic acid prevents progression to cirrhosis and liver failure. We aimed at investigating liver histology in patients with normal ALP level and positive AMA and/or PBC-specific ANA.

Methods

We searched the Swiss PBC Cohort Study database, which includes subjects with positive PBC autoimmune serology and normal ALP levels, for patients who underwent a liver biopsy. Histological slides were centrally reviewed by an expert liver pathologist, and sera were centrally re-tested for AMA and ANA.

Results

30 patients were included; 90% females, median age 53 (range 27–72) years. Twenty-four (80%) had liver histology typical for (n = 2), consistent with (n = 16) or suggestive of (n = 6) PBC, including three of four AMA-negative ANA-positive patients. Among 22 ursodeoxycholic acid treated patients, 14 had elevated GGT levels before treatment; a significant decrease of the median GGT level between pre- (1.46 x ULN) and post- (0.43 x ULN) treatment (p = 0.0018) was observed.

Conclusions

In our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation.

中文翻译：

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碱性磷酸酶正常的原发性胆汁性胆管炎：一个被忽视的临床实体挑战当前指南

背景与目标

原发性胆汁性胆管炎 (PBC) 是一种罕见的免疫介导的胆汁淤积性肝病，其诊断基于循环抗线粒体 (AMA) 和/或 PBC 特异性抗核自身抗体 (ANA) 阳性以及血清碱性磷酸酶升高(ALP) 水平。及时开始用熊去氧胆酸治疗可防止进展为肝硬化和肝功能衰竭。我们旨在研究 ALP 水平正常且 AMA 和/或 PBC 特异性 ANA 阳性患者的肝脏组织学。

方法

我们搜索了瑞士 PBC 队列研究数据库，其中包括 PBC 自身免疫血清学阳性和 ALP 水平正常的受试者，以寻找接受肝活检的患者。组织学切片由专家肝脏病理学家集中审查，并集中重新测试血清的 AMA 和 ANA。

结果

包括 30 名患者；90% 女性，中位年龄 53（范围 27-72）岁。二十四名 (80%) 的肝脏组织学典型 (n = 2)，符合 (n = 16) 或提示 (n = 6) PBC，包括四名 AMA 阴性 ANA 阳性患者中的三名。在接受熊去氧胆酸治疗的 22 名患者中，14 名治疗前 GGT 水平升高；观察到治疗前 (1.46 x ULN) 和治疗后 (0.43 x ULN) 的中位 GGT 水平显着降低 (p = 0.0018)。

结论

在我们的系列中，高比例的 ALP 水平正常的 AMA 阳性患者患有 PBC。我们首次展示了 AMA 阴性/PBC 特异性 ANA 阳性受试者中 PBC 的组织学诊断，以及 GGT 作为具有正常基线 ALP 水平的 PBC 患者的生物标志物的潜在作用。目前的 PBC 诊断指南并未涵盖 PBC 表现的全部范围，在及时开始治疗方面具有重要的临床意义。