Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine: A Phase 3 Randomized Clinical Trial.

Importance: There is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection. Objectives: To demonstrate manufacturing equivalence of a 3-antigen (3A) HBV vaccine, evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV vs single-antigen (1A) HBV after 2 and 3 vaccine doses, and compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines. Design, Setting, and Participants: This phase 3, double-blinded, randomized clinical trial included healthy adults aged 18 to 45 years randomized to 1 of three 3A-HBV groups or 1 control group receiving 1A-HBV. The trial was conducted at 37 community clinics and academic hospitals in Canada, Europe, the United Kingdom, and the United States between December 2017 and October 2019. Participants were followed up for 48 weeks after the first vaccination. Interventions: Intramuscular administration of 3A-HBV (10 µg) or 1A-HBV (20 µg) on days 0, 28, and 168. Main Outcomes and Measures: Geometric mean concentration (GMC) of serum hepatitis B surface antibodies (anti-HBs) and proportion of participants achieving seroprotection. Results: Of 2838 participants, 1638 (57.8%) were women, 2595 (91.5%) were White, and 161 (5.7%) were Black or African American. A total of 712 participants (25.1%) were randomized to the 1A-HBV group and 2126 (74.9%) to 3A-HBV. The mean (SD) age at informed consent was 33.5 (8.0) years. The study demonstrated 3A-HBV lot-to-lot consistency, as the 2-sided 95% CIs for each pairwise comparison for the anti-HBs GMC ratios were within 0.67 and 1.50 (eg, adjusted GMC ratio, lot A vs lot B: 0.82; 95% CI, 0.67-1.00; lot A vs lot C: 0.95; 95% CI, 0.78-1.15; lot B vs lot C: 1.16; 95% CI, 0.95-1.41). The SPR of the pooled 3A-HBV was noninferior to 1A-HBV and higher than 1A-HBV after 2 vaccinations at day 168 (90.4% [95% CI, 89.0%-91.8%] vs 51.6% [95% CI, 47.5%-55.6%]) and 3 vaccinations at day 196 (99.3% [95% CI, 98.7%-99.6%] vs 94.8% [95% CI, 92.7%-96.4%]). The mean GMC of anti-HBs with 3A-HBV was 7.9 times higher after 2 vaccinations at day 168 and 3.5 times higher after 3 vaccinations at day 196 compared with 1A-HBV (after 2 vaccinations, 3A-HBV: GMC, 118.7 mIU/mL; 95% CI, 108.0-129.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: GMC, 15.0 mIU/mL; 95% CI, 12.9-17.5 mIU/mL; SE, 1.0 mIU/mL; after 3 vaccinations, 3A-HBV: GMC, 5442.4 mIU/mL; 95% CI, 4967.0-5963.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: 1567.2 mIU/mL; 95% CI, 1338.0-1834.0 mIU/mL; SE, 1.0 mIU/mL). Rates of local and systemic reactogenicities were higher with 3A-HBV compared with 1A-HBV (local: 1805 of 2124 [85.0%] vs 469 of 712 [65.9%]; systemic: 1445 [68.0%] vs 428 [60.1%]). Vaccine discontinuation due to adverse events (AE) was uncommon, and serious AEs were infrequent, reported in 42 participants (2.0%) and 3 participants (0.4%) in the 3A-HBV and 1A-HBV groups, respectively. Conclusions and Relevance: In this study, consistently higher antibody concentrations and SPRs were found with 3A-HBV after 2 and 3 doses vs 1A-HBV in adults aged 18 to 45 years old. The safety and efficacy of 3A-HBV shows its usefulness for the prevention of hepatitis B in young healthy adults. Trial Registration: Clinicaltrials.gov Identifier: NCT03408730; EU Clinical Trials Number: 2017-001820-22.

Kinetics of Hepatitis B Core-Related Antigen and Anti-Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus-Hepatitis B Coinfection.

