Telbivudine Research Articles

High Prevalence of Preexisting HBV Polymerase Mutations in Pregnant Women Does Not Limit the Antiviral Therapy Efficacy.

Background HBV-resistant mutants in treatment-naïve patients may lead to antiviral treatment failure. It is not clear if HBV mutants are present in pregnant women and about the influence of the preexisting mutants on the short-term antiviral therapy during pregnancy. Method We enrolled 73 pregnant women with high HBV DNA load and telbivudine (TBV) treatment during pregnancy in this retrospective study. The UDPS was used to detect the HBV mutations before and after the TBV treatment. Results Before TBV treatment, the complexity of HBV quasispecies of all subjects was 0.40 ± 0.09; 41.1% (30/73) and 53.4% (39/73) subjects had rtM204I/V and rtN236 T/A detected, respectively; and 9.6% (7/73) patients had more than 20% frequency mutation of rtM204I/V, which was also similar with high frequency of rtN236 T/A mutation (41.1% vs. 53.4%, P=0.136; frequencies >20%: 9.6% vs. 5.5%, P=0.347). After TBV treatment, 71.2% (52/73) subjects had HBV DNA load ≥ 103 IU/mL at delivery. Among them, 75.0% of patients with rtM204I positive had HBV DNA load ≥103 IU/mL at delivery, which was comparable with the subjects without rtM204I (75.0% vs. 70.8%, P=0.710). No changes were found in the frequencies and the complexity of HBV quasispecies of rtM204I mutation after the TVB treatment. Conclusion The prevalence of preexisting drug-resistant mutations among pregnant women was high using UPDS. However, the preexisting HBV mutation had limited influence on the efficacy of short-term TBV treatment, and TBV treatment during late pregnancy seemed not to increase the risk of emerging HBV-resistant mutants.

Analysis of prognostic factors for 24-month survival of hepatitis B virus-associated acute-on-chronic liver failure patients treated with telbivudine

Objective To investigate the baseline independent prognostic factors for 24 months survival of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) patients treated with telbivudine. Methods The prospective cohort study was conducted in HBV-associated ACLF patients who were hospitalized in Mengchao Hepatobiliary Hospital of Fujian Medical University and volunteered to be treated with telbivudine for more than 24 months. The patients were observed for survival at month 1, 3, 6, 12, and 24 after treatment. The baseline biochemical index, coagulant function, model for end-stage liver disease (MELD) score, HBV DNA level as well as comorbidities were analyzed in this study. The count data were compared with kappa test or Fisher′s exact test. For the normal distributed measurement data, the homogeneity test of variances (Levene test) was firstly used for comparison between groups. Further, the group t test was applied for variance homogeneity, while the approximate t test was applied for variance non-homogeneity and the Mann-Whitney U test was applied for the non-distributed measurement data. Results A total of 41 patients were enrolled, including 3 drop-outs and 38 accomplishments. Among these 38 patients, there were 3 females (7.9%) and 35 males (92.1%), with ages (38.5±11.1) years. There were 32 patients alive and 6 dead during 1 month′s follow-up, while baseline MELD score was the independent prognostic factor (RR=1.864, 95%CI: 1.151-3.019) for survival. There were 31 patients alive and 7 dead during 3 months′ follow-up, while baseline MELD score and upper gastrointestinal hemorrhage (UGH) were the independent prognostic factors (RR=2.053, 95%CI: 1.163-3.625; RR=394.939, 95%CI: 1.880-82 948.817). There were both 26 patients alive and 12 dead during 6 and 12 months′ follow-up, while baseline MELD score was the independent prognostic factor (RR=1.761, 95% CI: 1.230-2.523). At the end of 24 months′ follow-up, there were 15 patients alive and 23 dead. Viral rebounds were observed in 6 patients and 3 of them were dead. Baseline HBV DNA level, MELD score and electrolyte imbalance were the independent prognostic factors (RR=9.722, 95% CI: 1.607-58.821; RR=1.518, 95% CI: 1.066-2.162; RR=87.505, 95% CI: 2.263-3 384.232) for 24 months′survival. Conclusions Although telbivudine is not recommended as the first-line treatment, ACLF patients with low MELD score and low HBV DNA level at baseline, individualized treatment may improve patient's survival rate. UGH and electrolyte imbalance may affect the efficacy of telbivudine and reduce the survival rate of ACLF patient. Key words: Hepatitis B virus; Liver failure; Telbivudine; Survival analysis

Comparison of Telbivudine and Entecavir therapy on estimates of glomerular filtration rate in patients with hepatitis B virus-related compensated cirrhosis

