Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection: Single center study in Egypt

AIM:To identify possible maternal risk factors for hepatitis B virus(HBV)acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen(HBs Ag)positive mothers.METHODS:Screening of 2000 pregnant females wascarried out using rapid test and confirmed by enzyme immunoassay.A questionnaire consisting of 20 questions about the possible risk factors for acquisition of HBV infection was filled for every pregnant HBs Ag positive female in addition to at least 2 pregnant HBs Ag negative females for each positive case.Infants of HBs Ag positive women were offered passive and active immunoprophylaxis within the 1st 48 h after birth,in addition to 2nd and 3rd doses of HBV vaccine after1 and 6 mo respectively.Infants were tested for HBs Ag and hepatitis B surface antibodies(HBs Ab)at six months of age.RESULTS:HBs Ag was confirmed positive in 1.2%of tested pregnant women.Risk factors significantly associated with HBV positivity were;history of injections(OR=5.65),history of seeking medical advice in a clinic(OR=7.02),history of hospitalization(OR=6.82),history of surgery(OR=4)and family history of hepatitis(OR=3.89)(P<0.05).Dropout rate was 28%for HBs Ag women whose rapid test was not confirmed and could not be reached to provide immunoprophylaxis for thier newborns.Immunoprophylaxis failure was detected in only one newborn(3.7%)who tested positive for HBs Ag at 6 mo of age;and vaccine failure(seronegative to HBs Ab after 4 doses of the vaccine)was detected in another one(3.7%).The success rate of the immunoprophylaxis regimen was 92.6%.CONCLUSION:This pilot study shows that a successful national program for prevention of perinatal transmission of HBV needs to be preceded by an awareness campaign to avoid a high dropout rate.     

Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in Japan

Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32 (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed patients. Genotypes C accounted for more than 68% in northern as well as southern areas, contrasting with genotype A accounting for 34% in and around the Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from 5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant hepatitis was significantly more frequent in infection with genotype Bj (41%) than those with the other genotypes (p < 0.01). The core-promoter double mutation (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58% versus 10%, respectively, p < 0.01 for both). In conclusion, genotype A distributes unevenly over Japan, prevails in younger patients through sexual transmission and has increased with years. Furthermore, fulminant outcome was more frequent in patients with genotype Bj than those with the other genotypes.     

单项抗-HBe阳性患者中的隐匿性乙型肝炎病毒感染

目的 研究抗-HBe单项阳性患者中隐匿性HBV的感染情况及发生的可能原因.方法 收集HBV血清学标志物检测结果中抗HBe单项强阳性[吸光度(A)值≤0.1]的新鲜血清标本61份,采用实时定量PCR进行HBV DNA含量检测.对于HBV DNA定量阳性的标本,采用雅培试剂复测HBV血清学标志物,采用PCR扩增,并进行克隆测序.结果 61份标本中,2份HBVDNA定量阳性,HBsAg血清学漏检率为3.3％.其中l份标本经雅培试剂复测为抗-HBc单项阳性,其前S区缺失突变和前S2区起始密码子突变,并存在不同突变株混合感染;另1份标本经雅培试剂复测发现,除抗HBe强阳性外,HBsAg和抗- HBc为极弱阳性,未发现前S/S区突变.结论 抗HBe单项阳性患者中存在隐匿性HBV感染和HBsAg血清学漏检情况,后者不仅与前S/S区突变有关,而且与外周血中HBsAg低水平也有一定关系.     

慢性乙型肝炎肝组织内HBsAg、HBcAg的表达及临床研究进展

一直以来临床将血清乙型肝炎e抗原(HBeAg)、乙肝病毒DNA(HBV DNA)阳性作为乙肝病毒复制的标志,随着肝穿活检及抗病毒治疗的研究进展,肝活检组织中乙肝表面抗原(HBsAg)和乙肝核心抗原(HBcAg)的表达模式与血清乙型肝炎病毒(HBV)DNA定量、肝组织炎症活动度分级及纤维化分期之间关系的临床研究日益增多,本文就HBsAg和HBcAg在肝组织的表达模式及临床研究进展综述如下.     

