Immunogenicity of a recombinant hepatitis B vaccine in hemodialysis patients: a two-year follow-up.

The immunogenicity of a recombinant hepatitis B vaccine was evaluated in 35 hemodialysis patients who received a standard dose (20 micrograms) of the vaccine at 0, 1, 2 and 6 months. After the full vaccination course (month 7), 60% (21/35) of the patients had seroconverted (anti-HBs titer greater than or equal to 10 mIU/ml). The duration of protection lasted up to 18 months after the start of vaccination in 85.7% (18/21) of the responders. At that time, an additional dose was given to all the patients: 1-2 months later, the overall immunization rate had increased to 65.7% (23/35); lastly, in month 24 (i.e., 6 months after the booster dose), 62.5% (15/24) of the patients available for evaluation were still maintaining protective levels of anti-HBs antibodies. Comparable results had previously been obtained in 21 well-matched patients on our dialysis program who were vaccinated with a plasma-derived vaccine according to the recommended schedule.     

Complete seroconversion by low-dose intradermal injection of recombinant hepatitis B vaccine in hemodialysis patients.

The present study was undertaken to find out if the seroconversion rate of hemodialysis (HD) patients was enhanced by the intradermal (i.d.) inoculation of recombinant hepatitis B (HB) vaccine. Thirty-five HBs-Ag, HBs-Ab and HBc-Ag, HBc-Ab negative HD patients were divided into three groups: 14 patients in group I received 5 micrograms HBs Ag i.d. every 2 weeks, 13 patients in group II were given 2.5 micrograms HBs vaccine i.d. every 2 weeks, 5 times, then every week. The remaining 8 patients in group III were immunised with 10 micrograms HBs Ag every 4 weeks 5 times intramuscularly (i.m.), then 5 micrograms i.d., every 2 weeks until complete seroconversion. Antibody response to i.m. injection was poor and only 37.5% of patients developed anti-HBs at a titer of 10 mIU/ml or more at 16 weeks after the start of immunisation. However, this poor response was improved by i.d. injection. The time of seroconversion was significantly earlier and the rate of response was higher in group I. The poor response in group II was markedly improved by doubling the inoculation rate. Overall, 100% of seroconversion was finally obtained by multiple i.d. immunisation. However, the anti-HBs titers were lower in all patients and declined in some patients after the immunisation was stopped. The last seroconverted patient in each group lost protective antibody levels at the 39th week. These patients became antibody positive again at the 52nd week with a booster dose. We feel that the i.d. route remains a useful and cheaper method of obtaining prophylaxis against HBs in high-risk HD patients but it would seem to be prudent to monitor these patients serially to assess the persistence of anti-HBs in the serum.     

Immune response after vaccination with recombinant hepatitis surface antigen in maintenance hemodialysis patients and healthy controls.

We evaluated anti-HBs titers 2 months after vaccination with recombinant hepatitis surface antigen (rDNA-HBsAg) in 43 maintenance hemodialysis patients (MHP). Of these, 34 had not undergone hepatitis B virus vaccination previously (NV-MHP) and 9 had shown negative response to vaccination with plasma-derived HBsAg (HEVAC Pasteur; V-MHP). 120 healthy workers from the same hospital undergoing rDNA-HBsAg immunization were used as controls. All low responders (LR) (anti-HBs less than 100 mIU/ml) and nonresponders (NR; anti-HBs less than 10 mIU/ml) were given a booster dose 3 months after the last dose of vaccine. Seroconversion rates were lower in NV-MHP (52.9%) than in controls (98.4%). V-MHP showed higher seroconversion rates (88.9%) than NV-MHP. In each group, the number of responders (R; anti-HBs greater than or equal to 100 mIU/ml), LR and NR was as follows: controls 101, 17, 2; NV-MHP 6, 12, 16; V-MHP 8, 0, 1. After booster dose, 17/17 controls LR and no NV-MHP LR showed a rise in anti-HBs titers over 100 mIU/ml. Six months after the last dose of vaccine or the booster dose, anti-HBs titer fell under 10 mIU/ml in 4/12 MHP LR and under 100 mIU/ml in 6/14 MHP R. To achieve high seroconversion rates and to avoid the decline of anti-HBs to nonprotective titers in MHP, a booster injection should be made at different dates after the first vaccination.     

