Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. RESULTS: After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. CONCLUSIONS: Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.     

Isolated antibodies against the core antigen of hepatitis B virus in HIV-infected patients

The aim of this study was to describe the frequency and significance of isolated antibodies against the hepatitis B virus (HBV) core antigen (HBc) in 2185 HIV-infected patients of the Aquitaine Cohort. Antibodies against HBc were found in 372 subjects (17%). Patients with isolated anti-HBc antibodies were more frequently coinfected with hepatitis C virus (HCV) (58.2%) than those who were anti-HB surface (HBs) antibody positive (22.9%, P<0.001) and those who were dually reactive anti-HBs/anti-HBc antibody positive (27.3%, P<0.001). These results suggest interactions between HBV and HCV. As observed in patients not infected with HIV, the "anti-HBc-alone" serological profile could reflect essentially late immunity with undetectable anti-HBs antibodies. However, an occult HBV infection cannot be ruled out.     

Hepatitis B vaccination alone is not adequate for the categorizing of adult subjects with isolated anti-HBc

Abstract To evaluate the meaning of isolated antibody to hepatitis B core antigen (anti-HBc), 88 Chinese subjects with isolated anti-HBc received rescreening of hepatitis B virus (HBV) markers. Eighty (90.9%) of them were still positive for this antibody and 29 were also found to be positive for antibody to hepatitis B surface antigen (anti-HBs). The remaining 51 subjects (58.0%) were positive for anti-HBc alone; 50 of them received a four-dose schedule of hepatitis B (HB) vaccine. After the initial dose, only one vaccinee disclosed an amnestic anti-HBs response, that is, anti-HBs titre > 1000 miu/mL. Forty-five vaccinees completed the vaccination schedule and 44 (97.8%) had anti-HBs response. The anti-HBs responses in 25 of these vaccinees were compared with 25 age- and sex-matched normal susceptible vaccinees. The anti-HBs response rates in both groups were the same (96 vs 96%). However, the geometric mean titre was significantly lower in the vaccinees with isolated anti-HBc (512 mIU/mL vs 4688 mIU/mL, P < 0.001). Prevaccinated sera were available in 49 vaccinees with isolated anti-HBc for detection of antibody to hepatitis B e antigen (anti-HBe) and HBV DNA; 37 (75.5%) of them had one or two of these markers. As we regarded the rescreening of HBV markers, response to hepatitis B vaccination and presence or absence of anti-HBe and/or HBV DNA together for categorizing the 88 subjects with isolated anti-HBc, at least three-quarters of them had past infection of HBV. The subjects with false positive anti-HBc test were a minor group. We concluded that the presence or absence of amnestic anti-HBs response to HB vaccination is not a reliable indicator for categorizing subjects with isolated anti-HBc. Rescreening of HBV markers, with addition of anti-HBe and HBV DNA, may be helpful in determining the necessity of HB vaccination.     

Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen

Several recent reports have shown that hepatitis B virus (HBV) could be frequently transmitted to the recipients from donors who have antibodies to hepatitis B core antigen (anti-HBc) through liver transplantation. We provide here the molecular evidence of latent HBV infection accompanied with ongoing viral replication in the liver tissue of anti-HBc-positive healthy individuals. HBV DNA was detectable in 13 of 14 healthy donors who were positive for both anti-HBc and antibodies to hepatitis B surface antigen (anti-HBs), but in none of 3 who were positive for anti-HBs alone. The detected HBV genomes from these subjects included covalently closed circular DNA and pregenomic RNA, the replication intermediate of HBV. Notably, 5 of 7 cases tested were predominantly infected with wild type HBV strains without any mutations in the precore and core promoter regions under the presence of circulating antibody to hepatitis B e antigen. Interestingly, a predominant clone detected in one donor showed a 63-nucleotide deletion in the precore region including an encapsidation signal sequence. Our findings indicate that the majority of healthy individuals positive for anti-HBc, which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV accompanied by ongoing viral replication and few nucleotide mutations in the precore and core regions.     