BACKGROUND: The aim of the current study was to describe the kinetics of quantified hepatitis B core-related antigen (qHBcrAg) and quantified anti-hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus. METHODS: Serum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6-12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves. RESULTS: During a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (-0.051 and -0.011 log10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33-.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08-2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg <6.5 log10 U/mL at month 24 (Se, 1; Sp, 0.58) and baseline qAnti-HBc ≥4.1 log10 Paul Ehrlich Institute units/mL (Se, 0.42; Sp, 0.81). CONCLUSIONS: In coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance.

¿Influye la vitamina D en los anticuerpos de superficie de la hepatitis B en pacientes no vacunados en hemodiálisis? / Does vitamin D influence hepatitis B surface antibodies in non-vaccinated patients on hemodialysis?

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Hepatitis B Antibody Level Falls after Initial Phage of Chemotherapy in Childhood Haematological Malignancy.

Hepatitis B virus (HBV) infection is a worldwide one of the major public health problem. Vaccination against HBV is highly effective at a very low cost. During treatment and for a variable period after completion of chemotherapy and radiotherapy children became immunosuppress. The main laboratory marker used to assess hepatitis B immunity is IgG antibody to the surface antigen (HBsAg). Surgical procedures and multiple blood transfusions increase the risk of hepatitis B virus infection in these immune suppressed patients. In Bangladesh, data are unavailable regarding prevalence of HBsAg in children with cancer and their protective immune status against hepatitis B virus while on treatment or after completion of chemotherapy. The results of this study may aid physicians in the development of evidence-based guidelines for revaccination of children with cancer during and after treatment with chemotherapy. This observational study was conducted from November 2013 to February 2015 in the department of Paediatric Haematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Children were recruited from both the inpatient and outpatient units of the department of Paediatric Hematology and Oncology at BSMMU. Blood specimens were collected from the children who were receiving inpatient and outpatient care from the department of Pediatric Hematology and Oncology, 2.0ml of venous blood was drawn and serum was separated and stored at -20°C until testing then HBV antibody titer was assayed at the department of Virology laboratory of BSMMU. A structured questionnaire was used for data collection. Among 28 children, 19(67.9%) were male and 9(32.1%) female, male female ratio 2.1:1. Among the 28 children, ALL was in 24(85.7%), NHL 3(10.7%), and APML 1(3.7%). Among 28 children, anti-HBs titer was more than 10mIU/ml in all patients. But six month after initiation of chemotherapy, 8(28.57%) patients had anti-HBs titer less than 10mIU/ml. Hepatitis B antibody titre level significantly reduced after 6 months chemotherapy in children with hematological malignancies.

Role of nucleoside/nucleotide analogues and low-dose hepatitis B immune globülin in prophylaxis of hepatitis B recurrence among cadaveric liver transplant recipients.

BACKGROUND/AIMS: Hepatitis B core antibody (HBcAb) positivity of the donor or the recipient may pose a risk of hepatitis B virus (HBV) reactivation following liver transplantation (LT). We retrospectively investigated patient survival and reactivation among recipients who were given low-dose Hepatitis B Immune Globulin (HBIG) plus antiviral agent (AV) versus AV only. MATERIALS AND METHODS: Records of cadaveric LT recipients, between 2013 and 2016, with positive Hepatitis B surface Antigen (HBsAg) and/or HBcAb and recipients who had received LT from HBcAb-positive donors were reviewed. Patient characteristics and clinical data were extracted. Donor variables were retrieved from the United Network of Organ Sharing (UNOS) database. HBIG (1560 IU/mL) Intravenous (IV) was intraoperatively administered with three daily doses. Entecavir 1 mg daily was also given. STATA was used for statistical analysis. RESULTS: There were 53 recipients; 39 (73.6%) were male with a median age of 59 y. HCV was the major indication in 30 (55.6%) patients. There were 28 recipients (52.8%) who received HBIG plus AV and 25 (47.2%) received AV only. The Model of End Stage Liver Disease (MELD) score between the groups were similar. Survival rates at 6, 12, and 24 months were 100% (n=53), 93.2% (n=44), and 100.0% (n=26), respectively. There was no reactivation; two recipients in the AV group and one in the HBIG plus AV group died within 12 months. CONCLUSION: This study supports the use of low-dose HBIG and AV for post-LT prophylaxis to be as effective as conventionally used high-dose HBIG (9600 IU) plus AV. Future prospective larger studies are warranted to examine the potential benefits of using AV alone without HBIG.

Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta-analysis.

Patients with resolved hepatitis B virus (HBV) infection who are treated for hematological malignancies remain at risk for HBV reactivation. Because of conflicting studies about whether the antibody to hepatitis B surface antigen (anti-HBs) protects against reactivation in patients with resolved infection (hepatitis B surface antigen negative) receiving chemotherapy for hematological malignancies, we conducted a meta-analysis to determine if anti-HBs reduces HBV reactivation risk. We sought English-language studies through March 1, 2016, in Medline and other sources that examined reactivation in patients with resolved HBV infection receiving chemotherapy for hematologic malignancies. The absolute risks and odds ratio (OR) of reactivation with versus without anti-HBs were estimated in random-effects model meta-analyses. In 20 studies involving 1,672 patients not receiving antiviral prophylaxis, the reactivation risk was 14% (95% confidence interval [CI] 9.4%-19%) in 388 patients who had antibodies to hepatitis B core antigen only versus 5.0% (95% CI 3.0%-7.0%) in 1,284 patients who also had anti-HBs. Anti-HBs reduced reactivation risk with a pooled OR of 0.21 (95% CI 0.14-0.32) versus patients with antibody to hepatitis B core antigen only. Similar results were found when limiting the analysis to rituximab chemotherapy (OR = 0.19, 95% CI 0.11-0.32) and lymphoma (OR = 0.18, 95% CI 0.11-0.28). CONCLUSION: In patients with resolved HBV receiving chemotherapy for hematological malignancies without antiviral prophylaxis, anti-HBs positivity is associated with a decreased risk of reactivation; HBV screening in this patient population should include the routine use of anti-HBs, and those who are anti-HBs-negative should receive antiviral prophylaxis. Future studies should examine the effect of anti-HBs serum titers, the potential role for booster vaccinations, and antiviral prophylaxis prior to chemotherapy in this patient population. (Hepatology 2017;66:379-388).

Hepatitis B virus reactivation or reinfection in a FEM-PrEP participant: a case report.

INTRODUCTION: The FEM-PrEP trial was a pre-exposure prophylaxis clinical trial to test the safety and efficacy of Truvada (tenofovir disoproxil fumarate and emtricitabine) in the prevention of human immunodeficiency virus infection. Because Truvada can suppress hepatitis B virus replication, and withdrawal of Truvada can cause hepatic flares in patients with chronic hepatitis B, pre-enrollment screening included serological screening for hepatitis B virus markers. Women with chronic infections were not enrolled in the trial. Women found to be unprotected against hepatitis B were enrolled and offered three doses of hepatitis B vaccine. Reinfection and reactivation of previously resolved hepatitis B virus infections have been documented in immunosuppressed individuals but not in healthy individuals. We present the case of a participant enrolled in the FEM-PrEP clinical trial with baseline evidence of immunity against hepatitis B virus who subsequently developed acute hepatitis B. CASE PRESENTATION: A 21-year-old Black non-pregnant woman was enrolled in the FEM-PrEP trial. She was human immunodeficiency virus-negative and a serological test for hepatitis B virus was negative. She had evidence of low levels of protection against hepatitis B virus and normal liver function. She had no hepatitis B vaccination history, thus it was concluded that she had post-infection immunity. At week 36 she presented with severely elevated liver enzyme levels that, upon further investigation, were a result of acute hepatitis B virus infection. The infection followed an asymptomatic course until full recovery of her liver enzymes a few weeks later. At study unblinding, the participant was found to be on the Truvada arm. Retrospective plasma drug level testing found low levels of study drugs from week 4. The participant remained human immunodeficiency virus-negative throughout the study. CONCLUSION: Hepatitis B virus infection reactivation or reinfection is a rare phenomenon in healthy individuals. However, reactivations have been reported in patients being treated for chronic hepatitis B with the drugs contained in Truvada, after treatment had been withdrawn. This participant may have reactivated after stopping Truvada, or she may have reactivated spontaneously owing to relatively low levels of protective antibodies against hepatitis B. Alternatively, she may have been reinfected. Clinicians should be aware that hepatitis B virus reactivation or reinfection may cause elevated transaminases even in the presence of low baseline immunity.

