Immunogenicity of the hepatitis A vaccine 20 years after infant immunization.

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.

Impact of sustained virologic response on risk of type 2 diabetes among hepatitis C patients in the United States.

Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor-by-SVR interactions, and death as a competing risk. Among 5127 patients with an average follow-up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65-0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non-Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25-30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.

Distribution of disease phase, treatment prescription and severe liver disease among 1598 patients with chronic hepatitis B in the Chronic Hepatitis Cohort Study, 2006-2013.

BACKGROUND: Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B (CHB) in US general healthcare settings. AIM: To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. METHODS: We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. RESULTS: Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen (HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus (HBV) DNA >2000 IU/mL. CONCLUSIONS: Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels.

Higher all-cause hospitalization among patients with chronic hepatitis C: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2013.

In the United States, hospitalization among patients with chronic hepatitis C virus (HCV) infection is high. The healthcare burden associated with hospitalization is not clearly known. We analysed data from the Chronic Hepatitis Cohort Study, an observational cohort of patients receiving care at four integrated healthcare systems, collected from 2006 to 2013 to determine all-cause hospitalization rates of patients with chronic HCV infection and the other health system patients. To compare the hospitalization rates, we selected two health system patients for each chronic HCV patient using their propensity score (PS). Propensity score matching was conducted by site, gender, race, age and household income to minimize differences attributable to these characteristics. We also compared primary reason for hospitalization between chronic HCV patients and the other health system patients. Overall, 10 131 patients with chronic HCV infection and 20 262 health system patients were selected from the 1 867 802 health system patients and were matched by PS. All-cause hospitalization rates were 27.4 (27.0-27.8) and 7.4 (7.2-7.5) per 100 persons-year (PY) for chronic HCV patients and for the other health system patients, respectively. Compared to health system patients, hospitalization rates were significantly higher by site, gender, age group, race and household income among chronic HCV patients (P < 0.001). Compared to health system patients, chronic HCV patients were more likely to be hospitalized from liver-related conditions (RR = 24.8, P < 0.001). Hence, patients with chronic HCV infection had approximately 3.7-fold higher all-cause hospitalization rate than other health system patients. These findings highlight the incremental costs and healthcare burden of patients with chronic HCV infection associated with hospitalization.

Risk factors for hospitalisation and associated costs among patients with hepatitis A associated with imported pomegranate arils, United States, 2013.

OBJECTIVES: To assess hospitalisation risk factors and economic effects associated with a multistate hepatitis A outbreak in 2013. STUDY DESIGN: Retrospective case series. METHODS: Eligible outbreak-related cases confirmed by September 1, 2013, were defined as acute hepatitis symptoms and positive IgM anti-hepatitis A during March 15-August 12 among patients who consumed the food vehicle or had the outbreak genotype. We reviewed medical records, comparing demographic and clinical characteristics among hospitalized and non-hospitalized patients; we used logistic regression analysis to identify factors associated with hospitalization. We interviewed patients regarding symptom duration and healthcare usage and estimated per-patient and total costs. Health departments reported outbreak-related personnel hours. RESULTS: Medical records were reviewed for 147/159 (92%) eligible patients; median age was 48 (range: 1-84) years, and 64 (44%) patients were hospitalized. Having any chronic medical condition was independently associated with hospitalisation (odds ratio, 3.80; 95% confidence interval, 1.68-8.62). Interviews were completed for 114 (72%) eligible patients; estimated per-patient cost of healthcare and productivity loss was $13,467 for hospitalized and $2138 for non-hospitalized patients and $1,304,648 for all 165 outbreak-related cases. State and local public health personnel expenditures included 82 h and $3221/outbreak-related case. CONCLUSIONS: Hospitalisations in this outbreak were associated with chronic medical conditions and resulted in substantial healthcare usage and lost productivity. These data can be used to inform future evaluation of expansion of hepatitis A vaccination recommendations to include adults with chronic medical conditions.

Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance.

BACKGROUND: Hepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear. AIM: To compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance. METHODS: We selected persons with (case-patients) and without (control-patients) HBsAg seroclearance from a cohort of 1346 chronically HBV-infected AN patients followed during 1982-2013. We attempted to match two control-patients/case-patient on sex, HBV genotype, and age. Person-years of follow-up for case-patients began on the date of HBsAg resolution and for control-patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. We compared HCC risk using a Cox proportional hazards model. RESULTS: The 238 case-patients (4 with HCC) and 435 control-patients (9 with HCC) were similar in age [P-value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case-patients had longer person-years of follow-up than control-patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case- (132) and control-patients (178; P = 0.65). The adjusted hazard ratio comparing case- and control-patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2-2.4], increased for each 1-year increment for age (1.1; CI: 1.0-1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1-11.0; P = 0.03). CONCLUSIONS: Hepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance.

Increase in nonhepatic diagnoses among persons with hepatitis C hospitalized for any cause, United States, 2004-2011.

