Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F.

BACKGROUND & AIMS: Persistence of hepatitis B e antigen (HBeAg) in chronic hepatitis B has been associated with increased risk for development of cirrhosis and hepatocellular carcinoma. Five hepatitis B virus genotypes were identified in Alaska Native persons; we analyzed clearance of HBeAg by age and genotype. METHODS: In this prospective cohort study, 1158 Alaska Native persons throughout Alaska were tested serially for HBeAg for a median of 20.5 years and were genotyped. Initial and final HBeAg-positive specimens, time to clearance, age at clearance, and subsequent HBeAg results were analyzed for persons initially HBeAg-positive. Subsequent HBeAg results were analyzed for persons initially negative. RESULTS: Genotypes A, B, C, D, and F were identified. Genotype C persons initially HBeAg-positive were more likely than those with other genotypes to be positive on initial and final specimens (P < .001 for each) and time to HBeAg clearance was longer (P < .001). Age at which 50% of persons cleared HBeAg was <20 years for those infected with genotypes A, B, D, and F and 47.8 years in genotype C (P < .001). After losing HBeAg, those with genotypes C and F were more likely to revert to the HBeAg-positive state (P < .001). CONCLUSIONS: Genotype may have a strong effect on mode of transmission and outcome. Genotype C may have been responsible for most perinatal transmission, given that seroconversion from HBeAg occurs decades later than in other genotypes.

Results of a general hepatitis C lookback program for persons who received blood transfusions in a neonatal intensive care unit between January 1975 and July 1992.

OBJECTIVE: To notify persons who received a blood transfusion in a neonatal intensive care unit between January 1975 and July 1992 of their risk for hepatitis C infection and to encourage them to seek hepatitis C antibody testing. DESIGN: Neonatal intensive care unit, blood bank, and public access records were queried to identify current mailing addresses and persons deceased. All persons were notified by letter. SETTING: Anchorage, Alaska. PARTICIPANTS: Persons who received health care in an integrated health care system, the Alaska Native Medical Center, or in the private sector. Main Exposure Transfusion in the neonatal period. MAIN OUTCOME MEASURES: Prevalence of test results positive for the hepatitis C virus antibody and RNA and awareness of having received a blood transfusion in a neonatal intensive care unit. RESULTS: Alaska Native Medical Center (n = 401) and private sector (n = 1396) persons were targeted for notification. Letters were mailed to 277 Alaska Native Medical Center (69%) and 374 private sector (27%) persons, with 151 (55%) and 65 (17%) screened for hepatitis C, respectively. Among those screened (n = 216), 7 (3%) were hepatitis C antibody positive, with 6 (<3%) also hepatitis C virus-RNA positive. Among 147 persons who responded, 75 (51%) were unaware they had received a transfusion. CONCLUSIONS: Compared with the private sector, a higher proportion of persons were identified and tested from the integrated health care system and more than half of respondents were unaware of their transfusion history. It would be prudent to screen neonatal intensive care unit patients who received transfusions before July 1992 for hepatitis C virus infection.

Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F.

BACKGROUND: The 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. METHODS: From 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. RESULTS: Genotype 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. CONCLUSIONS: We 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.

Health services usage by Alaskan injection drug users.

OBJECTIVES: The purpose of this study was to explore health services usage among injection drug users in Anchorage, Alaska. DESIGN: 645 participants were recruited as part of a federally funded study of needle exchanges. They completed a health services usage questionnaire that elicited information on use of a health care provider (physician or nurse) and emergency room services. Chi-square and t-tests were used for the bivariate analyses, and multiple logistic regression was used to develop the final predictive models. RESULTS: The majority of respondents (n = 646) were male (77 percent). Race/ethnicity included 58 percent White, 22 percent Alaska Native, and 20 percent African American. The multivariate model predicting accessing a health care provider (HCP) included ever having had chlamydia (OR 2.7, CI 1.6, 4.5), current income from welfare or public assistance (OR 2.6, CI 1.7, 3.9), current income from disability (OR 5.0, CI 2.2, 11.4), current income from SSI (OR .30, CI .12, .77) and the number of days in the last 30 used opiates other than heroin (OR 1.04, CI 1.002, 1.078). The multivariate model predicting use of an emergency room (ER) was similar to that predicting use of an HCP, with the additional finding of a negative association between being African American and ER use. CONCLUSION: The role of public assistance benefits enabling access to health care for IDUs has policy implications. Large public programs, such as the Indian Health Service, paid for much of the health care received by the IDUs recruited as part of this study.

Results of a hepatitis C general transfusion lookback program for patients who received blood products before July 1992.

