Chronic Hepatitis B
Conditions
Keywords
chronic hepatitis B, hepatitis B viral DNA, antiviral therapy, Tenofovir
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.
Interventions
DRUGtenofovir disoproxil fumarate 300mg per day
tenofovir disoproxil fumarate 300mg per day for 3 years
DRUGPlacebo
Placebo, identical to TDF in appearance, once daily for 3years
Sponsors
Gilead Sciences
Taipei Institute of Pathology
E-DA Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of hepatic necroinflammation and fibrosis | 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
| Measure | Time frame | Description |
|---|---|---|
| Undetectable hepatitis B viral DNA | Within one month after completion of antiviral therapy | HBV DNA viral DNA not detected in serum |
| Normalization of serum alanine aminotransferase | Within one month after completion of antiviral therapy | serum ALT \<40 IU/mL |
| Serum level of HBsAg | Within one month after completion of antiviral therapy | quantification of serum HBV serface antigen |
| Serious adverse reaction | Within one month after completion of antiviral therapy | Defined as death, life threatening event, permanent or temporary disability, and hospitalization |
Countries
Taiwan
Outcome results
None listed