Antibody responses after hepatitis B vaccination among maintenance haemodialysis patients.

In haemodialysis patients, hepatitis B virus infection has higher mortality and is more likely to result in the carrier state. Although Hepatitis B vaccine is effective in producing protection against HBV infection, the antibody response may be variable. In this study, seroprotection rate of hepatitis B vaccine in maintenance haemodialysis patients was studied after primary vaccination and after completion of the full vaccine regime. 50 unvaccinated patients on maintenance haemodialysis were included in this study. Patients negative for HBsAg, Anti-HBc (total) and Anti-HCV were vaccinated with 40 microg of Engerix B following a schedule of 0, 1, and 2 months. The antibody titer was tested at 3rd month and if the titer was < 10 or between 10-100 mIU/ml, they were given another 4th dose of vaccine at 6th month, and their antibody titer was tested again at 7th month. In maintenance haemodialysis patients, the response rate to HBV vaccine was 44% after the primary vaccination and 80% after completion of the full vaccine regime.

Effects of oral levamisole as an adjuvant to hepatitis B vaccine in adults with end-stage renal disease: a meta-analysis of controlled clinical trials.

BACKGROUND: Many patients receiving long-term dialysis do not produce protective antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) after HBV vaccination. The results from several studies have suggested benefit of oral levamisole as an adjuvant to HBV vaccination in patients with end-stage renal disease (ESRD). However, reliable information is still lacking. OBJECTIVE: This meta-analysis assessed the efficacy and safety profile of oral levamisole as an adjuvant to HBV vaccine in patients with ESRD. METHODS: This meta-analysis included prospective controlled clinical trials identified using literature searches of MEDLINE, SCOPUS, Institute for Scientific Information bibliographic database, and Cochrane Collaboration's Central Register of Controlled Clinical Trials for controlled clinical trials that weighted the seroprotection rate in patients with ESRD who received oral levamisole + HBV vaccine versus those who received the HBV vaccine alone (control). The fixed-effects Mantel-Haenszel model was applied with the heterogeneity and sensitivity analyses. The response rate, defined as the proportion of patients with seroprotective concentrations of antibodies to HBsAg (>10 mIU/mL) at completion and 6 to 10 months after completion of the HBV vaccine schedule, was the end point of interest and was also analyzed separately. For the tolerability assessment, studies that reported dose reduction, levamisole discontinuation, and their adverse effects including laboratory abnormalities were included. RESULTS: The literature search identified 4 studies that fulfilled the inclusion criteria (328 patients). The mean ages of the patients in these studies ranged from 41 to 53 years, and sex distribution ranged from 52.6% to 68.0% male. Twenty-two patients received oral levamisole 100 mg/d for 12 days (from 6 days before to 6 days after each vaccination). A total of 106 patients received oral levamisole 80 to 120 mg for 4 to 6 months. Aggregation of study results suggested a significant increase in response rate in the group that received levamisole + HBV vaccine compared with the control group (pooled odds ratio [OR] = 2.77 [95% CI, 1.56-4.94]) after completion and 6 to 10 months after the vaccination period (pooled OR = 3.96 [95% CI, 1.71-9.18]). The test of heterogeneity was not statistically significant in either group. Five patients underwent dose reduction due to mild adverse events. In one trial, 3 patients died, 1 of whom was receiving levamisole; however, the authors did not provide the causes of death. No other serious adverse events were reported with levamisole administration. CONCLUSION: The results from this meta-analysis suggest significant benefit in the administration of levamisole as an adjuvant to HBV vaccine to increase seroprotection in patients with ESRD.

Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients.

