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Background. The duration of protection in children and adults resulting from hepatitis B vaccination is unknown. In 1981, we immunized a cohort of 1578 Alaska Native adults and children from 15 Alaska communities aged ≥6 months using 3 doses of plasma-derived hepatitis B vaccine. Methods. Persons were tested for antibody to hepatitis B surface antigen (anti-HBs) levels 30 years after receiving the primary series. Those with levels <10 mIU/mL received 1 booster dose of recombinant hepatitis B vaccine 2–4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days after the booster. Results. Among 243 persons (56%) who responded to the original primary series but received no subsequent doses during the 30-year period, 125 (51%) had an anti-HBs level ≥10 mIU/mL. Among participants with anti-HBs levels <10 mIU/mL who were available for follow-up, 75 of 85 (88%) responded to a booster dose with an anti-HBs level ≥10 mIU/mL at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 30 years. Conclusions. Based on anti-HBs level ≥10 mIU/mL at 30 years and an 88% booster dose response, we estimate that ≥90% of participants had evidence of protection 30 years later. Booster doses are not needed.

Background Chronic infection with hepatitis B virus (HBV) is associated with a high lifetime risk of developing hepatocellular carcinoma (HCC) and cirrhosis of the liver. Purpose To review the studies published to date regarding the association of HBV genotypes and subgenotypes in the development of adverse sequelae from HBV. Methods Review of the literature for articles describing studies of HBV genotype/subgenotypes and development of HCC, cirrhosis, and liver-related death. Results Eight genotypes of HBV (A through H), which differ from each other in viral genome sequence by more than 8%, and multiple subgenotypes, which differ from each other by 4–8% have been identified. Recently, studies investigating the association between the risks of developing HCC and cirrhosis by specific HBV genotypes and subgenotypes have reported marked differences in outcome. Certain HBV genotypes and subgenotypes, including genotype C, B2-5, and F1, appear to be associated with a higher risk of developing HCC, and others, including genotypes B1, B6, and A2, appear to be associated with a lower risk of complications of HBV. Our understanding of the role of HBV genotypes and subgenotypes on the outcome of HBV infection is limited, as few population-based prospective studies have been performed and most studies compare only the outcome in areas where two genotypes predominate whereas others have not examined subgenotypes. Conclusions Studies to date suggest that HBV genotypes/subgenotypes have important influences on the outcome of chronic HBV infection, but more population-based prospective studies examining multiple genotypes are needed.

BackgroundThe duration of protection in children and adults (including health care workers) resulting from the hepatitis B vaccine primary series is unknown MethodsTo determine the protection afforded by hepatitis B vaccine, Alaska Native persons who had received plasma-derived hepatitis B vaccine when they were >6 months of age were tested for antibody to hepatitis B surface antigen (anti-HBs) 22 years later. Those with levels <10 mIU/mL received 1 dose of recombinant hepatitis B vaccine and were evaluated on the basis of anti-HBs measurements at 10–14 days, 30–60 days, and 1 year ResultsOf 493 participants, 60% (298) had an anti-HBs level ⩾10 mIU/mL. A booster dose was administered to 164 persons, and 77% responded with an anti-HBs level ⩾10 mIU/mL at 10–14 days, reaching 81% by 60 days. Response to a booster dose was positively correlated with younger age, peak anti-HBs response after primary vaccination, and the presence of detectable anti-HBs before boosting. Considering persons with an anti-HBs level ⩾10 mIU/mL at 22 years and those who responded to the booster dose, protection was demonstrated in 87% of the participants. No new acute or chronic hepatitis B virus infections were identified ConclusionsThe protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 22 years. Booster doses are not needed

Background. Long-lasting protection resulting from hepatitis vaccine, despite loss of antibody against hepatitis virus (HBV) surface antigen (anti-HBs), is undetermined. Methods. We recruited persons from a cohort vaccinated with plasma-derived hepatitis vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥ 10 mlU/mL (group 1; n= 13) or <10 mlU/mL (group 2; n = 31). Results. All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor a, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection. Conclusions. Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis vaccine during childhood and adulthood lasts at least 32 years.

Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir- based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people. AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir. We included 501 patients with a mean age of 54.3 (range 21.3-78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria. In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.

New hepatitis B virus (HBV) therapies are expected to have breakthrough benefit for patients. HBV functional cure is sustained hepatitis B surface antigen loss and anti-HBs gain, with normalization of serum aminotransferases off therapy. Virologic or complete cure additionally includes loss of HBV covalently closed circular DNA. Currently available endpoints of therapy are inadequate to evaluate the efficacy of many of the new therapeutics. Therefore, either new ways of using the existing virologic endpoints and laboratory values or entirely new biomarkers are needed. In this review, we discuss the currently used endpoints, potential new endpoints, as well as what new markers are needed to assess the ability of HBV therapeutics to achieve functional and virologic cure in various phases of HBV infection. In addition, we discuss how patient selection from differing phases of HBV impacts the choice of HBV drug(s) needed to achieve cure.

BackgroundThe development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection has been associated with specific HBV genotypes and the presence of specific mutations MethodsFrom a cohort of Alaska Native people with chronic HBV infection, we genotyped 47 patients with HCC and 1129 patients without HCC, and we tested patients with HCC and control patients for mutations in the basal core promoter and precore regions ResultsGenotype F was found in 68% of patients with HCC, versus 18% of those without HCC (P<.001). For patients with genotype F, the median age at diagnosis of HCC was lower than that for patients with other genotypes (22.5 vs. 60 years, respectively; P=.002). Overall, there were no significant differences in the number of basal core promoter and precore region mutations between patients with HCC and control patients ConclusionsWe found a significant association between genotype F and the development of HCC among Alaska Native people with chronic HBV infection but no significant association between HCC and basal core promoter or precore mutations in genotype F

The duration of protection afforded by hepatitis B vaccination is unknown. To determine antibody persistence and protection from hepatitis B virus (HBV) infection. Prospective cohort study. 15 villages in southwest Alaska. 1578 Alaska Natives vaccinated at age 6 months or older. During 1981-1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years. Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants. Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV. The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up. Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.

Background. Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death. Methods. This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations. Results. The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate. Conclusions. Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States.

Pulsed laser ablation is an increasingly prevalent method for fast ion trap loading of various species, however characteristics of the ablation target source material can affect the ion-loading process. One factor which can reduce the atomic flux from a target is oxidation during atmospheric exposure when preparing or making changes to the ion trap vacuum system. Recent work has shown that perovskite ablation targets produce consistent atomic densities even after exposure to atmosphere when compared to elemental source targets. In this work, we directly compare calcium (Ca) and calcium-titanate (CaTiO3) ablation targets, characterizing the neutral atomic beam flux using resonant, time-resolved absorption spectroscopy of the 423 nm 1S0→1P1 transition in neutral Ca. We measure the ablation plume longitudinal and transverse temperatures, number density, ion production, and spot lifetime for each target. In addition, we compare the probe laser beam absorption for both targets before and after 21-h of exposure to atmosphere, demonstrating the relative robustness of the CaTiO3 source.