RESUMEN

Universal infant hepatitis B vaccination has been implemented more than three decades. This study aimed to determine the prevalence of antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc) in qualified blood donors in Nanjing, China. Plasmas of 815 qualified blood donors, collected from February through May 2019, were measured for anti-HBs and anti-HBc by enzyme-linked immunosorbent assay. There were 449 (55.1%) male and 366 (44.9%) female blood donors, with a median age of 28.9 years (18-60). The seroprevalence of anti-HBs was 58.8%, with no significant difference in different genders and different age groups. The overall prevalence of anti-HBc was 7.0%, with an increasing trend with age, from 0% in 18-20 years old group to 17.9% in 51-60 years old group (χ2 = 46.7965, p < .0001). The prevalence of anti-HBc in donors born after the implementation of universal hepatitis B vaccination was significantly lower than that in donors born before (1.0% vs 15.5%; χ2 = 63.6033, p < .0001). Our data suggest that more than half of the blood donors in Nanjing are anti-HBs positive. Since a blood recipient usually receives more than one unit of red blood cells or plasma, passively acquired anti-HBs in blood recipients may neutralize hepatitis B virus potentially presented in blood donors with occult hepatitis B infection. In addition, the presence of anti-HBs and/or anti-HBc in blood donors may cause unique hepatitis B serological profile in blood recipients.

Asunto(s)

RESUMEN

INTRODUCTION: Surveillance programs after hepatitis B surface antigen (HBsAg) loss are not yet well established, and the role of hepatitis B surface antibodies (anti-HBs) remains controversial. We aimed to evaluate the risk factors for increased mortality and the association between anti-HBs and all-cause and cause-specific mortality in a representative US (United States) population of patients with resolved HBV (Hepatitis B virus) infections. METHODS: Data were taken from the US National Health and Nutrition Examination Survey (NHANES) 1999-2018. A total of 3455 US adults with resolved HBV infection [defined as hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive] were enrolled in this study. The primary outcome measures were all-cause and cause-specific mortality from baseline until 31 December 2019. RESULTS: During a mean follow-up of 10.3 years, 741 deaths occurred. Age, race, marital status, smoking status, physical activity level, and presence of cirrhosis, diabetes, cardiovascular diseases, chronic obstructive pulmonary diseases, cancer, and anti-HBs were significant factors for increased mortality, and a nomogram tool was developed and validated for the risk stratification of mortality. Compared with participants who were anti-HBs positive, those who were anti-HBs negative had a 23% (hazard ratio 1.23, 95% CI 1.02-1.46) higher risk of all-cause mortality in NHANES 1999-2018. For cause-specific mortality, the fully adjusted hazard ratios of participants who were anti-HBs negative were 0.71 (95% CI 0.48-1.06) for heart disease, 1.44 (95% CI 1.01-2.05) for cancer, and 1.44 (95% CI 1.13-1.83) for other conditions, compared to those of participants who were anti-HBs positive. CONCLUSIONS: Among US adults with resolved HBV infections, anti-HBs-negative status was associated with an increased risk of death from all causes and cancer, implying that the role of anti-HBs in resolved HBV infection should not be ignored. On the public health level, more rigorous surveillance was needed for populations of individuals who were isolated anti-HBc positive.

RESUMEN

BACKGROUND: Among elder children/young adults who received hepatitis B virus (HBV) vaccination during infancy, the serological status of HBsAg-negative and anti-HBc-positive [HBsAg(-)/anti-HBc(+)] was frequently reported, indicating potential occult HBV infection (OBI). It is required to define the long-term protection of neonatal vaccination against OBI in their mature adulthood. METHODS: Building upon the 1983-1990 established Qidong Hepatitis B Intervention Study, we sampled 10% of the 28-35-year-old participants, who remained in the cohort by 2012. Each participant was tested for serological markers of HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc. HBV-DNA and relaxed circular DNA (rcDNA) were determined in some HBsAg(-)/anti-HBc(+) individuals. RESULTS: Totally, 3615 individuals from the neonatal vaccination group and 3100 individuals from the control group donated blood samples, respectively. In the vaccination group, the prevalence of HBsAg was 1.58% (57/3615), HBsAg(-)/anti-HBc(+) was 4.70% (170/3615), significantly lower than in the control group, which was 7.45% (231/3100) and 19.48% (640/3100) respectively (all p < 0.001). With aging, HBsAg(-)/anti-HBc(+) prevalence increased in the sampled participants from the control group (pfor trend < 0.001), but uncertain from the vaccination group. Of HBsAg(-)/anti-HBc(+), HBV-DNA was detected in 13.08% (17/130) from the vaccination group, and in 4.18% (12/287) from the control group. HBV rcDNA was detected in most sera that were tested positive for HBV-DNA. CONCLUSIONS: OBI occurred in some vaccinated adults. However, neonatal HBV vaccination kept the effective protection against OBI in mature adults.

