Department of Medicine, Division of Digestive Diseases, Beth Israel Medical Center of Albert Einstein College of Medicine, New York, NY 10003, USA.
Hepatology. 2013 Feb;57(2):700-7. doi: 10.1002/hep.26020.
Liver biopsy is important for diagnosing primary biliary cirrhosis (PBC). Prior investigations suggest that immunostaining for biliary keratin 19 (K19) may show the earliest changes suspicious for PBC, namely, loss of the canals of Hering (CoH). We aimed to study the clinical outcomes of patients whose biopsy specimens appeared histologically near normal or with minimal inflammatory changes, but in which K19 staining revealed widespread periportal CoH loss, a finding we termed "minimal change PBC." Ten patients were identified prospectively as having nearly normal or mildly inflamed biopsy specimens without diagnostic or suggestive histologic features of PBC, but with near complete CoH loss; six had available follow-up clinical data, one had follow-up biopsy. Controls for clinical and/or K19 analysis included six normal livers and biopsy specimens from 10 patients with confirmed early PBC, 10 with early stage chronic hepatitis C (CHC), and nine with resolving, self-limited hepatitis (RSLH). Staining for K19 in normal controls, livers with "minimal change" PBC, CHC, and RSLH showed 9.2 ± 6.0, 0.44 ± 0.37 (P < 0.0001), 5.7 ± 4.6 (n.s.), 4.1 ± 2.1 (P < 0.02) CoH per portal tract, respectively. Patients with available clinical follow up, compared to patients with diagnostic early-stage PBC biopsies, showed identical treatment responses to ursodeoxycholic acid, similar rates and types of nonhepatic autoimmune diseases, and/or subsequent development of autoimmune hepatitis overlap syndrome.
We suggest that CoH loss demonstrated by K19 immunostaining is an early feature in PBC. Clinical findings in the years following biopsy, including response to ursodeoxycholic acid, show identical changes to patients with biopsy confirmed PBC. We suggest that this "minimal change" feature may support a clinical diagnosis of PBC even in the absence of characteristic, granulomatous, duct destructive lesions.
肝活检对于原发性胆汁性肝硬化（PBC）的诊断很重要。先前的研究表明，胆管角蛋白 19（K19）的免疫染色可能显示出最早的 PBC 可疑变化，即 Hering 管（CoH）的丢失。我们旨在研究活检标本表现为组织学上接近正常或仅有轻微炎症改变，但 K19 染色显示广泛的门管区 CoH 丢失的患者的临床结局，我们将这种表现称为“最小变化 PBC”。前瞻性地确定了 10 名患者，他们的活检标本几乎正常或轻度炎症，没有 PBC 的诊断或提示性组织学特征，但 CoH 几乎完全丢失；其中 6 名患者有可用的随访临床数据，1 名患者有随访活检。临床和/或 K19 分析的对照包括 6 个正常肝脏和 10 个确诊的早期 PBC 患者、10 个早期慢性丙型肝炎（CHC）患者和 9 个自限性肝炎（RSLH）患者的活检标本。在正常对照、具有“最小变化”PBC、CHC 和 RSLH 的肝脏中，K19 染色分别显示每个门管区 CoH 为 9.2 ± 6.0、0.44 ± 0.37（P < 0.0001）、5.7 ± 4.6（n.s.）、4.1 ± 2.1（P < 0.02）。有可用临床随访的患者与具有诊断性早期 PBC 活检的患者相比，对熊去氧胆酸的治疗反应相同，非肝脏自身免疫性疾病的发生率和/或类型相同，并且/或者随后发展为自身免疫性肝炎重叠综合征。
我们认为 K19 免疫染色显示的 CoH 丢失是 PBC 的早期特征。活检后数年的临床发现，包括对熊去氧胆酸的反应，与活检证实的 PBC 患者的变化相同。我们建议，即使没有特征性的肉芽肿性、胆管破坏性病变，这种“最小变化”特征也可能支持 PBC 的临床诊断。
