Search

To test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles.Clinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers.Children (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (1%). Children with genotype B or C were more likely to be Asian (98% and 96%), more consistently hepatitis B envelope antigen positive (95% and 82%), had higher median HBV DNA levels (8.2 and 8.3 log10 IU/mL), and less frequently had elevated alanine aminotransferase values (43% and 57%) compared with children with other genotypes. The percentage of hepatitis B envelope antigen positivity and of those with HBV DNA ≥6 log₁₀ IU/mL declined with age.The majority of children in the Hepatitis B Research Network have HBV genotypes that reflect their international origins. Clinical and laboratory data differ substantially by patient age and HBV genotype. Use of these data can help drive the development of optimal strategies to manage and treat children with chronic hepatitis B.

Background & Aims T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB). Methods We enrolled 200 adults with CHB who participated in the National Institutes of Health−supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyte-associated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune-active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion. Results Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3 + CD127 − regulatory T cells and CD4 + T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg) + than HBeAg − patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyte-associated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg + than HBeAg − patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls. Conclusions HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell−based immune signatures for clinical phenotypes. These findings suggest additional T-cell−independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation.

To determine whether oral contraceptive (OC) use, childbearing, breastfeeding and tubal ligation differ between ovarian cancer cases with and without a BRCA1/2 mutation.A case-only study of 242 Jewish women with invasive epithelial ovarian cancer. Women were genotyped for three Ashkenazi founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). We obtained data on OC use, childbearing, breastfeeding, gynecologic surgeries and other reproductive factors from each woman. We compared the frequencies of these risk factors in carriers and non-carriers using unconditional logistic-regression, controlling for other covariates.Among the 242 cases, 64 (26.4%) carried one of the BRCA1 founder mutations, and 31 (12.8%) carried the BRCA2 mutation. Although there were no differences in the percent of nulliparous women between carriers and non-carriers, parous BRCA1 carriers reported fewer live births than non-carriers (average of 2.1 versus 2.5 live births, OR = 0.61, 95% CI = 0.39-0.95, adjusted for age at diagnosis, tubal ligation and duration of OC use). Carriers and non-carriers did not differ in their history of breastfeeding, or in their lifetime use of OCs. BRCA1 carriers were more likely than non-carriers to have had a tubal ligation (25.0 versus 10.2%, OR = 3.67, 95% CI = 1.55-8.70, adjusted for age at diagnosis, number of live births and OC duration).In general, OC use, childbearing and breastfeeding do not differ between BRCA1/2 carriers and non-carriers with ovarian cancer. However, the effects of tubal ligation may differ between BRCA1 carriers and non-carriers.

Some studies accomplished thus far have indicated that mammographic patterns may serve as risk indices for breast cancer. The present investigation was undertaken to determine whether patterns are familial. Mammograms from 110 mothers and their daughters and 122 sister pairs and a like number of unrelated controls matched for patient age, reproductive history, and personal and family history of breast cancer and drawn from the files of the Radiology Department of Hutzel Hospital, Detroit, Michigan, were compared. A familial influence was indicated by the finding that pattern similarities were significantly stronger in test cases than in unrelated controls. This influence appeared to be manifested by premature age changes in daughters and younger sisters and consisted, primarily, of a decrease in DY and an increase in P2 patterns. The data suggest that performing mammography on first degree relatives of women with high risk P2 and DY patterns should be considered.

Trends in cervical cancer in the United States are best expressed by incidence rates. Cancer incidence rates are defined as the annual rate of newly diagnosed cases within a specific population and are usually expressed as the number of cases per 100,000 persons in the population. In general, incidence data are considered the most useful type of descriptive measure because they reflect the probability of the development of a disease within a population and its sub-groups (Lillienfeld 1967). For carcinoma of the cervix in the United States, one can understand trends only through incidence data, since more than 75% of all cases are diagnosed as in situ disease.

One form of the double jeopardy hypothesis states that health declines more dramatically with age for blacks than it does for whites. This paper tests the hypothesis for black and white differences by age in cancer incidence rates. Age-specific incidence rates for 14 major cancer sites were compared in black and white, male and female populations in Detroit. Rates were based on 57,275 invasive cancer cases, diagnosed between 1973 and 1978, and drawn from the Michigan Cancer Foundation Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results program. For men, differences between blacks and whites for most sites dissipate with age, reflecting a leveling trend. For women, there is no consistent trend for most sites. Double jeopardy is reflected in rates for cervical cancer. Public health programs should be targeted to elderly black women for cervical cancer screening and to middle-aged black men for multiphasic cancer prevention services.