Incidence of hepatitis B virus infection in young Chinese blood donors born after mandatory implementation of neonatal hepatitis B vaccination nationwide

This study was carried out to determine the incidence of hepatitis B virus (HBV) infection in the young generation born after mandatory implementation of hepatitis B vaccination since 1992. Repeat blood donors born between 1992 and 1997 were enrolled, who gave blood at least twice during the past 3 years. Donors were tested for HBV infection markers of HBsAg, anti‐HBc, anti‐HBs and viral DNA by immunoassays (EIAs) and nucleic acid tests (NAT). A total of 14 937 pre‐donation screening qualified young repeat donors aged 18‐23 years were tested with 9 (0.06%) being HBsAg by EIA and 10 (1:1494) HBV DNA positive by Ultrio NAT (10.4 IU/mL), respectively. HBV DNA was further detected in 1:192 (9/1732) anti‐HBc+ repeat donors with Ultrio Plus NAT (3.4 IU/mL). Most cases were identified as occult HBV infection (OBI). Of 14 937 repeat donors, 20.9% were anti‐HBc+ positive, while approximately 50% of 12 024 repeat donors were anti‐HBs negative or had levels <100 IU/L. HBsAg+ or OBI strains were classified as wild type of genotype B or genotype C. Incident HBV infection in repeat donors was approximately 1:18.5 person‐years (1.1%/year) but significantly less frequent in donors with confirmed HBV vaccination (2.4%‐3.3%) than those unsure of vaccination status (10.5%; P = .0023). Hepatitis B virus vaccination appears largely protective of HBV infection, but incidence of infections increases in young adults with mostly undetectable or low anti‐HBs or occasionally high anti‐HBs. A boost of hepatitis B vaccine for adolescents prior to age 18 years may reduce HBV infection, and implementation of more sensitive NAT in blood donation screening may improve HBV safety in blood transfusion.     

A new method of concentrating hepatitis B virus (HBV) DNA and HBV surface antigen: an application of the method to the detection of occult HBV infection

Background The risk of post‐transfusion hepatitis B virus (HBV) infection has been reduced after the implementation of HBV nucleic acid amplification technology (NAT). However, the problem of HBV DNA‐positive and HBV surface antigen (HBsAg)‐negative occult HBV infections remains to be solved. This is in part due to the HBV DNA load being too low to detect these occult HBV infections using mini‐pool NAT. In Japan, the assay for the antibody against the HBV core antigen (anti‐HBc) has not completely excluded occult HBV infection. To solve this problem, we have developed a new method of concentrating HBV DNA and HBsAg simultaneously to increase the sensitivity of detection tests. Methods Virus concentration is achieved by the enhancement of the agglutination of viruses using poly‐L‐lysine in the presence of a bivalent metal. Poly‐L‐lysine‐coated magnetic beads are used to shorten the time of each step of the concentration procedure. Seventy‐seven anti‐HBc‐positive and HBsAg‐negative donations were examined. HBsAg and anti‐HBc were tested by enzyme immunoassay (EIA) (AxSYM; Abbott) and haemagglutination inhibition test (Japanese Red Cross), respectively. Results HBV surface antigen and HBV DNA levels were concentrated up to four‐ to sevenfold. Using this method, 35 of the 77 anti‐HBc‐positive and HBsAg‐negative donors were HBV DNA‐positive by individual NAT and a further five donors became HBV DNA‐positive by HBV concentration. Twenty‐seven of 40 occult HBV infections became HBsAg‐positive by HBsAg concentration. Conclusion Our new method of concentrating HBV and HBsAg increased the sensitivities of EIA and HBV NAT, and enabled us to detect 27 of 40 occult HBV infections by HBsAg EIA.     