Asunto(s)

RESUMEN

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

RESUMEN

OBJECTIVE: In India, Hepatitis B vaccination is recommended at 6 wk except for hospital-deliveries. The authors examined protection afforded by the birth dose. METHODS: A case-control study was done. HBsAg and HBcAb were tested in 2671 children, 1 to 5 y and HBsAb was evaluated in a subset of 1413 children. Vaccination history was recorded. Cases were HBsAg carriers. In another analysis, children who got infected (HBsAg and/or HBcAb positive) were considered as cases. Exposed were the unvaccinated. In another analysis, exposed were those vaccinated without the birth dose. RESULTS: The odds ratio (OR) for HBsAg positivity with birth vaccination was 0.35 (95% CI 0.19-0.66); while with vaccination at 6 wk was 0.29 (95%CI 0.14-0.61), both compared to unvaccinated. Birth vaccination has no added protection when compared to the unvaccinated. Unvaccinated children in index study had HBsAg positivity of 4.38%. The number needed to treat (NNT) to prevent one case of HBsAg positivity was 32.6 (95% CI, 20.9 to 73.6). The odds of getting HBV infection was 0.42 (CI 0.25-0.68) with birth dose and 0.49 (CI 0.30-0.82) without the birth dose compared to the unvaccinated. Protective antibody (HBsAb) was present in about 70% of the vaccinated. In the unimmunised, in the first 2 y HBsAb protection was present in 40%. The odds ratio (OR) for HBsAb in the fully vaccinated between 4 and 5 y was 1.4 (95%CI 0.9-2.18) compared to the unvaccinated. CONCLUSIONS: The present study lends support to the pragmatic approach of the Government to vaccinate babies born at home starting at 6 wk.

Asunto(s)

RESUMEN

BACKGROUND/AIMS: A birth dose of hepatitis B immunoglobulin (HBIG), in combination with hepatitis B vaccine (HepB), is recommended for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. However, the optimal dosage of HBIG remains to be resolved. This prospective cohort study aimed to compare the efficacy of two dosages of HBIG combined with HepB to prevent mother-to-child transmission (MTCT) of HBV. METHODS: From 2009 to 2011, we prospectively enrolled mother-infant pairs with positive maternal HBsAg in China. Infants were assigned to receive one dose of 100 IU or 200 IU HBIG within 12 h of birth according to maternal numbering, followed by completion of the 3-dose 10 µg HepB series. At 7 months, post-vaccination serologic testing (PVST) was performed in 545 and 632 infants in 100 IU and 200 IU HBIG groups, respectively, among whom, 451 and 529 were followed up to 12 months. RESULTS: Maternal and birth characteristics were comparable between infants in 100 IU and 200 IU HBIG groups. At 7 months, the rates of perinatal infection were 1.5% (8/545) and 1.9% (12/632) in 100 IU and 200 IU HBIG groups, respectively (p = .568). One non-responder infant in 200 IU HBIG group became newly infected at 12 months. The antibody to hepatitis B surface antigen (anti-HBs) positive rates were 98.5% (529/537) and 98.2% (609/620) in 100 IU and 200 IU HBIG groups at 7 months, respectively (p = .704), and the corresponding figures were 98.2% (431/439) and 97.1% (496/511) at 12 months (p = .266). The anti-HBs geometric mean concentrations were comparable between two groups at 7 months (707.95 mIU/mL vs. 602.56 mIU/mL, p = .062) and 12 months (245.47 mIU/mL vs. 229.09 mIU/mL, p = .407). CONCLUSIONS: One birth dose of 100 IU HBIG, combined with the HepB series, might be enough for preventing MTCT of HBV in infants born to HBsAg-positive mothers.

