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.

[Role of M-type phospholipase A2 receptor and its antibody in hepatitis B virus-associated membranous nephropathy].

OBJECTIVE: To examine levels of M-type phospholipase A2 receptor (PLA2R) and its antibody in the patients with hepatitis B virus-associated membranous nephropathy (HBV-MN), and to explore the correlation of PLA2R with laboratory parameters and pathological characteristics.
 Methods: A total of 49 adult patients with biopsy-proved HBV-MN were enrolled in this study. Levels of anti-PLA2R antibody in serum and PLA2R in renal tissue were detected. Patients were assigned into two groups: a positive PLA2R group and a negative PLA2R group. Differences in laboratory parameters and pathological characteristics were compared between the two groups.
 Results: Of 49 patients with HBV-MN, 17 had positive PLA2R expression in renal tissues. In the positive PLA2R group, 10 patients were positive for serum anti-PLA2R antibody. Patients with positive PLA2R expression in renal tissues showed higher levels of 24 hour urinary protein [(4.6±3.9) g/d], serum HbsAg (70.5%) and renal HbsAg expression (71%), while lower level of serum albumin [(24.1±7.5) g/L] than those of the negative group.
 Conclusion: PLA2R is expressed in the renal tissues and serum anti-PLA2R antibody can be detected in some HBV-MN patients. Positive PLA2R expression in renal tissue might be related to HbsAg deposition in serum and renal tissues. Patients with positive PLA2R expression in renal tissue have more severe glomerular sclerosis.

Hepatitis B Virus Revaccination With Standard Versus Pre-S Vaccine in Previously Immunized Patients With Celiac Disease.

OBJECTIVE: Previous studies have suggested that hepatitis B virus (HBV) vaccines may be less immunogenic in individuals with celiac disease (CD). A pre-S vaccine (Sci-B-Vac) has demonstrated superior immunogenicity compared with standard HBV vaccines in several diseases. We compared the short-term immunogenicity of a pre-S vaccine with a HBV vaccine (Engerix B) for repeat vaccination of seronegative, previously immunized patients with CD. METHODS: Participants were 1 to 18-year-old children with CD who despite standard HBV vaccines in infancy had nonprotective hepatitis B surface antibody (HBs-Ab) concentrations (≤10 mIU/mL). Patients were randomized to receive either Engerix B or pre-S vaccine. HBs-Ab concentrations were measured 1 month after the first dose. For those who had not responded after 1 dose, measurement was repeated after the third dose. RESULTS: Children (n = 82) were analyzed (42 pre-S vaccine and 40 Engerix B). Baseline characteristics were similar for both groups, including gluten-free diet status. Both arms showed high response rates following the first injection: 41 (98%) versus 35 (87%) for pre-S vaccine and Engerix B recipients, respectively (P = 0.08). All other patients responded when measured after dose 3. HBs-Ab concentrations (mIU/mL) were higher in the pre-S vaccine group (median 925, interquartile range [IQR] 424-1000) than the Engerix B group (median 363, IQR 106-996, P = 0.005). Twenty (48%) of the pre-S vaccine recipients were "high responders" (>1000 mIU/mL) versus 10 (25%) in Engerix B recipients (P = 0.008). CONCLUSIONS: Both vaccines elicited adequate booster responses in most previously vaccinated patients with CD with nonprotective HBs-Ab concentrations. Pre-S vaccine administration resulted in higher Hbs-Ab concentrations. Our data suggest that a single dose of either vaccine is sufficient to raise titers to protective levels in most patients with CD.

Responses to multiple injections with alum alone compared to injections with alum adsorbed to proteins in mice.

New effects and mechanisms of alum on innate immunity have emerged in recent years. A number of cellular and molecular mechanisms induced by aluminum adjuvant have been reported, while the role of NALP3 and inflammasome in the cellular pathway induced by alum is still controversial. The effect of injection of alum alone without vaccine antigen into human has not been reported so far. Recently, in a phase IIIa double-blinded placebo controlled clinical trial testing the therapeutic HBsAg-anti-HBs vaccine formulated with alum against chronic viral hepatitis B patients, the placebo group receiving alum only showed substantial therapeutic effects. To explore possible underlying therapeutic mechanisms, mice were treated either with multiple injections of alum alone or with alum adsorbed to proteins (HBsAg-anti-HBs). After 4 injections Gr1(+)/CD11b(+) cells in the spleen were increased in both alum alone and alum adsorbed in proteins groups. Increased Gr1(+)/CD11b(+) cells in spleens remained consistently high in the alum alone treated group, while Gr1(+)/CD11b(+)cells decreased in the alum adsorbed to proteins group after 6 injections. Both treatments triggered increased levels of TNF-alpha measured in the plasma, but only the alum alone treated mice showed increased levels of IL-10. Histology of the liver tissues revealed a higher number of spotty necrotic foci in the alum alone immunized group. Taken together, potent inflammatory responses were induced in the alum alone immunized mice, which suggests that the substantial therapeutic effects observed in chronic hepatitis B patients immunized with alum alone might be attributed to inflammatory responses.

Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age.

BACKGROUND: The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). METHODS: In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. RESULTS: A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. CONCLUSIONS: A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.

No inflammation? No cancer! Clear HBV early and live happily.

COMMENTARY ON: Clearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma in a cohort Chronically Infected with Hepatitis B Virus. Simonetti J, Bulkow L, McMahon BJ, Homan C, Snowball M, Negus S, Williams J, Livingston SE. Hepatology. 2009 Nov 30. [Epub ahead of print]. Copyright 2009. Reprinted with permission of John Wiley and Sons, Inc. Abstract: Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated. We performed a prospective population-based cohort study in 1271 Alaska native persons with chronic HBV infection followed for an average of 19.6 years to determine factors associated with loss of HBsAg and risk of developing HCC thereafter. HBsAg loss occurred in 158 persons for a rate of HBsAg clearance of 0.7%/year. Older age, but not sex, was associated with clearance of HBsAg, and loss of HBsAg was not associated with any particular HBV genotypes (A-D, and F) found in this population. Participants were followed for an average of 108.9 months after HBsAg loss. Six patients, two with cirrhosis and four without, developed HCC a mean of 7.3 years after HBsAg clearance (range, 2.0-15.5 years). The incidence of HCC after clearance of HBsAg was 36.8 per 100,000 per year (95% CI 13.5-80.0) which was significantly lower than the rate in those who remained HBsAg-positive (195.7 cases per 100,000 person-years of follow-up [95% CI 141.1-264.5; P<0.001). After loss of HBsAg, HBV DNA was detected in the sera of 28 (18%) of those who cleared a median of 3.6 years after clearance. CONCLUSION: HCC can occur in persons with chronic hepatitis B who have lost HBsAg, even in the absence of cirrhosis. These persons should still be followed with periodic liver ultrasound to detect HCC early.

Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults.

BACKGROUND: Many individuals do not respond to a three-dose series of hepatitis B vaccine (HBV) and most do not achieve a protective antibody response until after dose 2 or 3. METHODS: Healthy, seronegative 18-28 year old adults were randomly assigned in equal numbers to receive two doses of the experimental vaccine (HBV-ISS without alum) (0, 8 weeks) and placebo (24 weeks) or Engerix-B (0, 8, 24 weeks). Adverse events were collected during the first week and at 4 weeks after each injection. Antibodies were measured 4 weeks after dose 1; before, 1 and 4 weeks after dose 2, and before, 1 and 4 weeks after dose 3 and at 1 year. RESULTS: Ninety-nine participants were enrolled (65% female; mean age 22.6 years). 79% of HBV-ISS and 12% of Engerix-B recipients had a protective antibody response 4 weeks post dose 1 (geometric mean concentration [GMC] 23.0 and 1.87 mIU/mL, respectively). By 1 week post dose 2, 100% of HBV-ISS and 18% Engerix-B recipients had protective levels (GMC 1603 versus 2.40 mIU/mL). Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups. Mild injection-site tenderness was more common after HBV-ISS than Engerix-B after both doses (74-77% compared to 34-58%; p

A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant.

Certain oligodeoxynuclotides with CpG motifs provide enhanced immune response to co-delivered antigens. We performed a phase I, observer-blinded, randomized study in healthy anti-hepatitis B surface antigen (anti-HBsAg) antibody negative adults to explore safety and immunogenicity of co-injection of recombinant HBsAg combined with an immunostimulatory DNA sequence (ISS) 1018 ISS. Four ISS dosage groups (N=12 per group) were used: 300, 650, 1000 or 3000 microg. For each group, two controls received 20 microg HBsAg alone, two controls received ISS alone, and eight subjects received ISS+20 microg HBsAg. Subjects received two doses 8 weeks apart. Injection site reactions (tenderness and pain on limb movement) were more frequent at higher ISS+HBsAg doses but were mainly mild and of short duration. Higher anti-HBsAg antibody levels were associated with higher ISS doses. Four weeks after the first dose, a seroprotective titer (>or=10 mIU/ml) was noted for 0, 25, 75, and 87.5% of subjects by increasing ISS dose group (P<0.05) for those who received ISS+HBsAg; 1 month after the second dose this increased to 62.5, 100, 100, and 100%, respectively. Geometric mean anti-HBsAg antibody levels by increasing ISS+HBsAg dose were 1.22, 5.78, 24.75, and 206.5 mIU/ml after the first dose and 65.37, 877.6, 1545, and 3045 mIU/ml after the second dose. We conclude that 1018 ISS+HBsAg was well tolerated and immunogenic in this phase I study in healthy adults and may offer the potential for enhancement of hepatitis B virus (HBV) immunization and protection after one or two doses or in individuals who fail to respond to the standard vaccine regimen.