INTRODUCTION: Reactivation of hepatitis B virus (HBV) infection in patients with past infection has been described in 5% to 10% of individuals undergoing immunosuppressive therapies. No data are available to date on the outcome of patients treated by tumour necrosis factor-alpha (TNFalpha) inhibitors for chronic arthritis with a serological pattern of past HBV infection. The aim of our study was to monitor HBV markers in HBV surface antigen (HBsAg)-negative/anti-HBcAb-positive patients treated with a TNFalpha inhibitor for inflammatory arthritides. METHODS: Twenty-one HBsAg-negative/anti-HBcAb-positive patients were included. HBV serological patterns were compared with those determined before starting TNFalpha inhibitors. Serum HBV DNA testing by polymerase chain reaction was additionally performed. Spearman correlation analysis was used and P < 0.05 was chosen as the significance threshold. RESULTS: Before starting therapy, mean anti-HBsAb titre was 725 IU/L, no patient had an anti-HBsAb titre <10 IU/L, and 18 patients had an anti-HBsAb >100 IU/L. At a mean time of 27.2 months following therapy introduction, mean anti-HBsAb titre was 675 IU/L and anti-HBsAb titre remained >100 IU/L in 17 patients. There was a strong correlation between the first and second anti-HBsAb titres (r = 0.98, P = 0.013). Moreover, no patient had an anti-HBsAb titre below 10 IU/L or HBV reactivation (HBsAg seroreversion or positive HBV DNA detection). However, the anti-HBsAb titre decreased by more than 30% in 6 patients. The mean anti-HBsAb titre at baseline was significantly lower (P = 0.006) and the mean duration of anti-TNFalpha therapy, although non-significant (P = 0.09), was longer in these six patients as compared to patients without a decrease in anti-HBsAb titre. CONCLUSIONS: Anti-TNFalpha treatments are likely to be safe in patients with past hepatitis B serological pattern. However, the significant decrease of anti-HBsAb titre observed in a proportion of patients deserves HBV virological follow-up in these patients, especially in those with a low anti-HBsAb titre at baseline.

Epidemiology of hepatitis B virus infection among the tribes of Andaman and Nicobar Islands, India.

The Andaman and Nicobar Islands, Union Territory of India, are home to six primitive tribes, namely the Great Andamanese, Onges, Jarawas and Sentinelese (Negrito race), and the Shompens and Nicobarese (Mongoloid race). These tribes account for about 8% of the island's population and the Nicobarese constitute >95% of the tribal population. Hepatitis B virus (HBV) infection is highly endemic among them with the prevalence of hepatitis B surface antigen (HBsAg) ranging from 23% among the Nicobarese to 66% among the Jarawas. The high HBsAg prevalence among pregnant mothers (20.5%), a linear increase in the age-specific rates of HBV exposure and the presence of HBsAg-positive individuals in every family suggested a combination of perinatal and horizontal transmission among the Nicobarese. Molecular studies of HBV isolates from the Onges, Nicobarese and Great Andamanese indicated a predominance of genotype D and there was a close similarity between these isolates and isolates from mainland India, suggesting that HBV may have been introduced from mainland India. In contrast, genotype C predominated among the Jarawas, with isolates similar to strains from Southeast Asian countries. Due to its high prevalence, hepatitis B vaccine is included in the childhood vaccination programme in these islands. It might be worth considering a pilot screening programme for chronic HBV patients to detect hepatocellular carcinoma.

Immunogenicity and safety of a DTaP-IPV//PRP approximately T combination vaccine given with hepatitis B vaccine: a randomized open-label trial.

