Decrease in incidence of acute hepatitis B virus (HBV) infection has not been translated into a corresponding decrease in prevalence of chronic infection. Currently, immigration from endemic countries accounts for roughly 90% of all new cases of chronic HBV infection in the US. The diversity of race/ethnicity of the US population and the presence of many HBV genotypes presents an opportunity to study host-virus relationships and their association with clinical outcomes. Currently, there are 6 approved treatments for hepatitis B, but these treatments do not eradicate the virus. Most patients require long (or indefinite) durations of treatment to maintain virus suppression, leading to problems with antiviral resistance and affordability. The key questions regarding hepatitis B treatment are: when to start, which antiviral agent(s) should be used, when to stop, and what to do in patients with antiviral resistance? This Clinical Center application comprises 2 sites: University of Michigan in Ann Arbor and Hawaii Medical Center East/University of Hawaii in Honolulu. Dr. Lok is an international authority on hepatitis B and has a long record of success in hepatitis B research, she will be the PI. Dr. Tsai has a long standing clinical and research interest in hepatitis B and has extensive experience in community outreach programs, he will be the co-l. The goals of this Clinical Center application are to further our understanding of the natural history of chronic hepatitis B virus (HBV) infection, the mechanisms of spontaneous and treatment related virus clearance, the epidemiological and clinical impact of antiviral drug-resistant HBV mutations, and to determine the optimal treatment for patients with chronic hepatitis B. To achieve this goal, we will work in close collaboration with the other Clinical Centers, the Data Coordinating Center, the Immunology Center, the Virology Center, and the NIDDK Project Office;and will comply with the decisions of the HBV Clinical Research Network (CRN) Steering Committee and the policies of all HBV CRN committees. A database will be established to determine the spectrum of chronic HBV infection in the US, factors associated with disease progression, and incidence of antiviral drug resistance in clinical practice. A randomized trial comparing de novo combination of entecavir + tenofovir vs. entecavir vs. tenofovir in nucleoside na?ve HBeAg+ and HBeAg- patients with compensated liver disease with genotypic resistance as the primary endpoint is proposed. Clinical trials on other important topics such as treatment of patients in the immune tolerance phase and optimal management of patients with antiviral-resistant HBV are also discussed.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O1))
Program Officer
Doo, Edward
Project Start
Project End
Budget Start
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Fiscal Year
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Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code
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Hwang, Jessica P; Suarez-Almazor, Maria E; Cantor, Scott B et al. (2017) Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy. Cancer 123:3367-3376
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
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Khalili, Mandana; Lombardero, Manuel; Chung, Raymond T et al. (2015) Diabetes and prediabetes in patients with hepatitis B residing in North America. Hepatology 62:1364-74
Konerman, Monica A; Lok, Anna S (2015) Is it more cost-effective for patients with chronic hepatitis b to have a trial of interferon before considering Nucleos(t)ide analogue therapy? Clin Gastroenterol Hepatol 13:386-9
Ghany, Marc G; Perrillo, Robert; Li, Ruosha et al. (2015) Characteristics of adults in the hepatitis B research network in North America reflect their country of origin and hepatitis B virus genotype. Clin Gastroenterol Hepatol 13:183-92
Yapali, Suna; Talaat, Nizar; Fontana, Robert J et al. (2015) Outcomes of patients with chronic hepatitis B who do not meet criteria for antiviral treatment at presentation. Clin Gastroenterol Hepatol 13:193-201.e1

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