Hepatitis B vaccination in human immunodeficiency virus-infected adults receiving hemodialysis. Antibody level after hepatitis B vaccination in hemodialysis patients: influence of hepatitis C virus infection. Responsiveness to hepatitis B vaccine in immunocompromised patients by doubling the dose scheduling. The immune response to hepatitis B vaccine in humans: inheritance patterns in families The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Nutritional Status and Immune Functions in Maintenance Hemodialysis Patients Calcium, phosphate, and PTH levels in the hemodialysis population: a multicenter study. Response to the hepatitis B virus vaccine in haemodialysis patients: influence of malnutrition and its importance as a risk factor for morbidity and mortality. Association of response to hepatitis B vaccination and survival in dialysis patients The role of human leukocyte antigen tissue groups in hepatitis B virus vaccination in Turkey. Clinical and immunologic features of chronic dialysis patients who fail to respond to hepatitis B vaccine. Recombinant hepatitis B vaccine use in chronic hemodialysis patients. Long-term evaluation and cost-effectiveness analysis. Low Dose Intradermal Versus High Dose Intramuscular Hepatitis B Vaccination in Patients on Chronic Hemodialysis Hepatitis B vaccination in haemodialysis patients: a randomized clinical trial. Extra-high-dose hepatitis B vaccination does not confer longer serological protection in peritoneal dialysis patients: a randomized controlled trial. Prospective study of the immune effects of normalizing the hemoglobin concentration in hemodialysis patients who receive recombinant human erythropoietin. Persistence of hepatitis B vaccine immunity in hemodialysis patients. Prospective analysis of the factors influencing the antibody response to hepatitis B vaccine in hemodialysis patients. The accelerated hepatitis B virus vaccination schedule among hemodialysis patients, does it work? A randomized controlled trial Low Seroconversion with Hepatitis B Vaccination in Peritoneal Dialysis Patients A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF) INDUCED SERO-PROTECTION IN END STAGE RENAL FAILURE PATIENTS TO HEPATITIS B IN VACCINE NON-RESPONDERS A comparison of responsiveness to hepatitis B vaccination in patients on hemodialysis and peritoneal dialysis. Effects of a parathyroidectomy on the immune system and nutritional condition in chronic dialysis patients with secondary hyperparathyroidism. Antibody level after hepatitis-B vaccination in hemodialysis patients: impact of dialysis adequacy, chronic inflammation, local endemicity and nutritional status. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Antibodies to hepatitis B virus surface antigen and survival of hemodialysis patients – a prospective study Recombinant Hepatitis B Vaccine Adjuvanted With AS04 in Dialysis Patients: A Prospective Cohort Study
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 r and omly selected group of ESRD patients . The demographic information , laboratory data , and hepatitis B surface antibody ( anti-HBs ) titers were recorded from the Gambro Corporation data base 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 r and omly 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 Seroconversion after hepatitis B vaccine has been estimated to occur when the level of anti-HBs is higher than 10 IU/1 , but recently is has been considered that an antibody titer above 100 IU/1 is necessary to guarantee an efficacious protection . We prospect ively studied the evolution of anti-HBs after primary vaccination ( 3 doses ; Engerix B , 40 mu g each ) in 56 seronegative and not previously vaccinated hemodialysis patients . Three months after vaccine administration , seroconversion ( anti-HBs > 10 IU/1 ) was found in 43 patients ( 76.7 % ) , but an adequate response ( titer > 100 IU/1 ) was observed only in 30 ( 53.5 % ) . At 1 year after vaccination only 1 ( 3.3 % ) of the 30 cases with an effective response had lost his anti-HBs , while 12 of the 13 patients ( 92.3 % ) with an inadequate response ( anti-HBs between 10 and 100 IU/1 ) had no detectable antibodies ( p < 0.01 , chi2 ) . Considering that an antibody titer above 100 IU/1 following vaccination is necessary in order to maintain that level of antibody 1 year later , we analyzed the factors which influenced obtaining this level of antibody . Age , time on hemodialysis , serum albumin , Kt/V and protein catabolic rate did not affect the response to the vaccine . Females had a better response than males , and interestingly we found that hepatitis C virus ( HCV ) infection influenced the level of immunity . 27 out of the 43 HCV-negative cases ( 62.7 % ) obtained anti-HBs levels greater than 100 IU/1 , but only 3 out of the 13 HCV-infected patients ( 23 % ) had an anti-HBs above 100 IU/1 ( p < 0.01 , chi2 ) . Our results suggest that after hepatitis B vaccine , an antibody titer higher than 100 IU/1 is necessary to maintain the antibody level 1 year later , and that HCV infection may reduce the effectiveness of hepatitis B vaccine in hemodialysis patients The protective efficacy of three schedules of a recombinant hepatitis B vaccine was evaluated in 42 patients undergoing dialysis at a teaching hospital . The rate of seroconversion after vaccination was highest ( 82.3 % ) among the recipients of three 20-micrograms doses ( i.e. double the conventional dose for healthy adult ) at 0 , 1 and 2 months ( group II ) . The response was satisfactory ( 80 % ) among the recipients of three 20-micrograms doses at 0 , 1 and 6 months ( group III ) but was lowest with the single dose schedule of three 10-micrograms doses at 0 , 1 and 2 months ( group I ) . Seroconverters