慢性乙型肝炎患者HBV血清标志物与HBV DNA的相关性分析

目的探讨慢性乙型肝炎患者HBV血清标志物(HBV serum markers,HBV-M)HBsAg、HBeAg、HBeAb、HBcAb和HBcAb IgM含量与HBV DNA水平的相关性,为临床诊断和治疗提供依据。方法采用化学发光微粒子免疫测定法和荧光定量聚合酶链反应分别检测446例慢性乙型肝炎(chronic hepatitis B,CHB)患者血清HBsAg、HBeAg、HBeAb、HBcAb含量和HBV DNA水平,同时检测54例HBcAb IgM阳性患者的血清HBV DNA水平,统计分析HBV-M含量与HBV DNA水平的相关性。结果①CHB患者血清中,HBsAg和HBeAg含量与HBV DNA水平呈正相关(P<0.05),HBeAb和HBcAb含量与HBV DNA水平未见相关性(P>0.05);②HBcAb IgM阳性患者中HBcAb IgM含量与HBV DNA水平亦未见相关性(P>0.05)。结论 CHB患者血清HBsAg和HBeAg含量与HBV DNA水平呈正相关。定量检测HBV-M和HBV DNA能更好地了解HBV的动态变化,对诊断和治疗有重要指导意义。     

132例HBeAg阳性HBsAg阴性的乙型肝炎患者HBV-M演变结果分析

目的:了解某些乙型肝炎患者HBsAg阴性,HBeAg阳性特殊感染模式的不稳定性,分析其产生的可能原因。方法:对符合主题的132例乙型肝炎患者,用ELISA法检测、复查血清乙肝病毒标志物(HBV-M)。结果:132例HBsAg阴性、HBeAg阳性患者入院时抗-HBc阳性123例、HBV DNA阳性65例(49.2％)。第1次复查有75例HBsAg转为阳性,16例抗HBs阳性、60例HBeAg阳性、65例抗HBe阳性、131例抗HBc阳性。第2次复查HBsAg阳性83例、抗-HBs阳性15例,HBeAg阳性78例、抗-Hbe阳性53例、抗-HBc阳性131例,HBV DNA阳性69例(52.27％)。结论:这种乙肝病毒感染的特殊模式很不稳定,大部分可以转变为HBsAg阳性,一小部分确也可以转变成抗-HBs阳性。     

36例急性乙型肝炎临床分析

目的通过临床分析,探讨急性乙型病毒性肝炎发病规律。方法总结36例急性乙型肝炎患者的肝功能损伤指标变化、HBV-M、HBV DNA在急性乙型肝炎病程中的变化规律。结果入组患者在HBV感染的早期,HBV DNA阳性占50%,呈中、低水平复制。HBsAg早期呈高滴度,逐渐下降,直至低于检测下限,抗-HBs随病程的延长滴度逐渐升高,HBeAg及抗-HBc变化规律同HBsAg,但时间上较HBsAg滞后。肝功能损伤与HBV-M及HBV DNA复制水平无关联。结论急性乙型肝炎早期即可有HBV清除发生,病原学指标在短期内可低于检测下限,了解HBV-M、HBV DNA在急性乙型肝炎病程中的变化规律对急性乙型肝炎的诊断、治疗及预后判断有重要意义。     

三种乙型肝炎病毒DNA定量聚合酶链反应试剂比较及其假阴性原因分析

乙型肝炎e抗原（HBeAg）是乙型肝炎病毒（HBV）复制的一个标志，乙型肝炎表面抗原（HBsAg）阳性、HBeAg阳性、抗-HBc阳性的患者体内HBV DNA亦较高。有报道所有该类标本均可检测到HBV DNA，且绝大部分（83．33％）的HBV DNA滴度高于10^6拷贝／ml。然而，我们在对临床标本进行HBV DNA定量检测中发现，相当一部分该类血清标本不能检测到HBV DNA或检测结果低于试剂盒检测下限。为了排除所用试剂盒缺陷造成的可能，我们对目前国内医疗机构常用的三种HBV DNA荧光定量聚合酶链反应（PCR）试剂进行了比较与分析。     

