Tenofovir in Chronic Hepatitis B With Mild ALT Elevation
- Conditions
- Chronic Hepatitis B
- Interventions
- Drug: Placebo
- Registration Number
- NCT01522625
- Lead Sponsor
- E-DA Hospital
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 160
- 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,
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - TDF tenofovir disoproxil fumarate 300mg per day tenofovir disoproxil fumarate (TDF) 300mg
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
Trial Locations
- Locations (6)
Chia-Yi Christine Hospital
🇨🇳Chiayi City, Taiwan
E-Da Hospital
🇨🇳Kaohsiung, Taiwan
Mackay Memorial Hosp
🇨🇳Taipei, Taiwan
National Taiwan University Hospital Yun-Lin Branch
🇨🇳Yunlin, Taiwan
Chi Mei Medical Center, Liouying
🇨🇳Tainan, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan