Emily Henkle

Antiviral Therapy for Chronic Hepatitis B Virus Infection and Development of Hepatocellular Carcinoma in a US Population

BACKGROUND & AIMS Antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We evaluated the relationship between therapy for chronic HBV infection and HCC incidence using data from a longitudinal study of patients at 4 US healthcare centers. METHODS We analyzed electronic health records of 2671 adult participants in the Chronic Hepatitis Cohort Study who were diagnosed with chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were collected for a median of 5.2 years. Propensity-score adjustment was used to reduce bias, and Cox regression was used to estimate the relationship between antiviral treatment and HCC. The primary outcome was time to event of HCC incidence. RESULTS Of study subjects, 3% developed HCC during follow-up period: 20 cases among the 820 patients with a history of antiviral HBV therapy and 47 cases among the 1851 untreated patients. In propensity-adjusted Cox regression, patients who received antiviral therapy had a lower risk of HCC than those who did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine aminotransferase. In a subgroup analysis, antiviral treatment was associated with a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate subgroup analysis of patients with available data on HBV DNA viral load, treated patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC than untreated patients with viral loads >20,000 IU/mL. CONCLUSIONS In a large geographically, clinically, and racially diverse US cohort, antiviral therapy for chronic HBV infection was associated with a reduced risk for HCC.

Antibody Response to Influenza A(H1N1)pdm09 Among Healthcare Personnel Receiving Trivalent Inactivated Vaccine: Effect of Prior Monovalent Inactivated Vaccine

Abstract Background. Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. Methods. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010–2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. Results. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72–3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84–.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65–.88]), 52% among those who received MIIV only, and 12% among those receiving neither. Conclusions. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines.

Comparison of Laboratory-Confirmed Influenza and Noninfluenza Acute Respiratory Illness in Healthcare Personnel during the 2010-2011 Influenza Season

OBJECTIVE Compare the severity of illnesses associated with influenza and noninfluenza acute respiratory illness (ARI) in healthcare personnel (HCP). DESIGN Prospective observational cohort. PARTICIPANTS HCP at 2 healthcare organizations with direct patient contact were enrolled prior to the 2010-2011 influenza season. METHODS HCP who were fewer than 8 days from the start of fever/feverishness/chills and cough were eligible for real-time reverse-transcription polymerase chain reaction influenza virus testing of respiratory specimen. Illness severity was assessed by the sum of self-rated severity (0, absent; 3, severe) of 12 illness symptoms, subjective health (0, best health; 9, worst health), activities of daily living impairment (0, able to perform; 9, unable to perform), missed work, and duration of illness. RESULTS Of 1,701 HCP enrolled, 267 were tested for influenza, and 58 (22%) of these tested positive. Influenza compared with noninfluenza illnesses was associated with higher summed 12-symptom severity score (mean [standard deviation], 17.9 [5.4] vs 14.6 [4.8]; P < .001), worse subjective health (4.5 [1.8] vs 4.0 [1.8]; P <.05), greater impairment of activities of daily living (4.9 [2.5] vs 3.8 [2.5]; P < .01), and more missed work (12.1 [10.5] vs 7.8 [10.5] hours; P < .01). Differences in symptom severity, activities of daily living, and missed work remained significant after adjusting for illness and participant characteristics. CONCLUSIONS Influenza had a greater negative impact on HCP than noninfluenza ARIs, indicated by higher symptom severity scores, less ability to perform activities of daily living, and more missed work. These results highlight the importance of efforts to prevent influenza infection in HCP.

Consistency of Influenza A Virus Detection Test Results across Respiratory Specimen Collection Methods Using Real-Time Reverse Transcription-PCR

ABSTRACT In our prospective cohort study, we compared the performance of nasopharyngeal, oropharyngeal, and nasal swabs for the detection of influenza virus using real-time reverse transcription-PCR assay. Joint consideration of results from oropharyngeal and nasal swabs was as effective as consideration of results from nasopharyngeal swabs alone, as measured by sensitivity and noninferiority analysis.

Hepatitis A and B Immunity and Vaccination in Chronic Hepatitis B and C Patients in a Large United States Cohort

BACKGROUND Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. METHODS We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. RESULTS Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. CONCLUSIONS Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population.

Subjective social status predicts wintertime febrile acute respiratory illness among women healthcare personnel.