OBJECTIVE: To determine seroprotection and vaccine response rates produced by a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type-b conjugate (DTaP-IPV//PRP approximately T) vaccine containing a polyribosyl-ribitol-phosphate (PRP)-tetanus toxoid conjugate (Pentaxim) and given with a hepatitis B vaccine. METHODS: In this multicentre open-label trial, 424 infants who received DTaP-IPV//PRP approximately T at 6, 10 and 14 weeks of age were also randomized to receive hepatitis B vaccine at either 6, 10 and 14 weeks or 0, 6 and 14 weeks of age. Antibody levels were determined at 6 and 18 weeks of age, and reactogenicity was monitored using parental reports. FINDINGS: Immunogenicity was high for all vaccine antigens and was similar to that in a historical control study. After primary vaccination, 98.7% of all infants had an anti-PRP antibody titre > 0.15 microg/ml. Seroprotection against poliovirus type-1, -2 and -3 and tetanus was obtained in all infants, and against diphtheria, in 97.1%. Pertussis seroconversion, defined as a > fourfold increase in antibody titre, occurred in 95.3% for anti-pertussis toxoid antibody and in 89.0% for anti-filamentous haemagglutinin antibody. The hepatitis B seroprotection rate was 99.5% with administration at 0, 6 and 14 weeks, and 97.8%, at 6, 10 and 14 weeks. However, the antibody titre was higher with the 0, 6 and 14-week schedule (601 mIU/ml versus 207 mIU/ml). The reactogenicity of both vaccines was low. CONCLUSION: The DTaP-IPV//PRP approximately T vaccine was highly immunogenic. The anti-hepatitis B antibody response was seroprotective with both schedules, though the antibody titre was higher with the 0, 6 and 14-week schedule.

Plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B.

This work investigates the preparation and in vivo efficacy of plasmid DNA loaded chitosan nanoparticles for nasal mucosal immunization against hepatitis B. Chitosan pDNA nanoparticles were prepared using a complex coacervation process. Prepared nanoparticles were characterized for size, shape, surface charge, plasmid loading and ability of nanoparticles to protect DNA against nuclease digestion and for their transfection efficacy. Nasal administration of nanoparticles resulted in serum anti-HBsAg titre that was less compared to that elicited by naked DNA and alum adsorbed HBsAg, but the mice were seroprotective within 2 weeks and the immunoglobulin level was above the clinically protective level. However, intramuscular administration of naked DNA and alum adsorbed HBsAg did not elicit sIgA titre in mucosal secretions that was induced by nasal immunization with chitosan nanoparticles. Similarly, cellular responses (cytokine levels) were poor in case of alum adsorbed HBsAg. Chitosan nanoparticles thus produced humoral (both systemic and mucosal) and cellular immune responses upon nasal administration. The study signifies the potential of chitosan nanoparticles as DNA vaccine carrier and adjuvant for effective immunization through non-invasive nasal route.

Protective antibody levels and dose requirements for IV 5% Nabi Hepatitis B immune globulin combined with lamivudine in liver transplantation for hepatitis B-induced end stage liver disease.

Lamivudine combined with Hepatitis B immune globulin (HBIg) prevents post liver transplant (LT) HBV recurrence. The study was designed to assess the impact of lamivudine on hepatitis B antibody (anti-HBs) and dosage requirements of intravenous 5% HBIg (Nabi-HB) in the first 36 weeks post LT. Adults undergoing LT for chronic HBV received lamivudine prior to or at LT, and IV HBIg 20,000 IU on day of LT, 10,000 on days 1-7, weeks 4 and 8, and 5,000 every 4 weeks thereafter. Replicative status based on serum HBV DNA (> 5 pg/mL = replicator (R) or < or = 5 pg/mL = nonreplicator (N) was determined at initiation of lamivudine (R or N) and within 2 weeks of LT (r or n), resulting in 3 groups: Nn, Rn, and Rr. Between December 1999 and May 2001, 30 patients (10 Nn, 13 Rn, 6 Rr, and 1 unknown), mean age of 52 years underwent LT. HBsAg neutralization was achieved with anti-HBs > 300 IU/L during week 1 and > 200 IU/L during weeks 2-12. All but one patient were HBsAg-negative on last follow-up. Pre-LT suppression of HBV replication resulted in similar dose requirements and pK in the Rn and Nn groups within 1 week after LT. Comparatively, the Rr group had greater HBIg requirements during weeks 1-12 due to greater anti-HBs clearance and shortened t(1/2) during the entire 36-week follow-up. In conclusion, this study provides a rationale for the use of lower HBIg doses in HBV patients with suppressed replication undergoing LT.

