Treatment of multidrug resistant (MDR) chronic hepatitis B (CHB) is still a challenging issue. Hence, the investigators will perform a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)-based therapy for MDR CHB at real life settings.

Inclusion criteria were CHB patients with resistance to more than two classes of nucleos(t)ide analogues (NA) and hepatitis B virus (HBV) DNA level ≥200 IU/mL.

Patients will receive either TDF-base combination therapy or TDF monotherapy. The primary end point is virologic response (VR) defined by an undetectable HBV DNA (<20 IU/mL) at month 36.

Inclusion Criteria:

• CHB patients with:

  1. documented HBsAg positivity at least 6 months before enrollment
  2. age >18 years old,
  3. confirmed genotypic resistance to more than two classes of NAs
  4. HBV DNA level ≥ 200 IU/mL
  5. compensated liver diseases (defined by Child-Pugh-Turcotte score <7; prothrombin time <3 seconds above upper limit of normal or international normalized ratio <1.5; serum albumin >3 g/dL; total bilirubin <2.5 mg/dL; no history of esophago-gastric variceal bleeding, ascites, over hepatic encephalopathy)
  6. willingness to give an informed consent.

Exclusion Criteria:

1. laboratory abnormalities of low serum phosphorous level <2.0 mEq/dL, elevated serum creatinine >1.5 mg/dL, decreased creatinine clearance rate <50 mL/min, absolute neutrophil count <1000 cell/mL, or low hemoglobin level <10 g/dL (if female, <9 g/dL)
2. no definite evidence of genotypic resistance
3. positive antibody test for hepatitis C virus, hepatitis D virus, or human immunodeficiency virus
4. HCC
5. a proof of pregnant or lactating women
6. evidence of active alcohol consumption (140 g per a week for men and 70 g per a week for women)
7. any untreated malignancy.

Chronic hepatitis B patients with multiple drug resistance.

Confidential