Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Bruden DJ[original query] |
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Risk of end stage liver disease, hepatocellular carcinoma and liver-related death by fibrosis stage in the hepatitis C Alaska cohort
Bruden DJ , McMahon BJ , Townshend-Bulson L , Gounder P , Gove J , Plotnik J , Homan C , Hewitt A , Barbour Y , Spradling PR , Simons BC , McArdle S , Bruce M . Hepatology 2017 66 (1) 37-45 Long-term prospective studies of the outcomes associated with HCV infection are rare and critical for assessing the potential impact of HCV treatment. Using liver biopsy as a start point, we looked at development of end stage liver disease (ESLD), hepatocellular carcinoma (HCC) and liver-related death (LRD) according to fibrosis stage, among a cohort of American Indian/Alaska Native persons in Alaska. Persons were classified as having no/mild (Ishak=0,1), moderate (Ishak=2), or severe (Ishak=3,4) fibrosis or cirrhosis (Ishak=5,6). We examined time until development of ESLD, HCC and LRD and report survival probabilities at 3, 5, 7 and 10-years. Of 407 persons, 39%(n = 150) had no/mild fibrosis, 32%(n = 131) had moderate fibrosis, 22%(n = 88) had severe fibrosis and 9%(n = 38) had cirrhosis. The average time of follow-up was 7.3 years. Within 5 years of biopsy, 1.7% (95% confidence interval (CI):0.4,6.8) of persons with none/mild fibrosis developed ESLD compared to 7.9% (CI:4.0,15.2), 16.4% (CI:9.6,27.2) and 49.0% (CI:33.0,67.7) with moderate, severe fibrosis, and cirrhosis, respectively (p<0.01). The 5-year outcome of HCC was 1.0% (CI:0.1,7.0), 1.0% (CI 0.1,6.6), 1.1% (CI:0.2,7.7) and 13.4% (CI:4.4,36.7) among persons with none/mild, moderate fibrosis, severe fibrosis and cirrhosis, respectively (p<0.01). Five years following biopsy, 0.0% (CI:0.0,14.8) of persons with none/mild fibrosis had suffered an LRD compared to 1.0% (CI:0.2,7.5) of persons with moderate fibrosis, 4.7% (CI:1.5,14.1) with severe fibrosis and 16.3% (CI:7.0,35.1) with cirrhosis (p<0.01). Conclusion For prevention of HCC, LRD and ESLD in the short-term, HCV therapy should target those with more than mild fibrosis. This article is protected by copyright. All rights reserved. |
Does incorporating change in APRI or FIB-4 indices over time improve the accuracy of a single index for identifying liver fibrosis in persons with chronic hepatitis C virus infection?
Gounder PP , Haering C , Bruden DJ , Townshend-Bulson L , Simons BC , Spradling PR , McMahon BJ . J Clin Gastroenterol 2016 52 (1) 60-66 BACKGROUND: The aspartate aminotransferase-to-platelet ratio index (APRI) and a fibrosis index calculated using platelets (FIB-4) have been proposed as noninvasive markers of liver fibrosis. GOALS: To determine APRI/FIB-4 accuracy for predicting histologic liver fibrosis and evaluate whether incorporating change in index improves test accuracy in hepatitis C virus (HCV)-infected Alaska Native persons. STUDY: Using liver histology as the gold standard, we determined the test characteristics of APRI to predict Metavir ≥F2 fibrosis and FIB-4 to predict Metavir ≥F3 fibrosis. Index discrimination was measured as the area under the receiver operator characteristic curve. We fit a logistic regression model to determine whether incorporating change in APRI/FIB-4 over time improved index discrimination. RESULTS: Among 283 participants, 46% were female, 48% had a body mass index >30, 11% had diabetes mellitus, 8% reported current heavy alcohol use. Participants were infected with HCV genotypes 1 (68%), 2 (17%), or 3 (15%). On liver histology, 30% of study participants had ≥F2 fibrosis and 15% had ≥F3 fibrosis. The positive predictive value of an APRI>1.5/FIB-4>3.25 for identifying fibrosis was 77%/78%. The negative predictive value of an APRI<0.5/FIB-4<1.45 was 91%/87%. The area under the receiver operator characteristic curve of an APRI/FIB-4 for identifying fibrosis was 0.82/0.84. Incorporating change in APRI/FIB-4 did not improve index discrimination. CONCLUSIONS: The accuracy of APRI/FIB-4 for identifying liver fibrosis in HCV-infected Alaska Native persons is similar to that reported in other populations and could help prioritize patients for treatment living in areas without access to liver biopsy. Change in APRI/FIB-4 was not predictive of degree of fibrosis. |