[The HBeAg/antiHBe seroconversion as a result of lamivudine treatment in children with chronic hepatitis B unresponsive to previous interferon alpha therapy]. / Czestosc zjawiska serokonwersji w ukladzie HBeAg/antyHBe wywolanego leczeniem lamiwudyna u dzieci z przewleklym zapaleniem watroby typu B po nieskutecznej terapii interferonem alpha.

UNLABELLED: The aim of the study was evaluation the HBeAg/antiHBe seroconversion frequency as a result of lamivudine treatment in children who are nonresponders to previous IFN-alpha therapy. MATERIAL AND METHODS: The observation was carried out on 41 children, aged 4-17 years, with biopsy-proven chronic hepatitis B (HBeAg+) treated with lamivudine 3-4 mg/kg/d (max. 100 mg/d) for 12 months. RESULTS: After 6 months of lamivudine therapy 59.3% children normalized GPT activity and only 1 child (2.5%) lost HBeAg. At the end of 12 months of therapy 81.5% normalized GPT activity and 4 of them (10%) lost HBeAg and seroconverted to antiHBe. None of treated children lost HBsAg. The age, sex, pretreatment GPT activity and active histological disease were not predictors of lamivudine-induced HBeAg loss. There were no side effects of lamivudine therapy except one boy who had severe thrombocytopenia. CONCLUSIONS: The HBeAg/antiHBe seroconversion rate after one year trial of lamivudine in children with chronic hepatitis B unresponsive to previous IFN alpha therapy was 10%. The age, sex, pretreatment GPT activity and active histologic disease were not predictors of lamivudine-induced HBeAg loss.

Trial of lamivudine in hepatitis B surface antigen carriers with persistent hepatitis B core IgM antibody.

OBJECTIVE: The persistence of hepatitis B core immunoglobulin M (HBc IgM) antibody in hepatitis B surface antigen (HBsAg) carriers is a risk factor with hidden dangers and forecasts the existence of liver damage. A trial of lamivudine in such subset of carriers was carried out for the first time in this study. METHODS: A total of 62 HBsAg with hepatitis e antibody individuals (age range, 25-45 years) with persistent HBc IgM antibody were randomized to receive either 100 mg lamivudine (32/62) or placebo (30/62) daily for 6 months. The study was performed from June 2000 to October 2002. The carriers were regular attendees of the Virology Center in Mosul, North Iraq for follow up. Enzyme-linked immunosorbent assay technique was performed to detect the different hepatitis B virus markers. RESULTS: Among the lamivudine group, HBc IgM antibody seroclearance achievement rate was 81.3% and HBsAg seroconversion rate was 9.4% compared to 6.3% and 3.3% in the placebo group. Number of adverse clinical events were observed, but were of mild nature and tolerable by the participants who completed the study. CONCLUSION: The trial of lamivudine in this subset of HBsAg carriers proved to be safe and efficacious. More studies are needed prior to recommending the drug for routine use on selected HBV carriers.

Levamisole treatment enhances protective antibody response to hepatitis B vaccination in hemodialysis patients.

