Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 160
- Locations
- 6
- Primary Endpoint
- Severity of hepatic necroinflammation and fibrosis
Study Overview
Brief Summary
This study aims to clarify whether patients with chronic hepatitis B with high viral load will benefit from oral antiviral therapy despite only mildly elevated serum liver enzyme.
Detailed Description
Chronic hepatitis B (CHB) is a serious disease in Taiwan, leading to substantial morbidity and mortality including hepatic failure, liver cirrhosis, and hepatocellular carcinoma (HCC). Recently a large body of evidence supports that high level of serum HBV DNA is an independent risk factor for late complications in CHB patients. Nucleos(t)ide analogues (NUC) are effective antiviral therapy that can potently inhibit replication of hepatitis B virus (HBV), and has been widely used in management of patients with CHB. Current practice guidelines recommend using serum alanine aminotransferase (ALT) > 2 times of the upper limit of normal (ULN) as the prerequisite to initiate antiviral therapy in compensated CHB patients without liver cirrhosis. However, serum ALT level does not exactly correlate with serum HBV DNA or liver tissue injury. Whether antiviral therapy improves outcomes of patients with slightly elevated ALT (i.e. 1-2 folds of ULN) remains unknown.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 25 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •age between 25 to 70 years,
- •serum HBsAg positivity for more than 6 months,
- •positive or negative serum HBeAg,
- •serum HBV DNA more than 2,000 IU/mL,
- •highest serum ALT > 1 fold of ULN, but < 2 X ULN on at least two occasions (≧ 3 months apart) in the preceding one year,
Exclusion Criteria
- •co-infection with HIV, HCV, or HDV,
- •previous exposure to HBV antiviral therapy for more than 12 weeks,
- •presence of cirrhosis on histopathology,
- •hepatic decompensation defined as serum bilirubin > 2mg/dl and prolonged prothrombin time > 3 seconds,
- •concurrent malignant diseases including hepatocellular carcinoma,
- •severe co-morbidity with life expectancy < 1year,
- •pregnant or lactating women,
- •organ transplantation except cornea or hair transplant,
- •suspected or confirmed chronic liver diseases from etiologies other than HBV (e.g. alcoholic hepatitis, Wilson disease, Hemochromatosis...etc),
- •serum creatinine >1.5mg/dL
Arms & Interventions
TDF
tenofovir disoproxil fumarate (TDF) 300mg
Intervention: tenofovir disoproxil fumarate 300mg per day (Drug)
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Severity of hepatic necroinflammation and fibrosis
Time Frame: Within one month after completion of antiviral therapy
Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system
Secondary Outcomes
- Serum level of HBsAg(Within one month after completion of antiviral therapy)
- Serious adverse reaction(Within one month after completion of antiviral therapy)
- Undetectable hepatitis B viral DNA(Within one month after completion of antiviral therapy)
- Normalization of serum alanine aminotransferase(Within one month after completion of antiviral therapy)
Investigators
Tu, Yuan-Kun
superintendent
E-DA Hospital