Telbivudine:A new treatment for chronic hepatitis B

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include： standard interferon- alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues, which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel, orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no dose- limiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.

Clinical features of adverse reactions associated with telbivudine

AIM: To analyze the clinical features and risk factors of adverse reactions associated with telbivudine. METHODS: Clinical data were collected from cases that presented with serious adverse reactions to telbivudine. We analyzed general information and medicine status, clinical features, results of examination, and misdiagnosis. RESULTS: Out of 105 patients who were treated with telbivudine for hepatitis B in an outpatient department from January, 2007 to January, 2008, five presented with serious adverse drug reactions. Most of these five patients had used other nucleoside analogues in the past. Four were treated with a combination of telbivudine and interferon or another nucleoside analogue, while the other received an increased dose of telbivudine. The main adverse reactions were myalgia and general weakness. This was accompanied by cardiac arrhythmia in one patient, and nervous symptoms in three. Serum creatine kinase was elevated. The rate of misdiagnosis was high. CONCLUSION: The adverse reactions were related to telbivudine, but the biological mechanism of the reactions is not yet clear. Combination therapy with interferon or another nucleoside analogue and a high dose may increase the risk of adverse reactions.

Lactic acidosis during telbivudine treatment for HBV: A case report and literature review

All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy.A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B.After 11 mo of therapy,he developed anorexia,nausea,and vomiting with mild muscle weakness.The patient was found with elevated serum creatine phosphokinase up to 3683 U/L(upper limit of normal 170 U/L)and marked LA.LA did not resolve immediately following discontinuation of telbivudine.His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid.The patient fully recovered after 16 wk of treatment.This is the first documented case with severe LA caused by telbivudine monotherapy.Besides serum creatine phosphokinase,blood lactate level should also be closely monitored in patients receiving telbivudine.

Comprehensive review of telbivudine in pregnant women with chronic hepatitis B

AIM:To achieve an evidence-based conclusion regarding the safety and efficacy of telbivudine during pregnancy.METHODS:A pooled analysis of data from a literature search reported 1739 pregnancy outcomes(1673 live births)from 1725 non-overlapping pregnant women treated with telbivudine.The prevalence of live birth defects(3.6/1000)was similar to that of the nonantiviral controls(3.0/1000)and not increased as compared with overall prevalence(14.5 to 60/1000).No target organ toxicity was identified.The prevalence of spontaneous abortion in pregnant women treated with telbivudine(4.2/1000)was not increased compared with the overall prevalence(16/1000).The mother-to-child transmission rate was significantly reduced in pregnant women treated with telbivudine(0.70%)compared to those treated with the non-antiviral controls(11.9%;P<0.0001)or compared to the historical rates of hepatitis B virus(HBV)-infected population without antiviral treatment(10%-15%).RESULTS:Cumulatively 489 pregnancy cases have been reported in the telbivudine pharmacovigilance database(with a cut-off date 31 August 2014),of those,308 had known pregnancy outcomes with 249 cases of live births(239 cases of live birth without congenital anomaly and 10 cases of live birth with congenital anomaly).In the latest antiretroviral pregnancy registry report(1 January 1989 through 31 January 2015)of27 patients exposed to telbivudine during pregnancy(18,6 and 3 during first,second and third trimester,respectively)19 live births were reported and there were no cases of birth defects reported.CONCLUSION:Telbivudine treatment during pregnancy presents a favorable safety profile without increased rates of live birth defects,spontaneous abortion or elective termination,or fetal/neonatal toxicity.Exposure to telbivudine in the first,second and third trimester of pregnancy has been shown to significantly reduce the risk of HBV transmission from mother to child on the basis of standard immune prophylaxis procedure.

