Carol Christensen

Hepatitis A vaccine administration: comparison between jet-injector and needle injection

INTRODUCTION Type A hepatitis virus (HAV) is a serious health problem throughout the world and can be spread via fecal-oral contact. Both immune globulin and an HAV vaccine provide protection, but the vaccine gives complete protection. Efficacy of methods of vaccination in relation to the formation of anti-HAV antibodies is unclear; thus, this study seeks to determine if significant differences exist between the syringe as compared to the jet injection technique. The purpose of this study was to compare in a randomized trial Biojet jet-injection system to a needle-syringe method. To determine if a significant difference between these two methods in seroconversion rates or geometric mean titers of anti HAV antibody occurs at day 15, 30, and 210 days after vaccination. METHOD Anti-HAV IgG(-) adult hospital employees were randomized to receive 1440 EL.U of hepatitis a vaccine (HAVRIX(R)) in 2 doses by either needle or jet-injector (Biojector(R)) system at month 0 and 6. HAV seroconversion titer results were measured by the Boehringer-Mannheim method. RESULTS/DISCUSSION A higher proportion of persons who received HAV vaccine via the Biojector(R) seroconverted with anti-HAV level >/=20 mIU at day 15, 30, and month 7 when compared with a needle injection.Side-effect profiles reported by participants in both methods were below those identified in current published and insert information, but the Biojector(R) had greater local reactivity in all categories when compared to the needle method.

Epidemiology and risk factors for hepatitis C in Alaska Natives

Large cohorts of persons infected with hepatitis C virus (HCV) that include patients with multiple risk exposures and behaviors have been rarely reported. We herein describe a population‐based cohort of 759 Alaska Natives (AN) with HCV who were recruited into a long‐term follow‐up study. History of injection drug use (IDU) was reported by 60.1% and blood transfusion by 14.0%. The most common genotype was 1a (42.0%), followed by 1b (20.3%), 2b (14.7%), 3a (14.3%), and 2a (7.8%). By multivariable analysis, risk exposures (blood transfusion vs. other; P < 0.01; odds ratio [OR], 2.87; 95% confidence interval [CI], 1.51–5.45) and year of infection (P < 0.01; OR, 3.47; 95% CI, 1.34–8.96) were significantly associated with HCV RNA‐positivity. Having an RNA concentration ≥2 million copies/mL was associated with male gender (OR, 1.94) and genotype (P < 0.01 overall; 1a vs. 3a: OR, 1.92; 2b vs. 3a: OR, 3.17) by multivariable analysis. In conclusion, the two principal risk exposures for AN infected with HCV (IDU and blood transfusion) are the same as the overall U.S. population. Persons with a history of blood transfusion were more likely to be HCV RNA positive than those without such history. Higher RNA levels found in males may explain the more severe disease previously reported in this group. (HEPATOLOGY 2004;39:325–332.)

High Rate of Spontaneous Negativity for Hepatitis C Virus RNA after Establishment of Chronic Infection in Alaska Natives

BACKGROUND Hepatitis C virus (HCV) leads to chronic infection in 70%-85% of exposed patients. Spontaneous clearance of the virus after chronic infection is believed to occur rarely. METHODS Alaska Natives who tested positive for HCV antibodies were enrolled in a prospective study that began in 1994 and were followed up on a regular basis. Individuals who tested positive for HCV RNA on 3 separate dates, each of which were at least 1 year apart, were included. Being negative for the virus was defined as having at least 1 negative HCV RNA test result after chronic viremia had been established. RESULTS Of the 815 patients enrolled in the cohort, 139 met entry criteria and were observed for a mean period of 7.0 years. Eleven (8%) of the persons had at least 1 test in which HCV RNA was undetectable; 7 were classified as having either possible or probable clearance of the virus, corresponding to an annualized clearance rate of 0.74% per person-year (95% CI, 0.30%-1.53%). Of 9 patients who underwent subsequent HCV RNA testing, 5 (56%) had negative test results. A low HCV RNA level was significantly associated with spontaneous nondetectability of HCV RNA. CONCLUSION Spontaneous HCV RNA negativity during chronic HCV infection is a surprisingly frequent event and is associated with low HCV RNA titers. Knowledge of immunologic determinants of clearance may open up avenues of novel therapy.

Evaluation of the response to a booster dose of hepatitis B vaccine in previously immunized healthcare workers.

INTRODUCTION Hepatitis B vaccination is recommended for all healthcare workers (HCW) at risk of exposure to infectious body fluids. However, the absolute duration of protection from immunization is unknown. The purpose of this randomized comparison trial was to determine how previously immunized HCW respond to different booster doses of hepatitis B vaccine. METHOD Adult HCW (n=59) were classified by level of hepatitis B surface antigen (anti-HBs), either <10 milli-International Units per milliliter (mIU/ml) or 10-50 mIU/ml. Participants were then randomized to receive a 2.5 or 10 microg dose of hepatitis B vaccine. Evaluation of anti-HBs levels were conducted 10 to 14 days, one month and one year postbooster. RESULTS AND DISCUSSION All participants responded to the booster dose with increased anti-HBs levels. At 14 days, mean anti-HBs levels were significantly higher for those with higher levels at baseline (P=0.004) and those receiving the 10 microg dose (P=0.016). At one month, those with higher anti-HBs levels at baseline and those receiving the 10 microg dose were significantly higher (P<0.01 for both). At one year, the increase for the higher dose was no longer statistically significant when examined by itself (P=0.081); statistical significance (P=0.021) was achieved after adjusting for anti-HBs level at baseline. For all participants, the geometric mean anti-HBs level was 2618 mIU/ml at 14 days, 2175 mIU/ml at one month and 88.9 mIU/ml at one year. At all time points the increase in anti-HBs levels represented an increase over the geometric mean baseline level of anti-HBs (7.4 mIU/ml). Hepatitis B immunized adults responded to a booster dose of hepatitis B vaccine from 3 to 13 yr postvaccination series. Data support current recommendations that immunized HCW do not require periodic antibody testing or vaccine boosters.

