非活动性HBsAg携带者临床病理分析

目的 了解非活动性HBsAg携带者临床病理特点.方法 对80例患者进行生化、病毒标志物及病毒定量检测,并和肝脏病理进行相关性分析.结果 光镜下见肝组织基本正常者1例,病理诊断为慢性肝炎轻度者48例,中度以上者19例,占23.75%,活动性肝硬化者12例,占15%;抗Hbe阴性组纤维化程度要重于抗Hbe阳性组,其中大于S3的抗Hbe阴性组患者占总数的60%,阳性组为26%,但肝脏炎症程度与抗Hbe水平无关;血小板和胆碱酯酶对于代偿期肝硬化的诊断具有辅助价值.结论 对于非活动性HBsAg携带者应尽可能进行肝脏病理检查以明确诊断,并指导治疗.     

慢性HBsAg携带者及非活动性HBV感染状态的病理学研究

目的观察临床诊断为慢性HBsAg携带者及病理诊断为非活动性HBV感染状态患者的临床病理特点。方法总结慢性HBsAg携带者41例、非活动性HBV感染状态患者65例的临床资料,通过HE、组织化学及免疫组织化学染色观察其肝穿刺组织切片的病理变化。结果慢性HBsAg携带者41例无明显异常的症状体征,各项肝功能检查基本正常;但肝穿组织病理检查仅有10例无明显病变,30例为轻度慢性乙型肝炎,1例为静止性肝硬化。非活动性HBV感染状态患者65例中,少数患者有较轻的肝功能异常改变;病理检查无明显炎症和纤维化。结论慢性HBsAg携带者主要是一组以轻度慢性乙型肝炎表现为主的患者,非活动性HBV感染状态患者也仅有轻度的肝功能异常;慢性HBsAg携带者及非活动性HBV感染状态是临床医师和病理医师对同一类病变的不同诊断用词,对其诊断应结合临床和病理资料综合判断。     

聚乙二醇干扰素α治疗非活动性HBsAg携带者的疗效

目的 观察非活动性HBsAg携带者(IHC)经聚乙二醇干扰素α(Peg-IFN-α)治疗后HBsAg清除率及血清学转换率。方法 入组2019年1月至2021年12月就诊于深圳大学第三附属医院肝病门诊的IHC58例,根据患者治疗意愿分为治疗组(35例)和对照组(23例)。治疗组皮下注射Peg-IFN-α-2a或Peg-IFN-α-2b180μg/周,疗程为48周。对照组未给予抗病毒治疗。比较两组48周HBsAg清除率及血清学转换率,Logistic回归分析Peg-IFN-α治疗IHC发生HBsAg阴转的影响因素。结果 治疗组和对照组平均基线HBsAg水平分别为172.99U/ml和106.22U/ml。治疗48周,治疗组中40%(14/35)的IHC获得HBsAg清除,14.3%(5/35)患者获得HBsAg血清学转换,对照组中未观察到HBsAg的清除和血清学转换。治疗组HBsAg清除率和HBsAg血清学转换率明显高于对照组(P <0.05)。基线HBsAg水平、12周HBsAg降幅及24周HBsAg降幅是影响Peg-IFN-α治疗IHC发生HBsAg清除的独立影响因素。Peg-I...     

非活动性HBsAg携带者接受免疫抑制剂后致HBV再激活

病历摘要 患者女，36岁，HBsAg阳性10a，因乏力半月于2007年3月24日入院。患者于1997年3月查体发现HBsAg、抗HBe、抗HBc阳性，乙肝病毒（HBV）-DNA阴性，肝功能指标正常，B超示肝、胆、脾结构未见明显异常；后每6个月复查上述指标无变化。2004年7月因慢性肾功能衰竭开始血液透析治疗，每周2次。透析期间因贫血输全血1400ml，复查肝功能指标正常，HBsAg、抗HBe、抗HBc仍阳性。     