Asunto(s)

RESUMEN

BACKGROUND & AIMS: An extracellular vesicle (EV) is a nanovesicle that shuttles proteins, nucleic acids, and lipids, thereby influencing cell behavior. A recent crop of reports have shown that EVs are involved in infectious biology, influencing host immunity and playing a role in the viral life cycle. In the present work, we investigated the EV-mediated transmission of hepatitis B virus (HBV) infection. METHODS: We investigated the EV-mediated transmission of HBV infection by using a HBV infectious culture system that uses primary human hepatocytes derived from humanized chimeric mice (PXB-cells). Purified EVs were isolated by ultracentrifugation. To analyze the EVs and virions, we used stimulated emission depletion microscopy. RESULTS: Purified EVs from HBV-infected PXB-cells were shown to contain HBV DNA and to be capable of transmitting HBV DNA to naive PXB-cells. These HBV-DNA-transmitting EVs were shown to be generated through a ceramide-triggered EV production pathway. Furthermore, we showed that these HBV-DNA-transmitting EVs were resistant to antibody neutralization; stimulated emission depletion microscopy showed that EVs lacked hepatitis B surface antigen, the target of neutralizing antibodies. CONCLUSIONS: These findings suggest that EVs harbor a DNA cargo capable of transmitting viral DNA into hepatocytes during HBV infection, representing an additional antibody-neutralization-resistant route of HBV infection.

RESUMEN

AIM: Few studies concerning the protective management of hepatitis B virus (HBV) infection among health-care personnel (HCP), excluding occult HBV or carriers, have been reported. Therefore, we undertook a cross-sectional study of the updated status of HBV vaccine management by measuring the antibody to hepatitis B surface antigen (anti-HBs) along with the antibody to hepatitis B core antigen (anti-HBc). METHODS: Both anti-HBs and anti-HBc were assessed in 1085 HCP employed by our institute. Hepatitis B virus vaccination-related histories were recorded using self-administered questionnaires. RESULTS: Of 1085 HCP, 27 (2.5%) were positive for anti-HBc, and its positive rate increased with age. Of the 1058 subjects with negative anti-HBc, 879 (83.1%) were positive for anti-HBs. The median titer of anti-HBs was 71.1 mIU/mL, which was higher in female subjects (P = 0.037). By age group, the positive rate of anti-HBs were 77.5%, 89.3%, 90.8%, and 81.6% in the groups aged ≤29, 30-39, 40-49, and ≥50 years, respectively (P < 0.001). Of the 908 subjects who reported receiving HBV vaccination, 6 (0.7%) were positive for anti-HBc. Among them, one subject was suspected to have a possible subclinical HBV infection after the HBV vaccination. CONCLUSION: We report the current HBV vaccination-related seroprevalence of anti-HBs along with anti-HBc in a Japanese tertiary medical institution consisting of more than 1000 HCP, which was an level comparable to similar sized hospitals in developed countries. Anti-HBc would be important for understanding HBV status, but not necessary for general HBV vaccine management for HCP.

RESUMEN

AIM: Current guidelines recommend all patients scheduled to receive chemotherapy should be screened for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B virus core antigen (anti-HBc) status. However, still, more research is needed to identify the risk factors for hepatitis B virus (HBV) reactivation. We retrospectively investigated the incidence, risk factors and outcome of HBV reactivation in HBsAg negative patients with hematological malignancies. METHODS: Seven hundred and thirty-eight HBsAg negative patients with hematological malignancies were included in the study. HBV reactivation was defined as reverse seroconversion of HBsAg (HBsAg reappearance). Risk factors, cumulative incidence and overall survival of HBV reactivation were analyzed. RESULTS: Reactivation occurred in 23 of the 738 (3.1%) enrolled patients. As expected, the reactivation rate of the anti-HBc positive group was significantly higher than that of the anti-HBc negative group (5.4% vs 0.8%). Multivariate analysis indicated that loss of antibody to the hepatitis B surface antigen (anti-HBs) was an independent risk factor. Patients with acute lymphoblastic leukemia and multiple myeloma showed significantly higher reactivation rate than those with other diseases. The cumulative incidence of HBV reactivation after starting chemotherapy in the anti-HBc positive subgroup was 0.3% at 1 year, 1.7% at 2 years and 10.5% at 3 years. CONCLUSION: Close monitoring of HBV markers, including anti-HBs, should be performed for longer than 24 months. Further study is needed to establish a strategy to prevent HBV reactivation after chemotherapy in HBsAg negative patients with hematological malignancies.