乙型肝炎病毒宫内感染的传播途径及早期诊断

目的分析羊水、脐带血、母血、胎盘等组织中乙型肝炎病毒标志物(HBV M)及HBV DNA与胎儿感染的关系，探讨HBV母婴传播机制。方法采用微粒子化学发光及核酸扩增杂交梳技术对65例血液乙型肝炎表面抗原(HBsAg)阳性不同孕龄孕妇的羊水、母血、脐带血进行HBV M和HBV DNA检测，对自然流产胎儿或死亡婴儿的胎盘、肝脏、心脏、肺脏进行免疫组织化学检测。结果65例血液HBsAg阳性，不同孕龄孕妇的羊水中HBsAg阳性率为21．50％，脐带血阳性率为20．00％；母血、羊水．脐带血HBsAg、乙型肝炎e抗原(HBeAg)、抗-HBc、HBV DNA均阳性者为6．15％；HBsAg、抗-HBc、抗-HBc阳性、HBV DNA阴性者占13．85％。对4例血液、羊水、脐带血HBsAg、HBeAg、抗-HBc、HBV DNA阳性孕妇分娩或自然流产后胎盘、胎儿及死亡婴儿的肝脏、肺脏、心脏进行免疫组织化学检测发现，胎盘各层组织镜下均可见到HBsAg、HBcAg阳性细胞；在肝脏、肺脏组织中可见到HBsAg、乙型肝炎核心抗原(HBcAg)阳性细胞，心肌组织内未见有HBsAg、HBcAg阳性细胞。结论胎儿感染HBV与羊水、胎盘中的病毒相平行；HBV在宫内可感染胎儿血液、肝脏、肺脏等组织；羊水检测HBV M及HBV DNA可作为胎儿早期HBV感染的诊断依据之一。     

前S1蛋白与病毒DNA和核心抗原对乙型肝炎病毒复制诊断的对比

目的 分析前S1(Pre-S1)蛋白在诊断慢性乙型病毒性肝炎病毒复制中的作用。 方法 收集慢性乙型病毒性肝炎患者共104例,均经肝活组织检查证实。检测其Pre S1蛋白,HBV标志物与HBV DNA。结果 HBsAg、HBeAg、抗-HBc阳性者29例,HBV DNA与Pre-S1蛋白的检出率均达96.5％,这组患者存在病毒的高复制。HBsAg、抗-HBe和抗-HBc阳性者65例,HBV DNA与Pre-S1蛋白的检出率分别为81.5％和72.3％;HBsAg和抗-HBc阳性者8例,HBV DNA与Pre-S1蛋白的检出率分别为87.5％、75.0％,说明部分HBeAg阴性而抗-HBe阳性/阴性的患者仍存在着病毒复制。以HBV DNA定量>103拷贝/ml为诊断标准,HBV DNA阳性患者HBeAg、Pre-S1蛋白的检出率分别为31.5％(28/89)、80.9％(72/89);两者与HBV DNA的总符合率分别为40.0％(42/104)、82.0％(85/104)。HBV DNA与HBeAg检出率差异有显著性(x2=53.397,P<0.001);HBV DNA与Pre-S1蛋白检出率差异无显著性。 结论Pre-S1蛋白较HBeAg更敏感的反映了HBV复制的情况。     

乙型肝炎患者血清HBV标志物与HBV DNA相关性分析

目的探讨乙型肝炎患者血清学标志(HBVM)与HBV DNA的关系。方法对257例乙型肝炎患者同时检测HBVM与HBV DNA。HBVM检测用EHSA法，HBV DNA检测用PCR法。根据不同检测结果进行对比分析。结果在HBsAg HBeAg HBcAb阳性的血清中HBV DNA阳性率和含量最高，血清HBeAg与HBV DNA含量密切相关，但部分HBeAg阴性或抗-HBe阳性患者也有较高的HBV DNA阳性率及含量。结论PCR定量检测HBV DNA含量更有助于判断体内HBV复制的情况及传染性强弱，在临床上有重要意义。     

