Inhibition of hepatitis B virus replication by APOBEC3G in vitro and in vivo

AIM: To investigate the effect of APOBEC3G mediated antiviral activity against hepatitis B virus (HBV) in cell cultures and replication competent HBV vector-based mouse model. METHODS: The mammalian hepatoma cells Huh7 and HepG2 were cotransfected with various amounts of CMV-driven expression vector encoding APOBEC3G and replication competent 1.3 fold over-length HBV. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA. The expression of HBcAg in transfected cells was detected by western blot. HBV DNA and RNA from intracellular core particles were examined by Northern and Southern blot analyses. To assess activity of the APOBEC3G in vivo, an HBV vector-based model was used in which APOBEC3G and the HBV vector were co-delivered via high-volume tail vein injection. Levels of HBsAg and HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by ELISA and quantitative PCR analysis respectively. RESULTS: There was a dose dependent decrease in the levels of intracellular core-associated HBV DNA and extracellular production of HBsAg and HBeAg. The levels of intracellular core-associated viral RNA also decreased, but the expression of HBcAg in transfected cells showed almost no change. Consistent with In vitro results, levels of HBsAg in the sera of mice were dramatically decreased. More than 1.5 log 10 decrease in levels of serum HBV DNA and liver HBV RNA were observed in the APOBEC3G-treated groups compared with the control groups. CONCLUSION: These findings indicate that APOBEC3G could suppress HBV replication and antigen expression both in vivo and in vitro, promising an advance in treatment of HBV infection.     

e抗原阳性慢性乙型肝炎患者感染病毒的基因型与抗病毒治疗疗效的关系

目的 探讨HBV基因型与抗病毒治疗疗效的关系。方法 应用PCR-微板核酸分子杂交ELISA法检测90例HBeAg阳性CHB患者的HBV基因型,对其中41例患者给予拉米夫定（100 mg／d）抗病毒治疗48周,49例患者给子干扰素α（3 MU／次,隔日1次）抗病毒治疗48周,治疗前、治疗过程中和治疗结束时分别检测血清生化指标（ALT）、病毒学血清标志物（HBeAg和抗-HBe）和HBV DNA水平。结果 90例CHB患者中HBV B基因型者16例,C基因型者74例。41例患者应用拉米夫定治疗,感染B和C基因型患者48周时对拉米夫定治疗应答率分别为33.3％和20%,差异无统计学意义;49例患者应用干扰素α治疗,48周时感染基因B型患者的ALT复常率、HBeAg消失率和HBV DNA阴转率均高于感染基因C型患者（分别为60.0％和20．5％,50．0％和17．9％, 50．0％和17．9％）,两组比较差异有统计学意义,但HBeAg血清转换率差异无统计学意义。结论 基因B和C型对拉米夫定抗病毒治疗的疗效无影响,基因B型对干扰素α治疗的疗效优于C型。     

泉州地区慢性乙型肝炎患者HBV基因型、基因亚型及血清型分布调查

目的调查泉州地区慢性乙型肝炎患者HBV基因型、基因亚型及血清型的分布。方法采用巢式PCR法对48例样本S基因扩增后进行测序,应用Neighbor Joining构建系统进化树并分析其基因型和基因亚型,应用Magnius和Norder法进行血清型分析。结果48例慢性乙型肝炎患者中,检测出B基因型35例（68.8%）,C型13例（31.2%）;B基因型中Ba亚型占97.0%,adw2血清型占93.9%;C基因型中C2亚型占93.3%,adrq+血清型占80.0%。结论泉州地区慢性乙型肝炎患者以B基因型为主,其次是C基因型;B基因型样本中,以Ba亚型和adw2血清型为主,C基因型样本中,以C2亚型和adrq+血清型为主。     

Molecular analysis of hepatitis B virus isolates in Mexico： Predominant circulation of hepatitis B virus genotype H

INTRODUCTIONHepatitis B virus(HBV)is an important cause of morbidity and mortality worldwide.It is estimated that2billion people are infected with HBV and350million individuals suffer from chronic HBV infection in the world[1,2].Chronic HBV infection may …     

Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent

BACKGROUND AND AIM: Certain hepatitis B virus (HBV) genotypes have been alleged to be associated with the development of cirrhosis and hepatocellular carcinoma (HCC), and the response to interferon therapy in Taiwanese patients. We undertook to study the prevalence and significance of HBV genotypes in the Indian subcontinent. METHODS: One hundred and thirty histopathologically proven chronic HBV-infected patients, including 52 incidentally detected asymptomatic hepatitis B surface antigen (HBsAg)-positive subjects (IDAHS) with chronic HBV infection (group I), 48 cirrhotics (group II) and 30 hepatocellular carcinoma (HCC; group III) patients were studied. Hepatitis B virus genotypes were determined by using restriction fragment length polymorphism, and direct sequencing of the s gene including the 'a' determinant region. RESULTS: Only genotypes A (46%) and D (48%) were found in the chronic HBV-infected patients. A mixed infection with genotypes A and D was seen in 6% of patients. Genotype A was found in 42, 48 and 50%, and genotype D in 48, 50 and 47% of group I, II and III patients, respectively (P = NS). The patients who had mixed genotypes were significantly younger (P < 0.05). In group I (IDAHS) patients infected with genotype D, none had a histological activity index (HAI) of < four. Genotype D was significantly more common in group I patients with HAI > 4 as compared to genotype A (53 vs 32%, P < 0.05). Similarly, genotype D was associated with more severe liver diseases (61 vs 30%, P < 0.05). Genotype D was more prevalent in HCC patients of < 40 years of age, as compared to IDAHS (63 vs 44%, P = 0.06). CONCLUSIONS: (i) Hepatitis B virus genotypes A and D are prevalent in chronic liver disease patients of Indian origin; and (ii) HBV genotype D is associated with more severe diseases and may predict the occurrence of HCC in young patients.     

Hepatitis B virus genotypes in chronic liver disease patients from New Delhi, India

INTRODUCTION Approximately, two billion people in the world have been infected by Hepatitis B virus (HBV), 350 million of whom are chronic carriers of the virus[1,2]. Worldwide HBV isolates have been classified into eight genotypes: A, B, C, D, E, F, G an…     

HBV感染合并慢性肾脏疾病抗病毒治疗研究进展

乙型肝炎病毒（hepatitis B virus,HBV）感染是全球范围内的重大公共卫生问题,而HBV感染和慢性肾脏疾病（chronic kidney disease,CKD）之间存在一定关联,并且当CKD患者的肾脏病变处于不同阶段时,抗病毒治疗的药物选择和用药剂量存在差异。本文介绍了HBV感染与CKD的相关性,并重点综述了HBV感染合并CKD患者的抗病毒治疗药物选择和剂量调整等方面的进展,以及出现病毒学突破或持续的低病毒血症（low level viremia,LLV）等特殊情况下治疗策略的优化措施。     

丙型、乙型肝炎混合感染者病毒基因型与临床特征分析

探讨丙型、乙型肝炎病毒混合感染的基因型特点及临床特征。采用ELISA法进行病毒血清标志物检测 ,采用PCR -微板核酸杂交 -ELISA法进行HBV -DNA定量及HCV -RNA基因分型检测。丙型、乙型肝炎病毒混合感染者HCV -RNA及HBV -DNA阳性率 (72 5 1%和 30 4 1% )分别低于丙型、乙型肝炎病毒单独感染者 (85 4 2 %和 6 0 72 % ) ,Ⅰ / 1a型和Ⅲ / 2a型HCV与HBV混合感染较同类基因型HCV单独感染明显增加 ,Ⅱ / 1b型丙型肝炎病毒合并乙型肝炎病毒感染者血清转氨酶及总胆红素水平最高 ,白蛋白和胆碱酯酶水平最低 ,尽管HCV、HBV混合感染的临床症状可能更为严重 ,但在病毒学上两者的确存在着相互抑制作用     

Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life

AIM To investigate the different impact of genotypes B and C on the development of liver cirrhosis (LC) among different age groups of patients with chronic hepatitis B (CH-B).METHODS We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS In patients ＜ 30 years old, there were no significant predictors for development of LC. However,in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis (7 patients were positive for HBeAg). In the genotype B group, 4 of 8patients who developed LC were ≥ 50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at ＜ 30 years old. However,CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.     

Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: A multi-institution analysis

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69–76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.     

N-terminal and C-terminal cytosine deaminase domain of APOBEC3G inhibit hepatitis B virus replication

INTRODUCTION Hepatitis B virus (HBV) infects more than 350 million people worldwide and is a leading cause of end-stage liver disease and of hepatocellular carcinoma[1]. HBV is non- cytopathic for hepatocytes; however, most newly HBV-infected adult patien…     

慢性乙型肝炎病毒感染S区基因缺失及相关因素研究

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.     

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology

Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.     

HBV合并HEV感染导致慢加急性肝衰竭HBV-PC区变异及临床特征分析

目的分析乙型肝炎病毒合并戊型肝炎病毒导致的慢加急性肝衰竭的HBV-PC区变异及临床特征。方法回顾性分析HBV感染的慢加急性肝衰竭(ACLF)患者69例,其中单独HBV感染患者39例,HBV合并HEV感染患者30例;比较2组患者肝功能、HBV DNA水平、凝血功能、MELD评分以及预后情况;PCR扩增HBV-PC区序列,测序与ACLF相关的变异位点A1762T、G1764A、C1766T、T1768A、G1896A、A1762T+G1764A、G1764A+C1766T+T1768A,比较两组患者之间的差异。分析HBV合并HEV感染存活与死亡患者,Logistic回归分析重叠感染患者预后相关因素。结果与单纯HBV感染组比较,合并HEV感染组患者的TBil[(216.4±12.1)μmol/L对(364.2±170.24)μmol/L]、肝性脑病发生率(17.9%对33.3%)、MELD评分(21.26±6.65对28.26±8.65)均呈不同程度的升高;PTA[(33.3±22.4)%对(24.5±20.1)%]明显降低,差异均有统计学意义(P0.05);2组患者HBV-PC变异分析比较位点A1762T(66.7%对76.7%)、G1764A(69.2%对80.0%)、A1762T+G1764A(59.0%对70.0%)和G1764A+C1766T+T1768A(2.6%对10.0%)差异有统计学意义(P0.05)。HBV合并HEV感染患者存活组与死亡组比较,MELD评分和肝性脑病发生率明显升高,PTA明显降低,差异均有统计学意义(P0.05);HBV-PC变异分析比较G1764A+C1766T+T1768A三联变异差异有统计学意义(P0.05);Logistic回归分析显示,TBil(P=0.006,OR=2.672)、PTA(P=0.036,OR=2.115)、MELD评分(P=0.003,OR=1.682)、肝性脑病并发症(P=0.001,OR=3.631)和G1764A+C1766T+T1768A三联变异(P=0.043,OR=2.081)因素与预后有关。结论单独HBV与合并HEB感染导致的ACLF患者病情更加严重,预后更差。TBil、MELD评分、肝性脑病并发症和HBV-PC区G1764A+C1766T+T1768A三联变异发生率越高。PTA越低,ACLF患者预后越差。     