Although persons with hepatitis C virus (HCV) infection may experience nonhepatic illnesses, little is known about the frequency of and trends in such conditions in a population-based sample of HCV-infected persons. Using hospitalization data collected during 2004-2011 from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, we examined trends in comorbidities among all hospitalizations that included either a principal or secondary HCV diagnostic code (i.e., HCV was not necessarily the cause for hospitalization). We also compared comorbidities among all persons aged 45-64 years hospitalized with and without principal or secondary HCV diagnostic codes. The estimated number of hospitalizations among persons with HCV infection increased from 850,490 in 2004-2005 to 1,178,633 in 2010-2011; mean age at hospitalization was 50 years in 2004-2005 and 52.5 years in 2010-2011. There were significant increases in the prevalence of most medical and psychiatric comorbidities; the largest were for lipid disorders, chronic kidney disease and obesity. Among HCV-infected aged 45-64 persons hospitalized for any cause, the prevalence of alcohol /substance abuse, mental disorders, chronic kidney disease, pneumonia, hepatitis B virus infection and HIV infection were significantly higher than those aged 45-64 persons hospitalized without HCV infection (P < 0.001 for all). The prevalence of cryoglobulinaemia, vasculitis, nephrotic syndrome or membranoproliferative glomerulonephritis and porphyria cutanea tarda among hospitalizations with HCV infection was consistently low during the study period (i.e., <0.5%). The increase we observed in nonhepatic comorbidities associated with a high risk of HCV-related complications has important implications for the current HCV treatment recommendations in a greatly expanded treatment population.

Incidence of diabetes mellitus in a population-based cohort of persons with chronic hepatitis B virus infection.

To investigate the effect of hepatitis B virus (HBV) infection on the development of diabetes mellitus (DM), we compared DM incidence and characteristics of Alaska Native persons with and without HBV infection. From 1990 to 2010, there were 52 incident DM cases among 1309 persons with infection vs 4557 DM cases among 85 698 persons without infection (log-rank test, P = 0.20). Compared to infected persons without DM, those with DM were significantly older (57.0 vs 47.4 years, P < 0.001) and had higher body mass index (34.5 vs 28.4 kg/m(2) , P < 0.001). Genotype, immune active disease and the presence of cirrhosis were not associated with DM. In this population-based cohort with over 20 years of follow-up, there was no effect of HBV infection on DM development.

Treatment of hepatitis C virus (HCV) infection in patients coinfected with HIV in the HIV Outpatient Study (HOPS), 1999-2007.

Liver disease due to hepatitis C virus (HCV) infection is a leading cause of non-AIDS-related morbidity and mortality in patients infected with HIV. We assessed the frequency of and predictors for initiation of treatment for HCV infection among patients coinfected with HCV/HIV enrolled in the HIV Outpatient Study (HOPS) during 1999-2007. We included patients with confirmed HCV infection, at least 1 year of subsequent follow-up, and no evidence of prior HCV treatment. We assessed predictors of HCV treatment initiation using Cox proportional hazards analyses. During 1999-2007, 103 (20%) HOPS patients coinfected with HCV/HIV initiated HCV treatment during a median of 4.3 years of follow-up (interquartile range: 2.7, 6.7). In multivariable analysis, non-Hispanic black race/ethnicity (hazard ratio HR] 0.3; 95% confidence interval [CI] = 0.2, 0.6) was independently associated with a lower likelihood of HCV treatment. Elevated alanine aminotransferase (ALT; HR 3.5; 95% CI = 2.2, 5.6) and CD4+ cell count ≥500 cells/mm(3) (HR 1.8; 95% CI = 1.2, 2.8) at the start of observation were independently associated with higher likelihood of HCV treatment. For patients starting observation in 1999-2001, 2002-2004 and 2005-2007, 5%, 11% and 21% of patients initiated treatment during the first year of follow-up, respectively. Between 1999 and 2007, despite a stable low fraction of patients coinfected with HCV/HIV initiating treatment for HCV infection, an increasing proportion initiated treatment within the first year after the infection was confirmed. Treatment of HCV infection in patients coinfected with HCV/HIV should be considered a priority, given the increased risk of accelerated end-stage liver disease.

Prevalence of chronic hepatitis B virus infection among patients in the HIV Outpatient Study, 1996-2007.

Coinfection with hepatitis B virus (HBV) is an important and preventable cause of chronic liver disease among HIV-infected patients. We calculated the prevalence of chronic HBV infection annually from 1996 to 2007 by age, gender, race/ethnicity, and HIV transmission risk in a multisite observational cohort study of HIV-infected patients. Prevalence of chronic HBV infection was calculated as the number of patients with a positive HBsAg or detectable HBV DNA divided by the number of patients tested using either one of these assays. Among 4467 (59%) patients tested for chronic HBV infection from a total of 7618 patients active during 1996-2007, median age was 38.5 years, 77% were men, 49% were white, 35% were black, 13% were Hispanic, and 53% were men who had sex with men (MSM). Overall, 8.4% tested positive for HBsAg or detectable HBV DNA. Annual chronic HBV prevalence during 1996-2007 ranged from 7.8% to 8.6% without a statistically significant trend. Overall, prevalence was greater among men compared with women; among whites, blacks, and persons of other race compared with Hispanics; among MSM compared with injection drug users and high-risk heterosexuals; and among patients aged 35-44 years compared with younger or older patients. MSM constituted the greatest fraction (63-72%) of all HBV-infected patients in the HIV Outpatient Study (HOPS) over the period. Of eligible patients, 5.8%, 23.4%, and 31.6% had received at least one dose of HBV vaccine by years 1996, 2002, and 2007, respectively. Despite the availability of an effective HBV vaccine for over two decades and long-standing recommendations for immunization of persons (with or without HIV infection) at risk for HBV, the prevalence of chronic HBV infection in this study has been largely unchanged over the past decade among patients in all groups, and overall was 20 times as high as the national population prevalence.