Clinical trial NCT01522625: Tenofovir in Chronic Hepatitis B With Mild ALT Elevation
Official title: Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: chronic hepatitis B
hepatitis B viral DNA
antiviral therapy
Tenofovir
Lead sponsor: E-DA Hospital
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
name: Taipei Institute of Pathology
First posted: 2012-01-31
Enrollment: 160
Sex: ALL
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Severity of hepatic necroinflammation and fibrosis
timeFrame: Within one month after completion of antiviral therapy
Secondary outcomes:
measure: Undetectable hepatitis B viral DNA
timeFrame: Within one month after completion of antiviral therapy
measure: Normalization of serum alanine aminotransferase
timeFrame: Within one month after completion of antiviral therapy
measure: Serum level of HBsAg
timeFrame: Within one month after completion of antiviral therapy
measure: Serious adverse reaction
timeFrame: Within one month after completion of antiviral therapy
Other outcomes:
Locations:
city: Chiayi City
country: Taiwan
facility: Chia-Yi Christine Hospital
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center, Liouying
city: Taipei
country: Taiwan
facility: Mackay Memorial Hosp
city: Yunlin
country: Taiwan
facility: National Taiwan University Hospital Yun-Lin Branch
Study officials:
affiliation: E-Da Hospital, Kaohsiung, Taiwan
name: Yao-Chun Hsu, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University
name: Jaw-Town Lin, MD, PhD
role: STUDY_CHAIR
References:
citation: Hsu YC, Chen CY, Chang IW, Chang CY, Wu CY, Lee TY, Wu MS, Bair MJ, Chen JJ, Chen CC, Tseng CH, Tai CM, Huang YT, Ku WH, Mo LR, Lin JT. Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial. Lancet Infect Dis. 2021 Jun;21(6):823-833. doi: 10.1016/S1473-3099(20)30692-7. Epub 2021 Jan 29.