Occult Hepatitis B Virus Infection in Japanese Chronic Hemodialysis Patients

We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti‐HBc) was determined by various chemiluminescent immunoassays. HBV‐DNA was quantified in patients positive for anti‐HBc using quantitative real‐time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg‐positive and 218 (20.9%) were anti‐HBc‐positive. All HBsAg‐positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg‐negative and anti‐HBc‐positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.     

慢性乙型肝炎病毒感染者家族隐匿性乙型肝炎病毒感染的调查

目的 了解慢性HBV感染者家族隐匿性HBV感染的发生率及其与HBV标志物、年龄和性别等的关系.方法 ELISA方法检测慢性HBV感染者家族成员的HBV血清学标志物,套式PCR法检测136例HBsAg阴性家族成员的血清HBV DNA,并将隐匿性HBV感染者和HBsAg、HBV DNA均阴性者分别作为试验组和对照组进行HBV标志物、年龄、性别和生物化学检测结果的比较.两组均数比较采用t检验.率的比较采用χ~2检验或Fisher确切概率法检验.结果 在52个慢性HBV感染者家族中共检测到92例HBsAg阳性者和136例HBsAg阴性者,其中15例为隐匿性HBV感染者,慢性HBV感染者家族HBsAg阳性率和隐匿性HBV感染的发生率分别为40.4%和11.0%,15例隐匿性HBV感染者中有7例抗-HBc阳性(χ~2=5.341,P=0.02),但隐匿性HBV感染的存在与年龄、性别等无关.结论 HBV感染存在家庭聚集现象,且在其家族中存在隐匿性HBV感染,并在抗-HBc阳性者中发生率较高.     

＂Anti-HBc alone＂ in human immunodeficiency virus-positive and immuno-suppressed lymphoma patients

Hepatitis B virus （HBV） infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen （anti-HBc）, which could produce protective antibody to hepatitis B surface antigen （anti-HBs）. With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or ＂anti-HBc alone＂. In the context of immunodeficient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in ＂anti-HBc alone＂ patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients With Isolated Hepatitis B Core Antibody: A Multicenter Study

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%–8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%–73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients: A Concept for Consideration

Hemodialysis patients potentially have an increased risk of infection with parenterally transmitted viral agents due to an impaired host immune response and multiple transfusion requirements. Viral hepatitis is considered as a problem for hemodialysis patients because 1.9% of all deaths among this population are related to the consequence of viral hepatitis. Hepatitis B virus (HBV) is one of the most important causes of transmitted infections by the parenteral route in hemodialysis patients. Occult HBV infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg), which harbors potential risk of HBV transmission through hemodialysis. There are conflicting reports on the prevalence of occult HBV infection (OBI) in hemodialysis patients. Considering the importance of occult HBV infection in hemodialysis patients and the growing evidence on this subject, the purpose of this review is to provide comprehensive information on OBI prevalence in hemodialysis patients and highlight the most important points in this issue.     

血液透析患者乙、丙、庚型肝炎病毒感染状况分析

目的 探讨血液透析病人（HDP）乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、庚型肝炎病毒（HGV）的感染状况、感染方式及预防措施。方法 对160例HDP及30例对照组定期预留血清,检测HBsAg、抗HBs、HBeAg、抗HBe 、抗HBc、HBV DNA、抗HCV、HCV RNA、抗HGV。结果 HDP的HCV、HGV感染率明显高于对照组（P＜0.01及P＜0.05）。HBV感染率高于对照组,但其差异显著性（P＞0.05）。血透加输血组肝炎病毒感染率明显高于单纯血透组（P＜0.01）。肝炎病毒感染率随透析时间的延长,感染率逐渐增高。结论 HDP HCV、HGV感染率高,其中输血是一重要因素,其次与血液透析本身的医源性感染有关。故应加强对献血员的筛选,尽量少输血,加强透析过程中的消毒隔离措施。     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

Occult hepatitis B virus infection and lamivudine-resistant mutations in isolates from renal patients undergoing hemodialysis

