Tenofovir Disoproxil Fumarate vs. Entecavir in Chronic Hepatitis B Patients With Partial Virologic Response to Entecavir

The number of patients needed was calculated using PASS 2008. We hypothesized that two-thirds (65%) of the patients receiving TDF, and one-fifth (20%) of the patients receiving ETV, would achieve virologic response. We also assumed a 15% drop-out rate; thus, 22 patients were needed in each group to achieve 80% power to demonstrate a difference between the groups with a 5% level of significance.

The primary efficacy end point will be analyzed on a per-protocol basis, including only those patients who had completed the treatment schedule of study. In contrast, the intention-to-treat analysis will include all randomized subjects, even those dropped-out from the study before 12 months, as cases of treatment failure.

Inclusion criteria

• CHB patients (positive HBsAg more than 6 months)
• Age 19 years old
• HBeAg positive or negative patients
• Patients receiving entecavir 0.5 mg more than 12 months
• Detectable HBV DNA by real time PCR (HBV > 60 IU/mL)
• Compensated liver function (Child-Pugh-Turcotte score ≤7, prothrombin time 3 sec above ULN or INR ≤1.5, serum albumin >3 g/dL, total bilirubin <2.5 mg/dL, no history of variceal bleeding, diuretics or ascites requiring paracentesis, hepatic encephalopathy)

Exclusion criteria

• History of treatment with nucleotide analogue other than 0.5 mg of ETV
• Serum creatinine level > 1.5 mg/dL or creatinine clearance < 50 mL/min
• Absolute neutrophil count ≤ 1000 cell/mL
• Hemoglobin level ≤ 10 g/dL in men or ≤ 9 g/dL in women
• Antiviral resistance mutations on rtT184, rtS202, or rtM250 + rtM204V/I
• A positive antibody test for human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
• Pregnancy or lactation
• HCC (in cases where alfa-fetoprotein levels were over 100 ng/mL, abdominal computed tomography or magnetic resonance image was performed to exclude HCC)
• Untreated malignancy other than HCC.