Long-term use of entecavir in nucleoside-naïve Japanese patients with chronic hepatitis B infection.
ABSTRACT To evaluate the long-term efficacy of entecavir in nucleoside-naïve chronic hepatitis B patients.
One hundred and sixty-seven patients treated with entecavir 0.01mg, 0.1mg or 0.5mg for 24-52weeks in Phase II studies entered rollover study ETV-060 and received entecavir 0.5mg daily. Responses were evaluated among patients with available samples.
After 96weeks in ETV-060 (120-148weeks total entecavir treatment time), 88% (127/144) of patients had HBV-DNA <400 copies/ml; 90.1% (128/142) had alanine aminotransferase (ALT) 1x the upper limit of normal (ULN) among those with abnormal baseline ALT; and 26% (32/121) achieved HBe seroconversion among those HBeAg(+) at baseline. A subset of 66 patients received entecavir 0.5mg (approved dose) from Phase II baseline: at week 96 in ETV-060, 83% (48/58) had HBV-DNA <400 copies/ml, 88% (52/59) had ALT 1x ULN, and 20% (10/49) achieved HBe seroconversion. Twenty-one out of 66 patients had paired baseline and on-treatment biopsies: 100% (21/21) and 57% (12/21) demonstrated histologic improvement, and improvement in fibrosis, respectively, over 3years. The 3-year cumulative probability of resistance was 3.3% for all patients and 1.7% for the 0.5mg subset.
Long-term entecavir for nucleoside-naïve patients resulted in high rates of virological, biochemical, and histological response, with minimal resistance.
SourceAvailable from: Ryosuke Tateishi[Show abstract] [Hide abstract]
ABSTRACT: Background The number of hepatocellular carcinoma (HCC) patients with non-viral etiologies is increasing in Japan. We conducted a nation-wide survey to examine the characteristics of those patients. Methods After we assessed the trend of patients who were first diagnosed with HCC at 53 tertiary care centers in Japan from 1991 to 2010, we collected detailed data of 5326 patients with non-viral etiology. The etiologies were categorized as autoimmune hepatitis, primary biliary cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), unclassified, and other. Baseline characteristics at initial diagnosis, the modality of the initial treatment, and survival status were collected via a website. Survival of the patients was assessed by the Kaplan–Meier method and Cox proportional hazard regression. Results The proportion of patients with non-viral etiologies increased from 10.0 % in 1991 to 24.1 % in 2010. Of the patients, 92 % were categorized as ALD, NAFLD, or unclassified. Body mass index (BMI) was ≥ 25 kg/m2 in 39 %. Diabetes was most prevalent in NAFLD (63 %), followed by unclassified etiology (46 %) and ALD (45 %). Approximately 80 % of patients underwent radical therapy, including resection, ablation, or transarterial chemoembolization. Survival rates at 3, 5, 10, 15, and 20 years were 58.2, 42.6, 21.5, 15.2, and 15.2 %, respectively. Multivariate analysis revealed that patients with BMI > 22 and ≤ 25 kg/m2 showed the best prognosis versus other BMI categories, after adjusting by age, gender, tumor-related factors, and Child-Pugh score. Conclusions Most cases of non-B, non-C HCC are related to lifestyle factors, including obesity and diabetes. Slightly overweight patients showed the best prognosis. Electronic supplementary material The online version of this article (doi:10.1007/s00535-014-0973-8) contains supplementary material, which is available to authorized users.Journal of Hepatology 06/2014; 50(3). DOI:10.1007/s00535-014-0973-8 · 10.40 Impact Factor
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ABSTRACT: Introduction: Liver cancer is one of the most common cancers. Hepatocellular carcinoma (HCC) represents > 90% of primary liver cancers and is a major global health problem today. Chronic hepatitis B virus (HBV) infection is associated with more than half of HCCs. Areas covered: Long-term therapy with nucleos(t)ide analogues (NUCs) improves outcomes in HBV-infected patients by slowing the progression of liver disease. It is associated with improvements in histological and clinical outcomes, improved patient survival, reduced need for liver transplantation and improved liver function in patients with decompensated liver disease. This review highlights the results of previous studies conducted on HCC prevention with long-term NUC therapy. Studies include the use of all available drugs in different clinical scenarios, and the comparison between treated and untreated patients. Expert opinion: NUCs have been studied extensively in HCC prevention. A comprehensive review of the literature has shown that they can be safely and effectively used for this purpose. Despite some discrepancies between studies, most of the evidence favors using NUC therapy for HCC prevention.Expert Opinion on Drug Safety 12/2014; 14(3):1-13. DOI:10.1517/14740338.2015.998649 · 2.74 Impact Factor
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ABSTRACT: Background and AimAlthough entecavir has been shown to have good efficacy and low resistance for the treatment of chronic hepatitis B (CHB), factors associated with a favorable response remain unknown. Methods This was a retrospective, multicenter study of 248 treatment‐naïve hepatitis B e antigen (HBeAg)‐positive patients (69.4% male; median age, 39.4 years) treated with entecavir for more than 1 year, and 15.7% of them had cirrhosis at baseline. The primary endpoints were HBeAg loss and/or seroconversion. ResultsThe median baseline levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA were 201 U/L (range, 27–2415 U/L) and 7.6 log10 IU/mL (range, 2.2–13.18), respectively. The median treatment period was 25.3 months (range, 12–69.6). The rates of ALT normalization at years 1, 2, and 3 were 83.1%, 87.9%, and 94.9%, respectively. The cumulative rates of HBeAg loss at years 1, 2, and 3 were 20.3%, 38.0%, and 48.9%, respectively. The rates of undetectable HBV‐DNA at years 1, 2, and 3 were 52.1%, 78.9%, and 82.5%, respectively. Using Cox proportional hazards model, multivariate analysis showed that baseline ALT greater than five times the upper limit of normal, and viral load were independent factors associated with HBeAg loss (hazard ratio: 1.81, and 0.812; 95% confidence interval: 1.062–3.085; 0.7–0.942, respectively). Conclusion Entecavir treatment for 3 years can achieve good biochemical and virologic responses in HBeAg‐positive CHB patients, but has a modest effect on HBeAg loss and/or seroconversion. In addition, baseline serum ALT and HBV‐DNA levels are independent factors associated with favorable treatment responses.Journal of Gastroenterology and Hepatology 01/2013; 28(1). DOI:10.1111/j.1440-1746.2012.07269.x · 3.63 Impact Factor