Prevalences of S region deletion and its related factors in patients with chronic HBV infection
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摘要: 目的测定慢性乙型肝炎病毒(HBV)感染者HBV DNA全序列,分析S区基因缺失模式、频率及相关因素。方法慢性HBV感染者59例,其中HBV携带7例,慢性肝炎31例,肝硬化10例,重型肝炎6例,原发性肝癌5例。结果25.4%(15/59)慢性HBV感染者有S区基因缺失,未发现S基因缺失。Pre-S基因缺失均见于C基因型患者。Pre-S基因缺失患者中,20%(3/15)HBsAg、抗HBs共存,与无S区缺失者比较有明显差异(P<0.05)。PreS基因缺失与病程(偏相关系数0.28,P=0.049)、抗病毒治疗(偏相关系数-0.451,P=0.036)有密切关系。结论Pre-S基因缺失在基因C型、严重肝病及活动性HBV复制患者多见,可能与病程长及抗病毒治疗有关。Pre-S基因缺失可导致HBV免疫逃避或免疫治疗失败,可能是肝脏疾病发展的重要原因。Abstract: Objective Hepatitis B virus (HBV) mutants with deletions in the S region have not well been evaluated.This study was to assay full-length of HBV DNA, to analyze the pattern, frequency and clinical factors of S region deletion of patients with chronic HBV infection.Methods Full-length sequences of HBV DNA were acquired in 59 patients who included 7 of HBV carrier, 31 of chronic hepatitis, 10 of liver cirrhosis, 6 of chronic severe hepatitis and 5 of primary carcinoma of liver.Genotype of HBV was analyzed with PCR-RFLP.Serum HBV DNA was quantitatively measures with teal-time PCR.The full genome of complete genome of HBV DNA was amplified with routine PCR and fulllength sequencing was directly performed.HBV DNA nucleotide and amino acid sequences were analyzed with bioinformatics technique analysis.Results 25.4% (15/59) of patients with chronic HBV infection had S region deletion.Pre-S gene deletion had a closedly related to genotype C.20% (3/15) patients with Pre-S gene deletion coexisted HBsAg and anti-HBs.There was significant difference compared with patients without Pre-S gene deletion (P<0.05) .Long HBV infection (coefficien 0.28, P=0.049) and antiviral therapy (coefficient-0.451, P=0.036) .Conclusion A greater frequency of Pre-S gene deletion mutants with genotype C, advanced liver disease and active viral replication are demonstrated.It is suggested that Pre-S gene deletion would leads to failure of HBV immune evasion or immunotherapy.
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Key words:
- hepatitis B virus /
- genotype /
- Pre-S deletion /
- chronic liver disease
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[1]Kao JH, Chen DS.Global control of hepatitis B virus infection[J].Lancet Infect Dis, 2002, 2 (7) ∶395-403. [2]Chen BF, Liu CJ, Jow GM, et al.High prevalence and mapping ofPre-S deletion in hepatitis B virus carrriers with progressive liverdiseases[J].Gastroenterology, 2006, 130 (4) ∶1153-1168. [3]Marschenz S, Endres AS, Brinckmann A, et al.Functional analysisof complex hepatitis B virus variants associated with development ofliver cirrhosis[J].Gastroenterology, 2006, 131 (3) ∶765-780. [4] 中华医学会.慢性乙型肝炎防治指南[J].中华肝脏病杂志, 2005, 13 (5) ∶881-891. [5]Sugauchi F, Ohno T, Orito E, et al.Influence of hepatitis B virusgenotype on the development of preS deletions and advanced liver dis-ease[J].J Med Virol, 2003, 70 (4) ∶537-544. [6]Kim DY, Lee DH, Lee JH, et al.Clinical significance of pre-Smutations in patients with genotype C hepatitis B virus infection[J].J Viral Hepat, 2007, 14 (3) ∶161-168. [7]Kalinina T, Riu A, Fischer L, et al.A dominant hepatitis B viruspopulation defective in virus secretion because of several S-genemutations from a patient with fulminant hepatitis[J].Hepatology, 2001, 34 (2) ∶385-394.
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