Background and Aims:  Patients undergoing hemodialysis are at risk of infection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). Occult HBV infection is usually associated with low levels of HBV and is frequently detected in HCV-infected patients. The aims of the present study were to compare the prevalence of occult HBV infection among anti-HCV-positive and anti-HCV-negative patients undergoing hemodialysis, and characterize the molecular patterns of HBV isolates from patients with occult infection.
Methods:  Serum samples from 100 patients negative for hepatitis B surface antigen undergoing hemodialysis, half of whom were positive for anti-HCV antibodies, were tested for the presence of HBV-DNA using semi-nested polymerase chain reaction (PCR). PCR products of the S gene were directly sequenced.
Results:  HBV-DNA was detected in 15 samples. There were no significant differences in HCV status, sex, age, time of dialysis, alanine aminotransferase levels or HBV serological markers between patients with or without occult HBV infection, with the exception of antibody to hepatitis B core antigen (anti-HBc)-only serological marker ( P  = 0.003). All six HBV isolates that could be sequenced were of genotype A/subgenotype A1. Four of these six HBV isolates contained mutations associated with lamivudine resistance in the DNA polymerase (two with L180M/M204V and two with rt173V/180M/204V) and a specific substitution (Y100C) in the HBV small surface protein.
Conclusions:  HBV isolates with the identified substitutions have the potential to spread silently by nosocomial transmission within the hemodialysis unit. These results have potential implications for the management of patients with occult HBV infection undergoing hemodialysis.     

Is Hepatitis C Virus Positivity a Contributing Factor to Occult Hepatitis B Virus Infection in Hemodialysis Patients?

Hepatitis B (HBV) infections continue to occur in adult hemodialysis units. Occult HBV infection (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive) may be a contributing factor in these patients. This study was designed to (1) investigate the prevalence of occult HBV infection in hemodialysis patients and (2) compare the prevalence of occult HBV infection among hepatitis C (HCV)-positive and HCV-negative hemodialysis patients. The study included 138 patients on chronic hemodialysis. Eighty-four patients were HCV positive and 54 were HCV negative. HBV DNA testing was performed by polymerase chain reaction. We also recorded general characteristics of the patients, duration of hemodialysis, and serum alanine aminotransferase and aspartate aminotransferase levels. Twenty-one (15.2%) of the 138 hemodialysis patients were HBV DNA positive. Nine (16.6%) of the 54 anti-HCV antibody negative hemodialysis patients were HBV DNA positive. Twelve (14.2%) of the 84 anti-HCV antibody positive patients were HBV DNA positive. The prevalence in anti-HCV Ab positive and negative hemodialysis patients were same (P > .05). Hemodialysis duration, demographic features, and biochemical parameters were not significantly different in patients with and without occult HBV infection in both HCV-positive and -negative hemodialysis patients (P > .05). HCV positivity is not a contributing factor to occult HBV infection in hemodialysis patients. None of the parameters tested help to distinguish patients with occult HBV infection from those who are HBV DNA negative.     

Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt

AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with     

唐山地区献血人群隐匿性乙型肝炎病毒感染分析

目的了解唐山地区无偿献血人群隐匿性乙型肝炎感染情况。方法用ELISA法检测无偿献血者的乙型肝炎血清标志物,对于HBsAg阴性样本,进行HBV核酸检测（NAT）,NAT阳性样本,用罗氏试剂确证HBV DNA载量。结果共检测116 741例血样,证实隐匿性乙型肝炎感染者35例,占总献血人数的0.29‰。其中97.1%隐匿性乙型肝炎感染者样本的HBV DNA滴度低于102IU/ml。在HBV DNA阳性人群中,抗-HBc阳性率较高,占81.5%,抗-HBs阳性或乙型肝炎病毒血清标志物全阴性也可检出HBV DNA分别占55.6%和22.9%。结论唐山地区献血人群中血清HBsAg阴性者存在一定比例的隐匿性HBV感染,其HBV病毒载量均较低,核酸检测能够提高HBV感染的检出率。     

Prevalence and time course of hepatitis B virus infection in patients with systemic lupus erythematosus under immunosuppressive therapy

Objective

To clarify the prevalence and time course of hepatitis B virus (HBV) infection in patients with systemic lupus erythematosus under immunosuppressive therapy.

Methods

We performed serological examination of 248 lupus patients to determine the presence of HBV, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). Serum HBV DNA levels were measured in HBsAg-positive patients or resolved HBV carriers (HBsAg-negative, anti-HBs-positive, and/or anti-HBc-positive). If possible, we repeatedly performed examination of markers of HBV infection in resolved carriers.