Immunogenicity of Intradermal Hepatitis B Vaccination in Renal Transplant Recipients

We investigated intradermal hepatitis B (HBV) vaccination in 24 renal transplant recipients who failed to develop hepatitis B surface antibody (anti-HBs) with intramuscular (i.m.) vaccination. All patients received recombinant HBV vaccine 5 microg intradermally every 2 weeks for 8 doses. Nine patients developed protective levels of anti-HBs (> 10 miu/mL) and two patients developed low levels of anti-HBs (4-6 miu/mL), giving an overall initial response rate of 45.8%. A booster of 40 microg was administered intramuscularly after 1 year. All initial responders developed an anti-HBs response (322.6 +/- 92.0 miu/mL). In addition, four patients who did not respond initially to the intradermal vaccination seroconverted after the booster. Responders (62.5%) and nonresponders had comparable age, gender, immunosuppressive medications, and duration of transplant. In conclusion, renal transplant patients who fail to respond to intramuscular HBV vaccination may benefit from intradermal vaccination followed by an intramuscular booster.     

Comparison of intramuscular and intradermal applications of hepatitis B vaccine in hemodialysis patients

This study compared the application of intramuscular recombinant hepatitis B vaccine in hemodialysis patients with the application of accelerated intradermal recombinant hepatitis B vaccine, which can be applied with one-tenth of the standard dose. Sixty seronegative patients for hepatitis B were randomly separated into two groups. Twenty mug of the recombinant hepatitis B vaccine was intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group (32 cases). One more dose was applied at month 12 to those whose anti-HBs titers remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied at 2 microg dose six times with one-month intervals to the second group (28 cases). Vaccine applications were continued in those whose anti-HBs titers remained below 100 mIU/mL at month 7 until antibody titers reached above this value or until the dose number became 12. Measurements of antibody titers were repeated at month 13 in both groups. As a result, in the vaccination of hemodialysis patients against hepatitis B, the accelerated ID application of hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than the standard dose vaccination schedules. Especially for hemodialysis patients, the time has come for routine application of ID hepatitis B vaccine as an alternative vaccination method.     

Treatment with recombinant human erythropoietin increases antibody titers after hepatitis B vaccination in dialysis patients

The effect of recombinant human erythropoietin (rHuEPO) on the immune system of hemodialysis patients has been studied by evaluating their response to hepatitis B (HB) vaccination. Fifty hemodialysis patients were given four doses of 20 micrograms recombinant DNA hepatitis B vaccine (SKF) at an interval of 0, 1, 2 and 6 months. Thirty-seven patients could be evaluated at one year. Twelve of 15 (80%) of the rHuEPO treated patients and 12 of 22 (54%) of non-rHuEPO treated dialysis patients developed anti-HBs antibodies. At the time of maximum immune response (8 months), the geometric mean anti-HBs titers (mIU/ml +/- SEM) of responders and all patients were five times (224.0 +/- 5.9 vs. 41.7 +/- 1.5, P less than 0.001), and eight times (57.6 +/- 8.7 vs. 6.7 +/- 1.8, P less than 0.05), respectively, higher in rHuEPO treated patients than in patients not receiving the drug. High antibody response (greater than 100 mIU/ml) prevailed in the group of rHuEPO treated patients and was associated with a high helper/suppressor ratio. Discriminant multivariate analysis (P = 0.038) revealed the influence of treatment with rHuEPO (40%) and helper/suppressor ratio (31%) on antibody concentration, while age, gender, duration of dialysis and previous blood transfusions were similar in both patient groups. Although changes in lymphocyte subsets observed in rHuEPO treated patients may be the result of a reduced administration of blood transfusions, immune reactivity seems also to be directly affected by the drug.     