OBJECTIVE We ask whether subjective social status (SSS) predicts rates of wintertime febrile acute respiratory illness (ARI). METHODS 1,373 women and 346 men were enrolled from September 1 through November 30, 2010 as part of a prospective cohort study of health care personnel (HCP) at two medical centers. A questionnaire was completed at enrollment followed by 20 weeks of surveillance. ARI was an illness with fever and cough self-reported via weekly telephone or Internet-based surveillance. RESULTS For both sexes, lower SSS was associated with younger age, less education, lower neighborhood household income, being unmarried, lower occupational status, working in outpatient settings, and poorer self-rated health status. Demographic and occupational covariates explained 23% and 42% of the variance (R²) in SSS among women and men, respectively. Smoking, exercise frequency, and sleep quality were also associated with SSS, but these factors explained little additional variance (3-4%). Among women HCP, lower SSS at enrollment was associated with higher rates of subsequent ARI (unadjusted β = -.21 [±.05], p < .001 for ordinal data). Adjusting for all covariates reduced the effect size of the SSS minimally (adjusted β = -.19 [±.06], p < .001). Among men HCP, there was no univariate SSS-ARI association and after adjusting for all covariates the effect was opposite of our hypothesis (adjusted β = .33 [±.17], p < .05). CONCLUSIONS Women (but not men) with lower SSS were more likely to report an ARI during surveillance, and the SSS-ARI association was independent of demographics, occupational status, health, and health behaviors.

CB3-02: Demographic Differences Between US-born and Foreign-born Asia Pacific Islanders Among the Hepatitis B Patients of Kaiser Permanente, Hawai’i

Background/Aims Approximately two billion people worldwide have been infected with hepatitis B virus (HBV) and about 350 million live with chronic infection. Over half of all liver cancer cases in the world are attributable to chronic, or persistent, HBV infection. Of US residents chronically infected with HBV, 40% to 70% are foreign-born immigrants, mainly Asian/Pacific Islanders (APIs). Disparity by race exists for APIs which makeup approximately 4% of the U.S. population and more than 2% of these races are affected with chronic HBV. The purpose of this study is to investigate the demographic differences between the foreign-born and US-born HBV infected APIs of Kaiser Permanente, Hawai’i (KPHI). Methods This substudy is a part of a prospective, dynamic, longitudinal and observational study, the Chronic Hepatitis Cohort Study (CHeCS). Patients included in this analysis were APIs identified from electronic medical records who met the CHeCS definition for chronic HBV infection at KPHI. Date of birth, race, gender, and country of origin (COO), household income and education were obtained from the Virtual Data Warehouse (VDW) demographic and census tables. Information about the country of origin was also supplemented by surveys and chart abstractions. Results Of the 513 HBV infected APIs, 76% were foreign-born and 24 % were US-born. HBV infected foreign-born APIs were significantly younger than the US-born APIs; approximately 50% of HBV infected foreign-born APIs were in 40–59 years old age group compared to 32% of the US-born. Foreign-born APIs also had significantly higher proportion of females (55%) than US-born (50%). Most of the HBV infected APIs had a median household income between 50,000 and 75,000 with no significant differences between the groups. Approximate prevalence was also calculated using the KPHI utilization data. APIs had an overall HBV prevalence of 0.7%; foreign-born APIs had 2.6% and US-born APIs had 0.3% prevalence. Discussion In summary, foreign-born APIs have higher prevalence of chronic HBV infections compared to US-born APIs in Kaiser Permanente Hawai’i. Foreign-born APIs infected with HBV are younger and more likely to be females than US-born APIs.

PS2-03: Chronic Hepatitis B Testing in US-born and Foreign-born Asia Pacific Islanders of Kaiser Permanente, Hawai’i

Background/Aims Approximately two billion people worldwide have been infected with hepatitis B virus (HBV) and about 350 million live with chronic infection. Over half of all liver cancer cases in the world are attributable to chronic, or persistent, HBV infection. Of US residents chronically infected with HBV, 40% to 70% are foreign-born immigrants, mainly Asian/Pacific Islanders (APIs). Disparity by race exists for APIs which makeup approximately 4% of the U.S population and more than 2% of these races are affected with chronic HBV. The purpose of this study is to estimate the prevalence of HBV in foreign and US born APIs and test the differences in these groups for testing (HBV DNA or HBsAg), testing positive for HBV, alanine aminotranferase (ALT) level and other demographic variables. Methods Utilization data from Kaiser Permanente, Hawai’i (KPHI) was used. All adults (18 yrs and older) with enrollment for any length of time from 2006 to 2008, with at least one health plan encounter and twelve months of continuous enrollment at any time were included. Persons with HBV diagnosis within six months of first encounter were excluded. We limited the analysis to Asians and Pacific Islanders. Date of birth, race, gender, and country of origin (COO), household income and education were obtained from the Virtual Data Warehouse (VDW) demographic and census tables. Results and Discussion Among who met the inclusion criteria (N= 191,335), 69,923 were APIs and of these 68% had information on country of origin. We plan to report the prevalence of HBV in foreign and US born APIs test the difference between the these two groups with respect to testing, testing positive for HBV infection, age, gender, annual income and ALT levels.