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Authors: Grace Lai-Hung Wong, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong
Journal: Hepatology (2014)

We thank Dr. Lo for his interest in our study.1 His first point related to the frequency of abdominal ultrasonography for surveillance of hepatocellular carcinoma every 1-2 years, instead of every 6 months, according to the international guidelines.2-4 This was the result of limited resources of radiology services in our public sector, which is often an issue in some regions.5 Instead, alpha-fetoprotein (AFP) was tested during every visit. In our recent analysis, the specificity of AFP was as high as 99% at a cut-off value of 20 µg/L in patients receiving entecavir.6 Dr. Lo also mentioned that variceal bleeding constituted the majority of the hepatic events, which could have been prevented by adequate endoscopic surveillance and treatment, either pharmacologically or endoscopically.7 In general esophageal variceal bleeding occurs at an annual rate of 5%-15% in patients that did not receive treatment for varices,8 which was significantly higher than the 3-year incident rate of 5.2% and 8.7% for variceal bleeding in the entecavir and control cohort, respectively. Furthermore, the surveillance provided to two cohorts of our patients was comparable or even better in the entecavir cohort because of advances in endoscopic therapy. Therefore, our observations still supported the conclusion that entecavir reduces hepatic events. Because of the nature of real-life cohort studies, there were significant differences in baseline characteristics between two cohorts of patients. We minimized bias by adjusting all clinical outcomes for the Model for End-Stage Liver Disease score, together with maintained viral suppression, another important difference,9 among patients with liver cirrhosis using Cox's proportional hazard model.1 Risk reduction remained robust. For example, the adjusted hazard ratio for hepatic events was 0.51 (95% confidence interval: 0.34-0.78; P = 0.002). Subsequent sensitivity analyses further highlighted the benefits of entecavir among patients at higher risk of events. The issue of inequality of follow-up duration in two cohorts was taken into account during the whole process of analysis. All clinical outcomes were estimated by survival analysis to allow for censoring of patients who had shorter follow-up durations.1 Besides, the cumulative probability of clinical events at 3 years was also lower in patients with cirrhosis receiving entecavir treatment. Finally, though it is true that the clinical benefit of antiviral therapy can only be firmly established by randomized, controlled trials, withholding treatment in patients with active liver injury or cirrhosis is no longer ethical. In such circumstances, one has to make clinical decisions based on the best available data. As such, well-characterized cohort studies offer valuable insights into the benefits and limitations of antiviral therapy.1, 10 Grace Lai-Hung Wong, M.D.1,2,3Henry Lik-Yuen Chan, M.D.1,2,3Vincent Wai-Sun Wong, M.D.1,2,3 1Institute of Digestive Disease The Chinese University of Hong Kong Hong Kong SAR, China 2Department of Medicine and Therapeutics The Chinese University of Hong Kong Hong Kong SAR, China 3State Key Laboratory of Digestive Disease The Chinese University of Hong Kong Hong Kong SAR, China