The evolution of hepatitis B virus serological patterns and the clinical relevance of isolated antibodies to hepatitis B core antigen in HIV infected patients

BACKGROUND/AIMS: The evolution of hepatitis B virus (HBV) serological patterns and the clinical relevance of isolated anti-HBc pattern are not well established in HIV infected patients. METHODS: A cohort of 240 patients was followed for 6.9+/-3.4 years, with iterative HBV serologic assays performed (mean interval of 2.2 years). RESULTS: Five patients without HBV markers at baseline subsequently developed positive anti-HBs (incidence 0.66/100 patient-year), as did two patients with chronic HBs antigenemia (incidence 1.66/100 patient-year). Only one patient with isolated anti-HBc pattern developed HBs chronic antigenemia. Persistent isolated anti-HBc pattern was observed in 37 patients (13 with detectable blood HBV DNA) and was strongly associated with positive hepatitis C virus (HCV) viremia (hazard ratio=9.5, confidence interval 95%: 4.5-20.0, P<0.0001). Hepatic lesions were more severe in HCV infected patients with persistent isolated anti-HBc pattern than in those without (Knodell score 9.2+/-4.6 versus 6.7+/-5.0, P=0.04). In time updated analysis, this pattern was not associated with an increased risk of hepatotoxicity, by contrast with HCV infection or positive HBs antigenemia. CONCLUSIONS: In HIV infected patients, HBV serological status must be systematically and regularly assessed, and systematic HBV vaccination must be proposed in those without HBV marker. Isolated anti-HBc pattern must be considered in the management of hepatitis C, but not for antiretroviral therapy.     

Response to hepatitis B vaccine in HIV-1-positive subjects who test positive for isolated antibody to hepatitis B core antigen: implications for hepatitis B vaccine strategies

BACKGROUND: Whether human immunodeficiency virus type 1 (HIV-1)-positive subjects who test positive for isolated antibody to hepatitis B core antigen (anti-HBc) should be vaccinated with hepatitis B vaccine is not certain. Development of an anamnestic response after vaccination would suggest previous hepatitis B virus (HBV) infection, in which case vaccination is not necessary. METHODS: Sixty-nine HIV-1-positive subjects who tested negative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) received vaccination with standard hepatitis B vaccine. Twenty-nine subjects (42%) tested positive for anti-HBc, and 40 (58%) tested negative for anti-HBc. An anamnestic response was defined as an anti-HBs titer of >or=10 IU/L within 4 weeks of the first vaccination. RESULTS: The overall anamnestic response rate was 16% and was not significantly different between subjects who tested positive for anti-HBc (24%) and those who tested negative for anti-HBc (10%) before vaccination (P=.18). Approximately 50% of subjects who tested positive for anti-HBc also tested positive for antibody to hepatitis Be antigen (anti-HBe). The anamnestic response rate was higher in subjects who tested positive for both anti-HBc and anti-HBe (43%) than in subjects who tested positive for anti-HBc but negative for anti-HBe (7%) (P=.035). After a complete series of vaccinations, HIV-1/hepatitis C virus (HCV)-coinfected subjects were less likely to achieve high anti-HBs titers than were subjects infected with HIV-1 alone. CONCLUSIONS: After hepatitis B vaccination, the anamnestic response rate in HIV-1-positive subjects who tested positive for isolated anti-HBc but negative for anti-HBe was low and was comparable to that in subjects who tested negative for anti-HBc. This finding suggests that testing for anti-HBc alone may not be a reliable assessment of protection from HBV infection. HIV-1/HCV coinfection may be associated with impaired responses to hepatitis B vaccine, and evaluation of strategies to improve immunogenicity of the vaccine in such individuals is warranted.     

Increased exposure to hepatitis B virus infection in HIV-positive South African antenatal women

The prevalence of markers for hepatitis B virus (HBV) exposure and active infection in HIV-positive (n=710) and HIV-negative (n=710) pregnant South African women was investigated. The following statistically significant increases in the HIV-positive group were found: anti-hepatitis B core antigen (anti-HBc) (37.3% versus 28.6%; odds ratio [OR]: 1.49); anti-hepatitis B surface antigen (anti-HBs) (29.5% versus 20.1%; OR: 1.66); exposure based on hepatitis B surface antigen (HBsAg) and anti-HBc (39.2% versus 30.1%; OR: 1.49); and exposure based on anti-HBs, anti-HBc and HBsAg (37.1% versus 24.5%; OR: 1.82). However, there was no increase in active HBV infections, with 2.4% of the HIV positives and 2.2% of the HIV negatives being HBV DNA positive. Although the impact that HIV has had on the prevalence of HBV in this population group is not as pronounced as that found in areas of low endemicity (where up to seven-fold increases have been reported), there is a statistically significant increased exposure to HBV.     

Study of hepatitis B (HB) vaccine non-responsiveness among health care workers from an endemic area (Taiwan).