from all the three groups received a booster dose ( each equal to his scheduled dose ) at 12 months . Those who did not seroconvert from groups I and II were shifted to group III . The rate of seroconversion was higher in female ( 88.9 % ) than in male patients ( 66.7 % ) and in younger patients less than 30 years ( 83.3 % ) than in elderly patients more than 50 years . Patients undergoing peritoneal dialysis also responded much better ( 93.3 % ) than the hemodialysis patients ( 66.7 % ) . In conclusion , a schedule of double the conventional dose of the vaccination for healthy adults at 0 , 1 , 2 , and 12 months seems to give a better seroconversion and higher response to the HB vaccine , but a further large-scale study is needed to confirm this finding and also to look into the difference in response between male and female , younger and older patients and the difference in response between HD and PD patients We have recently shown that the human antibody response to the  hepatitis B virus surface antigen ( HBsAg ) vaccine  is major histocompatibility complex ( MHC ) associated . In studies of nonresponders to the vaccine , we found an increased incidence of individuals homozygous for human histocompatibility leukocyte antigen ( HLA ) proteins associated with the extended ( conserved ) haplotype [ HLA- B8,SC01,DR3 ] . In later prospect i ve vaccination trials , we showed that none of five individuals homozygous for this haplotype developed more than 1,300 radioimmunoassay ( RIA ) units of antibody ( mean , 467 RIA units ) , while all heterozygotes made at least 2,500 RIA units ( mean antibody level , 15,608 units ) . Our results suggested that [ HLA- B8,SC01,DR3 ] lacks an immune response gene for HBsAg , and that response is inherited in a dominant fashion . To provide further evidence for this hypothesis , we have now analyzed the results of HBsAg immunization in families . 43 members of 10 families were immunized with the hepatitis B vaccine  , including seven families where at least one member bore the haplotype [ HLA-B8,SC01,DR3 ] , and three families where one member had already received , but failed to respond to , the vaccine . In two of these three families , the presence of [ HLA-B8,SC01,DR3 ] was subsequently found . Of nine MHC-identical sibling pairs in the study , both members of eight pairs had similar antibody responses ( five nonresponder and three responder pairs ) . In all families with such sibling pairs , including the discordant pair , rank-ordering members by antibody level demonstrated that no relative 's value came between the sibling pair values . Furthermore , of nine [HLA-B8,SC01,DR3]-haplotype- homozygous individuals , six were nonresponders , and two others had only low-normal responses . [HLA-B8,SC01,DR3]-heterozygous family members always had higher levels of antibody than their homozygous relatives . Linkage analysis of nonresponse to HLA haplotypes revealed a maximum likelihood LOD ( logarithm of the odds ) score of 6.3 at a recombination fraction of 0.1 . The MHC association with lack of antibody response to HBsAg was not seen with tetanus immunization , where 1 of 20 HBsAg responders and 1 of 21 poor or nonresponders had tetanus titers of less than 1:512 ; both tetanus nonresponders were [ HLA-B8,SC01,DR3 ] heterozygotes . Our results indicate that : ( a ) response to the HBsAg vaccine is MHC linked , and inherited in a dominant fashion ; ( b ) an abnormal or missing immune response ( Ir ) gene for HBsAg is a characteristic of most examples of the extended haplotype [ HLA- B8,SC01,DR3 ] ; and ( c ) other haplotypes also have abnormal or missing Ir genes for HBsAg Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Epidemiological studies suggest various kinds of immune dysregulation in hemodialysis ( HD ) patients . The aim of this study was to investigate the relationship between immune functions and nutritional status of HD patients . We studied 54 patients with ESRD on chronic HD , included 34 females and 20 males with mean age 46.6 ± 16.3 ( 18–77 ) years .  We measured the height and dry weight of all patients . The BMI was calculated by dividing weight ( kg ) by height squared ( m2 ) . In all patients serum urea , creatinine , albumin , iron , cholesterol , triglyceride , CRP , IgG , IgM , IgA , CD4 , CD8 , CD19 , CD16 - 56 lymphocytes were measured . Kt/V values were calculated according to DOQI guideline . In this study , a positive correlation between albumin , cholesterol , and triglyceride levels as nutritional parameters and immune functions in terms of total and subtype lymphocyte counts was observed . Further prospect i ve studies are needed to determine the clinical importance of this finding and the appropriate means of measurement and effects of nutrition on immune function in hemodialysis patients BACKGROUND Hyperphosphatemia is one of the main factors in the pathogenesis of secondary hyperparathyroidism . In addition , in dialysis patients elevated levels of phosphate and calcium times phosphate ( Ca x P ) ion product are associated with extraskeletal calcifications , as well as an increased risk of death . Cardiovascular calcifications may possibly be related to the high cardiovascular mortality seen in dialysis patients . In the USA the prevalence of hyperphosphatemia among dialysis patients is very high , over 60 % of patients having serum P levels > 5.5 mg/dl , but no data are available for the Italian population , which follows different diet and dialysis schedules . METHODS We looked at a r and om sample of 638 patients enrolled in 29 outpatient dialysis units in Southern Italy ( Campania and Sicily ) . Data were central ly analyzed after extraction from a computerized data