BACKGROUND: The Centers for Disease Control and Prevention recommend hepatitis C virus (HCV) antibody (anti-HCV) screening for persons who received blood products before July 1992. A general transfusion lookback program was implemented to identify, counsel, and screen persons who received transfusions at the Alaska Native Medical Center between January 1980 and July 1992. STUDY DESIGN AND METHODS: Hard-copy transfusion records data were entered, and available databases were queried to identify deceased patients and the mailing address of those living. Patients were notified by letter of their HCV risk and encouraged to seek counseling and testing. Serum samples were screened for anti-HCV and HCV RNA, and program costs were estimated. RESULTS: Overall, 3169 transfusion recipients were identified, with 1356 (43%) living and targeted for notification. Of 764 patients notified and screened by this program, 41 (5%) were anti-HCV-positive and 19 (2%) were HCV RNA-positive. There was a higher probability of detecting anti-HCV with each subsequent increase of a transfusion event. Among 298 lookback patients, 33 percent were unaware of having received a blood transfusion. The estimated cost per person sent notification was US$57 and to detect an anti-HCV-positive case it was US$3146. CONCLUSION: This general transfusion lookback program successfully notified and screened patients at a reasonable cost. Further investigation would be helpful in determining the role these programs or other measures could play in promoting HCV screening in persons receiving transfusions before July 1992, especially among those who are unaware of their transfusion history.

Estimating the date of hepatitis C virus infection from patient interviews and antibody tests on stored sera.

OBJECTIVES: Studies on the natural history and outcome of chronic hepatitis C virus (HCV) infection differ regarding the proportion of persons who develop serious sequelae over time. Most of these studies use an estimated date of HCV infection based on risk factor data obtained from patient interviews. The date of HCV infection is often estimated using the year of a pre-1992 blood transfusion (BT), or the first year of injecting drug use (IDU). We sought to determine the accuracy of these dates obtained by interview. METHODS: We compared BT dates reported by patients in a long-term HCV outcome study to dates confirmed in a BT-Lookback project, and also compared the reported first year of IDU to seroconversion dates estimated from HCV tests on historical sera. RESULTS: Of 28 BT recipients who were interviewed in the HCV outcome study and identified in the Lookback project, 14 (50%; 95% CI: 31-69%) were unaware they had received a BT. Of 25 persons identified in the BT-Lookback project with historical sera available, 9 (36%; 95% CI: 19-57%) had anti-HCV results that did not correlate with their confirmed BT date. Of 216 persons with a history of IDU and historical serum samples available, 66 (31%; 95% CI: 25-37%) had anti-HCV results that did not correlate with their reported first year of IDU. CONCLUSIONS: Inaccuracies in the length of HCV could occur in outcome studies that rely on patient recall of risk-factor history. Statistical methods that incorporate the uncertainty in assigning infection date are needed.

Hepatitis A vaccine: immunogenicity following administration of a delayed immunization schedule in infants, children and adults.

Current immunization schedules for hepatitis A vaccine specify administration of a booster within 6-12 or 6-18 months of the primary dose. However, there may be circumstances that disrupt this schedule and the efficacy of administering a booster beyond the recommended time is a practical concern for healthcare providers. In this study, a booster was administered to 268 participants (137: <18 years old), an average of 27 months (range 20-31) after the primary dose. In those tested after the booster, the median anti-HAV GMT was 1544 milli-international units per milliliter (mIU/ml). Response to a delayed booster was strong in children over 2 years old (GMT 1500-1960 mIU/ml) and adults (GMT 1622 mIU/ml), but was significantly lower in children under 2 years old (GMT 1109 mIU/ml). Findings suggest a booster administered 20-31 months after the primary dose is immunogenic and GMT in persons >2 years of age were comparable to those seen in adults and children who receive hepatitis A vaccine per schedule.

Needle exchange and injection drug use frequency: a randomized clinical trial.

Despite a lack of evidence that needle exchange programs (NEPs) cause an increase in injection drug use, there are still concerns over fostering increased injection behavior with NEPs. The design was a randomized controlled trial conducted from May 1997 to June 2000 comparing injection drug users (IDUs) who are randomly assigned to have access to an NEP versus training in how to purchase needles and syringes (NS) at pharmacies. Of 653 IDUs recruited into the study, 600 were randomized: 426 were followed-up at 6 months, and 369 were followed-up at 12 months. Four hundred ninety were followed up at least once. There was no difference in the number of injections over time between the NEP and the Pharmacy Sales arms of the study or in the percentage of positive urine test results over time between the NEP and the Pharmacy Sales arms of the study for morphine and amphetamine. The decrease in the presence of cocaine was marginally greater between the arms of the study. The results do not support the hypothesis of NEPs causing an increase in injection drug use. This clinical trial provides the strongest evidence to date that needle exchanges do not produce this negative effect.