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在原因不明的肝细胞癌患者中的隐匿性乙型肝炎病毒感染和HBV复制活性

作者: 沙秀娟 发布日期: 2012-05-23 阅读次数:
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 目的:我们的目的是研究在原因不明的肝细胞癌患者中隐匿性乙型肝炎病毒感染(OBI)的发生率,以及研究这些患者乙肝病毒复制的活性。从33例隐源性肝癌患者和28例有明确原因的原发性肝癌患者(13例慢性乙型肝炎,6例慢性丙型肝炎,9例酒精相关性肝病)中获得肿瘤和非肿瘤的肝组织。方法:隐匿性乙型肝炎病毒感染(OBI)是用巢式聚合酶链反应(PCR)来确认的。肝内的HBV DNA,共价闭合环状DNAcccDNA)和前基因组RNApgRNA)是分别用实时聚合酶链反应和逆转录聚合酶链反应(RT - PCR)定量的。结果:OBI24例(73%)隐源性肝癌,1例(17%)伴有HCV的原发性肝癌,5例(56%)酒精相关的肝癌患者中被确认存在。与慢性乙型肝炎相关的原发性肝癌相比,伴有OBI的隐源性肝癌患者则有较低的肝内总HBV DNA水平。只有六个(26%)伴有OBI的隐源性肝癌患者可检测出cccDNA,(中位数:< 0.0002拷贝/细胞),这是显著低于慢性乙型肝炎患者的(中位数:0.005拷贝/细胞;<0.0001)。在12个(52%)伴有OBI的隐源性肝癌患者中HBV pgRNA被检测出(中位数:0.0001拷贝/细胞),这是显著低于慢性乙型肝炎患者的(平均:2.90拷贝/细胞;<0.001)结论:73%似乎是不明原因的原发性肝癌患者与乙型肝炎病毒相关。检测率在非肿瘤组织高于肿瘤组织。在OBI患者中,低水平的肝内HBV DNApgRNA表明,持续的病毒复制和可能的乙肝病毒整合可能是发生原发性肝癌的原因。

 

 

吉林大学第一医院肝胆胰内科  沙秀娟  摘译

本文首次发表于[Hepatology. 2011,54(3):829-836]

 

Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepatocellular carcinoma

Abstract

BACKGROUND AND AIMS: We aimed to investigate the incidence of occult hepatitis B infection (OBI) in patients with "cryptogenic" hepatocellular carcinoma (HCC) and to study the HBV replicative activity in these patients. Tumorous and adjacent nontumorous liver tissues were obtained from 33 cryptogenic HCC patients and 28 HCC patients with identifiable causes (13 with chronic hepatitis B [CHB], six with chronic hepatitis C, and nine alcohol-related).

METHODS: OBI was identified by nested polymerase chain reaction (PCR). Intrahepatic HBV DNA, covalently closed circular DNA(cccDNA), and pregenomic RNA (pgRNA) were quantified by real-time PCR and reverse-transcription PCR (RT-PCR), respectively.

RESULTS: OBI was identified in 24 (73%) cryptogenic HCC patients, one (17%) HCC patient with HCV, and five (56%) patients with alcohol-related HCC. Cryptogenic HCC patients with OBI had lower intrahepatic total HBV DNA levels than HCC patients with CHB (median: 0.010 versus 3.19 copies/cell, respectively; P < 0.0001). Only six (26%)cryptogenic HCC patients with OBI had detectable cccDNA (median:<0.0002 copies/cell), which was significantly lower than that of the CHB patients (median: 0.005 copies/cell;P < 0.0001). HBV pgRNA were detectable in 12 (52%) cryptogenic HCC patients with OBI (median: 0.0001 copies/cell), which was significantly lower than that of the CHB patients (median: 2.90 copies/cell; P < 0.001).

CONCLUSIONS: 73% of patients with apparently unidentifiable causes for HCC were HBV-related. The detection rate was higher in nontumorous tissues than tumorous tissues. The low intrahepatic HBV DNA and pgRNA levels indicated that persistent viral replication and possibly HBV integration are the likely causes of HCC in OBI patients.

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作者: 沙秀娟 发布日期: 2012-05-23 阅读次数: