Variability in the performance characteristics of IgG anti-HEV assays and its impact on reliability of seroprevalence rates of hepatitis E.

Hepatitis E is a major public health problem in developing countries and is increasingly being recognized as a cause of substantial sporadic viral hepatitis infections in industrialized countries. Variable rates of hepatitis E seroprevalence have been reported from the same geographic regions depending on the assay used. In this study, we evaluated the performance characteristics of four assays which included two commercial assays, Wantai HEV-IgG ELISA kit (Wantai, China), and DS-EIA-ANTI-HEV-G kit (DSI, Italy), one NIH-developed immunoassay (NIH-55 K, Kuniholm et al. [2009] Journal of Infectious Diseases 200:48-56), previously used in several major seroprevalence studies and one in-house Western blot assay (CDC-WB). The limit of detection of IgG anti-HEV is 100 mIU/mL for Wantai assay, 200 mIU/mL for CDC-WB assay, 1000 mIU/mL for DSI assay, and 40 mIU/mL for NIH-55 K assay. Pairwise concordance between the four assays ranged from 56% to 87%. The concordance among all four assays was observed in 52% of the samples, while the concordance among three assays was observed in 37% of the samples. These data show a wide discordance between various IgG anti-HEV assays and warrant a comprehensive evaluation of all the assays using well characterized global serum reference panels.

The Burden of Hepatitis C Infection-Related Liver Fibrosis in the United States.

BACKGROUND: Knowledge of the estimated proportion of hepatitis C virus (HCV)-infected persons with advanced fibrosis or cirrhosis is critical to estimating healthcare needs. METHODS: We analyzed HCV-related testing conducted by Quest Diagnostics from January 2010 through December 2013. Tests included hepatitis C antibody, HCV RNA, HCV genotype (nucleic acid tests [NAT]), liver function tests, and platelet counts; patient age was also determined. Aspartate aminotransferase (AST)-to-platelet ratio (APRI) was calculated as = 100*(aspartate aminotransferase [AST]/upper limit of AST)/platelet. Fibrosis-4 (FIB-4) was calculated as (age × AST)/(platelet ×√ alanine aminotransferase [ALT]). Persons were "currently infected" if they had ≥1 positive HCV NAT; "in care" if a positive RNA test was followed <6 months by ≥1 additional NAT(s), or ALT, AST, and platelets <90 days, or any test ordered by an infectious diseases or gastroenterology specialist; and "evaluated for treatment" if they had a genotype test. RESULTS: Approximately 10 million HCV test results were analyzed, representing 5.6 million unique patients. Of the 2.6 million patients with data to estimate liver disease, 5% were currently infected. Among those currently infected, APRI and FIB-4 scores indicated that 23% overall-and 27% among the cohort born during 1945-1965-had advanced fibrosis or cirrhosis at first diagnosis. A total of 54% of infected were in care and 51% of infected with advanced fibrosis or cirrhosis were evaluated for treatment. CONCLUSIONS: Testing from a large US commercial laboratory indicates that about 1 in 4 HCV-infected persons have levels of liver disease put them at highest risk for complications and could benefit from immediate antiviral therapy.

Association of Hepatitis C Virus With Alcohol Use Among U.S. Adults: NHANES 2003-2010.

INTRODUCTION: Excessive alcohol use exacerbates morbidity and mortality among hepatitis C virus (HCV)-infected people. The purpose of this study was to describe self-reported patterns of alcohol use and examine the association with HCV infection and other sociodemographic and health-related factors. METHODS: Data from 20,042 participants in the 2003-2010 National Health and Nutrition Examination Survey were analyzed in 2014. Estimates were derived for self-reported demographic characteristics, HCV-RNA (indicative of current HCV infection) status, and alcohol use at four levels: lifetime abstainers, former drinkers, non-excessive current drinkers, and excessive current drinkers. RESULTS: Former drinkers and excessive current drinkers had a higher prevalence of HCV infection (2.2% and 1.5%, respectively) than never or non-excessive current drinkers (0.4% and 0.9%, respectively). HCV-infected adults were estimated to ever drink five or more drinks/day almost every day at some time during their lifetime about 3.3 times more often (43.8% vs 13.7%, p<0.001) than those who were never infected with HCV. Controlling for age, sex, race/ethnicity, education, and having a usual source of health care, HCV infection was significantly associated with excessive current drinking (adjusted prevalence ratio, 1.3; 95% CI=1.1, 1.6) and former drinking (adjusted prevalence ratio, 1.3; 95% CI=1.1, 1.6). CONCLUSIONS: Chronic HCV infection is associated with both former and excessive current drinking. Public health HCV strategies should implement interventions with emphasis on alcohol abuse, which negatively impacts disease progression for HCV-infected individuals.