项抗-HBc阳性患者预后的预测

部分HBV感染者的血清标志表现为单项抗-HBc阳性。过去认为这是HBsAg向抗-HBs转化的“窗口期”,约经3mo～6mo后出现抗-HBs。近来研究发现部分单项抗-HBc阳性患者可持续超过6mo,甚至再次出现HBsAg阳性。采用放射免疫法(RIA)和PCR等敏感的检测手段,一部分患者中尚能检出HBV DNA,HBsAg等HBV复制的血清标志。但目前尚不完全清楚HBV DNA检出与单项抗-HBc阳性持续存在或转变为HBsAg间的关系,以及HBV DNA及HBsAg对单项抗-HBc阳性患者预后是否具有预测作用。因而,我们进一步探讨单项抗-HBc患者HBV DNA检出情况以及与其转归的关系,找到早期预示预后不良指标,以便对预后不良患者及时进行相应治疗,从而改善其预后。     

HBsAg阴性/抗HBc阳性献血员HBV感染状况调查

目的 对431例HBsAg阴性献血员检测抗-HBc、抗-HBs,抗-HBc阳性者196例(45.5％),其中单项抗-HBc阳性者35例(17.9％),抗-HBc/抗-HBs阳性者161例(82.1％)。对抗-HBc阳性者检测抗-HBc IgM和HBV DNA(聚合酶链法),抗-HBc IgM的检出率为32.1％(63/196),其中抗-HBc/抗-HBs阳性者检出率为29.8％(48/161),单项抗-HBc阳性者检出率为42.9％(13/35),二者无差异;HBV DNA检出率为14.8％(29/196),单项抗-HBc阳性者HBV DNA检出率为25.7％,显著高于抗-HBs/抗-HBc阳性者(12.4％)(P<0.05);抗-HBc IgM阳性者HBV DNA检出率(39.7％)也显著高于抗-HBc IgM阴性者(3.0％)(P<0.001),二者阴阳性符合率则为78.6％(154/196)。HBsAg阴性/抗-HBc阳性献血员仍有传染性存在,尤以抗-HBc IgM阳性者最具血源传播HBV的危险性,因此,建议对HBsAg阴性献血员再进一步筛检抗-HBc IgM。     

HBsAg血清转换后乙型肝炎患者的临床与病理特点

目的 观察HBsAg阴转出现抗-HBs后,乙型肝炎患者的临床与病理学特征.方法 收集21例血清HBsAg阴转、出现抗-HBs的乙型肝炎患者,总结其临床特点,苏木精-伊红染色、Masson三色、Gomori网织纤维染色及HBsAg、HBcAg免疫组织化学染色分析肝穿刺组织病理形态特征.结果 21例乙型肝炎患者均有急性肝炎史,无肝炎家族史,血清抗-HBs、抗-HBe、抗-HBc阳性;其中2例血清HBV DNA检测阳性,分别为4.9×103和2.3×104拷贝/mL;组织学观察18例有轻度慢性炎性反应,15例有轻度纤维化;肝组织中HBsAg、HBcAg免疫组织化学染色均阴性.结论 发生HBsAg血清转换的乙型肝炎患者仍有肝脏炎性反应和纤维化,但病变较轻.     