Active hepatitis B vaccination of dialysis patients and medical staff

One hundred six patients with terminal renal insufficiency and 29 medical personnel were given three doses of hepatitis B vaccine at an interval of 0, 1, and 6 months (Merck, Sharp and Dohme, West Point, Pennsylvania, part of a joint study no. 649). Chronic hemodialysis patients (N = 99) received 40 micrograms vaccine (V) i.m. Uremic patients, who were just about to start chronic dialysis treatment (N = 7), were given 40 micrograms V, and at the first vaccination 3 ml hyperimmune globulin (HBIG) in addition. The medical personnel was alternately vaccinated with 20 micrograms V (N = 8), 40 micrograms (N = 11), 40 micrograms V, and 3 ml HBIG at the first vaccination (N = 10). After 12 months, 50% of the male dialysis patients, 66% of the female dialysis patients, and 95% of the medical staff developed anti-HBs antibodies. The anti-HBs titer of the dialysis patients was ten times lower than in the medical staff. The simultaneous passive immunization did not lead to any impairment of the anti-HBs titer in the dialysis patients and staff. The type of renal disease, length of time on dialysis, hematocrit, and immunoglobulin concentration did not influence the rate of immunization. After 12 months, 43 patients without antibody response were vaccinated a fourth time. Sixteen of these patients then developed anti-HBs, improving the immunization rate from 56.5 to 71.7%. A fifth vaccination only led to seroconversion, when brief or borderline anti-HBs could already be demonstrated previously. In dialysis patients who fail to develop anti-HBs after three doses of vaccine, a fourth vaccination is recommended after 12 months.     

Comparison of Intramuscular and Intradermal Applications of Hepatitis B Vaccine in Hemodialysis Patients

This study compared the application of intramuscular recombinant hepatitis B vaccine in hemodialysis patients with the application of accelerated intradermal recombinant hepatitis B vaccine, which can be applied with one-tenth of the standard dose. Sixty seronegative patients for hepatitis B were randomly separated into two groups. Twenty μg of the recombinant hepatitis B vaccine was intramuscularly applied at 0-, 1-, 2-, and 6-month intervals to the first group (32 cases). One more dose was applied at month 12 to those whose anti-HBs titers remained below 100 mIU/mL at month 7. The same vaccine was intradermally applied at 2μg dose six times with one-month intervals to the second group (28 cases). Vaccine applications were continued in those whose anti-HBs titers remained below 100 mIU/mL at month 7 until antibody titers reached above this value or until the dose number became 12. Measurements of antibody titers were repeated at month 13 in both groups. As a result, in the vaccination of hemodialysis patients against hepatitis B, the accelerated ID application of hepatitis B vaccine with a dose reduced to one-tenth is more cost-effective than the standard dose vaccination schedules. Especially for hemodialysis patients, the time has come for routine application of ID hepatitis B vaccine as an alternative vaccination method.     

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.     

Loss of hepatitis B immunity in hemodialysis patients acquired either naturally or after vaccination