慢性HBV携带孕妇产后自发HBeAg和HBsAg血清清除或转换的病毒学因素分析

探讨影响慢性乙型肝炎病毒（HBV）携带孕妇产后自发HBeAg和HBsAg血清清除或转换的相关病毒学特征。方法2002年8月～2004年7月本院诊断的慢性HBV携带孕妇,自2009年10月～2010年3月间随访,检测HBV血清学标志和病毒相关特性。结果在本组419例慢性HBV携带孕妇中,经随访平均6.4年,失访155例。在接受随访的264例（63.0%）中,76例（28.8%）孕期在入组时HBeAg阳性,其中42例（55.3%）随访时发生自发HBeAg转换,这些孕妇孕期HBV DNA、HBeAg 和HBsAg均低于34例未转换组（P值均〈0.01）。在6例血清HBV DNA 〈1×106 IU/ml、17例HBeAg 〈700 S/CO和13例HBsAg 〈1×104 IU/ml孕妇中,随访时自发HBeAg转换分别高达100.0%、100.0%和92.3%。随访时,38例（14.4%）孕妇自发HBsAg清除,HBsAg清除组孕期HB-sAg水平明显低于226例未清除组（P〈0.001）。在25例血清HBsAg 〈100 IU/mL孕妇中,随访时56.0%自发HBsAg清除。结论外周血HBV DNA载量低（〈1×106 IU/ml）、HBeAg水平低（〈700 S/CO）或HBsAg水平低（〈1×104 IU/ml）是自发HBeAg血清转换的有利因素,而当HBsAg 〈100 IU/mL时,更易发生自发HBsAg血清清除。     

HBsAg携带者与HBeAg阴性慢性乙型肝炎患者病毒学特征的比较

目的了解非活动性HBsAg携带者（Inactive HBsAg carrier,HBsAg-IaC）和HBeAg阴性慢性乙型肝炎患者（e^--CHB）病毒学特点的异同。方法对连续收集的HBsAg-IaC（n=187）和e^--CHB（n=99）采用直接序列测定法检测G1896和核心基因启动子突变;结合聚合酶链反应-限制性片段长度多态性方法判断HBV基因型。结果113例HBsAg-IaC者血清HBVDNA阳性,其中103份完成前C区测序。HBsAg-IaC群体中HBV基因B型比例高于e^--CHB患者（84/113对46/99,P〈0.001）;HBsAg-IaC的G1896A突变比例高于e^--CHB（69/103对39/99,P〈0.001）,但A1762/G1764突变株比例低于后者（38/103对65/99,P〈0.001）。男性（OR=7.681,95%CI=2.693～20.992,P〈0.001）、年龄超过40岁（OR=24.421,95%CI=5.187～114.969,P〈0.001）、基因C型感染（OR=2.695,95%CI=1.240～5.859,P=0.012）以及A1762/G1764突变（OR=2.116,95%CI=1.012～4.425,P=0.046）是与e^--CHB相关的危险因素。结论HBsAg-IaC在病毒学特征上与e^--CHB明显不同;HBV基因C型感染、发生A1762/G1764突变、年龄大的男性HBsAg-IaC群体可能需要更多关注。     

血清BAFF预测聚乙二醇干扰素-α治疗非活动性HBsAg携带者临床治愈的效能分析*

目的 探讨血清B细胞活化因子(BAFF)预测聚乙二醇干扰素-α(Peg-IFN-α)治疗非活动性HBsAg携带者(IHCs)临床治愈的效能。方法 2018年1月～2020年8月我院诊治的IHCs 54例,给予Peg-IFN-α治疗48 w,再随访24 w。采用ELISA法检测血清BAFF,应用Logistic回归分析影响临床治愈的因素,应用受试者工作特征曲线(ROC)及其曲线下面积(AUC)评价血清BAFF预测临床治愈的效能。结果 在72 w末,24例(44.4%)患者获得临床治愈,30例未获得临床治愈;治愈组与未治愈组基线血清BAFF水平分别为(670.9±105.9)pg/mL和(612.7±183.8)pg/mL,差异无统计学意义(P>0.05);在治疗12 w和24 w时,治愈组血清BAFF水平分别为(805.8±197.6)pg/mL和(895.3±227.4)pg/mL,显著高于未治愈组【分别为(675.3±190.8)pg/mL和(724.4±218.0)pg/mL,P 均<0.05】;多因素Logistic回归分析显示基线HBsAg定量、HBV DNA<20 IU/mL、治疗12 w和24 w时血清BAFF水平是影响临床治愈的独立因素;ROC分析显示,以Peg-IFN-α治疗12 w时血清BAFF水平大于704.3 pg/mL为截断点,其预测治疗应答的AUC=0.722, 敏感度为79.2%,特异度为66.7%,以24 w时血清BAFF水平大于741.9 pg/mL为截断点,其预测治疗应答的AUC=0.725,敏感度为75.0%,特异度为70.0%。结论 应用Peg-IFN-α治疗IHCs可获得约40%的应答率,在治疗过程中监测血清BAFF水平逐渐升高的患者可能获得满意的治疗结果。     