Progress Toward Eliminating Hepatitis A Disease in the United States.

Hepatitis A virus (HAV) disease disproportionately affects adolescents and young adults, American Indian/Alaska Native and Hispanic racial/ethnic groups, and disadvantaged populations. During 1996-2006, the Advisory Committee on Immunization Practices (ACIP) made incremental changes in hepatitis A (HepA) vaccination recommendations to increase coverage for children and persons at high risk for HAV infection. This report examines the temporal association of ACIP-recommended HepA vaccination and disparities (on the absolute scale) in cases of HAV disease and on seroprevalence of HAV-related protection (measured as antibody to HAV [anti-HAV]). ACIP-recommended childhood HepA vaccination in the United States has eliminated most absolute disparities in HAV disease by age, race/ethnicity, and geographic area with relatively modest ≥1-dose and ≥2-dose vaccine coverage. However, the increasing proportion of cases of HAV disease among adults with identified and unidentified sources of exposure underscores the importance of considering new strategies for preventing HAV infection among U.S. adults. For continued progress to be made toward elimination of HAV disease in the United States, additional strategies are needed to prevent HAV infection among an emerging population of susceptible adults. Notably, HAV infection remains endemic in much of the world, contributing to U.S. cases through international travel and the global food economy.

Decreasing immunity to hepatitis A virus infection among US adults: Findings from the National Health and Nutrition Examination Survey (NHANES), 1999-2012.

BACKGROUND: The clinical course of hepatitis A virus (HAV) infection is more severe with increased age. In the United States, surveillance data reported to CDC since 2011 indicate increases in both the absolute number of cases and the mean age of cases. Total antibody to HAV (anti-HAV) is a marker of immunity. METHODS: We analyzed National Health and Nutrition Examination Survey (NHANES) data for anti-HAV from respondents aged ≥ 2 years collected from 2007 to 2012 and compared with data collected 10 years earlier (1999-2006). For US-born adults aged ≥ 20 years, we estimated age-adjusted anti-HAV prevalence by demographic and other characteristics, evaluated factors associated with anti-HAV positivity and examined anti-HAV prevalence by decade of birth. RESULTS: The prevalence of anti-HAV among adults aged ≥ 20 years was 24.2% (95% CI 22.5-25.9) during 2007-2012, a significant decline from 29.5% (95% CI 28.0-31.1) during 1999-2006. Prevalence of anti-HAV was consistently lower in 2007-2012 compared to 1999-2006 by all characteristics examined. In 2007-2012, the lowest age-specific prevalence was among adults aged 30-49 years (16.1-17.6%). Factors significantly associated with anti-HAV positivity among adults were older age, Mexican American ethnicity, living below poverty, less education, and not having insurance. By decade of birth, the prevalence of anti-HAV was slightly lower in 2009-2012 than in 1999-2002, except among persons born from 1980 to 1989. CONCLUSIONS: NHANES data document very low prevalence of hepatitis A immunity among U.S. adults aged 30-49 years; waning of anti-HAV over time may be minimal. Improving vaccination coverage among susceptible adults should be considered.

Self-reported hepatitis A vaccination as a predictor of hepatitis A virus antibody protection in U.S. adults: National Health and Nutrition Examination Survey 2007-2012.

OBJECTIVES: To estimate the predictive value of self-reported hepatitis A vaccine (HepA) receipt for the presence of hepatitis A virus (HAV) antibody (anti-HAV) from either past infection or vaccination, as an indicator of HAV protection. METHODS: Using 2007-2012 National Health and Nutrition Examination Survey data, we assigned participants to 4 groups based on self-reported HepA receipt and anti-HAV results. We compared characteristics across groups and calculated three measures of agreement between self-report and serologic status (anti-HAV): percentage concordance, and positive (PPV) and negative (NPV) predictive values. Using logistic regression we investigated factors associated with agreement between self-reported vaccination status and serological results. RESULTS: Demographic and other characteristics varied significantly across the 4 groups. Overall agreement between self-reported HepA receipt and serological results was 63.6% (95% confidence interval [CI] 61.9-65.2); PPV and NPV of self-reported vaccination status for serological result were 47.0% (95% CI 44.2-49.8) and 69.4% (95% CI 67.0-71.8), respectively. Mexican American and foreign-born adults had the highest PPVs (71.5% [95% CI 65.9-76.5], and 75.8% [95% CI 71.4-79.7]) and the lowest NPVs (21.8% [95% CI 18.5-25.4], and 20.0% [95% CI 17.2-23.1]), respectively. Young (ages 20-29 years), US-born, and non-Hispanic White adults had the lowest PPVs (37.9% [95% CI 34.5-41.5], 39.1% [95% CI, 36.0-42.3], and 39.8% [36.1-43.7]), and the highest NPVs (76.9% [95% CI 72.2-81.0, 78.5% [95% CI 76.5-80.4)], and 80.6% [95% CI 78.2-82.8), respectively. Multivariate logistic analyses found age, race/ethnicity, education, place of birth and income to be significantly associated with agreement between self-reported vaccination status and serological results. CONCLUSIONS: When assessing hepatitis A protection, self-report of not having received HepA was most likely to identify persons at risk for hepatitis A infection (no anti-HAV) among young, US-born and non-Hispanic White adults, and self-report of HepA receipt was least likely to be reliable among adults with the same characteristics.

