Efficacy and Safety of TAF in Patients With Suboptimal Response to Other Nucleos(t)Ides

Inclusion Criteria: * Patients must be 18-80 years of age. * Patients must have documented compensated and stable chronic hepatitis B defined by all of the following: * HBsAg persistently positive \> 6 months. * Clinical history, physical findings, and test results are compatible with compensated chronic hepatitis B * Patients must have received nucleos(t)ide therapy consisting of LAM/LdT/ADV and its combinations with other second-line antivirals for 24 weeks, or with the first-line antiviral ETV or any antiviral combinations containing ETV for 48 weeks with medication adherence. * Although having undergone therapy, patients have had failure to achieve the levels of HBV-DNA below 300 IU/mL. * Patient is willing and able to comply with the study drug regimen and all other study requirements. * Patient must understand the risk, and be willing and able to provide written informed consent to participate in the study. Exclusion Criteria: * Pregnant women, and women who are breastfeeding or who believe they may wish to become pregnant during the course of the study. * Males and females of reproductive potential who are not willing to use an effective method of contraception during the study. For males, condoms should be used and for females, a barrier contraception method should be used in combination with one other form of contraception. * Unwilling and/or unable to provide written informed consent * Patients with CHB but are also co-infected with HIV or other viral hepatitis * Patients whose serum levels of HBV DNA are too low (i.e. about 300 IU/mL) to be analyzed for the genotypic mutation(s) at the onset of this trial, i.e. baseline * At the screening visit, nucleos(t)ide resistant mutants have been detected in the strain of HBV of the patient * The patient is under a clinical research protocol of phase I-III development; unable to consent or unlikely to complete one year follow up after the enrollment; and other medical condition may affect the ability to participate the study. * Decompensated liver disease defined as direct (conjugated) bilirubin ≥ 1.2 Upper Limit of Normal (ULN); Prothrombin Time (PT) ≥ 1.2 ULN, platelets ≤ 150,000/mm3, or serum albumin ≤ 3.5 g/dL * Prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy) or variceal hemorrhage * Serum α-fetoprotein ≥ 50 ng/mL * Evidence of hepatocellular carcinoma (HCC) * History of significant renal disease (e.g., nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease) * History of significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures) * Significant cardiovascular, pulmonary or neurological disease * Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications * History of solid organ or bone marrow transplantation * Ongoing therapy with any of the following: Nephrotoxic agents * Parenteral aminoglycoside antibiotics (e.g., gentamicin, tobramycin, amikacin) * Cidofovir * Cisplatin * Foscarnet * IV amphotericin B * IV pentamidine * Oral or IV ganciclovir * Cyclosporine * Tacrolimus * IV vancomycin * Chronic daily non-steroidal anti-inflammatory drug therapy * Competitors of renal excretion (e.g., probenecid) Systemic chemotherapeutic agents * Systemic corticosteroids * Interleukin-2 (IL-2) and other immunomodulating agents * Investigational agents (except with the expressed approval of the lead investigators) Note: administration of any of the above medications must be discontinued at least 30 days prior to the Baseline Visit and for the duration of the study period. * Known hypersensitivity to the study drugs, the metabolites or formulation excipients * Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigators, would make the subject unsuitable for the study or unable to comply with dosing requirements