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Hepatitis B virus (HBV), a major cause of liver disease, has infected approximately 2 billion people worldwide, and more than 350 million are chronically infected. Persistent viral replication increases the risk of progression to liver cirrhosis, development of hepatocellular carcinoma (HCC) and liver-related death. Therefore, the goals of antiviral therapy are to improve quality of life and survival by preventing progression of the disease to cirrhosis, HCC and death These goals can be achieved if HBV replication can be suppressed completely. Recent clinical studies showed that long-term suppression of HBV replication using anti-viral agents in patients with CHB can prevent progression to liver cirrhosis, hepatic failure and the development of HCC. Lamivudine (LAM), adefovir dipivoxil (ADV), telbivudine (Ltd), entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are available nucleos(t)ide analogues (NAs) for treating CHB patients worldwide. However, long-term treatment with NAs other than ETV and TDF increase the risk of drug resistance up to 80% because of low antiviral efficacy and low genetic barrier, Therefore, most guidelines recommend peg-interferon, ETV, or TDF in treatment-naïve patients. ADV add-on therapy has been widely used as a rescue therapy for patients with LAM-resistant CHB before TDF was not available. However, suboptimal response has been commonly observed in patients receiving ADV-based therapy. TDF, one of very potent antiviral agent with a high genetic barrier, showed excellent virologic response (VR), defined as serum HBV DNA level undetectably by sensitive PCR method, in NAsnaïve and NAs-resistant patients. Clinical efficacies of TDF therapy in NA-naïve and experienced patients are summarized in Table 1. In NA naïve patients, a significantly higher proportion of patients receiving TDF than of those receiving ADV had reached VR at 48 weeks (Table 1). Almost all patients who received TDF therapy showed VR without any evidence of resistance at seven year. In patients with LAM-resistant patients receiving TDF or TDF/emtricitabine (FTC), VR achieved in 89.4% and 86.3% at 96 weeks of therapy, respectively, without any evidence of TDF resistance during 5 years of follow-up. TDF also showed high See Article on Page 443

Switch to tenofovir-based therapy or to continue adefovir-based therapy in CHB patients with suboptimal response to adefovir-based combination?