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Factors associated with initiation and completion of the quadrivalent human papillomavirus vaccine series in an ontario cohort of grade 8 girls
Leah M Smith, Paul Brassard, Jeffrey C Kwong, Shelley L Deeks, Anne K Ellis, Linda E Lévesque
BMC Public Health , 2011, DOI: 10.1186/1471-2458-11-645
Abstract: Linking administrative health and immunization databases, we conducted a population-based, retrospective cohort study of girls eligible for Ontario's Grade 8 HPV vaccination program in Kingston, Frontenac, Lennox, and Addington. We determined the proportion of girls who initiated (at least one dose) and completed (all three doses) the vaccination series overall and according to socio-demographics, vaccination history, health services utilization, medical history, and program year. Multivariable logistic regression was used to estimate the strength of association between individual factors and initiation and completion, adjusted for all other factors.We identified a cohort of 2519 girls, 56.6% of whom received at least one dose of the HPV vaccine. Among vaccinated girls, 85.3% received all three doses. Vaccination history was the strongest predictor of initiation in that girls who received the measles-mumps-rubella, meningococcal C, and hepatitis B vaccines were considerably more likely to also receive the HPV vaccine (odds ratio 4.89; 95% confidence interval 4.04-5.92). Nevertheless, HPV vaccine uptake was more than 20% lower than that of these other vaccines. In addition, while series initiation was not influenced by income, series completion was. In particular, girls of low income were the least likely to receive all three indicated doses of the HPV vaccine (odds ratio 0.45; 95% confidence interval 0.28-0.72).The current low level of HPV vaccine acceptance in Kingston, Frontenac, Lennox, and Addington will likely have important implications in terms of the health benefits and cost-effectiveness of its publicly funded program. We identified important factors associated with series initiation and completion that should be considered in efforts to improve HPV vaccine use in this population.In July 2006, Health Canada approved Gardasil?, a quadrivalent human papillomavirus (HPV) vaccine designed to protect against strains of HPV that cause 70% of cervical cancers [1]
Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study
Nanna Hansen, Niels Obel, Peer B Christensen, Mette Kj?r, Alex L Laursen, Henrik B Krarup, Axel M?ller, Poul Schlichting, Jens Bukh, Nina Weis, the Danish Database for Hepatitis B and C (DANHEP)- group
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-177
Abstract: We determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis.The majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin.The effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.Combination therapy with peginterferon and ribavirin has improved treatment response in patients with chronic hepatitis C virus (HCV) infection, but the virus is still only eradicated in 50-80% of the patients receiving treatment [1-3], depending on HCV genotype. Treatment is lengthy and has severe side effects, which may lead to dose reduction or even prevent treatment completion. There are also several contraindications to starting treatment, such as ongoing psychiatric disease or active intravenous drug use (IDU). Progress has been made in the development of new direct-acting antiviral drugs, specifically targeting viral replication, and some of these antivirals have recently been studied in clinical trials. The results are promising especially for certain protease inhibitors expected to be licensed soon for the treatment of chronic HCV infection, as part of triple therapy with peginterferon and ribavirin [4]. It is, however, still uncertain when these new agents will be introd
Predictors of the outcomes of acute-on-chronic hepatitis B liver failure  [cached]
Hsiu-Lung Fan,Po-Sheng Yang,Hui-Wei Chen,Teng-Wei Chen
World Journal of Gastroenterology , 2012, DOI: 10.3748/wjg.v18.i36.5078
Abstract: AIM: To identify the risk factors in predicting the outcome of acute-on-chronic hepatitis B liver failure patients. METHODS: We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus (ACLF-HBV) and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy. Their demographic, clinical, and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test, Fisher’s exact test, and a multiple logistic regression analysis. RESULTS: The study included 113 patients (87 men and 26 women) with a mean age of 49.84 years. Fifty-two patients survived, and 61 patients died. Liver failure (85.2%), sepsis (34.4%), and multiple organ failure (39.3%) were the main causes of death. Multivariate analyses showed that Acute Physiology and Chronic Health Evaluation (APACHE) II scores ≥ 12 [odds ratio (OR) = 7.160, 95% CI: 2.834-18.092, P < 0.001] and positive blood culture (OR = 13.520, 95% CI: 2.740-66.721, P = 0.001) on the day of diagnosis and model for end-stage liver disease (MELD) scores ≥ 28 (OR = 8.182, 95% CI: 1.884-35.527, P = 0.005) after the first week of treatment were independent predictors of mortality. CONCLUSION: APACHE II scores on the day of diagnosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF-HBV patients.
Evaluation of the Significance of Pretreatment Liver Biopsy and Baseline Mental Health Disorder Diagnosis on Hepatitis C Treatment Completion Rates at a Veterans Affairs Medical Center  [PDF]
Joseph Kluck,Rose M. O’Flynn,David E. Kaplan,Kyong-Mi Chang
Hepatitis Research and Treatment , 2013, DOI: 10.1155/2013/653976
Abstract: Objectives. This study was performed to define the overall treatment response rates and treatment completion rates among the population of Hepatitis C infected patients at an urban VA Medical Center. Additionally, we examined whether pretreatment liver biopsy is a positive predictor for treatment completion and if the presence of mental health disorders is a negative predictor for treatment completion. Methods. Retrospective chart review was performed on the 375 patients that were treated for HCV and met the study inclusion parameters between January 1, 2003 and April 1, 2008 at our institution. Clinical data was obtained from the computerized patient record system and was analyzed for respective parameters. Results. Sustained virological response was achieved in 116 (31%) patients. 169 (45%) patients completed a full treatment course. Also, 44% of patients who received a pre-treatment liver biopsy completed treatment versus 46% completion rates for patients who did not receive a pretreatment liver biopsy. Baseline ICD9 diagnosis of a mental health disorder was not associated with higher treatment discontinuation rates. Conclusions. In conclusion, pretreatment liver biopsy was not a positive predictor for treatment completion, and the presence of mental health disorders was not a negative predictor for treatment completion. 1. Background Hepatitis C virus (HCV) is a highly persistent, hepatotropic RNA virus that causes chronic necroinflammatory liver disease [1]. HCV seroprevalence is 2.2% in the world, 1.6% in the USA and as high as 15-16% in select Veterans Affairs Medical Centers (VAMC) [2–6]. Comorbid factors common among the US veteran population, such as advanced age, obesity, HIV coinfection, immunosuppression, and alcohol intake, are associated with accelerated liver disease and progression to cirrhosis in chronically HCV-infected patients [7–9]. HCV-associated cirrhosis (occurring in 20–30% of HCV-infected individuals) results in increased morbidity and mortality due to end stage liver failure and hepatocellular carcinoma (HCC) that may warrant liver transplantation [10–12]. Thus, the goal of HCV therapy is to clear HCV RNA in an effort to prevent or delay liver-related death and/or complications [7, 9]. The desired objective outcome of HCV-directed therapy is a sustained virologic response (SVR), which is defined as an undetectable HCV viral load (VL) 24 weeks after therapy completion and denotes a cure of the infection [7]. Several variables are known to predict the likelihood of SVR with pegylated interferon and ribavirin treatment. Other
Hepatitis E Virus ORF2 Protein Activates the Pro-Apoptotic Gene CHOP and Anti-Apoptotic Heat Shock Proteins  [PDF]
Lijo John, Saijo Thomas, Ottmar Herchenr?der, Brigitte M. Pützer, Stephan Schaefer
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025378
Abstract: Background Hepatitis E virus (HEV) is a non-enveloped plus-strand RNA virus that causes acute hepatitis. The capsid protein open reading frame 2 (ORF2) is known to induce endoplasmic reticulum stress in ORF2 expressing cells. Methodology/Principal Findings In this study we found that HEV ORF2 activates the expression of the pro-apoptotic gene C/EBP homologous protein (CHOP). ORF2 stimulates the CHOP promoter mainly through AARE (amino acid response elements) and to a minor extent the ERSE (endoplasmic reticulum stress response elements). Activating transcription factor 4 (ATF4) protein binds and activates the AARE regulatory sites of the CHOP promoter. ORF2 expression also leads to increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) that in turn initiates the translation of ATF4 mRNA. The pro-apoptotic gene CHOP is an important trigger to initiate endoplasmic reticulum stress induced apoptosis. However, the activation of CHOP by ORF2 in this study did not induce apoptosis, nor did BCL2-associated X protein (Bax) translocate to mitochondria. Microarray analysis revealed an ORF2 specific increased expression of chaperones Hsp72, Hsp70B', and co-chaperone Hsp40. Co-immunoprecipitation (Co-IP) and in silico molecular docking analysis suggests that HEV ORF2 interacts with Hsp72. In addition, Hsp72 shows nuclear accumulation in ORF2 expressing cells. Conclusions/Significance These data provide new insight into simultaneously occurring counter-acting effects of HEV ORF2 that may be part of a strategy to prevent host suicide before completion of the viral replication cycle.