成人急性乙型肝炎HBsAg转阴时间的相关因素分析

目的分析成人急性乙型肝炎(急性乙肝)患者HBsAg转阴时间的相关因素。方法收集2012年1月至2014年12月的急性乙型肝炎住院病例,按HBsAg转阴时间的长短分为HBsAg转阴时间较长组和较短组(对照组),比较两组在年龄、性别、起病时间、住院天数、有无长期大量饮酒、血常规、肝功能、乙型肝炎病毒血清学标志物、HBV DNA定量、国际标准化比值(INR)等方面有无差异,然后将有差异的指标做二元Logistic回归分析相关因素。结果 1.HBsAg转阴时间较长组的住院天数33.09±9.16 d、直接胆红素/总胆红素比例56.43±9.18%、总胆汁酸154.22±99.59μmol/L、HBsAg滴度log值3.18±1.37、HBeAg滴度log值1.32(-0.49~3.02)、HBV DNA定量1.50×10~4(0~1.17×107~)拷贝/mL均高于对照组,P0.05;2.HBsAg滴度log值是急性乙型肝炎患者HBsAg转阴时间的危险因素,OR值为3.028,P0.05。结论成人急性乙型肝炎患者HBsAg转阴时间取决于HBsAg滴度。     

非活动性HBsAg携带状态人群临床治愈进展

非活动性HBsAg携带状态(IHCs)人群基数庞大, 往往因疾病进展隐匿、病情较轻而被忽视。随着IHCs临床治愈的研究证据不断丰富和夯实, IHCs通过基于聚乙二醇干扰素α的治疗策略可获得较高的临床治愈率, IHCs人群的治疗意愿也更加强烈。现综述目前国内外指南对IHCs的定义及其治疗建议、IHCs的疾病进展情况及临床治愈研究进展, 为IHCs的科学管理和合理治疗提供参考和依据。     

HBsAg自然转阴的慢性HBV感染者临床特征

目的分析HBsAg自然转阴的慢性HBV感染者的临床特征。方法纳入2014年9月至2016年5月在延安大学附属医院感染病科门诊就诊以及住院的HBsAg已经自然转阴(通过化学发光法检测HBsAg0.05 IU/mL)的慢性HBV感染者85例。收集患者的一般资料(包括年龄、性别)、肝功能、腹部B超、乙型肝炎病毒定量、乙型肝炎血清标志物定量,并对所得各项数据进行统计分析。结果 85例HBsAg自然转阴的慢性HBV感染者中男性57例(67.1%),女性28例(32.9%)。年龄21~73岁,平均年龄(47.7±12.1)岁。抗-HBs与ALT、AST的Pearson直线相关系数分别为-0.013(P0.05)、-0.075(P0.05)。抗-HBc与ALT、AST的Pearson直线相关系数分别为0.190(P0.05)、-0.008(P0.05)。抗-HBc与HBsAg的Pearson直线相关系数为-0.559(P=0.000)。HBsAg转阴时年龄(≤50岁与50岁者)与不同病情患者例数的行×列表分析的χ~2为29.509(P=0.000)。结论抗-HBs与ALT、AST无相关性,即抗-HBs升高,不预示肝功能损伤;抗-HBc与ALT、AST无相关性,即抗-HBc升高,不预示肝功能损伤;抗-HBc升高,HBsAg下降,提示抗-HBc水平升高预示HBsAg转阴的可能性;50岁以前HBsAg转阴患者预后较50岁以后HBsAg转阴患者发生肝硬化、肝细胞癌(HCC)的几率小。     

Analysis of hepatitis B surface antigen (HBsAg) using high‐sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays

Aim

We investigated the utility of high‐sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays.

Methods

Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut‐off value, 0.05 IU/mL), the amount of HBsAg was re‐examined by high‐sensitivity HBsAg assays (cut‐off value, 0.005 IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high‐sensitivity HBsAg assay only were defined as discrepant cases.

