Efficacy and safety of prolonged 3‐year telbivudine treatment in patients with chronic hepatitis B

Background: In the GLOBE trial, telbivudine demonstrated superior efficacy to lamivudine at 2 years in patients with chronic hepatitis B (CHB). Aims: To investigate the long‐term efficacy and safety of telbivudine in the telbivudine‐treated cohort from the GLOBE trial. Methods: Virological and biochemical responses were assessed in 213 HBeAg‐positive and 186 HBeAg‐negative CHB patients who continued telbivudine treatment for 3 years. Results: Undetectable hepatitis B virus DNA and HBeAg seroconversions were achieved by 77 and 37% of HBeAg‐positive patients respectively. Cumulative HBeAg seroconversion rate was 46%. HBeAg seroconversion was sustained at 52 weeks off therapy in 84% of the patients enrolled in the off‐treatment follow‐up arm of the study. Undetectable viraemia and normal alanine aminotransferase (ALT) levels at 3 years were achieved by 85 and 83% of HBeAg‐negative patients respectively. Genotypic resistance rates for the study population who continued therapy during the third year were 11.3 in HBeAg‐positive and 6.5% in HBeAg‐negative patients. Patients with undetectable viraemia at treatment week 24 had optimal outcomes at 3 years. In the HBeAg‐positive population, cumulative HBeAg seroconversion occurred in 58%. Resistance rates for HBeAg‐positive and HBeAg‐negative patients were 3.6 and 6.2% respectively. The telbivudine safety profile during prolonged therapy was similar to that in the GLOBE trial. Conclusions: Three years of telbivudine treatment yielded high rates of viral suppression and ALT normalization with a favourable safety profile. High rates of HBeAg seroconversion were achieved with prolonged telbivudine therapy and were sustained in the majority of patients over 52 weeks off therapy.     

Efficacy and safety of continuous 4‐year telbivudine treatment in patients with chronic hepatitis B

In the phase‐III GLOBE/015 studies, telbivudine demonstrated superior efficacy vs lamivudine during 2‐year treatment in HBeAg‐positive and HBeAg‐negative chronic hepatitis B (CHB). After completion, 847 patients had an option to continue telbivudine treatment for further 2 years. A total of 596 (70%) of telbivudine‐treated patients, who were serum HBV DNA positive or negative and without genotypic resistance to telbivudine at the end of the GLOBE/015 trials, were enrolled into a further 2‐year extension study. A group of 502 patients completed 4 years of continuous telbivudine treatment and were included in the telbivudine per‐protocol population. Amongst 293 HBeAg‐positive patients, 76.2% had undetectable serum HBV DNA and 86.0% had normal serum ALT at the end of 4 years. Notably, the cumulative rate of HBeAg seroconversion was 53.2%. Amongst 209 HBeAg‐negative patients, 86.4% had undetectable HBV DNA and 89.6% had normal serum ALT. In patients who had discontinued telbivudine treatment due to HBeAg seroconversion, the HBeAg response was durable in 82% of patients (median 111 weeks of off‐treatment follow‐up). The cumulative 4‐year resistance rate was 10.6% for HBeAg‐positive and 10.0% for HBeAg‐negative patients. Most adverse events were mild or moderate in severity and transient. Renal function measured by estimated glomerular filtration rate (eGFR) increased by 14.9 mL/min/1.73 m² (16.6%) from baseline to 4 years (P < 0.0001). In conclusion, in HBeAg‐positive and HBeAg‐negative CHB patients without resistance after 2 years, two additional years of telbivudine treatment continued to provide effective viral suppression with a favourable safety profile. Moreover, telbivudine achieved 53% of HBeAg seroconversion in HBeAg‐positive patients.     

Entecavir maleate versus entecavir in Chinese chronic hepatitis B predominantly genotype B or C: Results at week 144

Reports on the efficacy and safety of long‐term entecavir treatment in chronic hepatitis B (CHB) predominantly genotype B or C are insufficient. This study presents the efficacy and safety of entecavir maleate in Chinese CHB patients. Patients were randomly assigned to receive 48‐week treatment with either 0.5 mg/day entecavir (group A) or 0.5 mg/day entecavir maleate (group B), and then all patients received treatment with 0.5 mg/day entecavir maleate from week 49. Two hundred and seventy‐five patients with CHB (HBeAg‐positive: 218) were analysed, predominantly (98.5%) with genotype B or C. Baseline characteristics were balanced. For the HBeAg‐positive CHB patients, the mean HBV DNA level decreased similarly (A: by 6.36 log₁₀ IU/mL vs B: by 6.31 log₁₀ IU/mL) between groups at week 144. The percentages of patients who achieved undetectable HBV DNA were similar (A: 70.59% vs B: 66.67%) between groups. Similar HBeAg loss rates (A: 43.53% vs B: 40.23%; P>.05) and HBeAg seroconversion rates (A: 21.52% vs B: 21.18%) were achieved. For the HBeAg‐negative CHB patients, similar reductions in HBV DNA levels from baseline (A: by 6.13 log₁₀ IU/mL vs B: by 5.65 log₁₀ IU/mL) and percentages of patients who achieved undetectable HBV DNA (A: 100% vs B: 100%) were achieved. The overall incidence of adverse events was comparable between groups. In conclusions, 48‐week administration of entecavir maleate and entecavir showed similar efficacy and safety in Chinese patients with CHB. Long‐term entecavir maleate treatment was effective and safe in CHB patients.     

Comparison between quantitative hepatitis B surface antigen,hepatitis B e‐antigen and hepatitis B virus DNA levels for predicting virological response to pegylated interferon‐α‐2b therapy in hepatitis B e‐antigen‐positive chronic hepatitis B

Aim: The aim of this study was to compare the clinical applicability of quantitative serum hepatitis B surface antigen (HBsAg), hepatitis B e‐antigen (HBeAg) and hepatitis B virus (HBV) DNA for predicting virological response (VR) to pegylated interferon (PEG‐IFN) therapy. Methods: Thirty HBeAg‐positive chronic hepatitis B patients who received PEG‐IFN‐α‐2b for 48 weeks were enrolled. Quantitative HBsAg, HBeAg and HBV DNA were measured before, during and after the therapy. Paired liver biopsies were performed before and after treatment for covalently closed circular (ccc)DNA and intrahepatic HBV DNA analysis. Results: VR at 48 weeks post‐treatment, defined as HBeAg seroconversion and HBV DNA less than 10 000 copies/mL was achieved in 10 (33.3%) patients. Responders had significantly lower baseline HBsAg, HBeAg, cccDNA and intrahepatic HBV DNA levels than non‐responders. Baseline and reduced levels of log₁₀ HBsAg and log₁₀ HBeAg correlated well with those of log₁₀ cccDNA and log₁₀ total intrahepatic HBV DNA. Responders showed consistent decrease in serum HBsAg, HBeAg and HBV DNA levels during therapy. HBeAg level of 2.0 log₁₀ sample to cut‐off ratio at week 24 on therapy provided the best prediction of sustained virological response, with sensitivity and negative predictive values of 85% and 92%, respectively. One patient (3.3%) who cleared HBsAg at follow up exhibited a more rapid decline in serum HBsAg during therapy than those who developed VR without HBsAg clearance. Conclusion: Quantitative measurement of serum HBeAg during therapy may be superior to serum HBsAg and HBV DNA as a prediction of HBeAg seroconversion. Kinetics of HBsAg levels on therapy may help predict HBsAg clearance after treatment.     

Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir

Summary. Both entecavir (ETV) and tenofovir (TDF) are potent antiviral agents for hepatitis B virus (HBV). Suboptimal response (SOR) following antiviral therapy is associated with an increased risk of subsequent treatment failure and viral resistance. It remains unclear whether switching to TDF is a reasonable approach in patients with SOR to ETV treatment. This study was aimed to determine how HBV patients with SOR to ETV respond to TDF monotherapy. Data of patients with SOR to ETV (failure to achieve >1 log₁₀ HBV‐DNA reduction during the last 24 weeks of ETV treatment) who were switched to TDF monotherapy during 2005 and 2010 were reviewed. Treatment adherence was assessed by pill‐count. Fourteen patients (2.9%) were identified from a total cohort of 482 ETV‐treated patients. All 14 patients were Chinese and were infected with HBV genotype C (71%) or B (29%). Nine patients were men, and the median age was 41.5 years (19–64). Twelve were treatment naïve (one lamivudine‐ and one peginterferon‐experienced patient); 85.7% were HBeAg positive. The median baseline HBV‐DNA was 7.55 (5.30–9.40) log₁₀ copies/mL, and 57% had abnormal serum alanine aminotransferase (ALT) levels. Precore and/or basal core promoter mutations were detected in four patients, whereas no genotypic resistance was detected at baseline and before switching to TDF. The median duration of ETV treatment was 64.5 (26–126) weeks. The median HBV‐DNA at the time of switching to TDF was 3.69 (3.00–4.90) log₁₀ copies/mL. The median HBV‐DNA reduction from baseline and during the last 6‐month observation period prior to switching to TDF was 4.04 (0.51–6.06) log₁₀ and 0.43 (?0.09–1.13) log₁₀ copies/mL, respectively. After the switching to TDF, all 14 patients (100%) achieved undetectable HBV‐DNA and ALT normalization within a median duration of 30 weeks. In 12 patients who were HBeAg positive, HBeAg seroconversion was observed in two patients after TDF treatment of 75‐ and 84‐weeks duration. There was no virological breakthrough observed after switching to TDF with a median follow‐up period of 50 (24–160) weeks. TDF treatment was safe and well tolerated. In conclusion, suboptimal response to ETV is rare (approximately 3%). TDF monotherapy is safe and very effective in the management of HBV patients with SOR to ETV.     

A survey of chronic hepatitis B patient management practices in the European Union

Summary. The current study sought to evaluate the characteristics of chronic hepatitis B virus (HBV) infection and current management practices in the European Union by surveying physician and patient records. A detailed survey of physician practices and management of patients with CHB was conducted between July and October 2006 in France, Germany, Italy and Spain. A total of 200 physicians participated in the survey, and data were collected from 2023 patients with chronic HBV infection. Most patients were men (69%), who had hepatitis B e antigen (HBeAg)‐negative disease (64%), and demonstrated evidence of significant disease [53%; moderate fibrosis (35%), compensated cirrhosis (14%), or decompensated cirrhosis (4%)]. Among the 1665 HBV‐monoinfected patients surveyed, 1184 (71%) were currently receiving treatment for chronic HBV infection. At treatment initiation, 70% of HBeAg‐positive patients had both pretreatment serum HBV DNA levels ≤9 log₁₀ copies/mL and alanine aminotransferase (ALT) levels ≥2 × the upper limit of normal (ULN), and 81% of HBeAg‐negative patients had HBV DNA levels of ≤7 log₁₀ copies/mL. Among untreated patients, HBV DNA levels ≤5 log_10, ALT levels <2 × ULN, and mild or no liver fibrosis were present in 48% and 84% of HBeAg‐positive and HBeAg‐negative patients, respectively. In conclusion, the majority of European patients with CHB surveyed were HBeAg negative, Caucasian, men, and presented with significant histologic liver disease. At treatment initiation, most HBeAg‐positive patients had pretreatment serum HBV DNA levels ≤9 log₁₀ copies/mL and ALT levels ≥2 × ULN, while the HBeAg‐negative patients had HBV DNA levels ≤7 log₁₀ copies/mL.     

Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients

Background and Aims: Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B (CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen (HBeAg)‐negative patients and to explore potential predictive factors. Methods: Sixty one HBeAg‐negative CHB patients who had received lamivudine for at least 24 months and had maintained undetectable serum hepatitis B virus (HBV) DNA plus normal alanine aminotransferase for ≥ 18 months before withdrawal were included. They were followed up monthly during the first 4 months and at 3‐month or 6‐month intervals thereafter. Relapse was defined as serum HBV DNA ≥ 10⁴ copies/mL. Results: Thirty one of 61 patients relapsed during follow‐up, over 90% occurred within 18 months after lamivudine withdrawal. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 26.2%, 43.6%, 49.7%, 52.1%, 56.1% and 56.1%, respectively. Cox regression revealed that age was the only predictive factor for relapse, with lower relapse rates found in younger patients. Hepatitis B surface antigen (HBsAg) turned negative in eight patients, and none of them relapsed during follow‐up. Conclusion: Effectiveness of lamivudine treatment is not durable in HBeAg‐negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged ≤ 20 years. The ideal end point of lamivudine treatment is clearance of serum HBsAg.     

Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels

Summary. Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on‐treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty‐two patients with HBeAg‐positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on‐treatment factors, on‐treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log₁₀ IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940–1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On‐treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut‐off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log₁₀ PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on‐treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg‐positive CHB patients with entecavir treatment.     

Effect of nucleoside analog‐interferon sequential therapy on patients with acute exacerbation of chronic hepatitis B

Aim: Nucleoside analog (NA)‐interferon (IFN) sequential therapy may enable the long‐term control of chronic hepatitis B (CHB) and the withdrawal of the nucleoside analog. We evaluated the efficacy of NA‐IFN sequential therapy for acute exacerbation of CHB. Methods: A total of 12 patients with acute exacerbation of CHB, nine of whom were positive for hepatitis B e antigen (HBeAg), were enrolled in this study. All the patients were treated with lamivudine 100 mg/day alone for 20 weeks, then with both IFN‐α 6 megaunits three times per week and lamivudine for 4 weeks, and lastly, with IFN‐α alone for 20 weeks. Patients whose serum alanine aminotransferase (ALT) level was normalized, whose serum hepatitis B virus (HBV) DNA level decreased to less than 5 log copies/mL, and HBeAg level was absent 24 weeks after the end of treatment were defined as having sustained virological response (SVR). The other patients were defined as having no response (NR). Results: Four out of nine (44.4%) HBeAg‐positive and all three HBeAg‐negative patients achieved SVR. The levels of serum alanine aminotransferase (ALT), HBV DNA and HBV core‐related antigen were similar between SVR and NR patients at baseline. Three of four patients (75.0%) whose serum HBeAg became negative at the end of treatment achieved SVR, while one of five (20.0%) whose serum HBeAg remained positive achieved SVR. Conclusion: NA‐IFN sequential therapy for patients with acute exacerbation of CHB enables the withdrawal of treatment and is particularly effective for patients whose serum HBeAg has become undetectable by the end of the IFN treatment.     

The Roadmap concept: using early on-treatment virologic responses to optimize long-term outcomes for patients with chronic hepatitis B

Several large observational, longitudinal studies of the natural history of chronic hepatitis B (CHB) have demonstrated that high levels of hepatitis B virus (HBV) replication are associated with long-term risk of cirrhosis, decompensation, hepatocellular carcinoma, and liver-related mortality. The corollary is also true—profound and sustained suppression either spontaneously or during antiviral therapy will prevent disease progression and complications. Multiple analyses of various baseline factors and on-treatment responses have identified the absolute HBV DNA level after 24 weeks of therapy as the best predictor of long-term efficacy. Lower 24-week serum HBV DNA levels after lamivudine, telbivudine, or entecavir are associated with higher rates of maintained HBV DNA nondetectability, ALT normalization, HBeAg seroconversion, and lack of resistance. Patients with undetectable serum HBV DNA levels after 24 weeks have the best long-term outcomes while those with levels remaining above 10,000 copies per ml are unlikely to benefit from long-term therapy with that particular agent and either the addition or switch to another antiviral agent with increased potency but without cross resistance could be considered at this time point. In the future, improved on-treatment monitoring should facilitate treatment strategies to optimize long-term outcomes among patients receiving oral antiviral therapy for CHB.     

Efficacy and Safety of Tenofovir-Based Rescue Therapy for Chronic Hepatitis B Patients with Previous Nucleo(s/t)ide Treatment Failure

Background/Aims

We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies.

Methods

Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored.

Results

Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log₁₀ IU/mL to 2.0 log₁₀ IU/mL and to 1.6 log₁₀ IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed.

Conclusions

TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients'' adherence to medication is related to viral rebound.     

Safety and efficacy of telbivudine in late pregnancy to prevent mother‐to‐child transmission of hepatitis B virus: A multicenter prospective cohort study

Infection of hepatitis B virus (HBV) occurs in ~10% of infants of HBV‐infected mothers with positive hepatitis B e antigen (HBeAg) after immunoprophylaxis. We aimed to evaluate the safety and efficacy of telbivudine used during late pregnancy for preventing mother‐to‐child transmission of HBV. We conducted a multicenter prospective cohort study in 5 hospitals from 2012 to 2014, which enrolled HBV‐infected singleton pregnant women with positive HBeAg. By their choice, women were divided into therapy (telbivudine 600 mg/day, from gestation 28‐32 weeks to 3‐4 weeks postpartum) and control (no antiviral agent) groups. Infants received passive‐active immunoprophylaxis and follow‐up at the age of 7‐14 months. Totally, 328 pregnant women were included: 149 in the telbivudine group and 179 in the control group. Baseline HBV DNA levels were similar in the 2 groups (7.43 vs 7.37 log₁₀ IU/mL, P = .711). At delivery, HBV DNA levels in the telbivudine and control groups were 3.80 and 7.26 log₁₀ IU/mL, respectively (P < .0001). Of the infants, 128 (85.9%) in the telbivudine group and 156 (87.2%) in the control group were followed up. No infant in the telbivudine group had chronic infection, while 2 (1.28%) infants in the control group did (P = .503). Three (2.34%) infants in the telbivudine group, but none in the control group, had severe congenital or developmental abnormalities (P = .090). The data indicate that telbivudine may block perinatal HBV transmission. However, larger studies are required to clarify whether anti‐HBV therapy in pregnancy is associated with severe adverse effects in the foetuses and infants.     

替比夫定与恩替卡韦治疗e抗原阳性慢性乙型肝炎的近期疗效比较

目的 观察替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者近期疗效及安全性. 方法 80例患者随机分为替比夫定治疗组和恩替卡韦治疗组,分别在治疗前,治疗第12周和24周检测患者血清HBV DNA水平、ALT复常率、HBeAg阴转率和HBeAg/抗-HBe转换率,并比较不同基线血清HBV DNA水平患者治疗12周和24周时的血清HBV DNA下降值,HBV DNA低于检测值率,HBV DNA＜104拷贝/ml患者的比例.观察治疗过程中药物使用的安全性.结果 替比夫定和恩替卡韦组患者的基础人口学、临床和病毒学特征均具有可比性.治疗12周时,替比夫定组和恩替卡韦组患者HBV DNA低于检测值率均为50.0%,ALT复常率分别为52.5%和60.0%(P＞0.05),HBeAg阴转率分别为30.0%和5.0%(P＜0.01),HBeAg血清学转换率分别为20.0%和5.0%(P＜0.05);在治疗24周时,两组HBV DNA低于检测值率分别为80%和70%,(P＞0.05),ALT复常率分别为77.5%和75.0%(P＞0.05),HBeAg阴转率分别为45.0%和32.5%(P＞0.05),HBeAg血清学转换率分别为27.5%和17.5%(P＞0.05),两组均未发现明显不良反应.结论 替比夫定与恩替卡韦治疗HBeAg阳性的慢性乙型肝炎的近期HBV DNA水平低于检测值率,ALT复常率无明显差异;12周时替比夫定HBeAg血清学转换率高于思替卡韦组,但24周时两组间差异无统计学意义.     

Telbivudine in combination with adefovir versus adefovir monotherapy in HBeAg-positive, lamivudine-resistant chronic hepatitis B

Purpose

Lamivudine (LAM) resistance is common on lamivudine monotherapy for chronic hepatitis B. This study examined the safety and efficacy of telbivudine (LDT) given with adefovir (ADV) versus ADV monotherapy in patients with chronic, lamivudine-resistant HBV infection.