Pegylated interferon 2a and 2b in combination with ribavirin for the treatment of chronic hepatitis C in HIV infected patients
Ravinder Dhillon,Simona Rossi,Steven K Herrine
Therapeutics and Clinical Risk Management , 2008,
Abstract: Ravinder Dhillon, Simona Rossi, Steven K HerrineDepartment of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Coinfection with hepatitis C virus (HCV) and HIV is an increasingly recognized clinical dilemma, particularly since the advent of highly active antiretroviral therapy. Several studies of this population have demonstrated both more rapid progression of liver disease and poorer overall prognosis compared to HCV monoinfected patients. Consensus guidelines, based primarily on the results of 4 major randomized trials, recommend treatment with peginterferon and ribavirin for 48 weeks in coinfected patients. However, this current standard of care is associated with lower response rates to therapy than those seen in monoinfected patients. Important predictors of response include HCV genotype, pretreatment HCV RNA level, and presence of rapid virologic response (RVR) and early virologic response (EVR). Use of weight-based ribavirin dosing appears to be safe and enhances the likelihood of sustained virologic response (SVR). Adverse effects most commonly encountered are anemia and weight loss. Mitochondrial toxicity can occur in the setting of concomitant nucleoside reverse transcriptase inhibitor use, especially didanosine, abacavir, and zidovudine, and these should be discontinued before initiation of ribavirin therapy. Discontinuation of therapy should be considered in patients failing to demonstrate EVR, though ongoing trials are investigating a potential role for maintenance therapy in these patients. Peginterferon combined with weight-based ribavirin is appropriate and safe for treatment of HCV in HIV – HCV coinfected patients. This review summarizes the data supporting these recommendations.Keywords: hepatitis C, human immunodeficiency virus, peginterferon, ribavirin
Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation  [PDF]
Ji Hoon Kim equal contributor,Bo Hwa Sohn equal contributor,Hyun-Sung Lee,Sang-Bae Kim,Jeong Eun Yoo,Yun-Yong Park,Woojin Jeong,Sung Sook Lee,Eun Sung Park,Ahmed Kaseb,Baek Hui Kim,Wan Bae Kim,Jong Eun Yeon,Kwan Soo Byun,In-Sun Chu,Sung Soo Kim,Xin Wei Wang,Snorri S. Thorgeirsson,John M. Luk,Koo Jeong Kang,Jeonghoon Heo,Young Nyun Park,Ju-Seog Lee
PLOS Medicine , 2014, DOI: 10.1371/journal.pmed.1001770
Abstract: Background Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. Methods and Findings Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3–3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1–2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus–positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. Conclusions Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification. Please see later in the article for the Editors' Summary
Predictors of initiation and persistence of unhealthy weight control behaviours in adolescents
Jennifer A Linde, Melanie M Wall, Jess Haines, Dianne Neumark-Sztainer
International Journal of Behavioral Nutrition and Physical Activity , 2009, DOI: 10.1186/1479-5868-6-72
Abstract: A diverse sample included 1106 boys and 1362 girls from 31 middle schools and high schools in the United States who were enrolled in Project EAT (Eating Among Teens). Project EAT explored personal, behavioural, and socio-environmental factors associated with dietary intake and body weight in adolescence. Participants completed questionnaires to assess demographics, UWCB (including several methods of food restriction, purging by vomiting or medications, smoking to control weight, or food substitutions) and personal and socio-environmental variables at two time points, five years apart, between 1998 and 2004. Logistic regression models examined personal and socio-environmental predictors of initiation and persistence of UWCB among Project EAT participants.Results indicate that 15.5% of boys and 19.7% of girls initiated UWCB by Time 