Results

Two (0.8 %) patients were positive for HBsAg. Among 41 (16.5 %) patients who were considered as resolved HBV carriers, 1 (2.4 %) showed serum HBV DNA, which indicated occult HBV infection. The mean age and positive rate of anti-double stranded DNA antibody were significantly higher in resolved carriers than in anti-HBs- and anti-HBc-negative patients. Repeated examination showed that the anti-HBs and anti-HBc titer decreased below the threshold in 4 resolved carriers.

Conclusions

The prevalence of resolved HBV carriers in Japanese lupus patients was 16.5 %. Among them, occult HBV infection and decrease in anti-HBs and anti-HBc titer were observed. These findings indicated that all lupus patients should undergo serological examination for HBV before treatment. If patients have already been treated, we must carefully monitor their liver function, even when all HBV markers are negative.     

Diagnostic strategy for occult hepatitis B virus infection

In 2008,the European Association for the study of the liver(EASL) defined occult hepatitis B virus infection (OBI) as thepresence of hepatitis B virus(HBV) DNA in the liver(with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen(HBsAg) negative by currently available assays.Several aspects of occult HBV infection are still poorly understood,including the definition itself and a standardized approach for laboratory-based detection,which is the purpose of this ...     

Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection, and its relation to disease severity. METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study. RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc. Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%) and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR. The test was positive in 3 of them (12%; occult HBV infection). CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.     

Lack of association between occult hepatitis B virus DNA viral load and aminotransferase levels in patients with hepatitis C virus-related chronic liver disease

BACKGROUND AND AIM: Occult hepatitis B virus (HBV) infection in hepatitis C virus (HCV)-infected patients might enhance the severity of chronic liver disease (CLD). To elucidate the correlation between occult HBV infection and the clinical course of HCV-related CLD, we evaluated whether the fluctuation of occult HBV-DNA directly affects the serum alanine aminotransferase (ALT) level. METHODS: Forty-one patients with HCV-related CLD who received regular outpatient treatment and 42 age-, sex-, and antibody to hepatitis B core antigen positivity-matched healthy volunteers were enrolled. Serum HBV-DNA was quantitatively detected using real-time detection polymerase chain reaction (RTD-PCR). Serial serum samples in three patients were measured for HBV-DNA, ALT and HCV core antigen. RESULTS: Hepatitis B virus DNA was amplified in eight of the HCV-related CLD patients (19.5%), which was significantly higher than that of healthy volunteers (2.4%). No significant difference between the genotype 1 HCV-related CLD group and the genotype 2 group was found. Based on the analyses using serial serum samples, the elevation of HBV-DNA did not occur before the ALT flares, but occurred at the same time or after the ALT flares. CONCLUSIONS: The prevalence of occult HBV infection of HCV-related CLD is significantly higher than that of control. Occult HBV infection has no influence on ALT flares among patients with HCV-related CLD.     

2005年康定县雅拉乡乙型病毒性肝炎血清流行病学调查

目的了解康定县雅拉乡1～59岁人群乙型病毒性肝炎病毒(HBV)感染状况,为乙肝防治提供依据。方法采用多阶段分层随机抽样的方法抽取康定县雅拉乡312名1～59岁人群进行问卷调查和血清学检测,利用ELISA方法检测乙肝病毒表面抗原(HBsAg),乙肝病毒表面抗体(Anti-HBs),乙肝病毒e抗原(HBeAg)和乙肝病毒e抗体(Anti-HBe),乙肝病毒核心抗体(Anti-HBc),检测。结果康定县雅拉乡1～59岁人群乙肝病毒表面抗原(HBsAg),乙肝病毒表面抗体(Anti-HBs),乙肝病毒核心抗原(HBcAg)经标化后阳性率分别为2.10%、21.65%和15.65%;男、女性人群HBcAg阳性率分别为4.27%、0;HBsAg阳性人群中,乙肝病毒e抗原阳性率为1.92%。结论康定县雅拉乡1～59岁人群HBsAg阳性率明显下降,提示提高乙肝疫苗的接种率是降低人群HBsAg阳性率的关健措施。     

Testing for hepatitis B infection in prospective chemotherapy patients:A retrospective study