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM: To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.     

Global prevalence of hepatitis B virus serological markers among healthcare workers: A systematic review and meta-analysis

BACKGROUNDThe hepatitis B virus (HBV) infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths yearly. HBV is a blood-borne disease and healthcare workers (HCWs) are a high-risk group because of occupational hazard to patients’ blood. Different regions of the world show a highly variable proportion of HCWs infected and/or immunized against HBV. Global data on serologic markers of HBV infection and immunization in HCWs are very important to improve strategies for HBV control.AIMTo determine the worldwide prevalence of HBV serological markers among HCWs.METHODSIn this systematic review and meta–analyses, we searched PubMed and Excerpta Medica Database (Embase) to identify studies published between 1970 and 2019 on the prevalence of HBV serological markers in HCWs worldwide. We also manually searched for references of relevant articles. Four independent investigators selected studies and included those on the prevalence of each of the HBV serological markers including hepatitis B surface antigen (HBsAg), hepatitis e antigen (HBeAg), immunoglobulin M anti-HBc, and anti-HBs. Methodological quality of eligible studies was assessed and random-effect model meta-analysis resulted in the pooled prevalence of HBV serological markers HBV infection in HCWs. Heterogeneity (I²) was assessed using the χ² test on Cochran’s Q statistic and H parameters. Heterogeneity’ sources were explored through subgroup and metaregression analyses. This study is registered with PROSPERO, number CRD42019137144.RESULTSWe reviewed 14059 references, out of which 227 studies corresponding to 448 prevalence data among HCWs (224936 HCWs recruited from 1964 to 2019 in 71 countries) were included in this meta-analysis. The pooled seroprevalences of current HBsAg, current HBeAg, and acute HBV infection among HCWs were 2.3% [95% confidence interval (CI): 1.9-2.7], 0.2% (95%CI: 0.0-1.7), and 5.3% (95%CI: 1.4-11.2), respectively. The pooled seroprevalences of total immunity against HBV and immunity acquired by natural HBV infection in HCWs were 56.6% (95%CI: 48.7-63.4) and 9.2% (95%CI: 6.8-11.8), respectively. HBV infection was more prevalent in HCWs in low-income countries, particularly in Africa. The highest immunization rates against HBV in HCWs were recorded in urban areas and in high-income countries including Europe, the Eastern Mediterranean and the Western Pacific.CONCLUSIONNew strategies are needed to improve awareness, training, screening, vaccination, post-exposure management and treatment of HBV infection in HCWs, and particularly in low-income regions.     

Genetic variation of occult hepatitis B virus infection

Occult hepatitis B virus infection(OBI), characterized as the persistence of hepatitis B virus(HBV) surface antigen(HBs Ag) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant "α" determinant of S protein are "hot spots" that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBs Ag or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare.     

乙型肝炎核心抗原为载体进行丙型肝炎混合性治疗疫苗的实验

目的 以HBcAg为载体进行丙型肝炎混合性治疗疫苗的实验研究。方法 利用DNA重组技术将HCVT表位（131～140位氨基酸）和（1445～1453位氨基酸）分别插入HBcAg el—loop处，构建病毒颗粒样抗原表达载体pTrc-core-T1和pTrc-core-T2，并在大肠埃希菌DH5α中表达，蔗糖密度梯度离心提取纯化表达产物HBcAg—T1和HBcAg—T2。以T1和T2表位肽混合物、HBcAg—T1和HBcAg-T2混合蛋白免疫Balb／C小鼠，并设空白对照，适时行抑瘤实验；流式细胞仪检测CD4^＋、CD8^＋、IL-4及IFN-γ、IL-5，ELISA法检测IL-12；并行细胞杀伤实验，以观察混合蛋白的免疫原性。结果 PCR法鉴定质粒pTrc—core—T1和pTrc—core—T2正确。抑瘤实验中HBcAg—T1和HBcAg—T2混合蛋白免疫组仅1只小鼠形成瘤块，直径0．1cm，低于对照组的平均直径1．3cm、T1T2混合肽免疫组的0．9cm；混合蛋白免疫组脾细胞内CD8^＋T细胞占（20．21±2．01）％，高于混合肽免疫组的（15．33±1．45）％和空白对照组的（5．09±1．66）％（P〈0．01）；3组内脾细胞内IFN-γ阳性细胞百分比分别为（1．58±0．05）％、（0．88±0．02）％和（0．53±0．03）％（P〈0．01）；血清中IL-5较混合表位肽组有所下降（P〈0．01）；而ELISA检测混合蛋白组IL-12高于T1T2混合表位肽免疫组；混合蛋白免疫组小鼠HCV特异细胞毒性T淋巴细胞（CTL）活性明显高于T1T2混合表位肽免疫组（P〈0．01）。结论 HBcA乎T1和HBcAg～T2混合蛋白诱导出高水平的细胞免疫应答，可作为HCV治疗性疫苗的候选。     

