The objective of this study is to identify immunological mechanisms that contribute to normalization of liver inflammation in chronic hepatitis B (CHB) patients starting the antiviral nucleoside analogue, Tenofovir alafenamide (TAF).
Investigator-initiated, phase 4 study in which recruited patients will receive, TAF 25mg once daily, for 48 weeks (Figure 1 and Table 1). The total duration of the study to End of Follow-up (EOF) will be 48 weeks. After Week 48, participants will be offered 2 years of TAF therapy. Sample collection 0, 12, 24 w was chosen to analyze immune responses based on ALT normalization rates. This mono-center study will be conducted at Toronto Centre for Liver Disease, Canada.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
TAF 25mg once daily orally, for 48 weeks
Toronto General Hospital
Toronto, Ontario, Canada
RECRUITINGTAF-mediated reduction of inflammatory gene expression in intraheaptic immune cells
Longitudinal samples collected from each patient will be used to measure changes in intrahepatic and peripheral innate and adaptive immune composition, function and gene expression from baseline to ALT normalization after starting TAF.
Time frame: 3 years
TAF-mediated reduction of serological markers of HBV replication
Existing and experimental biomarkers of HBV replication will be measured to compare the viral response to the immune response 1. HBsAg/HBeAg seroclearance 2. HBsAg/HBeAg seroconversion, 3. Serum quantitative HBsAg/HBeAg levels, 4. Serum HBV DNA levels 5. HBV RNA levels 6. Hepatitis B core-related Antigen (HBcrAg) levels; 7. ALT levels.
Time frame: 3 years
TAF-mediated reduction of intrahepatic HBV replication intermediates and cccDNA levels
HBV replication intermediates and cccDNA measured as copies/mg of liver tissue
Time frame: 3 years
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