Methods

An open-label, 96?week study with planned recruitment of 150 HBeAg-positive, lamivudine-experienced Asian patients with a confirmed YMDD resistance mutation, randomized 1:1 to receive ADV alone or with LDT. The study was terminated early due to difficulty in enrolling monotherapy patients. At termination, 42 patients had received study medication for 8?C61?weeks. Due to incomplete enrolment, summary statistics only were prepared, without significance testing.

Results

A total of 42 patients underwent rescue therapy (switch to ADV or LDT?+?ADV; n?=?21 per group). Median treatment duration was 48?weeks in both groups. HBV DNA changes from baseline were greater in the LDT?+?ADV arm at all time points (Week 48: ?7.4 log₁₀ vs. ?4.9 log₁₀ copies/ml), and serum DNA was undetectable (<300?copies/mL) at week 48 in 38.5% (5/13) on LDT?+?ADV versus 0% (0/9) on ADV monotherapy Two patients (9.6%) on ADV monotherapy experienced virologic breakthrough without evidence of ADV resistance, but none on LDT?+?ADV; and no confirmed ADV resistance was observed in any on-treatment sample. HBeAg loss occurred in three patients on LDT?+?ADV and one patient on ADV monotherapy through week 48. Safety profiles were similar between the arms.

Conclusion

LDT?+?ADV combination treatment showed better outcomes against lamivudine resistant HBV than ADV alone, with a similar safety profile.     

Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial

Chronic hepatitis B and its life-threatening sequelae are highly prevalent in China. There is a need for effective new therapies to suppress hepatitis B virus (HBV) replication and ameliorate liver disease. In this study, we compared the efficacy of telbivudine, a nucleoside analogue, with lamivudine in Chinese patients. In this phase III, double-blind, multicenter trial conducted in China, 332 patients with compensated hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic hepatitis B were randomly assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine daily for 104 weeks. The primary efficacy endpoint was reduction in serum HBV DNA levels at week 52 of treatment. Secondary endpoints included clearance of HBV DNA to undetectable levels, HBeAg loss and seroconversion, therapeutic response, and alanine aminotransferase (ALT) normalization. Viral resistance and safety were assessed. At week 52, among 290 HBeAg-positive patients, mean reductions of serum HBV DNA were significantly greater in telbivudine recipients than lamivudine recipients (6.3 log(10) versus 5.5 log(10), P < 0.001), and HBV DNA was polymerase chain reaction-negative in significantly more telbivudine recipients than lamivudine recipients (67% versus 38%, P < 0.001). ALT normalization (87% versus 75%, P = 0.007), therapeutic response (85% versus 62%, P = 0.001), and HBeAg loss (31% versus 20%, P = 0.047) were also significantly more common in the telbivudine group. Treatment effects showed similar patterns in the smaller HBeAg-negative group (n = 42). Viral resistance in telbivudine recipients was approximately half that observed with lamivudine; however, this difference was not statistically significant. Clinical adverse events were similar in the two treatment groups. CONCLUSION: In Chinese patients with chronic hepatitis B, telbivudine treatment for 52 weeks provided greater antiviral and clinical efficacy than lamivudine, with less resistance.     

Efficacy and safety of entecavir treatment in a heterogeneous CHB population from a ‘real‐world’ clinical practice setting in China