Progressive and sufficient decrease of hepatitis B core antibody can predict the disappearance of hepatitis B virus DNA in Japanese patients with hepatitis B surface antigen clearance

The aim of this study was to elucidate the relationships among serum levels of hepatitis B virus (HBV) DNA, periods after hepatitis B surface (HBs) antigen clearance, and the titer of hepatitis B core (HBc) antibody in 200-fold diluted serum. Twelve patients who had clearance of HBs antigen from serum were studied. Five patients had not received any treatment (group A), and seven had received prednisolone withdrawal therapy. The patients in groups A and B were followed up for 86 months and 108 months (median), respectively. Serum HBV was measured by the nested polymerase chain reaction method. In both groups, serum HBV tended to become gradually undetectable after HBs antigen clearance. The positive rate of HBV in the sera 5 years or more after HBs antigen clearance was significantly lower than that in the sera at less than 5 years, both in group A (P = 0.004) and group B (P = 0.010). In both groups, the titer of HBs tended to decline every year after HBs antigen clearance. HBV was still detectable in the sera of some patients for a long period of time after they showed seroconversion to HBs antibody. The results suggest that detection of HBV was difficult in sera with an HBc titer of 30% or lower and at more than 5 years after HBs antigen clearance in both groups. It is important to note that HBV DNA rarely exists in the serum, even when HBs antigen and HBc are both negative. Received: November 22, 1999 / Accepted: April 28, 2000     

新型乙型肝炎病毒核心区核酸疫苗的免疫原性研究

目的观察新型乙型肝炎病毒(HBV)核心抗原(HBcAg)核酸疫苗的免疫原性。方法应用新型人体应用载体质粒pSW389l构建HBcAg核酸疫苗(pSW3891／HBc)，对照组和实验组Balb／c小鼠分别以基因枪法免疫对照载体质粒(PSW3891)和HBcAg核酸疫苗，采用酶联免疫吸附试验检测抗HBc，乳酸脱氢酶(LDH)释放测定法检测小鼠HBcAg特异性cTL杀伤活性。结果HBcAg核酸疫苗可在体外293T细胞中高效表达，免疫小鼠后可产生高滴度抗HBc(1：97200)，免疫鼠脾细胞HBc特异性CTL杀伤活性达73．25％。结论新型HBcAg核酸疫苗在Balb／c小鼠实验中表现出良好的体液和细胞免疫原性。     