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

AIM:To evaluate the efficacy and safety of telbivudine(LDT) in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients who have high baseline alanine aminotransferase(ALT) levels between 10 and 20 times the upper limit of normal.METHODS:Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk.Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as controls.We compared the virological,biochemical,serological and side effect profiles between the two groups at 52 wk.RESULTS:By week 52,the mean decrease in hepatitis B virus(HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group,respectively(P < 0.05).The proportion of patients in whom serum HBV DNA levels were undetectable by polymerase chain reaction assay was 72.5% in the high baseline ALT group and 60% in the control group,respectively(P < 0.05).In addition,45.0% of patients in the high baseline ALT group and 27.5% of controls became HBeAg-negative,and 37.5% of those in the high baseline group and 22.5% of controls,respectively,had HBeAg seroconversion(P < 0.05) at week 52.Moreover,in the high baseline group,4 out of 40 patients(10%) became hepatitis B surface antigen(HBsAg)-negative and 3(7.5%) of them seroconverted(became HBsAg-positive).Only 1 patient in the control group became HBsAg-negative,but had no seroconversion.The ALT normalization rate,viral breakthrough,genotypic resistance to LDT,and elevations in creatine kinase levels were similar in the two groups over the 52 wk.CONCLUSION:High baseline ALT level is a strong predictor for optimal results during LDT treatment.

Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study

AIMTo make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. METHODSThis was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA RESULTSA total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (&plusmn; 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level CONCLUSIONEfficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.

Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir

AIM:To examine the efficacy of telbivudine(LdT)+adefovir(ADV)vs continuation of lamivudine(LAM)+ADV in patients with LAM-resistant chronic hepatitis B(CHB)who show a suboptimal response to LAM+ADV.METHODS:This was a randomized,active-control,open-label,single-center,parallel trial.All eligible patients were enrolled in this study in Severance Hospital,Yonsei University College of Medicine,Seoul,South Korea,between March 2010 and March 2011.Hepatitis Be antigen(HBeAg)-positive CHB patients whose serum hepatitis B virus(HBV)DNA remained detectable despite at least 6 mo of LAM+ADV therapy were included.Enrolled patients were randomized to either switching to LdT(600 mg/d orally)plus ADV(10 mg/d orally)(LdT+ADV group)or to continuation with LAM(100 mg/d orally)plus ADV(10 mg/d orally)(LAM+ADV group),and were followed for 48 wk.One hundred and six patients completed the 48-wk treatment period.Serum HBV DNA,HBeAg status,liver biochemistry and safety were monitored at baseline and week 12,24,36 and 48.RESULTS:The duration of prior LAM+ADV treatment was 18.3(LdT+ADV)and 14.9 mo(LAM+ADV),respectively(P=0.131).No difference was seen in baseline serum HBV DNA between the two groups[3.66(LdT+ADV)vs 3.76(LAM+ADV)log10IU/mL,P=0.729].At week 48,although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT+ADV group and LAM+ADV group(-0.81 vs-0.47 log10IU/mL,P=0.167),more patients in the LdT+ADV group had undetectable HBV DNA levels compared to those in the LAM+ADV group(30.2%vs 11.5%,P=0.019).Three patients with LdT+ADV treatment and 2 patients with LAM+ADV treatment achieved HBeAg loss.The patients in both groups tolerated the treatment well without serious adverse events.The proportion of patients with estimated glomerular filtration rate≥90 mL/min per 1.73 m2in the LdT+ADV group increased from 49.1%(26/53)at baseline to 58.5%(31/53)at week 48,while that in the LAM+ADV group decreased from 37.7%(20/53)at baseline to 30.2%(16/53)at week 48.CONCLUSION:The switch to LdT+ADV in suboptimal responders to LAM+ADV showed a significantly higher rate of virologic response at week 48.These results suggest that LdT+ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.

Effects of telbivudine and entecavir for HBeAg-positive chronic hepatitis B: A meta-analysis