base . In each patient the average of two or more values obtained in the six-month observation period ( from Jan. 99 to June 99 ) was calculated . Mean age was 61.2 years ( 95 % CI 59.9 - 62.5 ) years , dialytic age 72.2 months ( 95 % CI 67.4 - 77.0 ) . RESULTS Mean + /- SD ( 95 % CI ) levels of phosphate were 5.74 + /- 1.57 ( 5.62 - 5.86 ) mg/dl ; total calcium 9.06 + /- 0.98 ( 8.98 - 9.14 ) mg/dl ; Ca x P 51.4 + /- 14.4 ( 50.3 - 52.5 ) mg2/dl2 ; alkaline phosphatase was 167 + /- 119 ( 157 - 177 ) IU/L ; intact parathyroid hormone ( PTH ) levels , available in a subset of 239 patients , were 318 + /- 413 ( 265 - 370 ) pg/ml . Among these patients 51.6 % had serum P > 5.5 mg/dl , 36 % > 6 mg/dl ; Ca x P levels were > 55 mg2/dl2 in 35.5 % of the population , 24 % > 60 mg2/dl2 ; iPTH levels were < 100 pg/ml in 43 % ; 25.4 % had hyperparathyroidism ( defined as iPTH > 400 pg/ml ) , and only 19.5 % of patients had PTH in the desired interval of 100 to 250 pg/ml . CONCLUSIONS Compared to data reported from the USA , mean levels of phosphate , Ca x P , and PTH seem better controlled in this Italian hemodialysis population . However , in a significant number of patients these parameters were still outside the normal range . Both over-suppression of PTH levels and hyperparathyroidism are present , although surprisingly the former was more frequent . Treatment of hyperphosphatemia should be more aggressive in hemodialysis patients ; PTH levels are difficult to maintain in the desired range of 100 - 250 pg/ml OBJECTIVE To assess if malnutrition influences the response to the hepatitis B virus vaccine in haemodialysis patients and whether this correlates with morbidity and mortality in these patients . DESIGN A 4-year prospect i ve open study . SETTING Haemodialysis unit of a 434-bed University Hospital . PATIENTS Sixty-four patients with end-stage chronic renal failure on maintenance haemodialysis . INTERVENTIONS Three-dose vaccination series with recombinant hepatitis B virus vaccine . MEASUREMENTS Antibody formation against the vaccine , predialysis serum urea , serum albumin and prealbumin , dialysis efficacy ( Kt/V ) , protein catabolic rate ( PCR ) , arm muscle circumference , triceps skinfold , serum parathyroid hormone concentration , mortality and morbidity ( hospital days per year of dialysis ) . RESULTS Increase in age negatively influences the formation of antibodies ( P = 0.01 ) , whereas serum albumin ( P = 0.008 ) and predialysis blood urea concentration ( P = 0.004 ) are positively correlated with the formation of antibodies . Responders had significantly higher levels of serum albumin and prealbumin and predialysis blood urea than non-responders . The percentage of non-responders was higher ( 70 % ) in the group with predialysis blood urea concentration between 90 and 125 mg/dl than in those with predialysis blood urea concentrations between 176 and 225 mg/dl ( 14.2 % ) . Patients with serum albumin levels between 3 and 3.5 g/dl were non-responders in a higher percentage ( 87.5 % ) than those with serum albumin levels between 4.5 and 5 g/dl ( 18.8 % ) . After a 4-year follow-up , survival was 20 % higher in the responder group ( P < 0.05 ) . Morbidity , expressed as hospital days per year of haemodialysis , was markedly lower in the responder group ( 10.4 + /- 2 versus 32 + /- 14 days , P = 0.03 ) . CONCLUSIONS Malnutrition negatively influences the response to the hepatitis B virus vaccine in haemodialysis patients . Non-responders have higher morbidity and mortality than responders , and therefore the absence of response to the hepatitis B vaccine can be considered as a risk factor in the haemodialysis population Background The status of immunocompromised patients is well recognized in end stage renal disease ( ESRD ) . As described recently , this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD . The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination ( HBV vaccination ) and the survival of  maintenance dialysis patients . Methods A total of 156 patients ( 103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis ) were recruited . After receiving a full dose of the HBV vaccination , all patients were followed up for to 5 years to evaluate the association of patient survival , cause of mortality , and immune response . Results The response rate to the  hepatitis B vaccination  was 70.5 % . There was no significant association between the immune response and the 5-year survival rate ( p = 0.600 ) or between the post-vaccination anti-HBs titers and the 5-year survival rate ( p = 0.201 ) . The logistic prediction model with the coefficient as non-response following HBV vaccination , diabetes mellitus , old age , and low albumin level could significantly predict infection-cause mortality ( sensitivity = 0.842 , specificity = 0.937 ) . Conclusion There was no significant association between the immune response to  HBV vaccination  and the 5-year survival rate . However , non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients BACKGROUND / PURPOSE Between 5 % and 10 % of the vaccinated population responds less well to st and ard vaccination schedules irrespective of hepatitis B virus ( HBV ) vaccination . This manuscript aims at describing possible correlation of different major histocompatibility complex ( MHC ) Class-I and MHC Class-II haplotype to anti-HBV humoral responsiveness following HBV vaccination . MATERIAL S AND METHODS The study was conducted on 944 vaccinated hospital staff members and concentrated on the 38 nonresponders as defined by enzyme-linked immunosorbent assay ( ELISA ) results . In order to define significance of the different haplotypes from the nonresponders , their frequency was compared to