AIM: The aim of our study was the long-term evolution of hepatitis B immunity and the titers of antibodies against the surface antigen (anti-HBs) acquired either naturally or after vaccination in hemodialysis (HD) patients with no history of hepatitis C virus (HCV) infection. METHODS: 36 HD patients were vaccinated with 4 doses of 40 microg recombinant B vaccine (Engerix, Rixensart, Belgium), intramuscularly at 0, 1, 2 and 6 months. 21 patients (60%) seroconverted developing anti-HBs titers > or = 10 IU/ml. Two patients were transferred to another unit before completion of 6 months after the last vaccine dose. We followed-up 19 HD patients who were immune against HBV after vaccination (Group A), and 30 immune patients (anti-HBs titers > or = 10 IU/ml) who had never been vaccinated and had antibodies against the core antigen (anti-HBc), diagnostic of natural HBV infection (Group B). In all patients of Groups A and B, anti-HBs were determined every 6 months, starting 6 months after the last dose in the vaccinated patients. Follow-up period lasted from October 2002 - April 2006. RESULTS: The mean follow-up in Group A was 21 +/- 12 months (range 6 - 36) and in Group B 29 +/- 12 months (range 6 - 42). Age, sex, presence of diabetes mellitus and duration of dialysis did not differ between the two groups. Five patients in Group A (26%) and 2 patients in Group B (9%) lost immunity (anti-HBs < 10 IU/ml) (p = 0.07). The median time to loss of immunity in Group A patients was 12 months (interquartile range 6 - 18 months), while in Group B patients it was 15 months (interquartile range 12 - 18 months). No booster dose was administered during the study. The 2 patients of Group B who lost immunity were the oldest of the group and redeveloped anti-HBs 6 and 12 months after they had lost it. During the first 6 months of the follow-up period, Group A had significantly higher anti-HBs titers than Group B (p < 0.05). However, this difference was lost later on, and after the first year of follow-up, anti-HBs titers were decreased significantly in Group A (p < 0.05), but remained unchanged in Group B throughout the follow-up period. CONCLUSIONS: In conclusion, HD patients lost hepatitis B immunity both after natural infection or vaccination, but naturally infected patients easily redeveloped protective anti-HBs titers. Anti-HBs titers decreased faster in vaccinated patients than in those with natural acquired immunity who held stable titers for a longer period. It is suggested that HD patients should be followed-up regularly for loss of HBV immunity after vaccination and receive a boosting dose when this occurs. In contrast, patients who acquired natural immunity do not need any anamnestic vaccination.     

Immunization and vaccination protocol in hemodialysis patients with naturally acquired hepatitis B antibody.

Long-term behavior of naturally acquired anti-HBs antibody was tested every 6 months for 3 years in 22 dialysis patients. Fifteen of them maintained protective levels throughout follow-up (102 and 85.5 mUI/ml at the beginning and the end, respectively). Seven of them became anti-HBs and were submitted to a 40-micrograms booster injection of hepatitis B vaccine. Seroconversion was observed in 6 of 7 patients (85.7%) with a mean anti-HBs titer of 90.4 and 47.3 mUI/ml after 3 and 6 months, respectively. Protective anti-HBs level may be maintained longer in patients with natural immunity than in HBsAg-negative vaccinated subjects. Effectiveness of a reduced vaccination protocol in patients who have lost their natural immunization should be confirmed with further studies.     

Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p < 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.     

Hepatitis B vaccination in human immunodeficiency virus-infected adults receiving hemodialysis

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends hepatitis B virus (HBV) immunization for all hemodialysis (HD) patients because they are at high risk of infection. Several studies have shown that the development of protective antibody titers after HBV vaccination is much lower in HD patients. We hypothesized that human immunodeficiency virus (HIV) infection in patients with end-stage renal disease (ESRD) would further impair the immune response to hepatitis B vaccination. METHODS: We performed a retrospective cohort study of patients undergoing long-term hemodialysis from 1990 to 2002 at the United States-based dialysis facilities of Gambro Corporation, North America. The response rate defined as an increase in anti-HBs levels >/=10 mIU/L after a month of the third dose of HBV vaccination was determined in HIV-infected and a randomly selected group of ESRD patients. The demographic information, laboratory data, and hepatitis B surface antibody (anti-HBs) titers were recorded from the Gambro Corporation database on these patients. RESULTS: Of the 347 adult HIV ESRD patients, 116 received three doses of recombinant hepatitis B vaccination. Seventy percent were male, and the majority (86%) were black. Of the 116 patients who received three doses of HBV vaccination, 62 (53.4%) developed protective antibody titers. This was comparable to the response rate of 50.4% in the randomly selected 220 non-HIV hemodialysis patients. Among HIV ESRD patients, the mean hemoglobin (Hgb) was higher in patients who developed protective antibody titers (Hgb 11.61 +/- 2 vs. 10.55 +/- 1.86, P value <0.01). On multivariate logistic regression analysis, higher Hgb was associated with protective antibody titers (odds ratio: 1.34, 95% CI 0.99-1.72). Seventy percent of the HIV-infected responders maintained protective antibody titers 6 months after vaccination. CONCLUSION: Hepatitis B vaccination should be offered to all HIV-infected ESRD patients because over half of the patients with HIV and ESRD can develop protective antibodies.     

