Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,

Inclusion Criteria:

1. HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months)
2. Age ≥ 18 years old, and ≤70 years old
3. Previous treatment with lamivudine more than 6 months
4. Being on lamivudine at the time of screening
5. Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
6. Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir)
7. HBV DNA ≥ 20,000 IU/mL
8. Patient willing to give an informed consent (If patient is <20 years old, the parent or legal guardian also need to give an informed consent)

Exclusion Criteria:

1. Out of inclusion criteria
2. Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
3. Laboratory abnormalities as follows at screening: AFP>100 ng/mL, serum phosphorous level<2.4 mg/dL, serum creatinine level> 1.5 mg/dL or creatinine clearance < 50 mL/min
4. Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP>7 points should be excluded.
5. History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks
6. History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening
7. Liver transplant patient
8. Patient co-infected with HIV, HCV, or HDV
9. Patient with metabolic or genetic liver disease that may affect serum ALT level
10. Habitual alcohol consumption (>140 g/week for male, >70 g/week for female)
11. Patient not able to stop drugs that may affect ALT or HBV DNA level during study periods (ie. Steroid, immune-suppressants, non-steroidal anti-inflammatory drugs, acetaminophen,)
12. Pregnant or lactating woman
13. Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation)
14. Patient with hepatocellular carcinoma (treated or not treated)
15. Patient with any untreated malignancy
16. Patient with history of malignancy cured within 5 years of screening