Donor screening for hepatitis B virus infection in a cell and tissue bank

Abstract: Background and objectives. Hepatitis B virus (HBV) has been transmitted by tissue transplantation. In order to reduce the risk of HBV transmission, testing for antibody to HBV core antigen (anti‐HBc) is used in addition to testing for hepatitis B surface antigen (HBsAg) in many blood centers and tissue banks. Design and methods. We retrospectively analyzed the results of HBV assays in tissue donors. All tissue donors were tested for HBsAg and anti‐HBc. All anti‐HBc positive sera were tested for the antibody to HBsAg (anti‐HBs). From July 2006, an HBV nucleic acid testing (NAT) assay was also performed. Results. A total of 6855 tissue donors from January 1999 till July 2007 were tested for HBV assays: 4756 women and 2099 men. Positive HBsAg was found in 23 (0.36%) living donors, while no multiorgan or cord blood (CB) donor was found to be positive for HBsAg. Positive anti‐HBc was found in 80 multiorgan donors (12.94%), 599 living donors (17.84%), and 103 CB donors (3.57%) (P<0.005), while isolated anti‐HBc was found in 12 multiorgan (1.94%), in 126 living tissue donors (3.75%), and in 8 CB donors (0.28%). A total of 1310 donors were analyzed for single‐sample DNA HBV NAT assay. Discussion. We consider that anti‐HBc and NAT assays must both still be performed in addition to HBsAg assay for HBV screening in tissue donors. All these tests will be useful in order to define an algorithm for safe and efficient management of the tissue bank.     

Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections

Background The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion‐transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Study Design and Methods Post‐transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre‐transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre‐transfusion specimen was non‐reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti‐HBc titres or high anti‐HBc with high anti‐HBs titres. Results Transfusion‐transmitted HCV and HIV infections were not observed. One case of post‐transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451–41 841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty‐four anti‐HBc‐ and/or anti‐HBs‐reactive blood components were transfused to 52 patients non‐reactive for anti‐HBc or anti‐HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). Conclusion This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.     

Transfusion‐transmitted hepatitis B virus (HBV) infection from an individual‐donation nucleic acid (ID‐NAT) non‐reactive donor

Lookback was initiated upon notification of an acute HBV infection in a repeat Irish donor, 108 days post‐donation. The donation screened non‐reactive by individual‐donation nucleic acid testing (ID‐NAT) using the Procleix Ultrio Elite multiplex assay and again when the archived sample was retested, but the discriminatory assay for HBV was reactive. The immunocompromised recipient of the implicated red cell component was tested 110 days post‐transfusion, revealing a HBV DNA viral load of 470 IU/ml. Genotype C2 sequences identical across two regions of the HBV genome were found in samples from the donor and recipient.     

De novo acute hepatitis B infection in a previously vaccinated liver transplant recipient due to a strain of HBV with a Met 133 Thr mutation in the “a” determinant

Abstract: De novo HBV infection post‐liver transplantation (LT) from an anti‐HBc seropositive donor rarely presents as acute failure. We report a 42‐year‐old Caucasian female, HBsAg and anti‐HBc seronegative, with primary biliary cirrhosis who received an allograft from a HBsAg negative, anti‐HBc seropositive donor. The patient, previously vaccinated years pre‐LT, was re‐vaccinated against HBV and 1 year post‐LT had an anti‐HBs titre of 256 IU/l. Two years post‐LT, elevated serum aminotransferases and worsening liver function with an INR of 2.0 developed. The HBsAg became positive, anti‐HBs undetectable and serum HBV‐DNA >2000 pg/ml by hybridisation assay. Liver biopsy revealed significant ballooning degeneration, piecemeal necrosis and positive immunostaining for HBsAg. Progressive liver failure developed followed by sepsis and terminal multi‐organ failure. Subsequent analysis of the predominant HBV strain revealed mutations in the “a” determinant: Met 133 Thr (codon change ATG to ACG) and Asn 131 Thr. Conclusion: Acute de novo HBV infection from an anti‐HBc sero‐positive donor may occur long after LT despite protective anti‐HBs titres post‐vaccination secondary to the emergence of “a” determinant mutated strains of HBV.     

Ultrio and Ultrio Plus non‐discriminating reactives: false reactives or not?