Intradermal versus intramuscular hepatitis B re-vaccination in non-responsive chronic dialysis patients: A prospective randomized study with cost-effectiveness evaluation

Background. It has been calculated that 30% of chronic uraemic patients fail to produce antibodies to HBsAg antigen after hepatitis B (HB) vaccination. Low-dose intradermal (i.d.) inoculations and supplementary intramuscular (i.m.) injections have been reported to improve the response rate in previous non-responder chronic uraemic patients, but no cost-effectiveness evaluations have been made about this issue. Methods. We re-vaccinated 50 chronic dialysis patients, who did not have any detectable anti-HBs antibody after a reinforced protocol of hepatitis B vaccine given by i.m. route, with hepatitis B recombinant DNA yeast vaccine (80 &mgr;g) by intradermal (25 patients) or intramuscular (25 patients) administration (randomly allocated). We used the same amount of HBsAg in order to exclude the confounding effect of the dose level administered on the immune response of uraemic patients. We studied, over a 20-month follow-up, the persistence of anti-HBs antibodies in our responder vaccinees. We made a comparison between the costs of our re-vaccination protocol and the other re-vaccination strategies that have been recently suggested. Results. One month after completion of re-vaccination protocol, seroconversion rates (100% vs 48%, P=0.008) and proportion of patients who elicited protective anti-HBs titres (96% vs 40%, P=0.0001) were significantly higher in i.d. compared to i.m. patients. The levels of anti-HBs, expressed as geometric mean titres and 95% confidence intervals (GMT (95% CI)), were significantly increased in i.d. than in i.m. groups, 100 (44-187) vs 26 (14-52) mUI/ml (P=0.018). At month 12, the seroconversion rates were 57 vs 14% in i.d. and i.m. groups respectively (P=0.158); the seroprotection rate was higher in i.d. individuals in comparison with i.m. patients, 50 vs 0%, P=0.072. At month 20, the seroconversion rates were 54 and 0% among i.d. and i.m. patients respectively (P=0.055); the seroprotection rate was higher in i.d. than in i.m. group (30 vs 0%, P=0.2). At month 20, the median anti-HBs titres in i.d. patients were 21 mUI/ml, and GMT (95% CI) were 20.9 (2-54) mUI/ml. No important general or local side-effects were observed. The cost of our schedule was $92 US whereas the costs of other re-vaccination protocols ranged between 138 and $807 US. Conclusions. Our results show that the unresponsiveness to recombinant yeast-derived vaccine may be mostly reversed by repeated low-dose i.d. injections of the same agent. In spite of an equal amount of HBsAg received, i.d. hepatitis B re-vaccination shows higher immunogenicity compared to i.m. administration over a 20-month observation period. Cost-effectiveness analysis demonstrated that the intradermal administration of HB vaccine is the most clinically effective re-vaccination strategy; it is also the most unexpensive one. We strongly recommend low-dose intradermal inoculations in order to re-vaccinate chronic dialysis patients who fail to respond to hepatitis B vaccination.     