Prevalence and clinical relevance of occult hepatitis B in the fibrosis progression and antiviral response to INF therapy in HIV-HCV-coinfected patients

Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies (HBcAb) and HBV DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. This situation has been frequently described in patients with chronic hepatitis C virus (HCV) infection. The objective of this study was to evaluate the prevalence of occult hepatitis B in HIV-HCV-coinfected patients and its clinical relevance in liver histology and viral response after interferon therapy for HCV. A total of 238 HIV-HCV-infected patients,negative for HBsAg, were included. Serum samples were analyzed for the presence of HBV DNA and HBcAb.HBV DNA quantification was determined with the Cobas TaqMan HBV Test (detection limit 6 IU/ml). Data from liver biopsy and laboratory tests were also analyzed. HBcAb resulted in 142 (60%) patients, being the independent associated factors: male gender, previous history of intravenous drug use, age, CD4 count,and HAV antibody presence. Among 90 HBcAb patients that we could analyze, HBV DNA was positive in 15 (16.7% of occult hepatitis B infection in this group, and 6.3% in the whole HIV-HCV cohort studied). No baseline factors, liver histology, or HCV therapy response were related to the presence of HBV DNA. We found that occult hepatitis B is a frequent condition present in at least 6.3% of our HCV-HIV patients and in more than 16% of those with HBcAb. Despite the high prevalence, this phenomenon does not seem to affect the clinical evolution of chronic hepatitis C or modify the viral response to interferon-based HCV therapies     

Correlation between Hepatitis delta virus infection and heptitis B virus serum markers

AIM: To analyse the correlation between HDV infection and HBV serum markers. METHODS: Patients who were positive for HBV serum markers were selected and HDV infection was examined in them. Blood donors were used as a control group. Both HDV infection and HBV serum markers were tested by enzyme-linked immunosorbent assay. RESULTS: HDV infection was detected in 40 of 289 patients who were positive for HBV serum markers. The overall positive rate of HDV infection was 13.8%. The positive rates of HDV infection in HBsAg(+) group, HBcAb(+) group and HBeAb(+) group were 17.6%, 18.8% and 25.2%, respectively, which were higher than that in HBeAg(+) group (10.9%), and none was detected in HBsAb(+) group. HDV infection appeared in HBsAg(+)HBcAb(+)HBeAb(+) patients with a positive rate of 26.2%, which was much higher than that in HBsAg(+)HBcAb(+)HBeAg(+) patients (10.9%). CONCLUSION: HDV coinfection is more frequent in HBsAg(+) HBcAb(+)HBeAb(+) patients than in BsAg(+)HBcAb(+)HBeAg(+) patients. HDV infection is not completely related with the speed and amount of HBV replication.     

乙型肝炎患者血清Pre-S-2抗原的意义

目的研究ＰｒｅＳ２抗原与乙型肝炎患者ＨＢＶ标记的关系．方法血清ＨＢｓＡｇ（＋），ＨＢｅＡｇ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者２６例，血清ＨＢｓＡｇ（＋），ＨＢｅＡｂ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者４７例及健康献血者２０例，血清用ＲＩＡ法检测ＰｒｅＳ２抗原及用ＰＣＲ法检测ＨＢＶＤＮＡ．结果血清ＨＢｓＡｇ（＋），ＨＢｅＡｇ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者２６例，ＰｒｅＳ２抗原与ＨＢＶＤＮＡ均阳性（１００％）；血清ＨＢｓＡｇ（＋），ＨＢｅＡｂ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者４７例，ＰｒｅＳ２抗原３０例阳性（６３８％），１７例阴性（３６２％），ＨＢＶＤＮＡ３２例阳性（６８１％），１５例阴性（３１９％），ＰｒｅＳ２抗原与ＨＢＶＤＮＡ均阳性２８例（５９６％），均阴性１４例（３００％）．健康献血者２０例，ＰｒｅＳ２抗原阳性１例（５０％），阴性１９例（９５０％），ＨＢＶＤＮＡ阳性２例（１００％），阴性１８例（８００％），ＰｒｅＳ２抗原及ＨＢＶＤＮＡ均阳性０例（０％），均阴性１８例（８００％）．结论ＰｒｅＳ２抗原可作为预测慢性乙型肝炎患者病情活动与传染的标志．     