应用抑制性消减杂交技术筛选乙型肝炎病毒e抗原调节基因

目的 筛选与克隆HBeAg激活基因，了解其在体内的凋节功能线索。方法 以HBeAg表达质粒pcDNA3．1(-)-HBeAg转染HepG2细胞，以空载体pcDNA3．1(-)为平行对照，制备转染后的细胞裂解液，提取mRNA并逆转录为eDNA，经RsaⅠ酶切后，将实验组cDNA分成两组，分别与两种不同的接头衔接，再与对照组cDNA进行两次消减杂交及两次抑制性聚合酶链反应(PCR)，将产物与T／A载体连接，构建cDNA消减文库，并转染人肠杆菌进行文库扩增，随机挑选克隆PCR扩增后进行测序及同源性分析。结果 成功构建人HBeAg激活基因差异表达的cDNA消减文库。文库扩增后得到40个阳性克隆，进行菌落PCR分析，均得到200～800bp插入片段。对插入片段测序，并通过生物信息学分析获得其全长基因序列，结果共获得12种编码基因，包括11种已知基因和1种未知基因。结论 筛选到的cDNA全长序列，包括一些与细胞生长调节、信号转导、肿瘤免疫发生及物质代谢密切相关的蛋白编码基因，推测了HBeAg在体内可能存在的调控机制的线索，尚需进一步的实验证明。     

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg（＋） and HBeAg（-） patients

AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time poly...     

A review of strategies to prevent mother-to-infant transmission of hepatitis B virus infection

Hepatitis B virus (HBV) infection causes long-term, life-threatening liver diseases worldwide. HBV is transmitted through either the horizontal or mother-to-infant route, which is the major route of transmission in endemic areas. Administration of hepatitis B immunoglobulin and hepatitis B vaccine to newborns of infected mothers prevents mother-to-infant transmission. Implementation of a universal hepatitis B vaccination program has proven successful in eliminating the infection and related complications. Nevertheless, efforts are still needed to improve global coverage of the hepatitis B vaccine. Infants born to highly viremic mothers are still at risk of infection despite current immunoprophylaxis. An increasing number of reports have shown promising efficacy and safety profiles with the use of nucleoside/nucleotide analogues in highly viremic pregnant women to prevent mother-to-infant transmission.     

Induced immunity against hepatitis B virus

Prevention of hepatitis B virus (HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance of HBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination.     

HBsAg levels in HBeAg-positive chronic hepatitis B patients with different immune conditions

AIM:To investigate hepatitis B surface antigen(HBsAg)levels in patients with HBeAg-positive chronic hepatitis B(CHB)and different immune conditions.METHODS:HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study.These patients were grouped according to the following criteria:immune-tolerant patients,IT group;patients with a mild immune response in the immune clearance phase,IC-Mild group;and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure(ACLF),ACLF group.All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of2:2:1.Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus(HBV)DNA level were evaluated in these groups.RESULTS:In total,180 HBeAg-positive CHB patients[IT group(n=72),IC-Mild group(n=72),and ACLF group(n=36)]were enrolled in this study.The median serum HBsAg levels varied among the groups(P<0.001):IT,4.86 log10IU/mL;IC-Mild,3.97 log10IU/mL;and ACLF,3.57 log10IU/mL.Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group(r=0.60,P<0.001),but exhibited a weaker correlation in the IT(r=0.52,P<0.001)and ACLF groups(r=0.51,P=0.001).The ratio of HBsAg/HBV DNA did not differ significantly among the IT,IC-Mild,and ACLF groups(medians:0.56,0.55,and 0.56,respectively;P=0.179).CONCLUSION:Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions.These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients.     

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

AIM: To study the intrahepatic expression of hepatitis B surface antigen(HBs Ag) and hepatitis B core antigen(HBc Ag) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients(mean age of 40.3 ± 2.5 years), comprising of 14 HBe Ag positive and 19 HBe Ag negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma(mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBc Ag and HBs Ag was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBc Agand HBs Ag staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBe Ag negative patients, the HBe Ag positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBe Ag positive patients had intrahepatic HBc Ag staining; predominantly with "diffuse" distribution(79%) and "mixed cytoplasmic/nuclear " pattern(79%). In comparison, only 5% of the HBe Ag-negative patients had intrahepatic HBc Ag staining. However, the intrahepatic HBs Ag staining has wider distribution among the HBe Ag negative patients, namely; majority of the HBe Ag negative cases had "patchy" HBs Ag distribution compared to "rare" distribution among the HBe Ag positive cases. All but one patient with HCC were HBe Ag negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBc Ag and HBs Ag were seen in 13(100%) and 10(77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBc Ag and HBs Ag were detected in tumor tissues but not the adjacent liver in 4(44%) and 1(11%) patient respectively. CONCLUSION: Isolated intrahepatic HBc Ag and HBs Ag can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.     

Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection

Purpose  In patients chronically infected with hepatitis B virus, interferon has been used for the purpose of viral suppression by loss of hepatitis B e antigen (HBeAg) with or without seroconversion to antibody to HBeAg (anti-HBe). However, discussion about the effect of interferon on the development of hepatocellular carcinoma (HCC) has been controversial. Methods  We conducted a meta-analysis of published studies. Eight studies were retrieved (1,303 patients), including two randomized controlled trials (RCTs) and six non-RCTs (553 patients received interferon treatment). Results  The pooled estimate of the preventive effect of treatment was significantly in favor of interferon (risk difference −5.0%; 95% CI −9.4 to −0.5, P = 0.028). By subgroup analyses, the preventive effect of interferon treatment was shown in the Asian population (risk difference −8.5%; 95%CI −13.6 to −3.6, P = 0.0012), the population with the incidental rate of HCC ≥10% if untreted with interferon (risk difference −9.4%; 95%CI −14.2 to −4.6, P = 0.0001), and the population with the proportion of HBeAg-positive patients to the study population ≥70% (RD −6.0%; 95%CI −11.8 to −0.2, P = 0.043). However, the preventive effect of interferon was not shown in the European population, the population with a lower incidental rate of HCC if untreated with interferon, and the population with the lower proportion of HBeAg-positive patients to the study population. An evaluation using the Begg method indicated no evidence of publication bias. Conclusions  Interferon treatment is considered to restrain HCC development in patients with chronic hepatitis B virus infection, especially in HBeAg-positive Asians.     

血清HBsAg滴度监测对恩替卡韦治疗的HBeAg阳性慢性乙型肝炎患者应答反应的预测价值

目的探讨HBeAg阳性慢性乙型肝炎（CHB）患者血清HBsAg滴度的动态变化对恩替卡韦（ETV）治疗反应的预测价值。方法选择2011年1月～2012年1月在我肝病中心住院及门诊接受ETV（0.5mg/d）治疗的HBeAg阳性CHB患者78例,随访1年。于抗病毒治疗的0、3、6、9和12 m分别收集患者血清,采用化学发光法定量检测各时间点的HBsAg和HBeAg滴度;采用实时荧光定量PCR法检测血清HBV DNA载量;采用Pearson相关分析分析HBsAg与HBV DNA水平相关性,采用受试者工作特征曲线（ROC）预测患者的病毒学应答和确定最佳临界值。结果在78例患者中,69例（88.5%）患者发生病毒学应答（VR）,9例未发生病毒学应答;VR组患者基线ALT水平[（141.8±27.2）IU/ml]与未发生VR患者[（136.2±29.7）IU/ml]比,无统计学意义（t=0.27,P=0.793）;HBV DNA[（6.7±1.0）lg IU/ml]明显低于未发生VR患者[（7.6±0.8）lg IU/ml,t=-2.27,P=0.033];HBsAg滴度与未发生VR患者比,无统计学意义[（3.8±0.6）lg IU/ml对（4.0±0.4）lg IU/ml,t=-1.75,P=0.094）];HBsAg与HBV DNA水平呈正相关（r=0.45,P=0.02）;HBsAg在治疗开始的前3个月下降较快,3个月后下降较缓慢,从基线到治疗3个月时,VR组患者较未发生VR患者HBsAg下降更快[（0.3±0.2）lg IU/ml对（0.2±0.1）lg IU/ml,t=2.245,P=0.035）];在治疗3个月时,lg HBsAg滴度的ROC曲线下面积最大（AUC=0.840,P=0.005）,临界值为3.85 lg IU/ml的Youden指数最大（0.602）,其诊断敏感度为84.2%,特异度为78.7%。结论 ETV治疗3个月时lg HBsAg≤3.85 lg IU/ml可作为预测ETV治疗1年发生病毒学应答的指标。