Tenofovir Combination or Mono-therapy for MDR CHB

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Tenofovir-based Combination Therapy or Monotherapy for Multi-drug Resistant Chronic Hepatitis B; Real World Data From Multicenter Cohort Study

Conditions
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Chronic Hepatitis b With Multidrug Resistance

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CHB patients with: documented HBsAg positivity at least 6 months before enrollment age >18 years old, confirmed genotypic resistance to more than two classes of NAs HBV DNA level ≥ 200 IU/mL 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) willingness to give an informed consent. Exclusion Criteria: 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) no definite evidence of genotypic resistance positive antibody test for hepatitis C virus, hepatitis D virus, or human immunodeficiency virus HCC a proof of pregnant or lactating women evidence of active alcohol consumption (140 g per a week for men and 70 g per a week for women) any untreated malignancy.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Response | undetectable HBV DNA (<20 IU/mL) | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Response | undetectable HBV DNA (<20 IU/mL) | 60 months | 
| mean HBV DNA | mean HBV DNA levels | 36 months, 60 months | 
| ALT normalization | rates of ALT normalization | 36 months, 60 months | 
| Hepatitis B e antigen (HBeAg) seroconversion | rates of Hepatitis B e antigen (HBeAg) seroconversion | 36 months, 60 months | 
| virologic breakthrough | Incidence of virologic breakthrough defined by increase of HBV DNA more than 1 log IU/mL from nar dir. | 36 months, 60 months | 
| Genotypic resistance | Detection of previously known mutations to be resistant to the drugs being administered. | 36 months, 60 months |