The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population.

Approximately 5% of vaccinees display an inadequate response after the administration of the standard three dose hepatitis B vaccine. A new hepatitis B vaccine (HBsAg/AS04) formulated with the adjuvant AS04 which contains 3'-deacylated monophosphoryl lipid A (3D-MPL) and alum has been developed. AS04 enhances the immune response which may be beneficial to non-responders. In a single-blind, randomised study, we tested the immunogenicity and reactogenicity of the new vaccine with that of commercially established hepatitis B vaccine, both on a 0, 1, 6 months schedule in 20-60 years old non-responders (titre <10 m IU/ml after four doses of hepatitis B vaccine). One month after the first dose the seroprotection rate was 44% for group 1 (58 subjects) receiving the established vaccine versus 66% for group 2 receiving HBsAg/AS04 (57 subjects) (P=0.03). One month after the second dose this was 58 and 81%, respectively (P<0.005) and 1 month after the third dose this was 68 and 98%, respectively (P<0.001). One month after each dose, GMTs were 34, 56 and 111 mIU/ml for group 1 versus 123222 and 1937 mIU/ml for the HBsAg/AS04 group (P<0.05, <0.01 and 0.0001, respectively). Pain at the injection site was the most commonly reported local symptom and very few symptoms were scored as severe. In this group of adult non-responders to previous hepatitis vaccination, the HBsAg/AS04 vaccine was well tolerated and induced, at all time-points, a superior immune response compared to the licensed hepatitis B vaccine.

New vaccination strategies for low- and non-responders to hepatitis B vaccine.

The currently available recombinant hepatitis B vaccines are safe, efficacious and immunogenic. Nevertheless, a high rate of low- and nonresponsiveness to the current vaccine poses a problem since this group remains susceptible to infection with hepatitis B virus. Efforts are underway to develop new vaccines and strategies to enhance seroprotection rates. One possibility under investigation is the low-dose intradermal administration of vaccine since the immune system is well represented in both the epidermis and the dermis. Despite encouraging results concerning the immunogenicity in previous non-responders, the main difficulty is the technique of administration and unacceptable local adverse effects. Promising data have emerged from clinical trials evaluating the immunogenicity of new recombinant vaccines containing the complete pre-S1 and pre-S2 regions of HbsAg and, more recently, of novel adjuvanted hepatitis B vaccines. Future approaches include DNA vaccination and expression of HbsAg determinants in live recombinant vectors.

A prophylactic hepatitis B vaccine with a novel adjuvant system.

Studies with recombinant hepatitis B vaccines show seroprotection rates varying between 91 and 100%. Thus, a limited risk may remain for non-responding populations (e.g. non-responders, haemodialysis patients, elderly) who could benefit from a more immunogenic hepatitis B vaccine. One strategy to enhance the immune response is the use of novel adjuvants. SmithKline Beecham has developed a new adjuvant system containing alum and 3-deacylated monophosphoryl lipid A: SBAS4 (SmithKline Beecham Adjuvant System 4). Pilot studies showed that SBAS4 improved in vivo humoral and in vitro cellular immune responses compared to the response to classical recombinant hepatitis B vaccines and was safe and well-tolerated. Several studies assessed the profile of the HBsAg/SBAS4 vaccine in a healthy population, non-responders or elderly. In general the HBsAg/SBAS4 vaccine was well tolerated. Compared to an established recombinant hepatitis B vaccine, we observed an increased local reactogenicity but few symptoms were reported as severe. The HBsAg/SBAS4 vaccine elicits a strong immune response: subjects are protected faster and the GMTs are usually much higher. HBsAg/SBAS4 thus has the potential to protect those subjects who fail to be protected by well established hepatitis B vaccines.

Nonassociation of aflatoxin with primary liver cancer in a cross-sectional ecological survey in the People's Republic of China.

