We have established the Midwest Hepatitis B Consortium, comprising investigators from several institutions with considerable expertise in hepatitis B, to act as a clinical center for the Hepatitis B Network. This consortium maximizes our access to patients with HBV infection for enrollment in Network studies. The consortium allows is to bring unique strengths to bear including having two pediatric hepatologists to develop and conduct studies in children with hepatitis B and a nationally recognized liver pathologist (Elizabeth Brunt M.D.) with the knowledge, equipment and expertise to scan and digitize liver biopsy slides from all subjects enrolled in Network studies.
Specific aim 1 is to establish a database of HBsAg-positive subjects from all consortium sites.
One aim of the database is to determine the proportion of patients with chronic HBV infection who initially meet criteria for antiviral therapy. Those who are not initially treated will be followed at 6 month intervals over the next 5 years to determine the proportion who reactivate and become eligible for treatment. The second specific aim is to conduct a randomized double-blind controlled trial of entecavir vs, tenofovir vs. the combination of these two agents for 4 yrs, with 1 yr of follow up with the primary endpoint being the proportion of patients at year 5 (1 year follow up after stopping therapy) in whom HBV DNA is undetectable in serum (PCR negative). The third specific aim is to conduct a series of ancillary studies aimed at answering key questions about chronic hepatitis B. We propose ancillary studies to be considered by the Network steering committee including a pilot, exploratory study of entecavir in children, aimed at determining the pharmacokinetics and optimal dosing because of the limited treatment options available to children with hepatitis B. We propose pilot, exploratory studies of treatment of under-studied groups including patients in the immune tolerant and inactive carrier phases of chronic hepatitis B. We propose virology studies to be carried out in collaboration with the Virology Center, including full length cloning of HBV isolates from each subject to study viral variables contributing to resistance and genetic covariance network analysis, as we have successfully done in hepatitis C. Finally, we propose studies on Health-Related Quality of Life (HRQOL) using the Hepatitis B Quality of Life instrument, version 1.0, HBQOL v1.0 developed and validated by Dr Fasiha Kanwal, consortium P.I. at the St. Louis VAMC.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O1))
Program Officer
Doo, Edward
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Saint Louis University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
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Khalili, Mandana; Shuhart, Margaret C; Lombardero, Manuel et al. (2018) Relationship Between Metabolic Syndrome, Alanine Aminotransferase Levels, and Liver Disease Severity in a Multiethnic North American Cohort With Chronic Hepatitis B. Diabetes Care 41:1251-1259
Rosenthal, Philip; Ling, Simon C; Belle, Steven H et al. (2018) Combination of entecavir/ peginterferon alfa-2a in children with HBeAg-positive immune tolerant chronic hepatitis B virus infection. Hepatology :
Di Bisceglie, A M; Lombardero, M; Teckman, J et al. (2017) Determination of hepatitis B phenotype using biochemical and serological markers. J Viral Hepat 24:320-329
Lomonosova, Elena; Zlotnick, Adam; Tavis, John E (2017) Synergistic Interactions between Hepatitis B Virus RNase H Antagonists and Other Inhibitors. Antimicrob Agents Chemother 61:
Lok, A S; Ganova-Raeva, L; Cloonan, Y et al. (2017) Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment. J Viral Hepat 24:1032-1042
Schwarzenberg, Sarah Jane; Ling, Simon C; Cloonan, Yona Keich et al. (2017) Health-related Quality of Life in Pediatric Patients With Chronic Hepatitis B Living in the United States and Canada. J Pediatr Gastroenterol Nutr 64:760-769
Lomonosova, Elena; Tavis, John E (2017) In Vitro Enzymatic and Cell Culture-Based Assays for Measuring Activity of HBV RNaseH Inhibitors. Methods Mol Biol 1540:179-192
Ren, Yi; Wang, Weihua; Zhang, Xiaoan et al. (2016) Evidence for deleterious hepatitis C virus quasispecies mutation loads that differentiate the response patterns in IFN-based antiviral therapy. J Gen Virol 97:334-43
Villa, Juan Antonio; Pike, Daniel P; Patel, Kunjan B et al. (2016) Purification and enzymatic characterization of the hepatitis B virus ribonuclease H, a new target for antiviral inhibitors. Antiviral Res 132:186-95
Evon, Donna M; Wahed, Abdus S; Johnson, Geoffrey et al. (2016) Fatigue in Patients with Chronic Hepatitis B Living in North America: Results from the Hepatitis B Research Network (HBRN). Dig Dis Sci 61:1186-96

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