AIM:To compare the effects of telbivudine (LDT) and entecavir (ETV) in treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B by meta-analysis. METHODS:We conducted a literature search using PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, the VIP database, the Wanfang database and the Cochrane Controlled Trial Register for all relevant articles published before April 1, 2012. Randomized controlled trials (RCTs) comparing LDT with ETV for treatment of HBeAg-positive chronic hepatitis B were included. The data was analyzed with Review Manager Software 5.0. We used relative risk (RR) as an effect measure, and reported its 95% CI. Meta-analysis was performed using either a fixedeffect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data indepen- dently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, alanine aminotransferase (ALT) normalization, HBeAg loss, HBeAg seroconversion, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics with the therapeutic effects of the two agents. RESULTS:Thirteen eligible trials (3925 patients in total) were included and evaluated for methodological quality and heterogeneity. In various treatment durations of 4 wk, 8 wk, 12 wk, 24 wk, 36 wk, 48 wk, 52 wk, 60 wk and 72 wk, the rates of HBV DNA undetectability and ALT normalization in the two groups were similar, without statistical significance. At 4 wk and 8 wk of the treatment, no statistical differences were found in the rate of HBeAg loss between the two groups, while the rate in the LDT group was higher than in the ETV group at 12 wk, 24 wk, 48 wk and 52 wk, respectively (RR 2.28, 95% CI 1.16, 7.03, P = 0.02; RR 1.45, 95% CI 1.16, 1.82, P = 0.001; RR 1.45, 95% CI 1.11, 1.89, P = 0.006; and RR 1.86, 95% CI 1.04, 3.32, P = 0.04). At 4 wk, 8 wk, 60 wk and 72 wk of the treatment, there were no significant differences in the rate of HBeAg seroconversion between the two groups, while at 12 wk, 24 wk, 48 wk and 52 wk, the rate in the LDT group was higher than in the ETV group (RR 2.10, 95% CI 1.36, 3.24, P = 0.0008; RR 1.71, 95% CI 1.29, 2.28, P = 0.0002; RR 1.86, 95% CI 1.36, 2.54, P < 0.0001; and RR 1.87, 95% CI 1.21, 2.90, P = 0.005). The rate of drug-resistance was higher in the LDT group than in the ETV group (RR 3.76, 95% CI 1.28, 11.01, P = 0.02). In addition, no severe adverse drug reactions were observed in the two groups. And the rate of increased creatine kinase in the LDT group was higher than in the ETV group (RR 5.58, 95% CI 2.22, 13.98, P = 0.0002). CONCLUSION:LDT and ETV have similar virological and biomedical responses, and both are safe and well tolerated. However, LDT has better serological response and higher drug-resistance.

Meta-analysis on Treatment of Chronic Hepatitis B with Telbivudine and Entecavir

Objective To evaluate the therapeutic effects of telbivudine and entecavir on patients with chronic hepatitis B by meta-analysis method. Methods Databases including the Cochrane Library, PubMed, EMBASE and HighWire were searched from January 2008 to October 2012. Randomized controlled trials on treatment of chronic hepatitis B with telbivudine and entecavir were included. According to the Cochrane systematic reviews, the methodological quality of the included studies was evaluated and effective data was extracted from these studies and analyzed. Results Six studies were included eventually. The telbivudine group included 417 cases and the entecavir group included 396 cases. For 12-week antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 39.1% with telbivudine and 38.6% with entecavir [OR = 1.04, 95% CI(0.62, 1.73), P > 0.05]; for treatment of HBeAg(+) hepatitis B, the HBeAg clearance rate was 23.8% with telbivudine and 3.8% with entecavir [OR= 8.07, 95% CI(2.69, 24.21), P < 0.05], and the HBeAg seroconversion rate was 6.7% with telbivudine and 3.8% with entecavir [OR = 4.95, 95% CI(1.60, 15.31), P < 0.05]; the ALT normalization rate was 54.3% with telbivudine and 58.5% with entecavir [OR = 0.84, 95% CI(0.49, 1.45), P > 0.05]; and for early-stage treatment, the incidence of adverse events was 17.2% with telbivudine and 22.0% with entecavir [OR = 0.66, 95% CI(0.33, 1.32), P > 0.05]. For 1-year antiviral treatment of chronic hepatitis B, the rate of undetectable HBV DNA was 79.4% with telbivudine and 89.7% with entecavir [OR = 0.46, 95% CI(0.28, 0.74), P < 0.05]; for treatment of HBeAg(+) hepatitis B, the HBeAg clearance rate was 28.9% with telbivudine and 15.6% with entecavir [OR = 2.21, 95% CI(1.06, 4.58), P < 0.05], and the HBeAg seroconversion rate was 31.2% with telbivudine and 18.5% with entecavir [OR = 2.31, 95% CI(1.23, 4.31), P < 0.05]; the ALT normalization rate was 85.8% with telbivudine and 84.9% with entecavir [OR = 0.90, 95% CI(0.29, 2.84), P > 0.05]; and the resistance rate was 6.0% with telbivudine and 0.76% with entecavir [OR = 5.71, 95% CI(1.67, 19.47), P < 0.05]. Conclusions For 1-year treatment of chronic hepatitis B, the difference in ALT normalization between telbivudine and entecavir was not statistically significant; and telbivudine was superior over entecavir in terms of HBeAg undetectable and HBeAg seroconversion; entecavir was superior over telbivudine in terms of HBV DNA undetectable and resistance; and both drugs had similar rates of adverse events in early-stage treatment and no severe adverse event was noted. Both telbivudine and entecavir are effective antiviral drugs against hepatitis B.

