These patients were chronically monoinfected with HBV and were confirmed as hepatitis B s antigen (HBsAg)-positive for at least 6 months. As a general rule, ETV was initiated in a patient who had both abnormal alanine aminotransferase (ALT) levels (defined as ALT ≥45) and elevated HBV DNA levels of ≥4 log copies/mL. A patient with advanced fibrosis would be treated with ETV if the ALT level was normal; however, a patient without fibrosis or with a normal HBV DNA/ALT level would not be treated with ETV. Among the treated patients, 38 were excluded from the ETV group either because their follow-up period

was less than 1 year (n = 28) or because the clinical data or serum samples were incomplete (n = 10). The remaining 472 ETV-treated patients were included in the analysis (Fig. 1). No patient in the ETV group received other NAs before ETV treatment. The control group patients were recruited from Selleck Buparlisib 1973 to 1999. These patients were NA-naïve at baseline, as no NA therapy had yet been approved. Patients were excluded from the control group if (1) their follow-up duration was less than 1 year (n = 262); (2) corticosteroid withdrawal therapy (n = 120), IFN treatment (n = 305) or NA treatment (n = 273) was initiated

during follow-up; (3) clinical data or serum samples were incomplete (n = 153); or (4) patients were found selleck compound to be positive for anti-hepatitis C virus antibodies (HCV-Ab) (n = 76). The remaining 1,143 patients served as the control population (Fig. 1). We also made subanalyses to examine the difference of HCC suppression effect between NAs. To make this comparison, we recruited a cohort of 949 consecutive patients from our hospital who were treated with lamivudine (LAM) (September 1995 to September 2007). LAM-treated patients who met the same inclusion criteria as the ETV group, who had no rescue therapy (LAM group, n = 492), were used in the Isotretinoin comparison. We received informed consent from each patient at their entry into the study. Informed consent for the clinical data collection and storage of serum samples were obtained from each patient in the historical control group.

The study protocol was in accordance with the ethical guidelines of the Declaration of Helsinki and approved by the Toranomon Hospital Ethics Committee. All ETV-treated and untreated patients were followed at 1- to 3-month intervals, during which biochemical and HBV virological markers, blood counts, tumor markers (e.g., alpha-fetoprotein and des-γ-carboxylprothrombin), and cirrhosis and HCC status were monitored. Viral response in the ETV group was defined as a reduction in HBV DNA levels to below 400 copies/mL. Cirrhosis was determined by laparoscopy, liver biopsy, imaging modalities, or portal hypertension. HCC was diagnosed predominantly via imaging, including dynamic computed tomography, magnetic resonance imaging, and/or digital subtraction angiography.