RESUMEN

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for nucleoside analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described. METHODS: We compared the HBsAg kinetics and long-term serologic outcomes of 51 chronic hepatitis B patients achieving HBsAg seroclearance during NA therapy with those of 51 HBsAg-positive controls, matched for age, sex, hepatitis B e antigen status, NA type, and treatment duration. Viral profiles before and after HBsAg seroclearance during and after NA treatment cessation were determined. RESULTS: The median time to HBsAg seroclearance and the median follow-up duration after HBsAg seroclearance were 61.2 and 51.6 months respectively. Patients achieving HBsAg seroclearance maintained high median rates of HBsAg reduction throughout therapy (first 6 months, 0.40 IU/mL/year; after year 1, 0.39 IU/mL/year; p = 0.809). For controls, the median rate of HBsAg reduction was significantly slower with time (first 6 months and after year 1, 0.19 and 0.05 IU/mL/year; p = 0.006). The difference in the median HBsAg reduction rates after year 1 between the two groups was significant (p < 0.001). The cumulative rates of antibody to HBsAg development and HBsAg seroreversion 72 months after HBsAg seroclearance were 68.9 and 8.3% (one patient receiving immunosuppressive therapy; one patient with pre-S/S variant), respectively. Among 22 patients who discontinued therapy after HBsAg seroclearance, 21 remained HBsAg negative with undetectable hepatitis B virus DNA and one patient with reactivation had the pre-S/S variant. CONCLUSION: NA-treated patients achieving HBsAg seroclearance uniquely maintained high rates of HBsAg reduction throughout treatment, with HBsAg seroclearance durable in most of the patients after treatment cessation.

Asunto(s)

RESUMEN

The immune system becomes less effective with age, and older age is associated with an increased susceptibility to diseases and reduced responses to vaccination. Furthermore, some adult populations, such as those with diabetes mellitus, are at increased risk of acute hepatitis B virus (HBV) infection. Decreasing responses to vaccination with advanced age have been described, but it is not known at what age immunogenicity starts to reduce, or until what age immunogenicity remains acceptable (for example ≥ 80% seroprotection post-vaccination). We characterized the relationship between age and seroprotection rate induced by recombinant HBV vaccination by conducting a pooled analysis of clinical trial data. Healthy adults aged ≥ 20 y who had been vaccinated with 20 µg HBV vaccine (Engerix™ B, GSK Vaccines, Belgium) in a 0, 1, 6 months schedule in 11 studies since 1996 were included. The observed seroprotection rate, defined as an anti-HBV surface antigen antibody concentration ≥ 10 mIU/ml was 94.5% in the whole population (N = 2,620, Total vaccinated cohort), ranging from 98.6% in adults vaccinated at age 20-24 years, to 64.8% in those vaccinated at age ≥ 65 y A model on seroprotection rates showed a statistically significant decrease with age, and predicted that the anti-HBs seroprotection rate remains ≥ 90% up to 49 y of age and ≥ 80% up to 60 y of age. Individuals at risk of HBV infection should be vaccinated as early in life as possible to improve the likelihood of achieving seroprotection. Additional studies are needed to identify whether unvaccinated individuals older than 60 y would benefit from regimens that include additional or higher vaccine doses.