乙型肝炎患者血清中HBcAg与HBV复制指标的关系

目的探讨乙型肝炎患者血清ＨＢｃＡｇ与ＨＢＶ复制指标的关系及临床意义．方法对３１１例乙型肝炎患者进行了ＨＢｃＡｇ检测，并同时进行酶联法乙肝五项、地高辛法ＨＢＶＤＮＡ检测，其中２３７例进行乙肝ＤＮＡ聚合酶（ＤＮＡＰ）检测．结果ＨＢｃＡｇ阳性组的ＨＢＶＤＮＡ检出率（７７６％），明显高于ＨＢｃＡｇ阴性组（３５５％，Ｐ＜００１）；在ＨＢｃＡｇ阴性组中，抗ＨＢｅ阳性者仍能检出２９９％（４４／１４７）ＨＢＶＤＮＡ者阳性；ＨＢｅＡｇ，ＨＢｃＡｇ均阳性者其ＨＢＶＤＮＡ和ＤＮＡＰ的检出率高达８５９％；其他依次为ＨＢｅＡｇ、抗ＨＢｅ和ＨＢｃＡｇ均阳性者７１４％，抗ＨＢｅ，ＨＢｃＡｇ阳性者６９２％，ＨＢｅＡｇ阳性，ＨＢｃＡｇ阴性者６８４％，抗ＨＢｅ阳性，ＨＢｃＡｇ阴性者２７６％．结论血清ＨＢＶＤＮＡ，ＤＮＡＰ，ＨＢｅＡｇ和ＨＢｃＡｇ均是反映乙肝病毒复制的敏感指标，抗ＨＢｅ的出现并不表示病毒复制停止，应参考其他病毒复制指标情况．各种指标的不同组合可以清楚地反映出患者体内病毒复制状况．     

慢性肝病患者乙肝病毒血清学标志物转换规律及其意义

目的探讨乙肝病毒血清学标志物（HBVM）在慢性肝病患者中的转换规律及临床意义。方法选择慢性肝病患者包括慢性病毒性乙型肝炎、慢性重型乙型肝炎、肝炎肝硬化和原发性肝癌患者183例,采用ELISA方法对HBVM（HBsAg、HBsAb、HBeAg、HBeAb和HBcAb）进行检测,采用荧光定量聚酶链反应法进行HBV DNA检测,将HBV DNA检测值进行对数转换行统计学分析。结果慢性肝病患者的HBVM共有3种模式：大三阳（L3PP：HB-sAg、HBeAg和HBcAb）、小三阳（S3PP：HBsAg、HBeAb和HBcAb）和小二阳（S2PP：HBsAg和HBcAb）。L3PP HBVDNA水平高于S3PP和S2PP（P〈0.01）。随着慢性肝病病情发展,L3PP阳性率呈下降趋势,S3PP和S2PP阳性率呈上升趋势（P均〈0.01）;不同临床类型的慢性肝病患者3种HBVM模式的分布存在统计学差异（P〈0.01）。结论 L3PP慢性肝病患者HBV DNA复制水平高于S3PP或S2PP模式。随着慢性肝病病情的进展,HBVM的模式可发生转换,HBeAg阴转,L2PP转为S3PP或S2PP。     