Effectiveness of low-dose intramuscular anti-VHB immune globulin in the prophylaxis of viral B hepatitis reinfection after liver transplantation: preliminary report

INTRODUCTION: Prophylaxis using high-dose intravenous anti-HBV immune globulin (HBIG) is effective to prevent reinfection due to hepatitis B virus (HBV) after orthotopic liver transplantation (OLT). However, this treatment is expensive and intravenous administration is difficult during outpatient care. Our aim was to assess the effectiveness of low-dose intramuscular HBIG to prevent HBV reinfection after OLT. PATIENTS: Six patients (all men, mean age 41 years, negative HBV DNA without hepatotropic virus coinfection) were transplanted in our institution due to HBV cirrhosis and included in a prospective noncomparative study. Intramuscular HBIG (2000 IU) was administered during the anhepatic phase of OLT, followed by daily 2000 IU doses for 7 days and then monthly. HBV antibody titers were measured every month. Reinfection was defined as the recurrence of surface HBV antigen in serum after transplantation. RESULTS: After 1 year follow-up, none of the six patients had detectable HBV surface antigen and the liver biopsies were normal in all cases. Using 2000 IU, anti-HBs levels were: 880+/-356 IU/L at 1 month, 191+/-123 at 6 months, and 225+/-49 after 1 year. In all cases anti-HBs titers were above 100 IU/L during the follow-up. CONCLUSIONS: Monthly administration of low-dose (2000 IU) intramuscular HBIG effectively prevents recurrence of HBV infection as well as attains a protective level of anti-HBs antibodies (over 100 IU/L) for at least the first year after transplantation.     

Long-term immunogenicity and efficacy of hepatitis B vaccine in hemodialysis patients.

Although the efficacy of hepatitis B vaccines in patients under chronic hemodialysis treatment has been well documented, the persistence of immunity in this population remains largely unknown. In this study we have followed 60 hemodialysis patients up to 3 years after primary hepatitis B vaccination (four doses of recombinant hepatitis B vaccine; Engerix B, 20 mg/dose) to evaluate the persistence of immunity (as indicated by serum levels of antibody to hepatitis B surface antigen-anti-HBs-higher than or equal to 10 mIU/ml). Fourty-four (73%) patients developed anti-HBs levels above 10 mIU/ml after vaccination; the remaining 16 (27%) vaccinees were considered nonresponders and were given a booster dose that again failed to elicit an immunoresponse. After 3 years of follow-up, 18 out of 44 (41%) responders had no detectable anti-HBs levels in the serum (antibody loss occurring within 8 and 12 months in 3 cases, within 1 and 2 years in 13, and within 2 and 3 years in 2 other cases). When compared with the responders that lost their antibodies during the follow-up period, those who remained immunoreactive 3 years after vaccination was initiated were younger and had higher anti-HBs levels at 8 months of follow-up. Two hepatitis B virus infections were detected among nonresponders during the follow-up period. Based on these data, we conclude that patients undergoing chronic hemodialysis therapy not only have lower response rates to hepatitis B vaccination than healthy adults, but also that these are frequently transient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative immunogenicity of 2 recombinant hepatitis B vaccines (GeneVac-B and Engerix-B) in adult patients with chronic renal failure

BACKGROUND: Hepatitis B virus infection is often fatal or results in a carrier state with uremia. Vaccination protects against infection, but immune response may remain low. We aimed to study immune responses to 2 recombinant hepatitis B vaccines (Engerix-B and GeneVac-B) in patients with end-stage chronic renal failure. METHODS: Patients initially negative for hepatitis B (HB) surface antigen (HBsAg), and with core antibody (anti-HBc) and nonprotective anti-HBs titers (<100 mIU/mL) were selected. Four doses of 40 microng of either vaccine were administered intramuscularly, further doses being given 1, 2 and 6 months after the first dose. Seroconversion and seroprotection were defined as anti-HBs level above 10 mIU/mL and 100 mIU/mL, respectively. RESULTS: A total of 11 and 9 subjects receiving GeneVac-B and Engerix-B, respectively, completed the protocol. Seroconversion was achieved in 100% for both vaccines. Seroprotection occurred in 78% and 82% of the Engerix-B and the GeneVac-B recipients, respectively. Geometric mean titers 1 month after the fourth dose were 274 mIU/mL (95% confidence interval [95% CI], 71-1,057 mIU/mL) and 322 mIU/mL (95% CI, 142-730 mIU/mL), respectively. CONCLUSIONS: Both vaccines are highly immunogenic in renal failure and did not show significant differences between each other.     