Background The low, fluctuating levels of DNA characteristic of occult hepatitis B infection make its detection by nucleic acid testing (NAT) a challenge. Methods Four year’s routine use of the Ultrio and Ultrio Plus assays in blood donations in New Zealand was analysed. Results 0·09% of donations tested with Ultrio and Ultrio Plus assays showed reactivity in the multiplex assay, but non‐reactivity in all three discriminatory assays and relevant mandatory serological assays (anti‐HIV, anti‐HCV, HBsAg). These donations were more likely to be anti‐HBc reactive (Ultrio, 13%; Ultrio Plus, 57%; random donors, 6·8%). Thirty‐four per cent of these anti‐HBc‐reactive donations were also reactive in either an alternate NAT assay or on repeat multiplex testing. Thirteen per cent of the donors of the discriminatory‐negative, anti‐HBc‐reactive donations who had given other Ultrio‐ or Ultrio Plus‐tested donations had at least one other multiplex reactive donation. Conclusion These findings suggest that their HBV DNA levels are around the assay’s limit of detection, that false reactivity cannot be presumed when a donor fails to discriminate and that caution should be applied when deciding whether to continue accepting donations from such donors.     

Tissue donation and virus safety: more nucleic acid amplification testing is needed

A. Pruss, G. Caspari, D.H. Krüger, J. Blümel, C.M. Nübling, L. Gürtler, W.H. Gerlich. Tissue donation and virus safety: more nucleic acid amplification testing is needed.
Transpl Infect Dis 2010: 12: 375–386. All rights reserved Abstract: In tissue and organ transplantation, it is of great importance to avoid the transmission of blood‐borne viruses to the recipient. While serologic testing for anti‐human immunodeficiency virus (HIV)‐1 and ‐2, anti‐hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), anti‐hepatitis B core antigen (HBc), and Treponema pallidum infection is mandatory, there is until now in most countries no explicit demand for nucleic acid amplification testing (NAT) to detect HIV, hepatitis B virus (HBV), and HCV infection. After a review of reports in the literature on viral transmission events, tissue‐specific issues, and manufacturing and inactivation procedures, we evaluated the significance of HIV, HCV, and HBV detection using NAT in donors of various types of tissues and compared our results with the experiences of blood banking organizations. There is a significant risk of HIV, HCV, and HBV transmission by musculoskeletal tissues because of their high blood content and the high donor–recipient ratio. If no effective virus inactivation procedure for musculoskeletal tissue is applied, donors should be screened using NAT for HIV, HCV, and HBV. Serologically screened cardiovascular tissue carries a very low risk of HIV, HCV, or HBV transmission. Nevertheless, because effective virus inactivation is impossible (retention of tissue morphology) and the donor–recipient ratio may be as high as 1:10, we concluded that NAT should be performed for HIV, HCV, and HBV as an additional safety measure. Although cornea allografts carry the lowest risk of transmitting HIV, HCV, and HBV owing to corneal physiology, morphology, and the epidemiology of corneal diseases, NAT for HCV should still be performed. If the NAT screening of a donor for HIV, HCV, and HBV is negative, quarantine storage of the donor tissue seems dispensable. In view of numerous synergistic effects with transfusion medicine, it would be advantageous for tissue banks to cooperate with blood bank laboratories in performing virological tests.     

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%.     

Hepatitis B virus blood screening: impact of nucleic amplification technology testing implementation on identifying hepatitis B surface antigen non-reactive window period and chronic infections

Background Despite improvements in hepatitis B surface antigen (HBsAg) test sensitivity, post‐transfusion hepatitis B virus (HBV) infection still occurs because HBsAg is undetectable during the early window phase (WP) of the infection, in the convalescence core window phase of the infection, or in serologically silent chronic hepatitis or in mutant forms of HBV. HBV‐DNA screening using high sensitivity nucleic amplification technology (NAT) assays has recently been introduced to reduce the residual risk of transmission of HBV by transfusion of blood components. Materials Over 1 year 75 063 donations were individually screened for HBV‐DNA by the Ultrio Procleix assay on the Tigris platform. The donations were collected in the Latium region, an area of the central Italy, and they accounted for the 40% of the total blood units collected in this area per year. The initial reactive samples were re‐tested and confirmed by the discriminatory HBV assay. Additional HBV serological markers were also performed. Suspected WP infections were followed‐up to monitor the development of the immune response. All HBV‐DNA‐positive donors were called back to check up their infectious status. Results The results of testing the 75 063 donations are: 33 donations HBsAg positive, 31 out of them HBV‐DNA‐positive and two HBV‐DNA negative; 22 donations HBsAg‐negative but HBV‐DNA positive with low viral load. Six of the 22 were found to be consistently HBV‐DNA reactive whereas the remaining 16 donations showed inconsistent results on multiple NAT retesting. One WP infection was confirmed by the follow‐up of the donor for 3 months following the index blood donation. Conclusions In the donor population of the Latium region, NAT screening has revealed a higher than expected number of donors who were HBsAg non‐reactive but HBV‐DNA‐positive with three donors showing HBV‐DNA as the only marker of infection. The adoption of genome screening has increased the safety of the blood supply and has also contributed to the protection of donor health by identifying either WP or clinically silent infections.     

Reduction of the risk of transfusion‐transmitted viral infection by nucleic acid amplification testing in the Western Cape of South Africa: a 5‐year review

Background and Objectives In October 2005, individual donation nucleic acid amplification testing (ID‐NAT) for HIV, HBV and HCV was introduced in the Western Cape Province of South Africa. After 5 years, the impact on HIV, HBV and HCV transmission risk was assessed. Materials and Methods A total of 649 745 donations were tested by ID‐NAT using the Ultrio assay on the Tigris instrument (Novartis Diagnostics) and for anti‐HIV, HBsAg and anti‐HCV (Abbott Prism). Initial reactive samples were repeated in duplicate. Discrepant repeat reactive samples were subjected to confirmatory assays. ID‐NAT nonrepeat reactive donations were further screened for occult HBV infection (OBI) by anti‐HBc assay. Results ID‐NAT yielded 6 HIV‐RNA‐positive donations in the anti‐HIV‐negative window period (WP) but only 2 were p24 Ag nonreactive (1:325 000). Mathematical modelling estimated a similar HIV transmission risk for lapsed and repeat donations, in the order of 3 per million. The WP risk for HBV was 13 per million. Eight acute (1:81 000) and 13 chronic OBI yield cases (1:50 000) were interdicted. There were significantly more anti‐HBc‐positive donors in the Ultrio initial reactive/nonrepeat reactive group (12%) than in an Ultrio nonreactive control group (6%). Conclusion ID‐NAT in the Western Cape Province of South Africa has contributed significantly to enhancing blood safety, particularly for HBV transmission risk and to a lesser extent for HIV. Anti‐HBc testing of NAT nonrepeat reactive donations seems useful in identifying a subgroup of donors with OBI who may be at risk of transmitting HBV.     

抗—HBs阳性不同血清学模式病毒学及临床意义分析

目的：通过对抗－HBs阳性不同血清学模式病毒学和临床意义的分析,了解抗－HBs阳性不同血清学模式特点,探讨其形成机理及抗－HBs的作用。方法：采用Abbott和PCR定量、PCR定性方法分别检测抗－HBs阳性不同血清学模式病人的HBV血清标志物和HBV DNA。结果：抗－HBs、抗－HBe、抗－HBc阳性组与其它模式组比较,其抗－HBs值显著升高（P＜0．05）;HBsAg、抗－HBs、HBeAg阳性组与其它模式组比较,其HBV DNA含量显著增高（P＜0．01）;定性检测HBV DNA阳性组与HBV DNA阴性组比较抗－HBs值,前者抗－HBs值显著降低（P＜0．05）;抗－HBs阳性不同血清学模式病人生化指标比较无显著性差异（P＞0．05）;抗－HBs阳性不同血清学模式病人比较其肝炎临床类型的构成有非常显著性差异（P＜0．005）：即抗－HBs、抗－HBe、抗－HBc阳性组主要表现为急性肝炎,HBsAg、抗－HBS、HBeAg阳性组与HBsAg、抗－HBs阳性组主要表现为慢性肝炎。结论：抗－HBs阳性时HBV处于复制水平,但并不标志HBV复制的停止,仅预示病人感染相和恢复相的动态消长过程。如抗－HBs水平不断提高,则感染相向稳定的恢复相发展。同时从肝功能损伤的程度及肝炎临床类型分析,提示抗－HBs引发的免疫效应最终使部分病人由感染相进入恢复相。     