慢性乙型肝炎治疗药替比夫定(telbivudine)

本品适用于有病毒复制，并伴有血清转氨酶[丙氨酸氨基转移酶（ATL）或天冬氨酸氨基转移酶（AST）]持续升高，或肝脏组织学活动性病变的成年慢性乙型肝炎（HB）患者的治疗。

Acute Onset Pancreatitis in the Third Trimester of Pregnancy in HBV Carrier Women Taking Telbivudine for Blocking Mother-to-Infant Transmission

Acute pancreatitis in pregnancy(APIP) is rare and the reasons for APIP are biliary disease and congenital or acquired hypertriglyceridemia, which could occur during any trimester but more than 50% cases happened during the third trimester. In this report, one case of a young pregnant woman, a HBV carrier in her 37 th week + 5 d of gestation, was admitted to Emergency Department due to acute abdominal pain, vomiting and diarrhea. The patient was in antiretroviral treatment with telbivudine from 28 weeks of gestation to prevent motherto-child transmission of HBV. Laboratory tests demonstrated hypertriglyceridemia, abdominal computed tomography scan revealed peripancreatic edema. Hyperlipidemic pancreatitits was primary diagnosed and the patient was admitted to the intensive care unit. Considering the possible role in the pathogenesis of pancreatitis, telbivudine was interrupted after birth giving. After supportive treatment, her condition gradually improved. Since it is the first description of APIP during treatment with telbivudine, the association between pregnancy, hyperlipidemia, telbivudine and acute pancreatitis has been well investigated.

Telbivudine预计年前提出NDA

Novartis／Idenix公司将于年底前第一次提出其处于临床试验中的新药telbivudine（Ⅰ）在美国的新药上市申请（NDA）。这种核苷类似物用于乙型肝炎治疗。申请资料将包括关键性研究GLOBE的一年数据。结果表明，（Ⅰ）达到它的慢性乙型肝炎病人治疗应答的评价终点，即以病毒抑制（血清HBV DNA〈100，000拷贝／ml）与肝功能改善（ALT恢复正常）或可检测的乙型肝炎e-抗原（HBeAg）减少的组合终点。这项临床试验选录了1350多例病人，并随机给予他们日剂量600mg（Ⅰ）或100mg拉米夫定。这项为期两年的研究继续评估（Ⅰ）与拉米夫定对HBeAg阳性和阴性病人的疗效对比，但申请资料将全部以第一年的结果为基础。

递交telbivudine的欧盟申请

Novartis和Idenix医药公司为他们的核酸类似物telbivudine（I）向EMEA递交第二次申请，集中申请用于治疗乙型肝炎。2006年初已向美国提出申请，并且预计在三月末在主要的亚洲国家提交申请。

Telbivudine治疗中国慢性乙肝患者的效果胜过拉米夫定

据中国、美国研究者称，在对中国慢性乙肝患者的治疗上，Telbivudine（I）比拉米夫定（lamivudine）（Ⅱ）更有效。

HBeAg阳性慢性HBV感染患者每日1次的口服药物Telbivudine的剂量研究

Current therapy for chronic hepatitis B is suboptimal as a result of limited d urable response rates, cumulative viral resistance, and/or poor tolerability. Te lbivudine has potent antiviral activity against hepatitis B virus (HBV) in vitro and in the woodchuck model and has a promising preclinical safety profile. In t his first clinical study of telbivudine, safety, antiviral activity, and pharmac ok inetics were assessed in 43 adults with hepatitis B e antigen-positive chron ic hepatitis B. This placebocontrolled dose-escalation trial investigated 6 tel bivudine daily dosing levels (25, 50, 100, 200, 400, and 800 mg/d); treatment wa s given for 4 weeks, with 12 weeks’follow-up. Serum HBV DNA levels were monito red via quantitative polymerase chain reaction. The results indicate that telbiv udine was well tolerated at all dosing levels, with no dose-related or treatmen t-related clinical or laboratory adverse events. telbivudine plasma pharmacokin etics were dose-proportional within the studied dose range. Marked dose-relate d antiviral activity was evident, with a maximum at telbivudine doses of 400 mg/ d or more. In the 800mg/d cohort, the mean HBV DNA reduction was 3.75 log10 copi es/mL at week 4, comprising a 99.98%reduction in serum viral load. Correspondin gly, posttreatment return of viral load was slowest in the high-dose groups. Vi ral dynamic analyses suggested a high degree of efficiency of inhibition of HBV replication by telbivudine and helped refine selection of the optimal dose. In c onclusion, these results support expanded clinical studies of this new agent for the treatment of hepatitis B.