Decline in hepatitis E virus antibody prevalence in the United States from 1988-1994 to 2009-2010.

BACKGROUND: Previous population-based estimates in the United States have shown a relatively high prevalence of hepatitis E virus (HEV) antibody. We sought to determine whether changes in the prevalence of HEV antibody have occurred over time. METHODS: We analyzed data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and NHANES III (1988-1994). Using the same serologic assay, we compared the estimated anti-HEV immunoglobulin G (IgG) prevalence and risk factors for antibody positivity for the 2 periods. RESULTS: The prevalence of HEV antibody among those aged ≥6 years declined from 10.2% (95% confidence interval [CI], 9.1%-11.4%) during 1988-1994 to 6.0% (5.2%-6.8%) during 2009-2010, and the prevalence for those of US birth ranged from 9.6% (8.4%-10.9%) to 5.2% (4.4%-6.2%). Among US-born persons, the estimated HEV antibody prevalence declined significantly for all subgroups of age, sex, region of residence, and number of persons per room in the household; significant declines also were observed for persons at or above poverty level and for persons of non-Hispanic white, non-Hispanic black, and Mexican American race/ethnicity. No clear associations with food consumption were found. CONCLUSIONS: The anti-HEV prevalence is declining in the United States. Although the decline suggests a decrease in exposure to HEV over time, the risks associated with exposure remain unknown.

Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010.

BACKGROUND: Knowledge of the number of persons with chronic hepatitis C virus (HCV) infection in the United States is critical for public health and policy planning. OBJECTIVE: To estimate the prevalence of chronic HCV infection between 2003 and 2010 and to identify factors associated with this condition. DESIGN: Nationally representative household survey. SETTING: U.S. noninstitutionalized civilian population. PARTICIPANTS: 30,074 NHANES (National Health and Nutrition Examination Survey) participants between 2003 and 2010. MEASUREMENTS: Interviews to ascertain demographic characteristics and possible risks and exposures for HCV infection. Serum samples from participants aged 6 years or older were tested for antibody to HCV; if results were positive or indeterminate, the samples were tested for HCV RNA, which indicates current chronic infection. RESULTS: Based on 273 participants who tested positive for HCV RNA, the estimated prevalence of HCV infection was 1.0% (95% CI, 0.8% to 1.2%), corresponding to 2.7 million chronically infected persons (CI, 2.2 to 3.2 million persons) in the U.S. noninstitutionalized civilian population. Infected persons were more likely to be aged 40 to 59 years, male, and non-Hispanic black and to have less education and lower family income. Factors significantly associated with chronic HCV infection were illicit drug use (including injection drugs) and receipt of a blood transfusion before 1992; 49% of persons with HCV infection did not report either risk factor. LIMITATION: Incarcerated and homeless persons were not surveyed. CONCLUSION: This analysis estimated that approximately 2.7 million U.S. residents in the population sampled by NHANES have chronic HCV infection, about 500,000 fewer than estimated in a similar analysis between 1999 and 2002. These data underscore the urgency of identifying the millions of persons who remain infected and linking them to appropriate care and treatment. PRIMARY FUNDING SOURCE: None.

An assessment of the performance of self-reported vaccination status for hepatitis B, National Health and Nutrition Examination Survey 1999-2008.