慢性乙型肝炎患者血清HBV DNA水平与HBsAg和HBeAg水平的相关性分析

目的探讨慢性乙型肝炎患者血清HBV DNA水平与HBsAg和HBeAg滴度的关系。方法在951例慢性乙型肝炎患者,采用FQ-PCR法和Abbott化学发光微粒子免疫分析技术分别测定血清HBV DNA水平及HBsAg和HBeAg滴度,分析HBV DNA水平与HBsAg和HBeAg滴度的相关性。结果在951例患者中,HBVDNA阳性率为53.83%(512/951);患者血清HBV DNA水平与HBsAg和HBeAg滴度呈正相关(rs=0.45和re=0.49,P<0.05);在HBV DNA水平≥7lg拷贝/毫升患者,血清HBsAg和HBeAg滴度高于HBV DNA为3～7lg拷贝/毫升患者,HBV DNA为3～7lg拷贝/毫升患者血清HBsAg和HBeAg滴度大于HBV DNA<3lg拷贝/毫升患者,差异均有统计学意义(P<0.05);将HBsAg分为<1000 IU/ml、1000～10000 IU/ml和≥10000 IU/ml3组,结果不同HBsAg滴度患者血清HBV DNA水平差异有统计学意义(P<0.05)。结论在血清HBV DNA≥7lg拷贝/毫升和HBsAg滴度≥10000 IU/mL患者,HBV DNA水平与HBsAg滴度呈正相关,在HBV DNA>3 lg拷贝/毫升患者,血清HBV DNA水平与HBeAg滴度呈正相关。     

High prevalence of occult hepatitis B in Baltimore injection drug users

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in a serum or liver in the absence of hepatitis B surface antigen (HBsAg). The prevalence and clinical correlates of occult hepatitis B remain incompletely defined. A cross-sectional study was performed to determine the prevalence of occult hepatitis B in a high-risk cohort composed of 188 injection drug users in Baltimore, Maryland. All individuals had chronic hepatitis C viral infections confirmed by RNA detection and liver biopsy. Serologic assays for HBsAg and core antibody (HBcAb) were performed. Serum HBV DNA was detected using the COBAS HBV AMPLICOR monitor assay (lower limit of detection, 200 HBV copies per milliliter) and a semi-nested polymerase chain reaction (PCR) assay (lower limit of detection, 15 HBV copies per milliliter). Although almost all individuals (96%) were anti-HBC positive, only 8 of 188 (4%) were HBsAg positive. Occult hepatitis B was not identified using the COBAS assay, but was found in 81 of 180 (45%) of individuals using semi-nested PCR. Of the 8 HBsAg positive individuals, HBV DNA was found in 1/8 using the COBAS assay and 6/8 using the nested PCR assay. Overall, liver disease was mild, with a median serum alanine aminotransferase (ALT) of 38 IU/L, median activity grade of 3/18, and median fibrosis stage of 1/6. No association was found between the serum AST (aspartate aminotransferase), activity grade, or stage of liver disease and the presence of occult hepatitis B. Serum ALT levels were slightly higher in patients without occult hepatitis B (46 vs. 35 IU/L), and the median years since first injection drug use was somewhat longer in those without occult hepatitis B (24 vs. 20 years). In conclusion, although further research is needed to assess its clinical significance, there is a high prevalence of occult HBV infection in this cohort of HCV-infected injection drug users.     

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population‐level analysis

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause‐specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01‐1.65) and HCC (HR: 1.64, 95% CI: 1.09‐2.49), but not liver‐related death (HR: 1.02, 95% CI: 0.80‐1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.     

乙型肝炎病毒核酸定量检测与临床的关系

目的：探讨血清HBV DNA水平与HBV标志（HBV M）表现模式，肝功能状态，肝内炎症的关系。方法：对219例排除甲，丙，丁和戊型肝炎病毒的混合与重叠感染患者中的HBsAg阳性的慢性乙型肝炎患者进行肝穿刺病理检查。HBV DNA定量采用荧光定量PCR分析系统，HBV M采用ELISA法。结果：血清HBV DNA水平与HBVM表现模式有关，HBsAg与HBeAg的存在影响HBV DNA水平变化。在HBsAg阳性患者中，HBV DNA水平与Scheuer分级无明显相关。血清谷丙转氨酶水平与HBV DNA水平无明显相关。结论HBeAg和HBV DNA有明显的相关，抗－HBe阳性者病毒未完全停止复制，只是复制水平降低。单抗HBe阳性，单抗HBc阳性，抗HBs阳性和抗HBc阳性未检出HBV DNA，肝内炎症活动程度与血清HBV DNA水平无明显关系。     

Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy

With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid‐containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.