Hemodialysis shows a high risk for hepatitis B infection, and hepatitis B virus (HBV) vaccination has now become a routine procedure. Unfortunately, 40% to 50% of hemodialysis patients do not have adequate protective antibodies against the HBV vaccination which is thought to be due to depressed cell mediated immunity. Levamisole has been reported to stimulate depressed T-cell activity and enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune-depressed patients. We studied the effects of levamisole, an immunomodulatory agent, on the protective antibody response of hemodialysis patients to the HBV vaccination. Our hemodialysis patients with negative anti-HBs antibody routinely received 40 microg doses of recombinant HBV vaccine intramuscularly at 0, 1, and 6 months, and we followed serum anti-HBs levels. Patients with a serum antibody level of >10 mIU/ml were considered as responders. Study groups were classified as follows. Group 1 was comprised of 96 chronic hemodialysis patients with negative anti-HBs and HBV core antibody (52 male, 44 female, mean age of 45 +/- 15 years and mean hemodialysis duration of 46 +/- 40 months) who received HBV vaccination; 55 patients (57%) were found to be responders. Group 2 was comprised of 19 randomly selected patients who had never received hepatitis B vaccine (13 male, 6 female, mean age of 42 +/- 14 years, mean duration of hemodialysis 31 +/- 27 months) and who were started on an HBV vaccination protocol with levamisole per os 80 mg after each hemodialysis session for 4 months and followed up on serum anti-HBs levels. Seventeen of the patients completed this levamisole treatment. Fourteen of the 17 patients had the levels of the protective serum antibody indicating a higher response rate when compared with patients who did not receive levamisole (82% versus 57%, respectively, p < 0.05). Group 3 was comprised of 19 patients randomly selected from persons who did not respond to previous vaccination programs (10 male, 9 female, mean age of 51 +/- 14 years, mean duration of hemodialysis 41 +/- 31 months). A second HBV vaccination program was started with the same levamisole protocol. In this group, 18 patients completed this treatment model. Fourteen of them responded to the vaccination model. In Group 4, a second HBV vaccination program was applied without levamisole to 20 randomly selected persons who did not respond to the previous routine vaccination program (12 male, 8 female, mean age of 53 +/- 17 years, mean duration of dialysis 51 +/- 38 months). Only 3 of them responded to a second vaccination program. Comparing Group 3 with Group 4, there was a higher responder rate to HBV vaccination (77% versus 15%, respectively, p < 0.0001). These results show that levamisole treatment increases the response rate to the first HBV vaccination and of the previously unresponsive cases by modulating possible cellular immune response.

Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers--a single blind placebo-controlled and randomized clinical study.

Persons involved in the study, 21 per treatment arm, were consuming ubiquinone (Q10), 90 mg/day, 180 mg/day or placebo, for two weeks prior to hepatitis B vaccination. After 30 days this vaccination was repeated. Q10 was given as soft gelatin capsules containing 30 mg each. The consumption was continued throughout the study conducted for 90 days. Clinical observations and laboratory tests were performed throughout the study and no adverse effects were observed in any of the groups. Already after 30 days the two groups receiving Q10 showed a slightly titer of antibodies to hepatitis B surface antigen then the placebo group. This difference escalated and the immunopotentiating effect of Q10 was even more clear-cut in the residual part of the study. In addition, a dose response did also seem to be present when comparing the 90 mg group with the 180 mg group. Statistics revealed that Q10 in the dose 180 mg/day is able to increase antibody response in vivo in humans vaccinated against hepatitis B with up to 57% (p = 0.011).

Comparative study of the immunogenicity and safety of two doses of recombinant hepatitis B vaccine in healthy adolescents.

PURPOSE: A prospective, two-armed, open-label, randomized trial was performed to compare the geometric mean titers (GMT), seroprotection (SP) and seroconversion (SC) rates found after administration of two doses of recombinant hepatitis B vaccine. METHODS: Recombinant hepatitis B vaccine 10 or 20 micrograms was administered IM at 0, 1, and 6 months in healthy adolescents. RESULTS: Volunteers who received either dose of the vaccine had similarly high seroconversion and seroprotection rates at all visits. At Month 8, both doses of the vaccine were highly immunogenic with GMTs of 1989 mIU/mL (10 micrograms dose) and 7672 mIU/mL (20 micrograms dose) and nearly equivalent SP rates (97% and 99% in the 10 and 20 micrograms dose groups, respectively). The geometric mean titers of seroconverters at Months 3, 6 and 8 were significantly greater in the 20 micrograms group as compared to the 10 micrograms group (p < or = 0.003). Both doses were well-tolerated, with injection site pain the most common reported adverse event. Injection site pain was reported significantly (p = 0.004) more by volunteers who received the 20 micrograms dose (10.7%) compared with volunteers who received the 10 micrograms dose (3.8%). CONCLUSION: Vaccination with 10 micrograms of recombinant hepatitis B vaccine may provide a clinically effective and economical alternative to the use of the 20 micrograms dose in healthy adolescents.