the frequency of the same haplotype in 18 r and omly selected responders . Human leukocyte antigen (HLA)-A and HLA-B antigens were typed among total mononuclear cells using a st and ard two-stage microlymphocytotoxicity test . The typing method of HLA Class-II is based on a technique that involves amplification of the second exon of different HLA Class-II genes by PCR . RESULTS Positive correlations were found between four HLA-DR ( HLA-DRB1 * 04X , DRB1 * 0401X , DRB1 * 11/13 , and DRB1 * 0401X0201 ) haplotypes and nonresponders but there was a negative correlation with one Class-I ( HLA-B13 ) . CONCLUSION This study suggested that certain HLA types are associated with nonresponsiveness to vaccination . The different HLA of ethnic groups should also be kept in mind when evaluating the response to hepatitis vaccination . The different HLA gene frequencies of ethnic groups should be examined in further large-scale population -based studies Eighteen patients on chronic dialysis ( 15 haemodialysis , three peritoneal ) were evaluated to determine whether certain clinical features and /or in vitro indicators of immune function correlated with the response to hepatitis B vaccine . Only 44 % of patients developed antibody to hepatitis B surface antigen ( anti-HBS ) following vaccination and neither duration of dialysis , history of renal transplant , peripheral T cell numbers , T4/T8 ratios , nor mitogen induced lymphocyte proliferation correlated with response to vaccination . Advanced age , history of multiple blood transfusions and depressed levels of IgM may be associated with a poor antibody response to the vaccine . Future studies need to consider these variables when evaluating immunogenicity of new hepatitis B vaccine preparations The prevalence of hepatitis B virus ( HBV ) infection in our unit was 45 % ( 86/190 ) ; there were 77 ( 40.5 % ) and 9 ( 4.7 % ) patients with previous and persistent HBV infection , respectively . Recombinant hepatitis B vaccine was given to 118 chronic HD patients with a regimen of 3 double doses administered intramuscularly at 0 , 1 and 2 months , obtaining a seroprotection rate of 67 % ( 79/118 ) , 57 % ( 45/79 ) being high responders . At month 24 , 78 % ( 40/51 ) maintained protective levels of anti-HBs , 45 % ( 18/40 ) of them being high responders . There was a statistically significant difference between responder and non-responder patients with regard to nutritional parameters such as serum total proteins and mean levels of transferrinemia . The number of diabetic patients  was significantly increased in the nonresponder group . Patients with persistent antibodies ( ' persistent responders ' ) were younger and had a shorter duration of HD treatment compared to those responders who rapidly lost anti-HBs ( ' transient responders ' ) . Serological positivity for antibodies against hepatitis B core antigen significantly facilitates the decrease of anti-HBs antibodies over time . We detected seven episodes of HBV infection among HD patients at our unit before the beginning of the vaccination program . On the contrary , there were no episodes of HBV infection among responder vaccinees during the 24-month follow-up period . After the initial cost of vaccination , a savings of US$ 3,272 per year was realized by the elimination of frequent serologic screening of vaccine responders Patients with end-stage renal disease on hemodialysis ( HD ) are at high risk for hepatitis B infection . We r and omly assigned 86 new patients on HD to receive either 40 & mgr;g intramuscular ( group 1 ) or 20 & mgr;g intradermal ( group 2 ) recombinant hepatitis B vaccine , in three doses at 0 , 1 , and 4 months . All patients were seronegative at baseline for hepatitis B surface antigen ( HBs-Ag ) , hepatitis B surface antibody ( HBs-Ab ) , and hepatitis B core antibody ( HBc-Ab ) . HBs-Ab seroconversion rate and antibody titer ( ELISA assay ) were compared in 27 patients of group 1 and 35 patients of group 2 at 1 month , and in 20 patients of group 1 and 26 patients of group 2 at 6 months after the last vaccine dose . The seroconversion rates ( HBs-Ab titer > 10 IU/L ) were 55.6 % and 50 % in group 1 , and 54.3 % and 50 % in group 2 , at 1 and 6 months , respectively ( p = NS ) . Patients ’ age , body mass index , serum albumin concentration , and sex distribution were similar in the responders and nonresponders . Intradermal hepatitis B vaccination used at half dose may be a cost saving alternative to intramuscular vaccination in patients on HD . However , the low overall seroconversion rate m and ates seeking alternative ways of vaccination in this patient population AIM A short vaccination protocol against hepatitis B was compared to the st and ard approach in patients under haemodialysis who were primarily non-responsive to the vaccine . METHODS This r and omized , controlled open trial included 51 chronic haemodialysis subjects previously vaccinated against hepatitis B and with anti-HBs levels of less than 10 IU/mol/L. Twenty-six patients received 20 microg i.m . once a week for 8 weeks ( short protocol ) and 25 subjects three doses of 40 microg i.m . at months 0 , 1 and 6 ( st and ard protocol ) . Clinical and laboratory data were compared between responders and non-responders . A logistic regression model included selected parameters to assess risk factors for non-seroconversion . RESULTS Seroconversion rates to vaccine at 2 months were 80 % and 78 % in the short and st and ard protocol groups , respectively ( P = 0.99 ) . Median of anti-HBs levels were similar up to 6 months of follow up , but patients in the st and ard protocol showed a trend to higher anti-HBs in month 3 and a more steady decline in antibody titres . Non-responders