云南地区乙型肝炎病毒基因型分布与临床的相关性

目的: 了解云南地区乙型肝炎病毒基因型分布特征, 探讨其与慢性HBV感染者的性别和年龄、不同临床疾病谱、病毒复制水平的关系.方法:选择云南地区慢性HBV感染者117例, 其中慢性无症状乙型肝炎表面抗原携带者(ASC)26例、慢性乙型肝炎(CHB)55例(轻度21例、中度24例、重度10例)、慢性重型肝炎(CLF)18例、乙肝后肝硬化(LC)11例及原发性肝细胞肝癌(HCC)7例, 采用反向杂交技术(RDB)检测HBV基因型, 并对与其性别年龄、临床分型和病毒复制水平的关系进行分析.结果: 云南地区HBV基因型以B型和C型为主, 分别为41.0%(48/117)和54.7%(64/117) , 并以C型为最多(χ2 = 4.38, P = 0.036);D型1例(0.86%), B、C混合型2例(1.71%), A、C混合型2例(1.71%). B基因型在轻度慢乙肝组所占的比例显著高于中、重度慢乙肝组(χ2 = 8.27、11.98, P = 0.004、0.001)、ASC组(χ2 = 5.46, P = 0.02)、CLF组(χ2 = 4.13, P = 0.042)和LC/HCC组(χ2 = 11.3, P = 0.001). C基因型在LC/HCC组和重度慢乙肝组所占的比例均显著高于轻度慢乙肝组(χ2 = 11.3, P = 0.001;χ2 = 8.78, P = 0.003), 与其他各临床型组间的比较则无显著性差异(P>0.05). C基因型在HBV DNA( )组和HBeAg(-)组r所占的比例均分别显著高于HBV DNA(-)组(χ2 = 6.63, P = 0.01)和HBeAg( )组(χ2 = 7.12, P = 0.008). B基因型在HBV DNA低水平复制组中所占的比例显著高于高水平复制组(χ2 = 4.12, P = 0.042). C基因型在HBV DNA高水平复制组中所占的比例显著高于B基因型(χ2 = 3.89, P<0.05). C基因型在年龄≥30岁组中所占的比例(63.3%)高于年龄<30岁组(45.6%)(χ2 = 3.7, P = 0.05). HBV基因型在性别间的分布无统计学差异(P>0.05)结论:云南地区存在HBV的B、C、D、B C和A C基因型, 以B型和C型为主要基因型, 并以C型为最多. B基因型在轻度慢乙肝的比例显著高于其他各临床型HBV感染者, 并且与HBV的低水平复制和低年龄有关. C基因型主要分布于重度慢乙肝和LC/HCC、HBV DNA高水平复制、年龄≥30岁的患者中. 提示C基因型与慢乙肝重度、肝硬化、肝细胞肝癌及HBV DNA高水平复制关系密切.     

Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection

This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A-F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4 in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg- CHB and 1.4 in HBeAg- inactive carriers. Distribution of these genotypes was different between HBeAg+ CHB and HBeAg- CHB (P = 0.02), and between HBeAg- CHB and HBeAg- inactive carriers (P = 0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT (60.7%). There was a difference in genotype prevalence between chronic and acute infection (P = 0.03). The precore mutant correlated with high levels of HBV-DNA in genotype d HBeAg- CHB. Genotype D is not as highly prevalent in Spanish patients as would be expected in a Mediterranean area. The unequal prevalence of genotypes between acute and chronic infection suggests that genotype A is associated with a higher tendency to cause chronic infection.     

慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析*

目的 探讨慢性乙型肝炎（CHB）患者HBV基因型及其耐药突变发生情况。方法 纳入240例接受核苷（酸）类似物单药或联合或序贯治疗的CHB患者,采用PCR扩增HBV逆转录（RT）区和序列测定鉴定耐药基因突变,采用HBV S基因测序法鉴定基因型。结果 在35例单用拉米夫定治疗的CHB患者中,发生耐药突变14例（40.0%）,突变位点为rtL80I/V、rtVl73L、rtLl80M、rtM204V/I和rtV207I,23例单用阿德福韦治疗者发生耐药突变11例（47.8%）,突变位点为rtAl81T/V、rtS213T/N、rtV214A、rtQ215S/H/P、rtl233V、rtN236T、rtP237H和rtN/H238A/K/D/S,70例单用恩替卡韦治疗者发生耐药突变10例（14.3%）,突变位点为rtM204I,12例单用替比夫定治疗者发生耐药突变5例（41.7%）,突变位点为rtI169T、rtL180M、rtT184G/S/A/I/L/F、rtS202I/G、rtM204V和rtM250V/I/L,100例接受联合或序贯治疗者发生耐药突变51例（51.0%）,突变位点为rtA194T,恩替卡韦治疗患者耐药突变发生率最低（P<0.05）;240例CHB患者中,HBV基因B型21例（8.8%）、C型216例（90.0）和D型3例（1.2%）;在发生耐药突变的91例患者中,B型6例（6.6%）、C型83例（91.2%）和D型2例（2.2%,x²=1.22,P>0.05）;在发生耐药突变的6例B型感染者中有2例（33.3%）和83例C型感染者中有15例（18.1%）发生了多重耐药突变。结论 检测CHB患者感染HBV基因型并及时获得耐药突变基因分布,将有助于指导临床治疗。     