Chronic hepatitis B infection is an important cause of liver‐related mortality in China. This study assessed the efficacy and safety of entecavir in a heterogeneous patient population from a ‘real‐world’ clinical practice setting in China. This prospective, observational cohort provides 48‐week data on 2600 patients from 50 sites in China who received entecavir (0.5 or 1.0 mg) and were assessed for virologic, serologic and biochemical responses. Patients were nucleos(t)ide‐naïve or ‐experienced and had compensated or decompensated liver function. At Week 48, 1545/2424 (64%) patients with compensated liver disease and 30/44 (68%) patients with decompensated liver disease achieved HBV DNA <50 IU/mL. Greater proportions of nucleos(t)ide‐naïve than nucleos(t)ide‐experienced (69% vs 53%), and adefovir‐experienced than lamivudine/telbivudine‐experienced (62% vs 52%) patients achieved this endpoint. Most patients with HBV DNA <50 IU/mL also achieved HBV DNA <12 IU/L (60%, 45% and 61% of nucleos(t)ide‐naïve, nucleos(t)ide‐experienced and decompensated patients, respectively). In patients with compensated liver disease, ALT values normalized in 1532/1792 patients (85%), and HBeAg loss and HBeAg seroconversion were observed in 17% and 15% of treatment‐naïve and 15% and 11% of treatment‐experienced patients. Entecavir was generally well tolerated. Adverse event rates were comparable between treatment‐naïve and treatment‐experienced patients with compensated liver disease, but were higher in decompensated than in compensated patients, consistent with previous reports in these patients with more advanced disease. Four patients discontinued treatment due to adverse events. In a ‘real‐world’ setting, entecavir was efficacious and well tolerated throughout 48 weeks in a heterogeneous Chinese CHB population.     

拉米夫定治疗慢性乙型肝炎失败的相关因素分析

目的探讨拉米夫定治疗慢性乙型肝炎（CHB）失败的相关因素。方法回顾性分析224例拉米夫定治疗CHB患者的临床资料,根据其疗效分为失败组和成功组,比较两组年龄、性别、用药前ALT、HBV DNA水平、治疗24周后HBV DNA阴转、规则用药、HBeAg性质及HBV YMDD变异等因素。结果拉米夫定治疗失败96例,成功128例;与成功组比较,失败组治疗前ALT水平、治疗24周后HBV DNA阴转率、HBeAg阳性患者治疗中阴转和血清转换率低（P〈0.01）,治疗前HBV DNA水平和HBV YMDD变异率高,患者不规则用药（P〈0.01）,两组在年龄和性别间的差异无显著性意义（P〉0.05）。结论ALT、HBV DNA基线水平,治疗24周后HBV DNA阴转、用药规则,HBV YMDD变异及治疗后HBeAg性质改变均是影响拉米夫定治疗CHB疗效的相关因素。     

Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis

Summary. Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double‐blind trial randomized 232 treatment‐naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once‐daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child‐Turcotte‐Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent‐to‐treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol‐defined composite endpoint in intent‐to‐treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration.     

恩替卡韦和拉米夫定治疗慢性乙型肝炎二年病毒学、血清学和生化结果的随机对比研究

目的比较恩替卡韦（ETV）和拉米夫定（LVD）初治慢性乙型肝炎（CHB）患者2年的疗效和安全性。方法519例核苷类似物初治CHB患者随机分别接受ETV（0．5mg／d）或LVD（100mg／d）治疗,第一阶段疗程52周。在48周时获得综合应答的患者于52周停止治疗并随访。在48周时获得部分应答的患者将继续双盲治疗至96周。评估患者HBVDNA水平、丙氨酸氨基转移酶（ALT）复常、血清学标志和安全性方面的情况,并且对基线时HBeAg（＋）患者评估HBeAg转阴和血清转换。结果共338例患者进入96周治疗,其中ETV组193例,I。VD组145例。疗程结束时,ETV组有74％患者HBVDNA测不出（〈300拷贝／m1）,96％患者ALT复常。I。VD组HBVDNA测不出和ALT复常率分别为41％和82％。ETV组和LVD组实现HBeAg血清学转换的比例分别为11％和19％。总计2年内所有经治患者HBVDNA的累计转阴率ETV组为79％,LVD组为46％（P〈0．0001）。两组的不良事件和安全性特征相当。结论初治患者中,ETV治疗96周的HBVDNA抑制率和AI。T复常率优于I。VD,而两者的安全性相当。【关键词】乙型肝炎病毒;慢性乙型肝炎;恩替卡韦;拉米夫定;临床试验