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct‐acting antivirals

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct‐acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV‐RNA and HBV‐DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow‐up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV‐DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti‐HBc positive, 12 anti‐HBc/anti‐HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty‐seven patients (64.4%) were HCV‐RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg‐positive patients treated with NUCs remained HBV‐DNA negative, but three of four untreated patients showed an increase in HBV‐DNA of 2‐3 log without a biochemical flare and achieved HBV‐DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV‐DNA remained not detectable in all 37 anti‐HBc‐positive patients but in three of them (8.1%) HBV‐DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV‐coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre‐emptive therapy with NUCs should be considered in this setting. Anti‐HBc‐positive patients rarely reactivate HBV without clinical or virological outcomes.     

202例散发性成人急性乙型肝炎患者的流行病学特征和血清学变化

目的了解散发成人急性乙型肝炎(AHB)流行病学特征及其血清病毒标志物(HBV M)演变规律。方法以202例成人AHB患者为研究对象,收集患者流行病学资料并定期随访检测ALT、TBil、HBV DNA、HBV M及其定量,观察其动态变化,随访期为48周。计数资料采用非参数秩和检验,计量资料组间比较采用成组t检验,相关性分析采用Person检验。结果 AHB患者男性明显多于女性,平均(42.99±7.31)岁。微量血传播方式最多,占29.20%,异性性传播占17.33%,但高达48.02%的患者传播途径不明。就诊时仅49.01%的患者HBV DNA阳性。HBV DNA阳性组血清ALT平均值为(1973.2±445.3)U/L;阴性组为(1500.3±287.7)U/L,两者差异无统计学意义(t=1.852,P0.05);HBV DNA阳性组血清TBil平均值为(118.40±37.33)μmol/L;阴性组为(81.06±23.24)μmol/L,两者差异有统计学意义(t=2.765,P0.01)。初诊时HBV M呈现8种模式,以HBsAg、HBeAg、抗-HBc、抗-HBc IgM阳性和HBsAg、抗-HBe、抗-HBc、抗-HBc IgM阳性2种模式最多见,分别占39.11%和29.27%。资料完整的99例AHB患者HBV M动态观测显示:观测期内HBsAg阴转率为97.98%,平均阴转时间为2.5周;抗-HBs累计阳转率为83.84%;HBeAg阳性患者HBeAg阴转率为100.00%,全部于发病4周内阴转;在48周的随访期内抗-HBe阳转率为80.81%;血清抗-HBc始终为阳性。202例患者急性期HBsAg定量均低于200 ng/ml;急性期HBsAg定量水平与HBsAg阴转时间呈反比。结论经微量血传播及性接触传播已成为成人散发AHB的主要传播途径;HBV DNA快速清除和HBsAg、HBeAg快速血清学转换是成人散发AHB的显著特点;急性期HBsAg定量水平对判定AHB转归有一定意义,本文2例患者最终转化为慢性HBV感染。     

Evidence of protection against clinical and chronic hepatitis B infection 20 years after infant vaccination in a high endemicity region

Summary. Vaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg ?/+ and HBeAg ?/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0‐1‐2‐12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti‐HBs antibodies and serological markers of hepatitis B infection (anti‐HBc, HBsAg, and in selected cases HBeAg, anti‐HBe, HBV DNA). During the 20‐year follow‐up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti‐HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti‐HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long‐term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure. ( http://www.clinicaltrials.gov NCT00240500 and NCT00456625)     