阿德福韦酯治疗HBeAg阴性慢性乙型肝炎疗效与HBV基因型的关系

目的探讨阿德福韦酯（ADv）治疗HBeAg阴性慢性乙型肝炎（chronic hepatitis B,CHB）的疗效与HBv基因型的关系。方法选择71例HBVDNA〉1×10^4copies／ml、ALT〉2倍正常值上限、TBIL正常的HBeAg阴性cHB患者,其中B基因型40例,C基因型31例,所有患者均口服ADV 10mg,1／d,治疗52周,动态观察治疗过程中HBV DNA和ALT水平的变化。结果在治疗12、24、52周时,B基因型患者ALT变化、血清HBVDNA水平下降≥2log。完全抑制比例与C基因型患者相比差异无统计学意义（P〉0．05）。结论ADV能有效抑制HBeAg阴性CHB患者HBV复制,促进肝功能好转,其疗效与HBV基因型B或C型无关。     

乙型肝炎相关性肝癌患者围手术期HBV DNA的变化及其影响因素

目的探讨乙型肝炎相关性肝癌患者围手术期HBV DNA水平变化的影响因素,比较抗病毒治疗与未抗病毒治疗对患者术后肝功能恢复的影响。方法选择65例未达到抗病毒治疗标准的乙型肝炎相关性肝癌患者,定量检测其术前和术后第3天的HBV DNA载量及白细胞介素(IL)-6、IL-10、IL-27的水平。根据术后HBV DNA载量,将患者分成HBV DNA升高(激活)组和不变组。升高组给予抗病毒治疗。记录所有患者术前、术后肝功能指标。用SPSS 17.0进行统计学分析。结果入组患者HBV激活率为37%(24/65),术前HBV DNA1×104 IU/ml的患者,术后HBV激活率为75%(18/24)。Logistic回归分析显示肿瘤直径(P=0.006)及肝切缘无水酒精注射(P=0.004)是引起HBV再激活的独立危险因素。ELISA结果示术后IL-10升高与HBV再激活有关(P=0.001),IL-6升高及IL-27降低与HBV不变有关(P=0.000)。术后HBV DNA升高且行抗病毒治疗的患者,术后肝功能恢复情况与其他患者比较差异无统计学意义(P0.05)。结论肝癌切除术可能引起患者HBV再激活,围手术期内应监测HBV DNA载量的变化。肿瘤直径、术中行肝切缘无水酒精注射术是HBV再激活的独立危险因素。患者术后IL-10、IL-6水平的变化可能与HBV DNA的变化有关。术后HBV再激活近期不会加重肝功能损伤,术后抗病毒治疗对患者近期肝功能的恢复无明显促进作用。     

A new polymorphism in the GRP78 is not associated with HBV invasion

AIM: To examine the association between-86 bp (T > A) in the glucose-regulated protein 78 gene ( GRP78) and hepatitis B virus (HBV) invasion.METHODS: DNA was genotyped for the single-nucleotide polymorphism by polymerase chain reaction followed by sequencing in a sample of 382 unrelated HBV carriers and a total of 350 sex-and age-matched healthy controls. Serological markers for HBV infection were determined by enzyme-linked immunosorbent assay kits or clinical chemistry testing.RESULTS: The distributions of allelotype and genotype in cases were not signi.cantly different from those in controls. In addition, our .ndings suggested that neither alanine aminotransferase/hepatitis B e antigen nor HBV-DNA were associated with the allele/genotype variation in HBV infected individuals.CONCLUSION:-86 bp T > A polymorphism in GRP78 gene is not related to the clinical risk and acute exacerbation of HBV invasion.