A comprehensive cross-sectional survey was undertaken in The People's Republic of China of possible risk factors for primary liver cancer (PLC) to include 48 survey sites, an approximately 600-fold aflatoxin exposure range, a 39-fold range of PLC mortality rates, a 28-fold range of hepatitis B virus surface antigen (HBsAg+) carrier prevalence, and estimation of exposures for a large number of other nutritional, dietary, and life-style features. PLC mortality was unrelated to aflatoxin intake (r = -0.17) but was positively correlated with HBsAg+ prevalence (P less than 0.001), plasma cholesterol (P less than 0.01), frequency of liquor consumption (P less than 0.01), and mean daily intake of cadmium from foods of plant origin (P less than 0.01). Multiple regression analyses for various combinations of risk factors showed that aflatoxin exposure consistently remained unassociated with PLC mortality regardless of variable adjustment. In contrast, associations of PLC mortality with HBsAg+, plasma cholesterol, and cadmium intake remained, regardless of model specification, while the association with liquor consumption was markedly attenuated (was nonsignificant) with adjustment for plasma cholesterol. The sharp contrast between the findings of no aflatoxin effect upon PLC prevalence in this survey and the positive correlation reported for previous but more restricted surveys is discussed. Based on the results of this survey and the data of laboratory animal and in vitro studies, an explanatory model for the etiology of PLC is proposed, taking into consideration the role of nutrition in the etiology of this disease.

[Evaluation of the treatment of chronic active hepatitis (HBsAg+) with isoprinosine. II. Immunological studies]. / Ocena leczenia przewleklego aktywnego zapalenia watroby (HBsAg+) izoprynozyna. II. Badania immunologiczne.

A two-month treatment of the chronic active hepatitis (HBsAg+) with isoprinosine produced quantitative and functional T-cells populations in patients with cellular response disorders. Immunological studies have shown that such an effect of isoprinosine lasted for about 4-5 months. Repeated administration of isoprinosine for one month normalized recurrent abnormalities in the monitored immunological parameters.

[Specific safety and immunogenicity of a subunit vaccine against hepatitis B]. / Izuchenie spetsificheskoi bezvrednosti i immunogennosti sub"edinichnoi vaktsiny protiv gepatita B.

The results of trials of a subunit vaccine against hepatitis B in volunteers are presented. The active substance of the vaccine was HBsAg isolated from the plasma of asymptomatic antigen carriers. The preparation under study is highly immunogenic, shows poor reactogenicity, and safety in use.

Accidental hepatitis-B-surface-antigen-positive inoculations. Use of e antigen to estimate infectivity.

We assessed the ability of radioimmunoassay for hepatitis B e antigen (HBeAg) to predict infectivity in exposed medical personnel by analyzing 390 samples of sera positive for hepatitis B surface antigen (HBsAg) that were implicated in accidental inoculations of known outcome. The radioimmunoassay detected HBeAg or its antibody (anti-HBe) in 91% of the donor sera. The incidence of hepatitis B was 19% (44 of 234) in recipients of HBeAg-positive sera but was only 2.5% (three of 121) in recipients of sera positive for anti-HBe, and nil (none of 35) in recipients of sera negative for HBeAg and anti-HBe. The known relation of HBeAg and infectivity was quantified by radioimmunoassay as a risk ratio of 10:1 (HBeAg-positive to HBeAg-negative) for this type of exposure. The sensitivity of the radioimmunoassay also showed that a large proportion (55%) of donor sera not producing hepatitis were positive for HBeAg; therefore, even the most flagrant needlestick exposures to HBsAg-positive sera often must involve subthreshold amounts of infective material.

Autoimmune hemolytic anemia in children.

Autoimmune hemolytic anemia may represent an acute medical emergency. The anemia is normocytic normochromic and is usually associated with an elevated reticulocyte count. The diagnosis is confirmed by positive direct and indirect Coombs tests. Treatment consists of blood transfusion if the anemia is life-threatening. Steroids promote a decrease in the serum immunoglobulin level and block binding of antibody to the red blood cell. Splenectomy is reserved for those patients who fail to respond to steroids.

Methods of hepatitis B virus transfer in oral surgery.

There are a variety of modes of transmission of the hepatitis B virus. Although the traditional parenteral mechanism of direct transfer of the virus via a needle containing infected serum or plasma is the most common, nontraditional parenteral mechanisms have been documented. These include transfer of the virus via saliva and plasma through minute skin abrasions, through mucosal surfaces, and indirectly via inanimate environmental surfaces. Current evidence does not support an intestinal mode of transmission. The various modes of transmission. The various modes of transfer of hepatitis B virus cause particular problems for people in the dental health care profession. However, knowledge of the different modes of virus transmission will allow the dental practitioner to take appropriate precautions to prevent transfer of hepatitis B virus from patient to dentist.

Hepatitis B infection in patients with end stage renal disease: some characteristics and consequences.

Susceptibility to hepatitis B infection appears to be in part genetically determined. The HLA specificity Bw35 is commonly associated with a higher frequency of both transient and persistent hepatitis B surface antigen in the serum. Persistent hepatitis B surface antigenemia occurring in patients with end stage renal disease while on dialysis is associated with a poor prognosis and markedly decreased survival regardless of whether the individual is treated subsequently by chronic dialysis or by transplantation. We conclude that persistent hepatitis B surface antigenemia is not a contraindication to transplantation since outcome is not improved by management on hemodialysis.