Efficacy of a Pre-S Containing Vaccine in Patients Receiving Lamivudine Prophylaxis after Liver Transplantation for Chronic Hepatitis B

Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double-doses (20 microg) of third-generation recombinant pre-S containing vaccine (Sci-B-Vac) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390-2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti-HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti-HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci-B-Vac is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.     

Response to a Vaccination Schedule With 4 Doses of 40 μg Against Hepatitis B Virus in Cirrhotic Patients Evaluated for Liver Transplantation

We conducted a retrospective study to evaluate the response to recombinant hepatitis B vaccine after 4 intramuscular doses (40 μg) administered at 0, 1, 2, and 6 months in 157 cirrhotic patients who were liver transplant candidates. Seventeen nonresponders were revaccinated with the same schedule. We studied the association between the following variables and the vaccine response: age, gender, etiology of cirrhosis, diabetes, severity of liver disease (Child-Pugh class and Model for End-Stage Liver Disease [MELD] score), and the number of administered doses. The response rates were: 1 dose, 40% (2/5); 2 doses, 0% (0/7); 3 doses, 32.7% (16/49); and 4 doses, 31.3% (30/96) of patients. The median hepatitis B surface antibody (anti-HBs) titer was 45 mU/mL (range, 11-620 mU/mL). The response rate to revaccination was 41.2% (median anti-HBs titer, 88 mU/mL; range, 18-190 mU/mL). Diabetics showed a lower response rate than nondiabetic patients (17.2% vs 35.3%; P = .046). No association was observed between the response rate to vaccine and the other variables. In conclusion, the response rate to hepatitis B vaccine reached a little more than 30% in cirrhotic patients who received 3 or 4 doses. No higher response rate was observed among patients who received 4 doses. Diabetes was associated with a lower response rate. Anti-HBs seroconversion rates were not associated with the other variables. Revaccination may significantly increase the response rate to hepatitis B vaccine in cirrhotic patients, and may be considered in nonresponders after the third dose. Early vaccination against HBV should be considered in such patients.     

The effect of erythropoietin therapy and hemoglobin levels on the immune response to Engerix-B vaccination in chronic kidney disease

BACKGROUND: Patients undergoing chronic hemodialysis have an increased risk of acquiring hepatitis B infection. Only 43-66% of dialysis patients develop effective anti-HBs titers after vaccination. AIM: To evaluate the effect of recombinant erythropoietin (rEPO) therapy and basal hemoglobin levels on the outcome of the immune response to four doses of IM 40 microg Engerix-B vaccination in hemodialysis and chronic kidney disease (CKD) patients before starting replacement therapy. SUBJECTS AND METHODS: One hundred and three patients were included in the study: 34 hemodialysis patients treated with rEPO (Group A), 36 predialytic patients who did not treated with rEPO (Group B) and 33 predialytic patients treated with rEPO (Group C). Plasma creatinine in predialytic patients was 2-7 mg/dL. All patients' HBsAg and anti-HBs antibodies were negative. Patients were immunized with IM 40 microg Engerix-B at 0, 1, 3, and 6 months. Anti-HBs titers were measured at 7th month. RESULTS: Eighty seven point one percent of patients from group C developed protective anti-HBs titers compared with 69.4% from group B and 44.1% from group A (p = 0.001). Patients from all groups with baseline hemoglobin levels above 11 gr/dL developed protective anti-HBs titers significantly more than patients with baseline hemoglobin levels below 11 gr/dL (p < 0.05). CONCLUSION: Predialytic patients treated with rEPO and with hemoglobin levels higher than 11 gr/dL had significantly better immune response outcomes to Engerix-B vaccination. Immunization against hepatitis B infection should be considered at early stages of CKD prior to the deterioration in kidney functions and the development of renal anemia.