Evaluation on telbivudine-associated rhabdomyolysis

To investigate clinical characteristics and related factors of telbivudine-associated rhabdomyolysis（RM）, we searched domestic and foreign medical literature databases as well as Beijing Adverse Drug Reaction Monitoring Database. Cases of telbivudine-associated RM were collected. General information of patients and information of medications were extracted. Onset of adverse drug reactions（ADRs）, clinical manifestations, treatments and outcomes were investigated and analyzed. After reviewing 226 literatures and 71 reports, a total of 22 RM cases were collected. All the cases were male patients with an average age of（34.5±11.2） years, and all these patients had chronic hepatitis B and received telbivudine 600 mg/day. The occurrence time of RM varied. One case occurred within 5 months（4.5%）, 11 cases occurred within 6 to 10 months（50.0%）, 8 cases occurred within 11 to 15 months（31.8%）, and 3 cases occurred after 15 months（13.6%）. Clinical manifestations were mostly nausea, vomiting, palpitations, weakness and edema of the lower extremities. After the telbivudine treatment was discontinued and symptomatic treatments were provided, 12 patients were clinically improved, 4 patients were physically impaired, 2 patients showed unknow results, and 4 deaths were reported. However, age（P = 0.61）, duration of medication（P = 0.54） and CK value（P = 0.07） were not statistically associated with death. Clinicians are advised to monitor clinical manifestations in patients receiving telbivudine. Monitoring on serum creatinine level is suggested if necessary. Telbivudine should be promptly discontinued, and symptomatic treatment should be given when ADRs occur.

Synthesis of telbivudine 3'-O-acetyl-5'-O-phenyl-N-alkylphosphramidates and evaluation of their anti-HBV activities

A series of telbivudine 3′-O-acetyl-5′-O-phenyl-N-alkylphosphramidate derivatives have been synthesized and their structures were confirmed by El-MS, ^1H NMR and ^13C NMR. We evaluated their anti-HBV activity in vitro. Two compounds 6d and 6f, turned out to be more active than telbivudine.

Serum HBV DNA level at week 12 is superior to viral response at week 24 in predicting long-term treatment outcome of telbivudine for chronic hepatitis B patients

Background Telbivudine,one of the five nucleos（t）ide antiviral drugs,was reported to be superior to lamivudine in a better biochemical,virological,and histological response for treatment-naive patients in the GLOBE trial.The aim of this study was to determine the antiviral potency,viral resistance,and the significance of early response for long-term telbivudine treatment.Methods We recruited 161 patients of chronic hepatitis B （CHB） on telbivudine between January 2009 and September 2011 in Macao,China.The serum hepatitis B virus DNA levels,hepatitis B e antigen （HBeAg） seroconversion,alanine aminotransferese （ALT） normalization,and viral resistance were analyzed.Results The median age and follow-up duration were 48 years and 16.9 months.All patients were followed up for at least 6 months,while data were collected for 132,120,95,and 53 patients at 12,24,48,and 96 weeks respectively.The cumulative HBeAg seroconversion rate was 20.8% and only three patients （1.9%） presented with telbivudine low level resistance.The ALT normalization rates were 76.9% at 48 weeks and 77.6% at 96 weeks.Undetectable HBV DNA was achieved by 1.8%,31.6%,60%,and 74.1% in HBeAg positive patients and 29.3%,60.3%,84%,and 84.6% in HBeAg negative patients at each time point.Week 12 HBV DNA level 〈1000 copies/ml （〈200 IU/ml） was a better predictor of viral suppression at 2-year follow-up （P=-0.001,OR=27.00） than undetectable HBV DNA level at week 24 （P=0.120,OR=4.81）.Conclusions Two-year telbivudine treatment yielded high rates of viral suppression and ALT normalization.Serum HBV DNA level at week 12 is a superior predictor for long-term viral suppression.