A longitudinal hepatitis B vaccine cohort demonstrates long-lasting hepatitis B virus (HBV) cellular immunity despite loss of antibody against HBV surface antigen
Simons BC , Spradling PR , Bruden DJ , Zanis C , Case S , Choromanski TL , Apodaca M , Brogdon HD , Dwyer G , Snowball M , Negus S , Bruce MG , Morishima C , Knall C , McMahon BJ . J Infect Dis 2016 214 (2) 273-80 BACKGROUND: Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined. METHODS: We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31). RESULTS: All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor alpha, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection. CONCLUSIONS: Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years. |
Results of interferon-based treatments in Alaska Native and American Indian population with chronic hepatitis C
Livingston SE , Townshend-Bulson LJ , Bruden DJ , Homan CE , Gove JE , Plotnik JN , Simons BC , Spradling PR , McMahon BJ . Int J Circumpolar Health 2016 75 30696 BACKGROUND: There have been few reports of hepatitis C virus (HCV) treatment results with interferon-based regimens in indigenous populations. OBJECTIVE: To determine interferon-based treatment outcome among Alaska Native and American Indian (AN/AI) population. DESIGN: In an outcomes study of 1,379 AN/AI persons with chronic HCV infection from 1995 through 2013, we examined treatment results of 189 persons treated with standard interferon, interferon plus ribavirin, pegylated interferon plus ribavirin and triple therapy with a protease inhibitor. For individuals treated with pegylated interferon and ribavirin, the effect of patient characteristics on response was also examined. RESULTS: Sustained virologic response (SVR) with standard interferon was 16.7% (3/18) and with standard interferon and ribavirin was 29.7% (11/37). Of 119 persons treated with pegylated interferon and ribavirin, 61 achieved SVR (51.3%), including 10 of 46 with genotype 1 (21.7%), 38 of 51 with genotype 2 (74.5%) and 13 of 22 with genotype 3 (59.1%). By multivariate analysis, SVR in the pegylated interferon group was associated with female sex (p=0.002), estimated duration of infection (p=0.034) and HCV genotype (p<0.0001). There was a high discontinuation rate due to side effects in those treated with pegylated interferon and ribavirin for genotype 1 (52.2%). Seven of 15 genotype 1 patients treated with pegylated interferon, ribavirin and telaprevir or boceprevir achieved SVR (46.7%). CONCLUSIONS: We had success with pegylated interferon-based treatment of AN/AI people with genotypes 2 and 3. However, there were low SVR and high discontinuation rates for those with genotype 1. |
Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae, Alaska, 2000-2010
Gounder PP , Brewster M , Bruce MG , Bruden DJ , Rudolph K , Hurlburt DA , Hennessy TW . Pediatr Infect Dis J 2015 34 (11) 1223-9 BACKGROUND: We describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic resistant pneumococci in urban Alaskan children during 2000-2010. METHODS: We obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use < 90 days before enrollment was determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS. RESULTS: We recruited 3,496 children (median: 452/year). During 2000-2010, a range of 18-29%/year of children used PCN/amoxicillin (p-value for trend [p] = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0%-90%; p <0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53%-<1%; p <0.01) and non-PCV7-serotype proportion increased (43%-95%; p <0.01). PCN-R pneumococcal colonizationprevalence decreased (23%-9%, p <0.01) and PCN-I pneumococcal colonization prevalence increased (13%-24%, p <0.01); overall PCN-NS pneumococcalcolonizationprevalence was unchanged. PCN-NS among colonizing PCV7-type and non-PCV7-type pneumococci remained unchanged; a mean of 31%/year of PCV7-type and 10%/year of non-PCV7-type isolates were PCN-R, and 10%/year of PCV7 and 20%/year of non-PCV7-type isolates were PCN-I. CONCLUSIONS: Overall PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype-groups (PCV7 versus non-PCV7) despite stable penicillin use in our population. |