Results

There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high‐sensitivity HBsAg assays was 0.005–0.056 IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti‐HBs contributed to the discrepancies between the two assays. Cumulative anti‐HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1 year, 3 years, and 5 years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1 year, and 36.8% and 95.7% at 3 years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases.

Conclusions

Re‐examination by high‐sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti‐HBs seroconversion rates and HBV‐DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion.     

Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance

There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg‐positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.     

Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

AIM: To examine the association between interferon(IFN) therapy and loss of hepatitis B surface antigen(HBs Ag) in inactive HBs Ag carriers. METHODS: This was a retrospective cohort study in inactive HBs Ag carriers, who were treatment-naive, with a serum HBs Ag level 100 IU/m L and an undetectable hepatitis B virus(HBV) DNA level( 100 IU/m L). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBs Ag, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen(65.0%) of 20 treated patients achieved HBs Ag loss, 12 of whom achieved HBs Ag seroconversion. Mean HBs Ag level in treated patients decreased to 6.69 ± 13.04 IU/m L after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/m L. Serum HBV DNA level remained undetectable( 100 IU/m L) in all treated patients during the study. HBs Ag level of the control group decreased from 25.72 ± 25.58 IU/m L at baseline to 17.11 ± 21.62 IU/m L at week 96(P = 0.108). In the control group, no patient experienced HBs Ag loss/seroconversion, and two(5.0%) developed HBV reactivation.CONCLUSION: IFN treatment results in HBs Ag loss and seroconversion in a considerable proportion of inactive HBs Ag carriers with low HBs Ag concentrations.     

Frequent delayed spontaneous seroclearance of hepatitis B virus after incident HBV infection among adult high‐risk groups

High rates (~25%) of developing chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg)‐positive for > 6 months following infection) have been observed in people who use drugs (PWUD) and men who have sex with men (MSM). We aimed to estimate the frequency of delayed HBsAg seroclearance, along with its determinants, and time to delayed HBsAg seroclearance. Data were used from MSM and PWUD enrolled in the Amsterdam Cohort Studies (1985‐2002) who had anti‐hepatitis B core antibody seroconversion. Potential determinants for standard HBsAg seroclearance, delayed HBsAg seroclearance and chronic HBV were examined using multinominal logistic regression. Time to HBsAg seroclearance was estimated using Kaplan‐Meier curves. A total of 147 incident HBV infections occurred during follow‐up. On initial HBsAg testing after infection (6‐12 months), 42 (29%) were HBsAg‐positive and 105 (71%) were HBsAg‐negative (‘standard HBsAg seroclearance’). Of the 42 initially HBsAg‐positive individuals, 22 subsequently tested HBsAg‐negative (of whom 7 (31.8%) were HBV DNA positive at last visit, suggesting occult HBV). Overall, 15 became HBsAg‐negative and HBV DNA‐negative (‘delayed HBsAg seroclearance’), while 27 remained HBsAg and/or HBV DNA‐positive (‘chronic HBV’). The 5‐year cumulative probability of delayed HBsAg seroclearance was 41.6% for initially HBsAg‐positive individuals. Delayed HBsAg seroclearance and remaining chronically infected were associated with younger age and HIV/hepatitis C virus (HCV)‐co‐infection. In conclusion, delayed HBsAg seroclearance is common in these key adult populations at‐risk for HBV, while proportion developing HBV chronicity (18%) is still higher compared to the general population (~5%). Given the proportion of individuals with occult HBV infection and that HCV direct‐acting antivirals can lead to HBV reactivation, HBV DNA testing in HCV co‐infected MSM/PWUD are warranted prior to treatment initiation.     

The HBV DNA cutoff value for discriminating patients with HBeAgnegative chronic hepatitis B from inactive carriers

Background

Patients with HBeAg-negative chronic hepatitis B (CHB) has a significantly different prognosis than inactive carriers; there is however, no reliable strategy for accurately differentiating these two disease conditions.

Objectives

To determine a strategy for discriminating patients with HBeAg-negative CHB from inactive carriers.