were older , had longer duration of dialysis and a higher prevalence of a prior renal transplant and hepatitis C. In multivariate analysis , only advanced age and hepatitis C remained independently associated with non-responsiveness to vaccination . CONCLUSION In haemodialysis patients , a short vaccination protocol against hepatitis B did not provide any benefit compared to the st and ard approach with respect to peak anti-HBs titres or a higher rate of seroprotection at the end of follow up . Other strategies to increase seroconversion rates should be explored , especially in the elderly and in patients with hepatitis BACKGROUND The response to recombinant hepatitis B vaccine remains suboptimal among the dialysis population . METHODS In this multi-centre r and omized controlled trial , we studied the factors that modify the response to intramuscular Engerix-B vaccination in patients on peritoneal dialysis . The primary aim was to study if a three-dose schedule of extra-high dose ( 80 microg ) of Engerix-B would offer better primary seroconversion and more persistent serological protection than the conventional 40-microg dose . RESULTS Forty-two peritoneal dialysis patients were r and omized to receive the conventional 40-microg Engerix-B dose and 45 patients to 80-microg dose .  Seroconversion [ hepatitis B surface antibody ( anti-HBs ) level > or = 10 IU/l 3 months after completion of the third dose ] occurred in 78.6 % of patients after 40-microg Engerix-B dosage treatment versus 62.2 % for those receiving 80-microg Engerix-B treatment ( P = 0.11 ) . After 12 months , the persistence of protective anti-HBs also did not differ between 40- ( 45.2 % ) and 80-microg ( 51.1 % ) treatment groups ( P = 0.67 ) . In contrast , patients with seroconversion 3 months after the third dose of Engerix-B had a higher normalized protein nitrogen appearance ( nPNA ) than patients without seroconversion ( 1.16 + /- 0.25 versus 0.96 + /- 0.23 g/kg/day , P = 0.001 ) . Conclusions . We found no evidence of a worthwhile clinical benefit from increasing the three-dose intramuscular Engerix-B vaccine from 40- to 80-microg dose . An unplanned analysis suggested a role of improved protein intake to improve the immune response to hepatitis B vaccine in peritoneal dialysis patients Partial correction of anemia by erythropoietin improves hemodialysis (HD)-associated immunosuppression . It is not known whether hemoglobin normalization improves immune status further . The authors prospect ively compared the immune function of HD patients with congestive heart failure or ischemic heart disease on erythropoietin therapy r and omized to normal versus anemic blood hemoglobin concentration . HD patients were r and omized into a normal hemoglobin group ( n = 17 , target hemoglobin of 14 + /- 1 g/dl ) or an anemic hemoglobin group ( n = 18 , target hemoglobin 10 + /- 1 g/dl ) . Delayed-type hypersensitivity , CD4 and CD8 counts , anti-tetanus toxoid antibody levels , erythrocyte complement receptor 1 expression , and lymphocyte proliferative responsiveness were measured . The observation period was 1 yr , and the trial was open label . Target hemoglobin was achieved and maintained in both groups . Significantly improved cutaneous reactivity was seen in the normal hemoglobin group ( P = 0.003 ) . The prevalence of anergy decreased in the normal hemoglobin group ( from 60 to 20 % ) but increased in the anemic hemoglobin group ( from 57 to 86 % ) . The anemic hemoglobin group had higher CD8 counts compared with baseline ( P = 0.0001 ) and compared with the normal hemoglobin group ( P = 0.038 ) . Both groups had significant increases in tetanus toxoid antibody levels after vaccination but without significant differences between groups . The anemic hemoglobin group had a progressive increase in erythrocyte complement receptor 1 levels compared with baseline ( P = 0.002 ) and relative to the normal hemoglobin group ( P = 0.023 ) . There was no consistent pattern of altered proliferative responsiveness of lymphocytes . The data suggest that certain aspects of immune function , particularly delayed-type hypersensitivity , may be improved in HD patients by normalization of hemoglobin through the administration of increased doses of erythropoietin Although the efficacy of hepatitis B vaccines in patients undergoing chronic hemodialysis ( HD ) treatment has been documented , the persistence of immunity in this population remains largely unknown . In this study we evaluated the persistence of hepatitis B vaccine immunity in HD patients . We followed 37 hepatitis B vaccinated HD patients ( following a four-dose vaccination schedule of 40 mug injections intramuscularly in the deltoid muscle at 0 , 1 , 2 , and 6 months ) for up to one year to evaluate the persistence of immunity ( as indicated by serum levels of hepatitis B surface antibody ( anti-HBs ) equal to or higher than 10 IU/L ) . One year after vaccination , 18.9 % of patients had lost their anti-HBs ( transient responders ) , while 81.1 % still had detectable antibodies in the serum ( persistent responders ) . From 81.1 % of persistent responders 11.5 % and 88.5 % were weak and high responders , respectively . There was no significant difference between persistent and transient responders regarding age , sex , or nutritional factors . We did not find any factors that related to maintaining protective levels of anti-HBs in HD patients . It seems that an antibody titer above 100 IU/L following vaccination is necessary in order to maintain that level of antibody one year later Hepatitis B vaccine is effective in producing protection against hepatitis B virus ( HBV ) infection in hemodialysis ( HD ) patients , but the antibody