Asunto(s)

RESUMEN

OBJECTIVE: The aim of the study was to estimate long-term cost­effectiveness of a hepatitis B vaccination catch-up program among children born between 1994 and 2001 (when they were 8­15 y old) in Shandong province, China, to provide information for nationwide evaluation and future policy making. METHODS: We determined the cost-effectiveness of the catch-up program compared with the status quo (no catch-up program). We combined a Decision Tree model and a Markov model to simulate vaccination and clinical progression after hepatitis B virus (HBV) infection. Parameters in the models were from the literature, a field survey, program files, and the National Notifiable Disease Reporting System (NNDRS). The incremental cost­effectiveness ratio (ICER) was used to compare the 2 alternative strategies. One-way sensitivity analysis, 2-way sensitivity analysis, and probability sensitivity analysis were used to assess parameter uncertainties. RESULTS: The catch-up program was dominant compared with the status quo. Using a total of 5.53 million doses of vaccines, the catch-up program could prevent 21,865 cases of symptomatic acute hepatitis B, 3,088 carrier states with positive hepatitis B surface antigen (HBsAg), and 812 deaths due to HBV infection. The catch-up program could add 28,888 quality-adjusted life years (QALYs) and save $192.01 million in the targeted population in the future. The models were robust, considering parameter uncertainties. CONCLUSION: The catch-up program in Shandong province among children born between 1994 and 2001 was 'very cost-saving.' It could save life years and reduce total future costs. Our study supported the desirability and impact of such a catch-up program throughout China.

Asunto(s)

RESUMEN

BACKGROUND: A high prevalence of reactivation of hepatitis B has been documented among immunosuppressed individuals in the inactive phase of chronic hepatitis B; However, the proportion of and the risk factors for reactivation are largely unknown among non-immunosuppressed persons. OBJECTIVES: Estimate the incidence rate of and risk factors for hepatitis B reactivation in a population-based cohort of persons in the inactive phase of chronic hepatitis B in Alaska. STUDY DESIGN: A cohort of 414 Alaska Native Persons in the inactive phase of hepatitis B (HBV DNA<2000 IU/mL and normal alanine aminotransferase (ALT) for 12 months) was followed-up for 10 years. Reactivation of hepatitis B was defined as HBV DNA≥2000 IU/mL and ALT≥40 IU/L. Cox-proportional hazards regression models were used to identify factors associated with reactivation. RESULTS: A total of 36 (9%) persons had reactivation during 2984 person-years of follow-up, with an annual incidence of 1.2%. Persons aged ≥50 years (1.8%) at study entry had the highest incidence rates of reactivation although incidence rates were not significantly different by age group. Risk factors for hepatitis B reactivation were male sex (Hazard Ratio (HR)=2.41; 95% Confidence Interval (CI): 1.17-4.96), HBV DNA≥1000 IU/mL at study entry (HR=7.61; 95% CI: 2.81-20.6), and HBV genotype B (HR=6.08; 95% CI: 1.32-28.0). CONCLUSIONS: The incidence of hepatitis B reactivation was low during the 10 years of follow-up. However, given the higher risk of reactivation than their counterparts, males, and those with HBV DNA≥1000 IU/mL need to be followed-up more frequently.

Asunto(s)

RESUMEN

BACKGROUND: Liver disease is more severe in patients with chronic hepatitis B virus (HBV) infections and alcohol-induced liver injury. Whether the same is true for alcoholic patients with cirrhosis who have recovered from previous HBV infections remains to be determined. OBJECTIVES: To document the extent of liver disease in alcoholic patients with cirrhosis who test negative for hepatitis B surface antigen (HBsAg) and test positive for antibody to hepatitis B core antigen (anti-HBc). METHODS: Two hundred fifty-four alcoholic patients with cirrhosis were divided into anti-HBc-positive (N = 171) and anti-HBc-negative (N = 83) cohorts. Demographic, clinical, and biochemical features were retrospectively analyzed. Prognostic scores and the prevalence of patients at high risk for short-term mortality were calculated. Logistic regression was used to identify factors associated with an increased risk for short-term mortality. RESULTS: Jaundice was more common in the anti-HBc-positive cohort (32.2% vs. 18.1%, p = 0.02). This cohort also had higher serum bilirubin (70.9 vs. 50.4 µM/L, p = 0.03), prothrombin times (15.6 vs. 14.4 s, p = 0.01), MELD scores (8.5 vs. 4.6, p = 0.01), i-MELD scores (28.6 vs. 24.7, p = 0.03), MDF scores (14.2 vs. 6.8, p = 0.02) and ABIC scores (7.2 vs. 6.6, p = 0.01). In addition, anti-HBC-positive patients were more often at high risk for short-term mortality (40.4% vs. 26.5%, p = 0.03). Multivariate analysis identified anti-HBc-positive status (OR: 1.84; 95% CI: 1.10-3.36) and alcohol intake ≥150 g/day (OR: 2.01; 95% CI: 1.10-3.66) as independent risk factors for high risk of mortality. CONCLUSION: The anti-HBc-positive state is associated with more advanced liver disease in alcoholic patients with cirrhosis. A prospective study including HBV-DNA testing and liver biopsies should be considered to validate and further elucidate these findings.

