Tenofovir in Chronic Hepatitis B With Mild ALT Elevation

E-DA Hospital160 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

160

Conditions

Chronic Hepatitis B

Interventions

tenofovir disoproxil fumarate 300mg per dayDRUG

tenofovir disoproxil fumarate 300mg per day for 3 years

PlaceboDRUG

Placebo, identical to TDF in appearance, once daily for 3years

Eligibility

Sex: ALLMin age: 25 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (6)

Chia-Yi Christine Hospital

Chiayi City, Taiwan

E-Da Hospital

Kaohsiung City, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

Chi Mei Medical Center, Liouying

Tainan, Taiwan

Outcomes

Primary Outcomes

Severity of hepatic necroinflammation and fibrosis

Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system