The primary objective of this study is to evaluate hepatitis B surface antigen (HBsAg) loss and seroconversion in participants who stop tenofovir disoproxil fumarate (TDF) (Stop TDF arm) compared to participants who continue TDF (Continue TDF arm).

Only participants who already are on treatment with TDF monotherapy or TDF in combination with lamivudine or emtricitabine for at least 4 years and who achieved and maintained virologic suppression (< 400 copies/mL) for 3.5 or more years will be included in this study. One treatment arm will stop the TDF therapy while the other treatment arm will continue the TDF therapy. Participants in the Stop TDF arm will be monitored very closely with special focus on biochemical flares (especially alanine aminotransferase (ALT) increases) and virological relapses (Hepatitis B viral load increases). If any participant in the Stop TDF arm exceeds one or more predefined limits for such flares or relapses, TDF treatment will be reinstituted.

Key Inclusion Criteria:

• Chronic hepatitis B, hepatitis B e-antigen negative, hepatitis B e-antibody positive, and hepatitis B surface antigen-positive
• Hepatitis B e Antigen (HBeAg)-negative at the beginning of TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine)
• Received continuous TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine) treatment for at least 4 years prior to screening. If TDF has been used in combination with lamivudine or emtricitabine, lamivudine or emtricitabine must have been stopped at least 12 weeks prior to screening
• Documented hepatitis B virus DNA (HBV DNA) < 400 copies/mL for at least 3.5 years prior to screening and at screening
• ALT within normal range
• α-fetoprotein (AFP) <= 50 ng/mL
• Calculated creatinine clearance >= 70 mL/min by Cockcroft-Gault formula using ideal body weight
• <= 10 kPa on Fibroscan assessment
• A negative serum pregnancy test for female subjects
• Adult subjects >= 18 years of age

Key Exclusion Criteria:

• Known cirrhosis
• Evidence of fibrosis >= Stage 3 (METAVIR) on liver biopsy or Fibroscan > 10 kPa within 6 months prior to screening
• Documentation of confirmed episodes (i.e., 2 consecutive values) of HBV DNA > 400 copies/mL within 3.5 years prior to screening
• History of decompensated liver disease (defined as direct [conjugated] bilirubin > 1.5 x upper limit of normal, prothrombin time (PT) > 1.5 x upper limit of normal, platelets < 75,000/mm³, serum albumin < 3.0 g/dL
• History of clinical hepatic decompensation in the judgement of the investigator
• Evidence of hepatocellular carcinoma
• Significant bone disease (in the judgment of the investigator)
• Serological evidence of coinfection with human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D infection
• Known hypersensitivity to TDF, its metabolites, or formulation excipients
• Concomitant therapy with disallowed medications
• History of malignant disease
• Lactating females
• Females wishing to became pregnant during the duration of the stud
• Subjects participating in another clinical trial can only be enrolled at the discretion of the Medical Monitor

Note: Other protocol defined inclusion/Exclusion criteria may apply.

Safety Analysis Set: participants who were either randomized to Arm A (Stop TDF) and had a baseline visit, or who were randomized to Arm B (Continue TDF) and received at least one dose of study drug

Up to 144 weeks

• Safety Analysis Set
• TDF-emergent Events (Restart TDF and Continue TDF): events began on/after date of TDF restart until last dose day for subjects who restarted TDF in the Stop TDF group and on/after Study Day 1 until last dose day for subjects in the Continue TDF group
• Termination-emergent Events (TDF-Free): events began on/after Study Day 1 for the Stop TDF group until last study day for subjects who did not restart TDF and prior to date of restart for subjects who restarted TDF