Asunto(s)

RESUMEN

BACKGROUND & AIMS: Infection with hepatitis B virus (HBV) can be prevented by vaccination with HB surface (HBs) antigen, which induces HBs-specific antibodies and T cells. However, the duration of vaccine-induced protective immunity is poorly defined for health care workers who were vaccinated as adults. METHODS: We investigated the immune mechanisms (antibody and T-cell responses) of long-term protection by the HBV vaccine in 90 health care workers with or without occupational exposure to HBV, 10-28 years after vaccination. RESULTS: Fifty-nine of 90 health care workers (65%) had levels of antibodies to HBs antigen above the cut-off (>12 mIU/mL) and 30 of 90 (33%) had HBs-specific T cells that produced interferon-gamma. Titers of antibodies to HBs antigen correlated with numbers of HBs-specific interferon-gamma-producing T cells, but not with time after vaccination. Although occupational exposure to HBV after vaccination did not induce antibodies to the HBV core protein (HBcore), the standard biomarker for HBV infection, CD4(+) and CD8(+) T cells against HBcore and polymerase antigens were detected. Similar numbers of HBcore- and polymerase-specific CD4(+) and CD8(+) T cells were detected in health care workers with occupational exposure to HBV and in patients who acquired immunity via HBV infection. Most of the HBcore- and polymerase-specific T cells were CD45RO(+)CCR7(-)CD127(-) effector memory cells in exposed health care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cells were CD45RO(-)CCR7(-)CD127(-) terminally differentiated cells. CONCLUSIONS: HBs antigen vaccine-induced immunity protects against future infection but does not provide sterilizing immunity, as evidenced by HBcore- and polymerase-specific CD8(+) T cells in vaccinated health care workers with occupational exposure to HBV. The presence of HBcore- and HBV polymerase-specific T-cell responses is a more sensitive indicator of HBV exposure than detection of HBcore-specific antibodies.

Asunto(s)

RESUMEN

OBJECTIVE: HEPLISAV™ is an adult hepatitis B vaccine that requires fewer doses over a shorter period of time and elicits higher and earlier seroprotection compared to Engerix-B to reduce the risk of hepatitis B infection. The objective of this analysis was to evaluate the cost-effectiveness of vaccination with HEPLISAV vs. Engerix-B(®) to prevent hepatitis B infection in select populations. METHODS: Markov models were developed for the following populations: diabetics, patients with chronic or end stage kidney disease, healthcare workers and international travelers to countries with high HBV infection prevalence. Hepatitis B disease progression was modeled using 11 health states: seroprotected, susceptible, acute infection, chronic infection, fulminant hepatic failure, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-transplant care, and death. Seroprotection rates were obtained from two phase 3 clinical trials comparing HEPLISAV with Engerix-B and ranged across various populations from 89-96% for HEPLISAV and 62-81% for Engerix-B. Higher vaccination completion rates were assumed for HEPLISAV compared with Engerix-B given that fewer doses of HEPLISAV are required in a shorter period of time to achieve seroprotection for the evaluated populations. Each cycle length after the first year in the model was 1-year. All future costs and benefits were discounted at 3%. A lifetime analysis and a U.S. payer perspective were used. RESULTS: HEPLISAV has a favorable cost-effectiveness profile with incremental cost effectiveness ratios <$25,000 across all populations studied. In the patients with chronic or end stage kidney disease, HEPLISAV was the dominant option and was cost-saving compared with Engerix-B. The cost of vaccine, regimen completion rates, and seroprotection rates were the sensitive variables in the models. CONCLUSIONS: HEPLISAV is a cost-effective option to provide high rates of seroprotection and early seroprotection across a range of populations from health care workers to patients with chronic or end stage kidney disease.

Asunto(s)