Materials and Methods

Consecutive inactive carriers (i.e. HBeAg-negativity, anti-HBe-positivity, normal ALT levels, and HBV DNA < 2000 IU/mL) were enrolled. HBV reactivation was defined as the elevation of the HBV DNA level to ≥ 2000 IU/mL. Patients were classified into true inactive carriers when their HBV DNA levels remained at < 2000 IU/mL or false inactive carriers when their HBV DNA levels increased to ≥ 2000 IU/mL during the first year.

Results

The Mean ± SD age of 208 inactive carriers (140 males) was 47.7 ± 12.6 years. The Mean ± SD serum ALT and HBV DNA levels were 22.8 ± 8.6 IU/L and 360 ± 482 IU/mL, respectively. HBV reactivation developed in 41 (19.7%) patients during the first year. Baseline HBV DNA and ALT levels differed significantly between true inactive and false inactive carriers. The AUROCs of the baseline ALT and HBV DNA levels for predicting a false inactive carrier were 0.609 and 0.831, respectively. HBV reactivation developed more often in patients with a baseline HBV DNA level of ≥ 200 IU/mL than in those with a baseline HBV DNA level of < 200 IU/mL during a Mean ± SD follow-up of 622 ± 199 days.

Conclusions

The HBV DNA level was useful for discriminating patients with HBeAg-negative CHB from true inactive carriers. The follow-up strategies applied to inactive carriers need to vary with their HBV DNA levels.     

Identification of a hepatitis B virus S gene mutant in lamivudine-treated patients experiencing HBsAg seroclearance

BACKGROUND & AIMS: Seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is a rare event in chronic hepatitis B patients receiving lamivudine therapy. It is generally believed to be a benevolent sign, implicating clearance of viremia. The aim of this study is to examine the authenticity of this dogma. METHODS: In a 5-year period, 11 patients treated with lamivudine experienced seroclearance of HBsAg. The clinical data were examined. The HBV S gene sequences derived from the patient's serum samples before and after seroclearance of HBsAg were analyzed. RESULTS: Serum HBV-DNA could be detected by nested polymerase chain reaction (PCR) in all 11 patients, by 1-step PCR in 8, and by Cobas Amplicor HBV-DNA test (>200 copies/mL) in 5. A mutation hot spot, P120A in the S gene, was identified in 6 of the 11 patients. Site-directed mutagenesis experiments indicated that the Ausria-II RIA test failed to detect this mutant. Decreased sensitivity of detection was also observed when other monoclonal antibodies were applied. CONCLUSIONS: Seroclearance of HBsAg during lamivudine therapy may not indicate viral clearance. Specifically, it may be caused by a point mutation in the S gene, which results in detection failure. In such patients, further verification and follow-up using a sensitive HBV-DNA test are advised.     

Relationship between polymorphisms near the IL28B gene and spontaneous HBsAg seroclearance: a systematic review and meta‐analysis

Polymorphisms near the interleukin (IL) 28B gene have been proposed to be associated with spontaneous clearance of the hepatitis C virus. The purpose of this study was to assess the relationship between IL28B polymorphisms and the rate of spontaneous hepatitis B surface antigen (HBsAg) seroclearance by means of meta‐analysis. MEDLINE/PubMed and EMBASE were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analyses were mainly performed according to ethnicity. A total of 4028 cases with persistent chronic hepatitis B and 2327 spontaneously recovered controls were included from 11 studies. The single nucleotide polymorphism (SNP), rs12979860, had no significant association with HBsAg seroclearance (OR = 0.98, 95% CI: 0.84–1.14 in the dominant model; OR = 1.00, 95% CI: 0.68–1.46 in the recessive model; and OR = 0.95, 95% CI: 0.82–1.09 in the allelic model). The SNP, rs12980275, had no significant association either (OR = 1.03, 95% CI: 0.84–1.26 in the dominant model; OR = 1.17, 95% CI: 0.46–2.96 in the recessive model; and OR = 1.04, 95% CI: 0.86–1.26 in the allelic model), nor did the SNP, rs8099917 (OR = 0.94, 95% CI: 0.77–1.15 in the dominant model; OR = 0.74, 95% CI: 0.34–1.62 in the recessive model; and OR = 0.93, 95% CI: 0.77–1.13 in the allelic model). Similarly, the results of subgroup analyses by ethnicity also showed no association in either the Asian group or non‐Asian group. We concluded that there was no significant association between common IL28B polymorphisms and the rate of spontaneous HBsAg seroclearance.