AIM:To estimate hepatitis B virus (HBV) infection testing rate in cancer patients before chemotherapy with a focus on HBV reactivation.METHODS:A retrospective study was conducted from January 1,2009 to June 30,2010.Inclusion required that patients be na ve to cancer chemotherapy but have indications for it.Patients who did not receive chemotherapy for any reason were excluded.Important clinical information,such as the levels of HBV DNA and serological markers were collected.HBV reactivation was defined as an increase in serum HBV DNA to > 1 log higher than that of the pre-exacerbation baseline,or serum HBV DNA conversion from negative to positive.HBV DNA levels > 1000 copies/mL were defined as HBV DNA positive.The χ 2 or Fisher’s exacttest was used for analysis of categorized data.Multiple logistic regression analysis was used to estimate the odd ratio and 95%CI of the HBV screening rate.RESULTS:Of 6646 patients,5616 (84.5%) received chemotherapy.Only 17.1% of the cancer patients received pre-chemotherapy HBV testing (43.2% for hematological malignancies and 14.9% for solid tumors).Patients who had received rituximab therapy,had elevated aminotransferase levels,or had hematological malignancies were more likely to receive HBV testing.The prevalence of hepatitis B surface antigen (HBsAg) positivity was 13.4%.HBV reactivation (appearance of HBV DNA or an increase in HBV DNA levels by 1 log 10) was observed in 33.1% (53/160) of the patients after chemotherapy.Among patients without prophylactic antiviral therapy,the reactivation rate was 43.9% (43/98) in the solid tumor group.Two reactivation cases occurred in patients who were HBsAg negative,but positive for hepatitis B core antibody.HBV reactivation was more likely to occur in patients with lymphoma,high levels of HBV DNA,or hepatitis B e antigen,and in men.CONCLUSION:Less than 20% of patients received HBV testing before chemotherapy.HBV reactivation would have occurred in about 50% of infected patients with solid tumors without antiviral prophylaxis.     

Chemotherapy-related reactivation of hepatitis B infection: Updates in 2013

Hepatitis B reactivation is a potentially serious complication of anticancer chemotherapy, which occurs during and after therapy. This condition affects primarily hepatitis B surface antigen (HBsAg)-positive patients, but sometimes HBsAg-negative patients can be at risk, based only on evidence of past infection or occult infection with a low titer of detectable hepatitis B virus (HBV) DNA. The clinical outcomes vary with the different degrees of virologic and biochemical rebound, ranging from asymptomatic elevations in liver enzymes to hepatic failure and even death. Despite the remarkable advancement in the treatment of chronic hepatitis B over the past decade, proper strategies for the prevention and management of HBV reactivation remain elusive. Moreover, with the increasing use of rituximab in patients with lymphoma, HBV reactivation in occult or past infections has become increasingly problematic, especially in HBV-endemic regions. This review addresses the current knowledge on the clinical aspects and management of chemotherapy-related HBV reactivation, updates from recent reports, several unresolved issues and future perspectives.     

Hepatitis C virus core antigen testing: Role in diagnosis,disease monitoring and treatment

While hepatitis B virus(HBV)screening relies on hepatitis B surface antigen to confirm HBV infection since the early days of hepatitis B disease management,hepatitis C virus(HCV)infection screening is based on anti-HCV testing which does not discriminate active from past infection.Thus to confirm infection HCV RNA testing has been required;recently a HCV core antigen assay became widely commercially available which could serve to confirm infection.That assay is less sensitive than current HCV RNA assays,but as more than 50%of anti-HCV positive persons will be HCV core antigen positive,HCV core antigen testing can be a cost effective and reflex test to confirm HCV infection in anti-HCV positive individuals and will be easier as it can be applied on the same platform.For treatment monitoring,more data need to be generated,but the early data available at present suggest that HCV core antigen may be an alternative to HCV RNA monitoring.With direct antivirals,HCV core antigen could even be superior to HCV RNA testing,as direct antivirals might already prevent virus formation when HCV core antigen is still produced and thereby correlates better with eventual viral clearance.     

"Anti-HBc alone" in human immunodeficiency virus-positive and immuno-suppressed lymphoma patients

Hepatitis B virus (HBV) infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen (anti-HBc), which could produce protective antibody to hepatitis B surface antigen (anti-HBs). With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or "anti-HBc alone". In the context of immunodeficient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in "anti-HBc alone" patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.