Anvari Fatemeh Akhavan, Alavian Seyed Moayyed, Norouzi Mehdi, Mahabadi Mostafa, Jazayeri Seyed Mohammad
Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, PO Box: 15155-6446, Tehran, Iran. Tel/
Baqiyatallah University of Medical Sciences, Baqiyatallah Research Center for Gastroenterology and Liver Disease, P.O. Box: 15155-6446, Tehran, Iran.
Oman Med J. 2014 Mar;29(2):92-6. doi: 10.5001/omj.2014.23.
The aims of this study are to investigate the prevalence of occult hepatitis B virus infection among patients with cryptogenic cirrhosis and to analyze the relationship between surface protein variability and occult hepatitis B virus infection, which may be related to the pathogenesis of occult hepatitis B virus infection in cryptogenic cirrhosis. Occult hepatitis B virus infection is a well-recognized clinical entity characterized by the detection of hepatitis B virus DNA in serum and/or liver in the absence of detectable hepatitis B virus surface antigen, with or without any serological markers of a past infection.
Sera from patients with cryptogenic chronic liver disease were tested for hepatitis B virus DNA using both real-time and nested PCR. In the detected hepatitis B virus DNA samples, the surface gene was analyzed for mutations.
Hepatitis B virus DNA was detected in 38% of patients, all of whom had a viral load below 10,000 copies/mL. All hepatitis B virus belonged to genotype D. There were no significant associations between occult hepatitis B virus infection status and age, gender, ALT/AST levels, viral load or serologic markers of previous hepatitis B virus infection. There were 14 mutations found in 5 patients; 6 were in the major hydrophilic region, of which 4 were Y134F assigning for the "a" determinant region. All patients who acquired Y134F contained S207R (within HLA-A2-restricted CTL epitope) as a combination.
Hepatitis B virus surface antigen variants may arise as a result of natural selection to evade the immune surveillance of the infected host, and subsequently may go undetected by conventional hepatitis B virus surface antigen screening tests. Etiological diagnosis of cryptogenic cirrhosis is significantly underestimated with current serology testing methods alone.
本研究旨在调查隐源性肝硬化患者中隐匿性乙型肝炎病毒感染的患病率，并分析表面蛋白变异性与隐匿性乙型肝炎病毒感染之间的关系，这可能与隐源性肝硬化中隐匿性乙型肝炎病毒感染的发病机制有关。隐匿性乙型肝炎病毒感染是一种公认的临床实体，其特征是在血清和/或肝脏中检测到乙型肝炎病毒DNA，而不存在可检测到的乙型肝炎病毒表面抗原，无论是否有既往感染的任何血清学标志物。
使用实时荧光定量PCR和巢式PCR检测隐源性慢性肝病患者的血清中的乙型肝炎病毒DNA。在检测到的乙型肝炎病毒DNA样本中，分析表面基因的突变情况。
38%的患者检测到乙型肝炎病毒DNA，所有患者的病毒载量均低于10,000拷贝/毫升。所有乙型肝炎病毒均属于D基因型。隐匿性乙型肝炎病毒感染状态与年龄、性别、ALT/AST水平、病毒载量或既往乙型肝炎病毒感染的血清学标志物之间无显著关联。5例患者中发现14个突变；6个在主要亲水区，其中4个为Y134F，位于“a”决定簇区域。所有获得Y134F的患者均含有S207R（在HLA-A2限制性CTL表位内）作为组合。
乙型肝炎病毒表面抗原变异体可能是自然选择的结果，以逃避感染宿主的免疫监视，随后可能无法通过传统的乙型肝炎病毒表面抗原筛查试验检测到。仅用目前的血清学检测方法，隐源性肝硬化的病因诊断被严重低估。