OBJECTIVE: To evaluate the etiology of non-responsiveness to hepatitis B (HB) vaccination in adults from an endemic area. METHODS: A total of 250 subjects who were HBsAg negative and anti-HBs<10 mIU/ml received three-dose HB-vaccine series. Anti-HBs 'negative' was defined as a level<1.5 mIU/ml. 'Weakly' positive was defined as 1.5-10 mIU/ml at pre-vaccination testing. Anti-HBs response was defined as a level >10 mIU/ml at post-vaccination testing. Among non-responders who were anti-HBc positive, serum anti-HBe and hepatitis B virus (HBV) DNA were tested. RESULTS: Three variables were associated with non-responsiveness by univariate analysis: anti-HBc positive, male gender, and age >40 years. Multivariate analysis additionally showed that anti-HBs negative was associated with non-responsiveness. Among 23 non-responders in anti-HBc positive subjects, post-vaccination serum was available in 16 subjects. HBV-DNA in all subjects was under detectable level by PCR assay. Anti-HBe positive were found in 13 of 16 subjects and were assumed to be occult HBV infection. CONCLUSION: Male gender, age >40 years and anti-HBc positive are associated with non-responsiveness to HB vaccination. Most of non-responders among anti-HBc positive subjects were assumed to be occult HBV infection. Subjects with weakly positive anti-HBs were associated with responsiveness which may be the effect of immune memory.     

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.     

Lack of occult hepatitis B virus infection among blood donors with isolated hepatitis B core antibody living in an HBV low prevalence region of Iran

BackgroundOccult hepatitis B virus (HBV) infection in blood donors is considered a potential threat for the safety of the blood supply, however conclusive studies on this issue are lacking. The aim of this study was to assess the occult HBV infection in blood donors with isolated hepatitis B core antibody (anti-HBc) living in the city of Arak, in the Central Province of Iran, as a low prevalence region for HBV.MethodsA total of 531 voluntary blood donors in Arak, Iran were included in this study. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), anti-HBc, and hepatitis C antibody (anti-HCV) were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of cases 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.ResultsOf 531 subjects enrolled in this study, 11 (2.1%, 95% confidence interval 0.8–3.2%) had isolated anti-HBc. HBV-DNA was not detected in any of the cases with isolated anti-HBc.ConclusionsOur study showed that all the blood donors with isolated anti-HBc were negative for HBV-DNA, and occult HBV infection did not occur in the blood donors of this low prevalence region for HBV infection.     

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.     

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.     

The response of isolated anti-HBc positive subjects to recombinant hepatitis B vaccine.

OBJECTIVE: The aim of this study was to evaluate the response to hepatitis B vaccination in isolated anti-HBc positive subjects. PATIENTS AND METHODS: Forty-eight subjects with persistent isolated core antibody were included in the study. Fifty healthy people who were negative for HBsAg, anti-HBs and anti-HBc were included in the study as a control group. They all were vaccinated with recombinant hepatitis B vaccine at 0, 1 and 2 months. RESULTS: Thirty days after each dose of vaccination, serum levels over 10IU/l of anti-HBs are found in 50% of the subjects with isolated anti-HBc after first; in 68.7% after second and in 89.6% after third vaccination. There were no statistical differences between the two groups (P > 0.05). Twenty subjects in isolated anti-HBc group (41.6%) but none of the subjects from the control group responded with a titer of > 50IU/l after 30 days, which suggested an anamnestic response due to prior infection and immunity. Furthermore, 23 subjects in isolated anti-HBc group (47.9%) finally responded after three doses of vaccination (anti-HBs titer > 10IU/l) thus excluding chronic infection and suggesting initial false positive results. CONCLUSIONS: In isolated anti-HBc subjects false positive results (primary response) or prior infection by HBV (anamnestic response) can be detected by anti-HBs response after HBV vaccination.     

Clinical significance of“anti-HBc alone” in human immunodeficiency virus-positive patients

AIM: To determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection ("anti-HBc alone") among human immunodeficiency virus (HIV) type-1 infected patients. Occult hepatitis B infection frequency was also evaluated.METHODS: Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus (HBV) infection were classified into three groups: past hepatitis, "anti-HBc alone" and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus (HCV) were performed on "anti-HBc alone" patients.RESULTS: One hundred and eighty seven (53.7%) HIV-positive patients had markers of HBV infection: 118 past infection (63.1%), 14 chronic hepatitis (7.5%) and 55 "anti-HBc alone" (29.4%). Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals (CI) 1.33-4.00] and antibodies to HCV infection [odds ratio (OR) 2.87; 95% CI 1.10-7.48] were factors independently associated with the "anti-HBc alone" pattern. No differences in liver disease frequency were detected between both groups.Serum levels of anti-HBs were not associated with HCV infection (nor viral replication or HCV genotype), or with HIV replication or CD4 level. No "anti-HBc alone" patient tested positive for HBV DNA.CONCLUSION: "Anti-HBc alone" prevalence in HIVpositive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury.     

＂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.     

"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.     