2, and 15.9% of boys and 43.3% of girls persisted with these behaviours from Time 1 to Time 2. After controlling for race/ethnicity and weight status changes between assessments, logistic regression models indicated that similar factors and patterns of factors were associated significantly with initiation and persistence of UWCB. For both boys and girls, personal factors had more predictive value than socio-environmental factors (Initiation models: for boys: R2 = 0.35 for personal vs. 0.27 for socio-environmental factors; for girls, R2 = 0.46 for personal vs. 0.26 for socio-environmental factors. Persistence models: for boys: R2 = 0.53 for personal vs. 0.33 for socio-environmental factors; for girls, R2 = 0.41 for personal vs. 0.19 for socio-environmental factors). The weight concerns model was the strongest predictor among all individual models [Initiation odds ratios (ORs) and 95% confidence interval (CI): 4.84 (3.32-7.01) for boys and 5.09 (3.55-7.30) for girls; persistence OR (CI): 4.55 (2.86-7.14) for boys and 3.45 (2.50-4.76) for girls].In general, predictors of initiation and persistence of UWCB were similar, suggesting that universa
Laboratory predictors of advanced fibrosis in Saudi patients with chronic hepatitis B and C  [cached]
Abdo Ayman
Saudi Journal of Gastroenterology , 2006,
Abstract: Objective: To identify laboratory predictors of advanced fibrosis in Saudi Arabian patients with hepatitis B and C. Materials and Methods: Histopathology reports were obtained on all patients who had liver biopsy in the last 5 years, and relevant laboratory data were collected. Results: A total of 328 patients (246 with hepatitis C and 82 with hepatitis B) were included. With logistic regression analysis, four factors were found to be the best predictors of fibrosis, namely, platelet count, ALT, AST and GGT levels. An equation for calculating the risk of advanced fibrosis was developed. The model had a sensitivity of 62%, a specificity of 92.4% and an overall accuracy of 84%. Conclusion: Platelet count, ALT, AST and GGT levels were found to be the best predictors of advanced fibrosis on liver biopsy in Saudi patients with chronic hepatitis B and C. An equation was developed that helps in calculating this risk.
Association of Early Age at Establishment of Chronic Hepatitis B Infection with Persistent Viral Replication, Liver Cirrhosis and Hepatocellular Carcinoma: A Systematic Review  [PDF]
Yusuke Shimakawa, Hong-Jing Yan, Naho Tsuchiya, Christian Bottomley, Andrew J. Hall
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069430
Abstract: Age at infection with hepatitis B virus (HBV) is a known risk factor for chronic HBV infection. However, in addition, there is some evidence that early age at infection further increases the risk of primary liver cancer beyond its association with increased risk of chronic infection. This systematic review of observational studies assesses the association between age at initiation of chronic HBV infection and liver cirrhosis, hepatocellular carcinoma, and their predictors including indicators of ongoing viral replication and hepatic damage. The review includes birth order and maternal HBV serology as proxies for age at infection. Electronic searches in two English-language (Medline and Embase, until Jan 2012) and two Chinese-language (CNKI and SinoMed, until Sep 2012) databases without language restriction and manual search through reference lists identified 7,077 papers, of which 19 studies of 21 outcomes (8 primary liver cancer, 1 liver cirrhosis, 10 viral replication and 2 liver inflammation) are included. One study directly examined the age at infection in a longitudinal cohort, 12 assessed maternal sero-status and 6 investigated birth order. The direction of associations in all studies was in accordance with our hypothesis that earlier age at infection is associated with worse outcomes in addition to its effect of increasing the probability of chronic HBV infection. This has implications for the control of hepatitis B.
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