A study on sequence variations in pre-S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non-B, non-C hepatocellular carcinoma patients in Taiwan

A study on sequence variations in pre-S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non-B, non-C hepatocellular carcinoma patients in Taiwan
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DOI:
10.1002/ijc.24416
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发表时间:
2009-08-01
影响因子:
6.4
通讯作者:
Lu, Sheng-Nan
Lu, Sheng-Nan
中科院分区:
医学1区
文献类型:
--
作者:
Chen, Chien-Hung;Changchien, Chi-Sin;Lu, Sheng-Nan

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本研究旨在探讨台湾地区无乙型肝炎表面抗原(HBsAg)或抗丙型肝炎病毒(非乙型、非丙型)的肝癌患者隐匿性乙型肝炎病毒(HBV)感染的临床意义及病毒学因素。222例非b、非c型HCC患者中有90例检测到血清HBV DNA(隐匿HBV), 300例非b、非c型对照组中有24例未检测到HCC。在90例隐匿性HBV感染的HCC患者中,对40例患者的HBV前s /表面、X和增强子II/核心启动子/前癌基因序列进行分析。这些基因的直接测序也在24例非b型、非c型无HCC对照和40例hbsag阳性HCC对照中进行。与非b相比,。非c组、非b组、非c组HCC患者隐匿性HBV患病率显著高于非c组(p < 0.0001)。隐匿性hbv感染的HCC患者中,pre-S2基因的M1I、Q2K和G1721A比非HCC患者更常见。隐匿性hbv感染HCC患者与hbsag阳性HCC对照组相比,前s2基因M1I和Q2K、表面基因G185R和S210N、X基因A36T和A44L、增强子11基因G1721A的频率更高,核心启动子/前体细胞基因A1762T/GI764A、A1846T、G1896A和G1899A的缺失率更低。多因素分析显示,前s2基因Q2K、G1721A和A1846T是隐匿性hbv感染HCC的独立因素。我们的研究提示隐匿性HBV感染与hbsag阳性患者HCC相关的HBV病毒学因素存在差异。前s2基因中的G1721A、M1I和Q2K可能是隐匿性HBV携带者HCC的有用病毒标志物。(c) 2009年
This study was to investigate the clinical significance and virologic factors of occult hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) patients without hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (non-B, non-C) in Taiwan. Serum HBV DNA (occult HBV) was detected in 90 of 222 non-B, non-C HCC patients and 24 of 300 non-B, non-C controls without HCC. Of 90 occult HBV-infected HCC patients, the sequences of HBV pre-S/surface, X and enhancer II/core promoter/precore genes were analyzed from 40 patients. Direct sequencing of such genes was also performed in 24 non-B, non-C controls without HCC and 40 HBsAg-positive HCC controls. Compared with non-B,.non-C controls without HCC, non-B, non-C subjects with HCC had significantly higher prevalence of occult HBV (p < 0.0001). Moreover, M1I and Q2K in pre-S2 gene and G1721A were more common in occult HBV-infected patients with HCC than in those without HCC. Compared with the HBsAg-positive HCC controls, occult HBV-infected HCC patients had higher frequencies of M1I and Q2K in pre-S2 gene, G185R and S210N in surface gene, A36T and A44L in X gene, and G1721A in enhancer 11 gene, and had lower rates of pre-S deletions and A1762T/GI764A, A1846T, G1896A and G1899A in core promoter/precore genes. Multivariate analysis showed Q2K in pre-S2 gene, G1721A and A1846T were independent factors for occult HBV-infected HCC. Our study suggested that the virological factors of HBV related to HCC were different between occult HBV-infected and HBsAg-positive patients. The G1721A, M1I and Q2K in pre-S2 gene may be useful viral markers for HCC in occult HBV carriers. (C) 2009 UICC