SARS-associated viral hepatitis caused by a novel coronavirus: Report of three cases
SARS-associated viral hepatitis caused by a novel coronavirus: Report of three cases
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DOI：
10.1002/hep.20111
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发表时间：
2004-02-01
期刊：
影响因子：
13.5
通讯作者：
Lai, CL
中科院分区：
文献类型：
--
作者：
Chau, TN;Lee, KC;Lai, CL
据报道，高达60%的严重急性呼吸综合征(SARS)患者会出现肝脏损害。本文报告三例SARS合并肝损害患者的临床病程和肝脏病理改变。纳入符合世界卫生组织疑似SARS病例定义并出现丙氨酸转氨酶显著升高的三名患者。行经皮肝活检。取肝标本进行光镜、电子显微镜和免疫组织化学检查。应用增强实时聚合酶链式反应(RT-PCR)寻找SARS相关冠状病毒感染的证据。有丝分裂中有2例细胞明显积聚，3例均有细胞凋亡。其他常见的病理特征包括肝细胞肿胀和轻至中度的小叶淋巴细胞浸润。未发现嗜酸性细胞浸润、肉芽肿、胆汁淤积、纤维化或纤维蛋白沉积。免疫组织化学检测显示，0.5%至11.4%的细胞核呈增殖抗原Ki-67阳性。RT-PCR显示，在肝组织中有SARS相关冠状病毒的证据，但在所有3名患者的血清中均未发现。然而，电子显微镜无法识别病毒颗粒。未见巨大线粒体、微泡状或大泡状脂肪变性。总而言之，SARS患者的肝脏损害是由于SARS相关冠状病毒感染肝脏所致。肝细胞有丝分裂活动的突出是独一无二的，可能是由于有或没有冠状病毒破坏细胞周期的过度增殖状态。随着对发病机制的更好了解，特定的治疗可能有针对性地减少病毒复制和改变病程。
Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse-transcriptase polymerase chain reaction (RT-PCR) using enhanced real-time PCR was applied to look for evidence of SARS-associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki-67. RT-PCR showed evidence of SARS-associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro- or macro-vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS-associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course.