response is variable . To identify those factors implicated in the vaccine response , in a prospect i ve study over a 24-month period , we vaccinated 80 seronegative patients on HD ( group A ) and monitored clinical , biochemical , and immunologic parameters . The protective immunity acquired by vaccination was compared with that developed through HBV infection in 22 age-matched HD patients ( group B ) . The anti-HBs antibody-seronegative patients followed a four-dose vaccination schedule ( 0 , 1 , 2 , and 6 months ) with 40 microg DNA-recombinant hepatitis B vaccine . One month after vaccination , 77.5 % of the patients had seroconverted , and 72.5 % achieved high antibody response , whereas 22.5 % were nonresponders . Patients aged younger than 40 years seroconverted 100 % ; those aged 40 to 60 years , 75 % ( P < 0.01 ) ; and patients older than 60 years , 74 % ( P < 0.001 ) . No differences between responders and nonresponders concerning sex , time on HD , HD dose , nutritional status , hemoglobin level , HD membrane , iPTH level , calcitriol treatment , or number of transfusions during vaccination were found . The presence of other factors , such as recombinant human erythropoietin ( rHuEPO ) therapy or hepatitis C virus ( HCV ) infection , did not significantly influence antibody responses to hepatitis B immunization . A greater frequency of DR3 ( 53.8 % v 25.7 % , P < 0.05 ) , DR7 ( 53.8 % v 18.6 % , P < 0.01 ) , and DQ2 ( 76.9 % v 44.1 % , P < 0.05 ) , and a lesser frequency of A2 ( 7.7 % v 37.2 % , P < 0.05 ) were found in nonresponders compared with responders . Eighteen months after vaccination , the analysis showed similar antibody titers but lower seroconversion rates in group A as compared with group B. In conclusion , unresponsiveness to hepatitis B vaccine in HD patients was related to factors such as older age , the presence of DR3 , DR7 , and DQ2 , and the absence of A2 alleles . Although the seroprotection produced by the vaccine was less than that achieved through natural HBV infection , our protocol of vaccination was sufficiently immunogenic and provided lasting protection Background Hemodialysis patients possess particular attributes which increase the susceptibility to hepatitis B virus ( HBV ) infections . HBV vaccination significantly decreased the number of new HBV-infected patients . However , the conventional vaccination schedule requires a 6-months duration . This study aim ed to examine the efficacy the accelerated vaccination schedule among hemodialysis patients . Methods In this study , 202 consecutive hemodialysis patients at New Jeddah hospital were enrolled . The inclusion criteria were : ( 1 ) age was above 18 years , ( 2 ) all patients had undetectable HBV surface antigen and antibody . Exclusion criteria included : ( 1 ) patient had a positive serum HBV surface antigen and antibody using enzyme-linked immunosorbent assay ; ( 2 ) patient received a previous course of HBV vaccine , ( 3 ) patient who was pregnant . Patients were sequentially r and omized to receive either Hepatitis B recombinant DNA vaccine ( conventional schedule ) or to receive combined hepatitis A and B vaccine injection ( accelerated schedule ) . Testing for HBV surface antibodies was done one and three months after completion of the dosage schedule . The primary outcome was the proportion of seroprotection ( defined by serum HBV surface antibodies ≥ 10 mIU/ml ) . Adverse reactions were evaluated regarding both fever and post-injection pain scale . Results Patients ’ age ranged from 18 to 71 years . After 1 and 3 months of completion of the vaccination schedule , there was no statistical difference in the proportion of seroprotected patients among both groups . Conclusion Accelerated vaccination schedule using combined hepatitis A and B vaccine may be beneficial for HBV seroprotection among hemodialysis patients Objective To compare seroconversion using hepatitis B vaccine between hemodialysis ( HD ) and peritoneal dialysis ( PD ) patients . Design Data on PD patients vaccinated were collected retrospectively for the period 1992 to 1995 . The data on HD patients were collected prospect ively from 1991 to 1994 . Setting A university outpatient dialysis center . Participants All adult patients who received all four doses of hepatitis B vaccine while on dialysis were included ( 47 PD and 50 HD patients ) . Intervention Recombinant hepatitis B vaccine ( Engerix ) , 40 μg IM was administered at 0 , 1 , 2 , and 6 months . Main Outcome Measure Seroconversion was measured after completion of the vaccination series . Results 74 % of the HD patients seroconverted compared to 53 % of PD patients ( p = 0.03 ) . Older , heavier patients compared to all the other patients had a lower seroconversion rate in both the HD patients ( 55 % vs. 78 % ) and PD patients ( 38 % vs. 59 % ) ( p = 0.03 ) . Conclusion The seroconversion rate to recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear reasons . Further studies are required to determine the etiology of this difference Background Dialysis patients have a suboptimal response to hepatitis B ( HBV ) vaccination . This study aim ed to compare the immunogenicity of two vaccines : the third-generation Sci-B-Vac ™ vs. the second-generation Engerix B ® . The cohort included two groups of dialysis patients : naïve and previously vaccinated non-responders . Primary endpoints were antibody titers ≥10 IU/L at 3 and 7 month post-vaccination . Secondary objectives were seroprotection rates in vaccine-naïve patients and in previously vaccinated non-responders . Methods Eighty-six patients were assigned to  vaccine ( Sci-B-Vac ™ or Engerix B ® ) using computer-generated r and omization , stratified by age , gender , diabetes , and previous HBV vaccination . Sci-B-Vac ™ was administered in three doses , 10 μg , at 0 , 1 , and 6 months in naïve patients ; or 20 μg in previously vaccinated non-responders . Engerix B ® included four doses , 40 μg at 0 , 1 , 2 , and 6 months . Results Each group had 43 patients . Seroconversion was 69.8 % with Engerix B ® vs. 73.2 % with Sci-B-Vac  ™ . Antibody titers at 7 months were higher with Sci-B-Vac ™ ( 266.4 ± 383.9 , median 53.4 ) than with Engerix ® ( 193.2 ± 328.9 , median 19 ) . However , these differences were not significant , perhaps due to a suboptimal sample size . Conclusions This study suggests comparable immunogenicity for both vaccines . Thus , we can not reject the null hypothesis that there is no difference in seroconversion by vaccine type . It is noteworthy that naïve patients were vaccinated with a st and ard dose of Sci-B-Vac ™ , while Engerix B ® was administered at a double dose . Similarly , although mean antibody titer levels in the Sci-B-Vac ™ group were higher than in the Engerix ® group , this difference did not reach significance . Consequently , a future clinical trial should recruit a larger cohort of patients , using a st and ard double-dose protocol in both groups Hepatitis B ( HB ) virus infection is a major health problem in dialysis dependent end stage renal failure ( ESRF ) patients . The sero-conversion rate after recombinant HB vaccine in ESRF patients is poor . Adjuvants like Granulocyte Macrophage-Colony Stimulating Factor ( GM-CSF ) have been found to improve response rate to vaccines . This study was conducted to evaluate the efficacy of GM-CSF as an adjuvant to HB vaccine in ESRF patients who were non-responders to the usual three double dose vaccinations ( primary non-responders ) . Fifty consecutive HBsAg negative and anti-HBs negative ESRF patients on hemodialysis over thirty months were prospect ively included ( Jan. 96-June 98 ) . All received 40 ug of recombinant HB vaccine at 0 , 1 , 2 month interval . Anti-HBs titres were subsequently tested after four weeks of the third dose . There were 19 ( 38 % ) primary non-responders ( antiHBs negative ) . Twelve ( Group I ) of primary non-responders were given an additional dose of HB vaccine with 300 ug ( 5–6 ug/kg ) of GM-CSF ( Leucomax ) and the remaining seven ( Group II ) received only an additional dose of HB vaccine .  Anti-HBs was determined by Abbott 's ELISA kit , and titre above 10 m IU/mL was considered as protective . In Group I , sero-protective titres were obtained in 11 out of 12 ( 91.6 % ) patients , whereas in Group II none of the patients achieved sero-protection ( p < 0.001 ) . The sero-conversion rate improved from initial 62 % ( 31/50 ) to overall 84 % ( 42/50 ) after the use of GM-CSF . There were no adverse events noted with the use of GM-CSF . At one year , 24 out of 32 ( 75 % ) who were sero-protected earlier continued to remain sero-protected . This study indicates that GM-CSF is a potent HB vaccine adjuvant for sero-conversion in primary non-responders The doses of hepatitis B vaccine given to peritoneal dialysis ( PD ) patients are currently based on responsiveness data from hemodialysis ( HD ) patients . To determine whether the doses are also appropriate from PD patients , we did a head-to-head comparison of short-term and 2-year responses to hepatitis B vaccination of HD patients and PD patients . We evaluated serum titers of the antibody to hepatitis B surface antigen ( anti-HBs ) after the patients had completed a course of four consecutive intramuscular vaccinations ( 40 microg of Engerix-B administered into the deltoid muscle at 0 , 1 , 2 , and 6 months ) in 69 dialysis patients ( 47 HD and 22 PD patients ) who were both hepatitis B surface antigen ( HBsAg ) and anti-HBs negative . No patients had received a hepatitis B vaccination prior to the study . There was no significant difference in response to hepatitis B vaccination between the HD and PD groups ( 78.7 % versus 77.3 % , p=0.33 ) . The seroconversion rate defined as anti-HBs > or = 10IU/L was influenced only by age ( p=0.011 ) . There was also no significant difference in responsiveness between the HD and PD groups ( 60 % versus 50 % , p=0.41 ) at a 2-year follow-up . We conclude that doses of HBV vaccine being used for HD patients are also appropriate for PD patients and a booster dose of vaccine is required to maintain seroprotection for those who lost protecting anti-HBs BACKGROUND Parathyroid hormone ( PTH ) has an adverse effect on the immune system and may cause immunologic disorders in patients with chronic renal failure . The in vivo effects of a parathyroidectomy on the immunologic parameters was examined . METHODS Thirty-four patients under dialysis therapy  received a parathyroidectomy ( PTx ) for secondary hyperparathyroidism ( HPT ) . They were prospect ively studied regarding serum immunoglobulins , complements , CD markers , and serum soluble IL-2 receptor ( sIL-2R ) until 12 months after PTx . RESULTS The serum levels of IgG , IgA and IgM showed significant increase until 12 months after PTx ( P<0.001 , respectively ) . C3 , C4 , and CH50 also indicated significant increase at 12 months after PTx . In cellular immunity , only serum sIL-2R showed significant increase 2 weeks after PTx ( P = 0.028 ) . The hematocrit and serum albumin also improved significantly at 12 months . CONCLUSIONS PTx showed beneficial effects on humoral immunological markers . The effects are probably due to the remarkable PTH reduction and partly improved nutritional state after PTx We prospect ively studied the evolution of HBsAg antibody ( HBsAb ) after primary vaccination ( four doses ; Engerix B , 40 pg i.m at 0 , one , two and six months ) in 