The epidemiology of hepatitis B virus infection in women of reproductive age in highly endemic areas in China

We describe the epidemiology of hepatitis B virus (HBV) infection among women of reproductive age residing in areas of China that are highly endemic for chronic HBV, and provide evidence useful for decision‐makers to guide strategies for preventing mother‐to‐child transmission of HBV, and assess the impact of perinatal transmission PMTCT by projecting HBsAg prevalence trends without interventions. We conducted a cross‐sectional HBV serological survey of women, 15‐49 years of age, residing in Fujian, Guangdong, Guangxi and Hainan provinces. Demographic and other subject‐level data were collected in face‐to‐face interviews, after which we obtain blood specimens. Specimens were tested for HBV sero‐markers by ELISA (Beijing Wantai Biological Pharmacy), and HBV DNA was tested with PCR (Hunan Sansure Biotech). Weighted HBsAg and HBV (either HBsAg+ or anti‐HBc+ indicating either present or past infection) prevalences were 11.82% and 57.16%, respectively. Among the HBsAg‐positive women, 27% were also HBeAg positive. The proportion of individuals with HBV DNA loads >10⁵IU/mL declined with increasing age. Among HBsAg‐negative women, 0.9% had occult HBV infection. The prevalence of chronic HBV infection among reproductive women in these highly endemic provinces is high, posing a threat to maternal health and risk of mother‐to‐child transmission. Prevention of mother‐to‐child transmission remains critically important.     

Clinical, biochemical, immunological and virological profiles of, and differential diagnosis between, patients with acute hepatitis B and chronic hepatitis B with acute flare

Background and Aim: In areas with high or intermediate endemicity for chronic hepatitis B virus (HBV) infection, it is difficult to distinguish acute hepatitis B (AHB) from chronic hepatitis B with an acute flare (CHB‐AF) in patients whose prior history of HBV infection has been unknown. The present study aimed to screen laboratory parameters other than immunoglobulin M antibody to hepatitis B core antigen (IgM anti‐HBc) to discriminate between the two conditions. Methods: A retrospective and prospective study was conducted in patients first presenting clinically as HBV‐related acute hepatitis to sort out acute self‐limited hepatitis B (ASL‐HB). Then, clinical and laboratory profiles were compared between patients with ASL‐HB and CHB‐AF. Parameters closely associated with ASL‐HB were chosen to evaluate sensitivity, specificity, accuracy, positive predictive values and negative predictive values for diagnosing AHB. Results: There were significant differences between patients with ASL‐HB and CHB‐AF in relation to clinical and laboratory aspects, with many outstanding differences in levels of serum HBV‐DNA, hepatitis B e antigen (HBeAg) and alpha‐fetoprotein (AFP) as well as IgM anti‐HBc. In particular, there was a greater difference between the two groups in low levels of HBeAg (ratio of the optical density of the sample to the cut‐off value [S/CO] <20) than in negativity for HBeAg (42.7% and 13.5% vs 49.3% and 45.9%). 1:10 000 IgM anti‐HBc had a sensitivity and specificity of 96.2% and 93.1%, respectively, for predicting ASL‐HB. Combining it with AFP, HBeAg or HBV‐DNA could improve diagnostic power. A combination of IgM anti‐HBc, HBV‐DNA and HBeAg had a predictive value of 98.9% and a negative predictive value of 100.0%, similar to that of a combination of IgM anti‐HBc and HBV‐DNA. Adding AFP to the combinations of IgM anti‐HBc and HBV‐DNA or HBeAg could further heighten the positive predictive value. The positive predictive value and negative predictive value of the combination of IgM anti‐HBc, HBV‐DNA and AFP were both 100.0%. Conclusions: (i) There are significant differences with respect to clinical, biochemical, immunological and virological aspects between ASL‐HB and CHB‐AF. (ii) Of several diagnostic combinations, IgM anti‐HBc jointing HBV‐DNA is most effective and most practicable in distinguishing ASL‐HB from CHB‐AF. (iii) A low HBeAg level is more useful than negative HBeAg in differential diagnosis between ASL‐HB and CHB‐AF. (iv) In those patients with a high level of IgM anti‐HBc, serum AFP level >10× upper reference limit could rule out a probability of ASL‐HB.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

