自身免疫性肝炎的病理学特点及肝移植疗效

Pathological characteristics and clinical effect of autoimmune hepatitis after liver transplantation

  • 摘要: 目的:探讨自身免疫性肝炎(AIH)的病理学特点及肝移植疗效。
    方法: 采用回顾性描述性研究方法。收集2011年6月至2015年12月西安交通大学第一附属医院收治的14例行肝移植治疗AIH患者的临床病理资料。14例患者均行经典原位肝移植,收集14例患者全肝切除标本及其中6例因行肝移植术后肝功能严重异常患者的移植肝穿刺标本,行HE染色;14例患者全肝切除标本进一步行网状纤维染色和免疫组织化学染色检测。在光镜下观察组织结构特点。观察指标:(1)术中及术后情况。(2)病理学检查结果。(3)随访情况。采用门诊和电话方式进行随访,随访时间截至2016年3月。随访患者免疫抑制治疗情况和生存情况。计量资料采用平均数(范围)表示。
    结果:(1)术中及术后情况:14例AIH患者均顺利完成肝移植手术,无围术期死亡患者;手术时间为402 min(353~405 min),无肝期时间为50 min(42~60 min),术中出血量为2 800 mL(1 325~4 050 mL),术后住院时间为19 d(12~24 d)。14例AIH患者行肝移植术后发生肺部感染6例,急性排异反应2例,胆道狭窄2例,急性肾衰竭1例,均经对症处理后好转。(2)病理学检查结果:HE染色:①全肝切除标本:不同程度“界板炎”14例,淋巴细胞“穿入”现象 14例,肝细胞桥接坏死及亚大块状坏死9例,伴浆细胞浸润9例,肝细胞点状及碎片状坏死5例,“玫瑰花结”样结构4例。②移植肝穿刺标本:肝细胞桥接坏死及亚大块状坏死4例,“玫瑰花结”样结构4例,胆汁淤积性肝硬化3例,急性轻度排斥反应2例,复发AIH 1例。网状纤维染色:汇管区纤维组织增生,分隔包绕肝细胞形成“假小叶”结构。免疫组织化学染色检测:肝组织内浸润炎症细胞主要为CD3、CD8阳性的T淋巴细胞,少部分为CD4阳性T淋巴细胞。14例患者术后均获得随访,随访时间为26个月(3~57个月)。14例患者均行规则免疫抑制治疗。(3)随访情况:随访期间,原发性移植物无功能患者1例,复发2例,死亡 3例。
    结论:  AIH行肝移植患者术后肺部感染及胆道并发症发生率较高,术后应加强激素治疗。组织学出现肝细胞桥接坏死、大块状坏死和“玫瑰花结”样结构可能提示预后不良。AIH肝移植术后恢复与调节性T淋巴细胞功能相关,可能成为预后判断及治疗的方向。

     

    Abstract: Objective:To investigate the pathological characteristics and clinical effect of autoimmune hepatitis (AIH) after liver transplantation.
    Methods:The retrospective descriptive crosssectional study was adopted. The clinicopathological data of 14 patients with AIH who underwent liver transplantation at the First Affiliated Hospital of Xi′an Jiaotong University between June 2011 and December 2015 were collected. Fourteen patients underwent orthotopic liver transplantation, specimens of total liver resection from 14 patients and aspiration specimens from liver allografts of 6 patients with severely abnormal liver function after liver transplantation were collected and detected by hematoxylineosin (HE) staining. Specimens of total liver resection continued to detect by reticular fiber staining and immunohistochemistry. The tissues construction was observed by light microscopy. Observation indicators included (1) intra and postoperative situations, (2) results of pathological examination, (3) followup. The followup using outpatient examination and telephone interview was performed to detect the situations of immunosuppressive therapy and survival of patients up to March 2016. Measurement data were represented as average (range).
    Results:(1) Intra and postoperative situations: all the 14 patients with AIH underwent successful liver transplantation without perioperative death. The operation time, duration of anhepatic period of liver transplantation, volume of intraoperative blood loss and duration of hospital stay were 402 minutes (range, 353-405 minutes), 50 minutes (range, 42-60 minutes), 2 800 mL (range, 1 325-4 050 mL) and 19 days (range, 12-24 days), respectively. Of 14 patients with AIH after liver transplantation, 6 were complicated with pulmonary infection, 2 with acute rejection, 2 with bile duct strictures and 1 with acute renal failure, and they were improved by symptomatic treatment. (2) Results of pathological examination: HE staining of specimens of total liver resection showed that different levels of “interface hepatitis” were detected in 14 patients, lymphocytes “penetration” phenomena in 14 patients, lymphoplasmacytic interface hepatocyte necrosis in 9 patients, infiltration of plasma cells in 9 patients, spotty and piecemeal necroses in 5 patients and “rosetteslike” structure in 4 patients. HE staining of specimens of liver allografts showed that lymphoplasmacytic interface hepatocyte necroses were detected in 4 patients, “rosetteslike” structure in 4 patients, cholestatic cirrhosis in 3 patients, mildly acute rejection in 2 patients and recurrence of AIH in 1 patient. Reticular fiber staining: fibrous tissues were proliferative in the portal area and then separated and surrounded hepatocytes to form “pseudolobule” structure. Immunohistochemistry: inflammatory cells infiltrated by liver tissues were composed of T cells with mainly positive CD3 and CD8 and with few positive CD4. (3) Followup: 14 patients were followed up for 26 months (range, 3-57 months). Fourteen patients received regular immunosuppressive therapy. During followup, 1 patient was complicated with primary transplants nonfunction, 2 had AIH recurrence and 3 were dead.
    Conclusions:Patients with AIH should enhance hormone therapy due to high incidences of bile duct complications and pulmonary infection after liver transplantation. Lymphoplasmacytic interface hepatocyte necrosis and “rosetteslike” structure probably have worse prognosis. Dysfunction of Regulatory T cells (Treg) may be a prognosis predictor for AIH after liver transplantation.

     

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