Clinical Characteristics, Natural Outcome and Treatment Optimization of Refractory

Inclusion Criteria:

• (1) The diagnostic criteria of chronic hepatitis B: HBsAg and/or HBV DNA positive formore than 6 months; (2) Conforming to the definition of refractory hepatitis B (3)Aged between 18 and 70 (including 18 and 70); (4) Willing to accept treatment and signinformed consent.

Exclusion Criteria:

• (1) Pregnant women or lactating women; (2) with active HEPATITIS A, hepatitis C, andhepatitis D (in hospitals where conditions permit), hepatitis E and/or HIV infection; (3) Decompensated cirrhosis (Child-Pugh score 6); (4) Symptoms and signs ofhepatocellular carcinoma, AFP> Patients with 100ng/ml of AFP would be excluded, butpatients whose AFP remained stable (increased by less than 10%) for more than 3 monthsprior to the trial could be enrolled in patients whose liver tumors were excluded byliver imaging if AFP> 20ng/mL but 100ng/mL can be selected; (5) In addition toviral hepatitis, other history or evidence related to chronic liver disease (such ashemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liverdisease, toxin exposure, thalassemia); (6) a history of serious mental illness,especially depression severe mental illness is defined as at least 3 months before theabove treatment dose antidepressant or antipsychotic drug treatment of severedepression or psychosis, or there are any medical history: once for attempted suicidewas hospitalized due to mental illness, or had a disability due to mental illness; (7)a history of severe seizures or current use of anticonvulsants; (8) a history ofchronic lung disease related to functional limitations; (9) A history of severe heartdisease (NYHA grade III or IV, myocardial infarction within 6 months, ventriculartachyarrhythmia requiring continued treatment, unstable angina or other importantcardiovascular disease); (10) patients who are participating in other trials or havebeen treated with the study drug in the 12 weeks prior to screening; (11) Patientswith a history of allergy to ETV, TDF and TAF; In addition to the above exclusioncriteria, patients who meet any of the contraindications in the experimental drugdescription; (12) Unable or unwilling to provide informed consent or comply with therequirements of the study.