Evidence that anti-HBc but not HBV DNA testing may prevent some HBV transmission by transfusion

Blood donor screening for antibody to hepatitis B core antigen (anti-HBc) implemented in some countries as a surrogate marker for non-A, non-B hepatitis has been superseded by anti-HCV screening. To assess the value of anti-HBc screening for the detection of hepatitis B surface antigen-negative blood donations that might contain infectious HBV, HBV genomic detection and recipient testing were used. Blood donations were screened and confirmed by multiple anti-HBc assays. Donations containing isolated anti-HBc and those with anti-hepatitis B surface antigen (anti-HBs) level < 0.1 IU/ml were tested for the presence of HBV DNA. Recipients of previous donations from the corresponding donors during the previous 5 years were traced and tested for markers of HBV infection. Of 103 869 donations screened, 586 (0.56%) were anti-HBc positive, two of which contained HBsAg, and 413 (0.4%) had protective (>/= 0.1 IU/ml) levels of anti-HBs. Anti-HBs < 0.1 IU/ml was found in 102 of these donations (0.1%) and isolated anti-HBc in 69 (0.07%). No donations with isolated anti-HBc were HBV DNA confirmed positive. Of 278 recipients of previous donations from 171 donors at risk of HBV carriage, 12 had markers of HBV infection. Six recipients had other identified risk factors. An association with blood transfusion was considered probable in two and possible in four recipients. None of the six corresponding donors had detectable HBV DNA 6-40 months after the implicated donation. The frequency of HBV transmission by chronic carriers negative for hepatitis B surface antigen was estimated in this study to be 1 in 52,000 donations (CI 0.3-7.8/100,000) from HBsAg-negative donors. Such HBV infectious donations may not be detected by DNA amplification.     

Factors associated with isolated anti‐hepatitis B core antibody in HIV‐positive patients: impact of compromised immunity

Summary. In regions that are hyperendemic for chronic hepatitis B virus (HBV) infection, prevalence of and risk factors associated with isolated anti‐hepatitis B core antibody (anti‐HBc) in HIV‐positive patients are less well described. HIV‐positive patients who were tested for hepatitis B surface antigen (HBsAg), anti‐hepatitis B surface antibody (anti‐HBs) and anti‐HBc at designated hospitals for HIV care in Taiwan were included for analysis. HBV DNA was detected by real‐time polymerase chain reaction in patients with and without isolated anti‐HBc. Of 2351 HIV‐positive patients, 450 (19.1%) were HBsAg positive, 411 (17.5%) were anti‐HBc positive alone and 963 (41.0%) for both anti‐HBs and anti‐HBc. Compared with patients who were positive for both anti‐HBs and anti‐HBc, patients with isolated anti‐HBc were older, less likely to have anti‐hepatitis C virus antibody (anti‐HCV), had lower CD4 lymphocyte counts and higher plasma HIV RNA loads. Older age (adjusted odds ratio, 1.029; 95% confidence interval, 1.015–1.043) and CD4 <100 cells/μL (adjusted odds ratio, 1.524; 95% confidence interval, 1.025–2.265) were independently associated with isolated anti‐HBc by logistic regression, while presence of anti‐HCV and injecting drug use were not. HBV DNA was detectable in 8.3% of 277 patients with isolated anti‐HBc and 14.3% of 56 patients with both anti‐HBs and anti‐HBc (P = 0.160). In a country hyperendemic for HBV infection, HIV‐positive patients at older age and with CD4 <100 cells/μL were more likely to have isolated anti‐HBc, suggesting that compromised immunity plays a role in the presence of this marker.