Hepatitis C Virus Dynamics during Natural Infection Are Associated with Long-Term Histological Outcome of Chronic Hepatitis C Disease

BACKGROUND The long-term dynamics of hepatitis C virus (HCV) infection and their association with hepatitis C disease are unknown. METHODS Fifty-two treatment-naive subjects with chronic HCV genotype 1 infection were selected from the Alaska Natives and American Indians cohort. Viral RNA levels were measured in 223 specimens (mean, 4.3 specimens/subject) over 457 patient-years. Viral quasispecies diversity was analyzed in 187 specimens (mean, 3.6 specimens/subject) over 365 patient-years. RESULTS Thirty-three subjects had minimal hepatic fibrosis, and 19 developed bridging fibrosis or cirrhosis. There was no significant difference in host variables, including alcohol consumption, between disease groups. Subjects with mild disease had higher serum RNA levels after 2 decades of infection (P=.013), greater fluctuations in RNA levels over time (P=.04), higher intraspecimen quasispecies diversity (P=.001), and higher rates of quasispecies diversification (P=.004) than did subjects with severe disease. On multivariate analysis, the odds of having severe disease were 15.3 (95% confidence interval, 2.3-99.6) times higher among persons with low quasispecies diversification rates compared with the odds among persons with high diversification rates. CONCLUSIONS Histological progression of hepatitis C is tightly associated with homogenization of HCV quasispecies, perhaps reflecting immune failure and/or selective outgrowth of aggressive viral variants.

Adverse outcomes in Alaska natives who recovered from or have chronic hepatitis C infection.

BACKGROUND & AIMS The factors associated with adverse outcome from hepatitis C virus (HCV) infection are incompletely understood. To determine the incidence and risk factors associated with the development of end-stage liver disease (ESLD) and liver-related death (LRD), we conducted a retrospective/prospective population-based study in a cohort of Alaska Native persons chronically infected with HCV from 1994 to 2005. METHODS We followed 960 persons prospectively for an average of 7.2 years and retrospectively for 12.1 years with data from medical records and serum samples. We compared data from subjects that were chronically infected with those who recovered from HCV infection, stratified by alcohol use. Survival models were used to examine factors associated with ESLD and LRD in chronically infected patients. RESULTS During prospective follow-up, 80 (8.8%) and 47 (5.2%) patients developed ESLD and LRD, respectively. In examining incidence per 100 person-years, no difference was found among heavy alcohol users in the incidence of LRD (2.28 versus 3.50; P = .34) or ESLD (3.21 versus 5.69; P = .13) in persons with chronic HCV compared with those recovered from HCV infection. In subjects that consumed <50 g alcohol/d, the incidences of LRD were 0.77 and 0.09 (P = .01) and of ESLD were 1.58 versus 0.36 (P = .002), respectively, in subjects with chronic infection versus those that recovered. Multivariate analysis showed that older age, heavy alcohol use, and HCV genotype 3 were associated with ESLD. CONCLUSIONS A history of heavy alcohol use is associated with the highest incidence of LRD and ESLD, regardless of whether patients are chronically infected or recover from HCV infection.

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.

Clinical significance of elevated alpha‐fetoprotein in Alaskan Native patients with chronic hepatitis C

Summary.  The clinical significance of elevated serum alpha‐fetoprotein (AFP) in patients with chronic hepatitis C virus (HCV) infection is not well defined. We analysed data from a population‐based cohort of patients with HCV infection to assess the prevalence of elevated serum AFP, to determine its association with clinical and virologic parameters and with clinical outcomes. We defined a slightly elevated serum AFP level as 8 to <15 and a high‐AFP level as ≥15 μg/L. Among 541 HCV‐RNA‐positive persons, 61 (11%) had a slightly elevated or high AFP at the time of consent. AFP ≥8 μg/L was associated with the older age, aspartate aminotransferase/alanine aminotransferase ratio >1, and higher alkaline phosphatase levels, but not with heavy alcohol use, IV drug use, genotype, viral load or duration of HCV infection. Among 192 persons with an AFP at liver biopsy, 17% had an AFP ≥8 μg/L. The sensitivity/specificity of an AFP level ≥8 in detecting Ishak 3–6 fibrosis was 39%/95%. Among 372 persons with a minimum of four AFP measurements over 6 years, 5% had persistently elevated AFP >8 μg/L, 19% had both elevated and normal AFP measurements, and 76% had persistently normal AFP. Elevated AFP at consent was associated with hepatocellular carcinoma (HCC) and end‐stage liver disease. Over 6 years of follow‐up, persistently elevated AFP was associated with the development of HCC; no person with AFP persistently <8 μg/mL developed HCC. Serial AFP measurements appear to be useful in identifying persons with advanced fibrosis and help to determine who needs periodic screening with liver ultrasound to detect HCC.

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 C infection in Alaska Natives with persistently normal, persistently elevated or fluctuating alanine aminotransferase levels

Abstract: Background/Aims: An estimated one‐third of patients with chronic hepatitis C virus (HCV) infection have persistently normal alanine transaminase (PNALT); however, in many previous studies alanine aminotransferase (ALT) levels were followed for ≤12 months.