Diagnosis and management of hepatitis B virus and HIV coinfection

HIV and hepatitis B virus (HBV) coinfection increases HIV and HBV replication, hepatitis flares, and risk of progression to chronic HBV infection, cirrhosis, and hepatocellular carcinoma. HIV and HBV coinfection decreases frequency of hepatitis Be antibody (anti-HBe) and hepatitis B surface antibody (anti-HBs) seroconversion, increases risk of antiretroviral therapy-related hepatotoxicity, and reduces efficacy of HBV therapy. All newly diagnosed HIV patients should be screened for hepatitis A, B, and C viruses and vaccinated if not immune to hepatitis A or B viruses. HBV serology often is atypical in coinfection. Diagnosis of HBV coinfection in HIV infection is made on the basis of hepatitis B surface antigen (HBsAg)-positive, hepatitis B core antibody (anti-HBc total)-positive, anti-HBs-positive status. Alanine aminotransferase levels in coinfected patients often are not reliable markers of liver inflammation. HBV infection should always be treated if coinfected patients are receiving antiretroviral therapy, since immune reconstitution under antiretroviral therapy poses risk for immune-associated liver damage in these patients. This article summarizes a presentation on HIV and HBV coinfection made by Marion G. Peters, MD, at an International AIDS Society-USA Continuing Medical Education course in San Francisco in May 2007.     

Suboptimal response to hepatitis B vaccine in drug users.

Fifty-five drug users institutionalized in a community for drug detoxification were vaccinated against hepatitis B virus (HBV) with a recombinant yeast-derived vaccine (Engerix B, Smith Kline Biologicals, Belgium). At 0, 1, and 6 months, 20 micrograms of vaccine was given in the deltoid to these patients, of whom 17 had no serum HBV markers, 15 had only the antibody to core antigen (anti-HBc), and 23 had anti-HBc and antibody to the surface antigen (anti-HBs) values lower than the allegedly "protective" value of 10 mIU/mL. Forty-one healthy controls were vaccinated in parallel. At month 7 (ie, 1 month after the third dose of vaccine), in 76% (13/17) of drug users with no HBV markers, 6% (1/15) of those with isolated anti-HBc, and 69% (16/23) of those with anti-HBc and nonprotective anti-HBs, protective anti-HBs titers (greater than or equal to 10 mIU/mL) developed, compared with 97% (40/41) of controls. At month 24, these rates fell to 43% for drug users with no HBV marker, 0% for those with anti-HBc, 31% for those with anti-HBc and anti-HBs, and 86% for controls. The drug users who did not respond to vaccination were more likely to be those with evidence of prior HBV infection and anergy to skin tests. This indicates that unresponsiveness to hepatitis B vaccine in drug users may be due to altered immunity.     

Long-term immunogenicity and efficacy of universal hepatitis B virus vaccination in Taiwan

The long-term immunogenicity of universal hepatitis B virus (HBV) vaccine is seldom studied in large-scale prospective community-based populations, especially in adolescents. This study enrolled 1200 children aged 7 years with complete HBV immunization in infancy and determined HBV surface antigen (HBsAg), its antibody (anti-HBs), and HBV core antibody (anti-HBc) annually until the children were aged 14 years. Eleven children had new HBV infections with anti-HBc positivity as the only marker. None became positive for HBsAg or had detectable HBV DNA by polymerase chain reaction. The percentage of protective anti-HBs in 951 children without booster vaccination gradually decreased from 71.1% at age 7 years to 37.4% at age 12 years. Only 1 of the 200 children in the booster group and 2 of the 258 children in the nonbooster group developed new anti-HBc positivity. The results suggest that routine booster vaccination may not be required to provide protection against chronic HBV infection before age 15 years.     

Response to hepatitis B vaccine in HBsAg/anti-HBs negative and anti-HBc positive subjects

Some anti-HBc positive subjects have been encountered in the absence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs). The aim of this study was to evaluate the response to hepatitis B vaccination in such cases. A total of 33 subjects who were HBsAg and anti-HBs negative, anti-HBc positive, with normal serum aminotransferase levels were included in the study. A recombinant hepatitis B vaccine was administered to subjects. Sera samples were obtained 1 month after each vaccination and tested for anti-HBs. HBV DNA and HBeAg were not detected in any subject. Anti-HBs levels were measured above 10 > or = mIU/ml in 48.4% of cases after the first vaccination, 63.6% after the second vaccination and 90.9% after the third vaccination. Only 3 subjects (9.1%) lacked antibody response in spite of the 3-dose vaccination. In conclusion, preventive antibody levels were obtained after HBV vaccination in most of the HBsAg, anti-HBs negative, anti-HBc positive persons.