The investigators' research is aimed at developing more effective, finite approaches for managing individual patients with chronic hepatitis B (CHB). This prospective clinical and basic scientific study exclusively focuses on patients with the early antigen negative form of disease, which in developed countries is treated indefinitely with antiviral drugs. The investigators' study "BeNEG-DO," directly offers patients who are already taking standard oral Hepatitis B Virus (HBV) antiviral therapy for at least 192 weeks the option to stop or continue treatment. Drawing on data from pilot studies, including the investigators' own University of California, San Francisco and Sutter Institutional Review Board-approved study, the investigators will examine a finite HBV treatment strategy on clinical outcome and safety. In conjunction, the investigators will study immunologic mechanisms and gene expression profiles that correlate with and predict the post-treatment clinical course. The BeNEG-DO study could seriously question, and potentially change, the current treatment paradigm for millions of patients with CHB and also lead to new disease-terminating antiviral therapeutics.
A prospective case-control study of safety and clinical outcomes, and of innate and adaptive immune responses and their genetic predictors, in adult human subjects with HBeAg-CHB who either continue or stop nucleoside or nucleotide analog (NA) antiviral therapy. Immune responses will be studied using liver tissue and serial peripheral blood samples. The immunological factors selected have been chosen based on preliminary and inferential evidence. Immunologic findings will be correlated with different serologic, virologic and biochemical outcomes. Genetic predictors of the type of response and respective clinical outcomes will also be sought.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
121
Cases will stop antiviral therapy
California Pacific Medical Center
San Francisco, California, United States
University of California, San Francisco
San Francisco, California, United States
Serologic response and rate: HBsAg persistence versus loss; HBsAb production (+/-). This clinically relevant endpoint evaluates chronic HBV clearance and persistence
Annual seroclearance rates of 0.5%-0.8% in controls are assumed (American Association for the Study of Liver Diseases 2012 Poster 374) and equivalent to the estimated spontaneous rate (Hepatology 2009; 49:S45-55). In cases, 5-6% (based on Gastroenterology 2012 143:629:636) 5 year rates for HBsAg seroconversion (5%) or HBsAg loss only.
Time frame: 10 years
Liver biochemical response: ALT level
These anticipated biochemical outcomes are based on Gastroenterology 2012 143:629-636
Time frame: 5 years
Virologic response: HBV DNA level
Hepatitis B Virus levels measured in International Units per milliliter
Time frame: 10 years
Case retreatment rate
As a measure of safety
Time frame: 10 years
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