Eighteen years of respiratory syncytial virus surveillance: changes in seasonality and hospitalization rates in southwestern Alaska native children
Bruden DJ , Singleton R , Hawk CS , Bulkow LR , Bentley S , Anderson LJ , Herrmann L , Chikoyak L , Hennessy TW . Pediatr Infect Dis J 2015 34 (9) 945-50 BACKGROUND: Alaska Native (AN) infants from the Yukon-Kuskokwim Delta (YKD) experienced respiratory syncytial virus (RSV) hospitalization rates five times higher and an RSV season twice as long as the general US infant population. We describe trends in hospitalization rates and seasonality during 18 years of continuous RSV surveillance in this population and explore contributions of climate and sociodemographic factors. METHODS: We abstracted clinical and RSV test information from computerized medical records at YKD Regional Hospital and Alaska Native Medical Center from 1994-2012 to determine hospitalization rates and RSV season timing. Descriptive village and weather data were acquired through the US Census and Alaska Climate Research Center, University of Alaska, Fairbanks, respectively. RESULTS: During 1994-2012, YKD infant RSV hospitalization rates declined nearly 3-fold, from 177/1,000 infants/year to 65. RSV season onset shifted later, from mid-October to late December, contributing to a significantly decreased season duration, from 30 weeks to 11 weeks. In a multivariate analysis, children from villages with more crowded households and lacking plumbed water had higher rates of RSV hospitalizations (RR 1.17, p=0.0005, and RR 1.45, p=0.0003). No association of temperature or dew point was found with the timing or severity of RSV season. CONCLUSIONS: Although the RSV hospitalization rate decreased 3-fold, YKD infants still experience a hospitalization rate 3-fold higher than the general US infant population. Overcrowding and lack of plumbed water were associated with RSV hospitalization. Dramatic changes occurred in RSV seasonality, not explained by changes in climate. |
Effect of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae - Alaska, 2008-2012
Gounder PP , Bruce MG , Bruden DJ , Singleton RJ , Rudolph K , Hurlburt DA , Hennessy TW , Wenger J . J Infect Dis 2014 209 (8) 1251-8 BACKGROUND: In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008 to 2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes. METHODS: We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age <60 months at 2 urban clinics. We conducted interviews/medical records review for all participants. RESULTS: A total of 18 207 nasopharyngeal swabs (rural = 16 098; urban = 2109) were collected. From 2008 to 2012, 84% of rural and 90% of urban children age <5 years were age-appropriately vaccinated with a PCV. Overall pneumococcal colonization prevalence remained stable among rural (66%) and urban (35%) children age <5 years, and adults age ≥18 years (14%). Colonization by PCV6+ serotypes declined significantly among rural children age <5 years, urban children age <5, and adults age ≥18 over the course of the study (25%-5%, 22%-9%, 22%-6%, respectively). CONCLUSIONS: PCV13 was rapidly introduced into the Alaska childhood immunization schedule and reduced colonization by PCV6+ serotypes among children. Unvaccinated adults also experienced comparable reductions in vaccine serotype colonization indicating substantial indirect protection from PCV13. |
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