29 patients who were seronegative ( HBsAb < 10 IU/L ) , had not been previously vaccinated and were on hemodialysis . Their mean age was 45.58 + /- 10.98 years , and the hemodialysis duration ranged from 1 - 21 years . In addition , we assessed dialysis adequacy for all cases on four different occasions beside the estimation of predialysis serum albumin , serum ferritin , C-reactive protein ( CRP ) , transferrin saturation ratio ( TSAT ) , body mass index ( BMI ) and subjective global assessment ( SGA ) . We measured anti-HBs titer eight weeks after the fourth dose . Our results showed that two patients ( 6.90 % ) were nonresponders ( HBsAb < 10 IU/L ) after the completion of vaccination . One patient ( 3.45 % ) was a weak responder ( 10 - 100 IU/L ) . Strikingly , 26 patients ( 89.65 % ) showed good antibody response ( > 100 IU/L ) . HBsAb titers showed no significant correlation with age , duration of HD therapy , serum albumin , CRP , TSAT level , BMI or SGA scores ( p > 0.05 ) . Responders to primary vaccination had significantly higher levels of urea reduction ratio ( % ) and Kt/V compared to nonresponders ( 63.61 + /- 6.97 % and 1.25 + /- 0.15 vs. 52.0 + /- 2.10 % and 0.92 + /- 0.13 , respectively , P < 0.05 ) . In conclusion , this was a preliminary study showing a very high response to hepatitis-B vaccination among hemodialysis patients that neither correlated with age , systemic inflammation nor nutritional status . Efficient hemodialysis was associated with good response to hepatitis-B vaccine BACKGROUND Hepatitis B virus infection remains an important public health problem in the United States . Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults , particularly in those who have diabetes mellitus , or are older , male , obese , or who smoke . METHODS Phase 3 observer-blinded , r and omized ( 2:1 HBsAg-1018 [HEPLISAV-B ™ ]:HBsAg-Eng [ Engerix-B ® ] ) , active-controlled trial in adults 18 - 70 years of age .  HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0 , 4 , and 24 . The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus . Secondary endpoints included seroprotection rates in the total trial population and by age , sex , body mass index , and smoking status . RESULTS Among 8374 participants r and omized , 961 participants in the per- protocol population had type 2 diabetes mellitus . In diabetes participants , the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0 % , compared with 65.1 % in the HBsAg-Eng group , with a difference of 24.9 % ( 95 % CI : 19.3 % , 30.7 % ) , which met the prospect ively-defined criteria for noninferiority and statistical significance . In the total study per- protocol population ( N = 6826 ) and each pre-specified sub population , the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group . CONCLUSION Two doses of HBsAg-1018 , administered over 4 weeks , induced significantly higher seroprotection rates than three doses of HBsAg-Eng , given over 24 weeks , in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors . With fewer doses in a shorter time , and greater immunogenicity , HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection . Trial Registration clinical trials.gov Identifier : NCT02117934 ABSTRACT Background : Antibodies to hepatitis B virus ( HBV ) surface antigen ( anti-HBs ) may develop in response to HBV vaccination or infection . We investigated whether anti-HBs are an independent predictor of survival in hemodialysis ( HD ) patients . Methods : A 6-year prospect i ve study was conducted in 532 HD patients .  Survival analyses were performed using the Kaplan-Meier method and the Cox proportional hazard model . Results : In HBV non-infected patients , age ( P = 0.005 ) , coronary artery disease ( P = 0.002 ) , and non-response to HBV vaccine ( P = 0.008 ) were the independent risk factors of all-cause mortality .  In HBV infected patients , the only independent predictor of all-cause mortality was coronary artery disease ( P = 0.002 ) . Conclusion : The ability to produce the protective anti-HBs titer in response to HBV vaccine is a positive predictor of survival in HBV non-infected HD patients Background / Aims : Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination , including to hepatitis B vaccine . A recombinant HB vaccine containing a new adjuvant system AS04 ( HBV-AS04 ) has been recently developed ; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis . All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospect ively included . Methods : Patients received four 20-mcg doses of HBV-AS04 by intramuscular route ( deltoid muscle ) at months 0,1,2 , and 3 . Anti-HB surface antibody concentrations were measured at intervals of 1 , 2 , 3 , 4 , and 12 months . Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine . Results : 102 patients were enrolled and 91 completed the study . At completion of the vaccination schedule , using per- protocol analysis , 76 of 91 ( 84 % ) had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations ( GMCs ) of 385.25 mIU/mL. The sero-protection rate at month 12 was 84 % ( 48/57 ) with lower GMCs ( 62.74 mIU/mL , P<0.0001 ) . Multivariate analysis revealed a detrimental role of age on the immune response to HB-AS04 vaccine ( F Ratio , 4.04 ; P<0.04 ) . Tolerance to HBV-AS04 was good and only minor side-effects were observed . Conclusions : HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present . Prospect i ve studies with HBV-AS04 on larger study groups and with longer follow-ups are under way
We performed a systematic review and meta- analysis to examine factors associated with HBV immune response in dialysis patients , and the association between the immune response to the HBV vaccine and mortality .