OBJECTIVES: We sought to assess the performance of self-reported vaccination with hepatitis B vaccine (HepB) compared with serological status for hepatitis B markers in the general US civilian population. METHODS: Using 1999 through 2008 National Health and Nutrition Examination Survey data, we calculated 3 measures of agreement between self-reported HepB vaccination status and serological status: percent concordance, and positive (PPV) and negative predictive values (NPV) of self-report. Logistic regression was used to identify factors associated with agreement between self-report and serological status. RESULTS: Overall agreement was 83% (95% CI = 82.3, 83.7), NPV of self-report was high (0.95; 95% CI = 0.93, 0.95) and PPV was low (0.53; 95% CI = 0.51, 0.54). Birth year relative to the 1991 recommendation for universal infant HepB vaccination had a strong association with agreement, however, the association was positive for those who reported receiving at least 3 doses and negative for those who reported receiving no doses. CONCLUSIONS: Although the low PPV in our study could be attributable in part to waning of vaccine-induced anti-HBs over time, national adult HepB vaccination coverage may be lower than previously estimated because national estimates usually depend on self-report of vaccine receipt.

Hepatitis B and C virus infection among 1.2 million persons with access to care: factors associated with testing and infection prevalence.

BACKGROUND: Little is known about viral hepatitis testing and infection prevalence among persons in private healthcare organizations (HCOs) in the United States. METHODS: To determine the frequency of and characteristics associated with viral hepatitis testing and infection prevalence among adults with access to care, we conducted an observational cohort study among 1.25 million adults from 4 US HCOs and included persons with ≥1 clinical encounter during 2006-2008 and ≥12 months of continuous follow-up before 2009. We compared the number of infections identified with the number expected based on adjusted data from the National Health and Nutrition Examination Survey (NHANES). RESULTS: Of 866,886 persons without a previous hepatitis B virus (HBV) diagnosis, 18.8% were tested for HBV infection, of whom 1.4% tested positive; among 865,659 without a previous hepatitis C virus (HCV) diagnosis, 12.7% were tested, of whom 5.5% tested positive. Less than half of those with ≥2 abnormal alanine aminotransferase (ALT) levels were subsequently tested for HBV or HCV. When tested, Asians (adjusted odds ratio [aOR] 6.33 relative to whites) were most likely HBV infected, whereas those aged 50-59 years were most likely HCV infected (aOR 6.04, relative to age <30 years). Based on estimates from NHANES, nearly one-half of HCV and one-fifth of HBV infections in this population were not identified. CONCLUSIONS: Even in this population with access to care and lengthy follow-up, only a fraction of expected viral hepatitis infections were identified. Abnormal ALT levels often but not consistently triggered testing. These findings have implications for the identification and care of 4-5 million US residents with HBV and HCV infection.

Awareness of infection, knowledge of hepatitis C, and medical follow-up among individuals testing positive for hepatitis C: National Health and Nutrition Examination Survey 2001-2008.

UNLABELLED: Many persons infected with hepatitis C virus (HCV) are unknown to the healthcare system because they may be asymptomatic for years, have not been tested for HCV infection, and only seek medical care when they develop liver-related complications. We analyzed data from persons who tested positive for past or current HCV infection during participation in the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2008. A follow-up survey was conducted 6 months after examination to determine (1) how many participants testing positive for HCV infection were aware of their HCV status before being notified by NHANES, (2) what actions participants took after becoming aware of their first positive test, and (3) participants' knowledge about hepatitis C. Of 30,140 participants tested, 393 (1.3%) had evidence of past or current HCV infection and 170 (43%) could be contacted during the follow-up survey and interviewed. Only 49.7% were aware of their positive HCV infection status before being notified by NHANES, and only 3.7% of these respondents reported that they had first been tested for HCV because they or their doctor thought they were at risk for infection. Overall, 85.4% had heard of hepatitis C; correct responses to questions about hepatitis C were higher among persons 40-59 years of age, white non-Hispanics, and respondents who saw a physician after their first positive HCV test. Eighty percent of respondents indicated they had seen a doctor about their first positive HCV test result. CONCLUSION: These data indicate that fewer than half of those infected with HCV may be aware of their infection. The findings suggest that more intensive efforts are needed to identify and test persons at risk for HCV infection.

Associations between Electronic Media Use and Involvement in Violence, Alcohol and Drug Use among United States High School Students.

OBJECTIVE: We identified associations between time spent watching television and time spent playing video or computer games or using computers and involvement in interpersonal violence, alcohol and drug use in a nationally representative sample of United States high school students. METHODS: We analyzed data from the 2007 national Youth Risk Behavior Survey. Exposure variables were time spent watching television and time spent playing computer or video games or using computers (hereafter denoted as "computer/video game use") on an average school day; outcome variables included multiple measures assessing involvement in violence and alcohol or drug use. Chi-square tests were used to identify statistically significant associations between each exposure variable and each of the outcome variables. We used logistic regression to obtain crude odds ratios for outcome variables with a significant chi-square p-value and to obtain adjusted odds ratios controlling for sex, race, and grade in school. RESULTS: Overall, 35.4% (95% CI=33.1%-37.7%) of students reported frequent television (TV) use and 24.9% (95% CI=22.9%-27.0%) reported frequent computer/video game use. A number of risk behaviors, including involvement in physical fights and initiation of alcohol use before age 13, were significantly associated with frequent TV use or frequent computer/video game use, even after controlling for sex, race/ethnicity and grade. CONCLUSION: Findings highlight the need for additional research to better understand the mechanisms by which electronic media exposure and health-risk behaviors are associated and for the development of strategies that seek to understand how the content and context (e.g., watching with peers, having computer in common area) of media use influence risk behaviors among youth.

Comparison of paper-and-pencil versus Web administration of the Youth Risk Behavior Survey (YRBS): risk behavior prevalence estimates.

The authors examined whether paper-and-pencil and Web surveys administered in the school setting yield equivalent risk behavior prevalence estimates. Data were from a methods study conducted by the Centers for Disease Control and Prevention (CDC) in spring 2008. Intact classes of 9th- or 10th-grade students were assigned randomly to complete a survey via paper-and-pencil or Web. Data from 5,227 students were analyzed using logistic regression to identify associations of mode with reporting of 74 risk behaviors. Mode was associated with reporting of only 7 of the 74 risk behaviors. Results indicate prevalence estimates from paper-and-pencil and Web school-based surveys are generally equivalent.

Viral hepatitis.

KEY FINDINGS: The prevalence of hepatitis A antibody, which is indicative of immunity to hepatitis A virus, increased among U.S. born persons aged 6-19, but decreased among persons aged 40 years and over. Hepatitis B virus (HBV) infection among persons aged 6-19 has decreased in recent years. By 2003-2006, over 90% of children had received at least one dose of the recommended three-dose series of hepatitis B vaccine. Prevalence of infection with hepatitis C virus (HCV) decreased among those at highest risk of infection including males and Mexican- American and non-Hispanic black populations. Despite this decrease, the prevalence of infection remains higher in the non-Hispanic black population. The peak prevalence of HCV infection has shifted over time from persons aged 30-39 years (3.9%) to those aged 40-49 years (4.3%).

Is absolute amount or change in exercise more associated with quality of life in adult cancer survivors?

BACKGROUND: The present study examined the association between quality of life (QOL) in adult cancer survivors and the (a) absolute current amount of exercise and (b) change in exercise since cancer diagnosis. METHODS: Three hundred fifty-two (mean age = 59.6) adult cancer survivors recruited from outpatient clinics in four states (Iowa, Wisconsin, Minnesota, and Georgia) and a minority support groups completed a survey including demographic, medical, exercise behavior, and QOL questions. RESULTS: Hierarchical multiple regression analyses controlling for important demographic and medical variables showed that adult cancer survivors who currently exercised three times per week had significantly higher QOL than those who did not (beta = 0.13, P < 0.05). Furthermore, compared to adult cancer survivors who exercised less since their cancer diagnosis, those who maintained (beta = 0.28, P < 0.08) or increased (beta = 0.24, P < 0.01) the amount of exercise they performed since their cancer diagnosis had significantly higher QOL. Finally, examination of the DeltaR(2)(adjusted) between the two exercise models showed that the absolute current amount of exercise explained an additional 1% (DeltaR(2)(adjusted) = 0.01 P < 0.05) of the variance in QOL whereas the change in exercise explained an additional 7% (DeltaR(2)(adjusted) = 0.07, P < 0.01). CONCLUSION: Change in exercise since cancer diagnosis may be a more important correlate of QOL in adult cancer survivors than the absolute current amount of exercise.

Do adults change their lifestyle behaviors after a cancer diagnosis?

OBJECTIVE: To examine changes in lifestyle behaviors after a cancer diagnosis and medical and demographic influences on such changes. METHODS: Adult cancer survivors (n = 352) completed a survey including demographic, medical, and lifestyle behavior change questions. RESULTS: Results showed that since cancer diagnosis, 46% of smokers quit smoking, 47% improved their dietary habits, and 30.1% exercised less. Adult cancer survivors who changed their lifestyle behaviors varied, depending on various demographic and medical variables and physician recommendation. CONCLUSION: It appears from our data that cancer diagnosis in adults may have a positive influence on smoking and diet and a negative influence on exercise.