Objective To compare the impact of Telbivudine (LDT) and Entecavir (ETV) administration on estimates of glomerular filtration rate for anti-viral therapy in patients with hepatitis B virus (HBV)-related compensated cirrhosis by an open, prospective randomized controlled study. Methods Patients with HBV-related compensated cirrhosis at clinic or hospitalized in Shaoxing Municipal Hospital from January 2012 to June 2013 were included. A total of 170 patients were randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups at a ratio of 1∶1 according to the random number table method. All patients were treated for more than 36 months. The LDT group was optimized according to the roadmap.Patients with poor response or resistance in both treatment group were added with Adefovir dipivoxil (ADV) 10 mg/d for optimal treatment. The clinical outcome, creatinine (CR), estimated glomerular filtration rate (eGFR) of patients before and after 36 months of treatment were compared between two groups. All categorical data were analyzed using chi-square test and data accorded with normal distribution were compared by t test. Results After 36 months of treatment, the virological and biochemical responses in LDT group and ETV group were similar. The mean CR levels at month 24 and 36 in LDT group were (74.25±22.98) μmol/L and (70.72±24.75) μmol/L, respectively, which were both lower than baseline level ([83.09±17.68] μmol/L, t=2.811 and 3.145, respectively, both P<0.01). The mean CR levels at month 36 between two groups were statistically different (t=3.431, P=0.001). The mean eGFR levels at month 12, 24 and 36 in LDT group were all significantly lower than that at baseline (t=3.976, 8.297 and 10.629, respectively, all P<0.01). The mean eGFR levels at month 24 and 36 between two groups were statistically different (t=9.684 and 15.019, respectively, both P<0.01). A total of 64 patients including 34 in LDT group and 30 in ETV group had mild nephritic injury at baseline. The mean eGFR in patients with mild nephritic injury at baseline in LDT group at month 12, 24 and 36 were significantly different compared to baseline (t=6.098, 10.191 and 14.378, respectively, all P<0.01). The mean eGFR level at month 36 in ETV group had statistical difference compared to baseline (t=2.058, P<0.05). The mean eGFR levels at months 12, 24 and 36 were all statistical different between two groups (all P<0.01). The mean eGFR levels at month 24 and 36 in the optimized group were superior to ETV group (P<0.01). Conclusions In patients with HBV-related compensated cirrhosis, LDT and ETV treatment have similar clinical efficacy. LDT is more effective in protecting nephritic function than ETV. Key words: HBV related compensated cirrhosis; Estimates of glomerular filtration rate; Telbivudine; Entecavir

Cost-Effectiveness Comparison Between the Response-Guided Therapies and Monotherapies of Nucleos(t)ide Analogues for Chronic Hepatitis B Patients in China.

Nucleos(t)ide analogue (NA) monotherapies are typically used as the primary treatment for chronic hepatitis B (CHB) patients, including lamivudine (LAM), telbivudine (TBV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF). For high-resistance NAs (LAM, TBV, ADV), they can generate excellent clinical outcomes by using response-guided therapy; however, their pharmacoeconomic profiles remain unclear in China. We aimed to evaluate the cost effectiveness between response-guided therapies and monotherapies of NAs for Chinese hepatitis B e-antigen (HBeAg)-positive and -negative CHB patients. We constructed a Markov model to simulate CHB progression associated with 12 treatment strategies using effectiveness and cost data from the published literature. We measured the lifetime costs, quality adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity (especially to extend the range of the TDF price) and probabilistic sensitivity analyses were used to explore the uncertainties of the model. For both HBeAg-positive and -negative patients, no treatment strategy generated the lowest lifetime costs (US$31,185-US$31,338) and QALYs (7.54-7.58). ETV and TDF monotherapies were not dominated by other treatments, whereas, the ICER of ETV monotherapy was the lowest (US$6112/QALY-US$8533/QALY). For each high-resistance NA, compared with its monotherapy, the ICERs of its response-guided therapies were below the willingness-to-pay threshold of US$22,833/QALY. Additionally, TDF monotherapy was the preferred treatment when its price dropped to US$1820/year or lower. Among 12 treatment strategies evaluated, ETV monotherapy is the most cost-effective treatment for treatment-naive CHB patients in China. The response-guided therapies of high-resistance NAs are more cost-effective than their monotherapies.

Mutation analysis of hepatitis B virus polymerase gene sequence in chronic hepatitis B patients with virological rebound

Objective To investigate the sequence of hepatitis B virus (HBV) polymerase gene in chronic hepatitis B (CHB) patients with virological rebound. Methods A total of 141 serum samples from patients with viral rebound were collected, and the polymerase gene of HBV was sequenced directly using polymerase chain reaction products. Among the recruited patients, 59 cases were diagnosed with chronic hepatitis B (CHB), 68 cases of liver cirrhosis and 14 cases of primary hepatocellular carcinoma. Adefovir dipivoxil (ADV) was administered for 51 cases, lamivudine (LAM) or telbivudine (LdT) for 39 cases, entecavir (ETV) for 10 cases and LAM or LdT switching to ADV for 41 cases. Comparison of mutation rates between groups were compared by χ2 test. Results Among these 141 patients, drug-resistant mutations were detected in 20 (20/51, 39.2%) of ADV-treated patients, 28 (28/39, 71.8%) of LAM- or LdT-treated patients, 3 (3/10) of ETV patients and 30 (30/41, 82.1%) of LAM/LdT followed by ADV treated patients. The most prevalent mutations was rtM204I/V/S (35.5%), followed by rtL180M (22.7%) and then rtA181T/V mutation (19.1%). Conclusions The resistant mutation rate is the highest in LAM or LdT followed by ADV sequential therapy, while the lowest in ETV therapy. This study suggests that physicians should select the antiviral drugs rationally. Key words: Hepatitis B virus; Virologicalrebound; Resistant mutation

Efficacy and Safety of Telbivudine in Chronic Hepatitis B Treatment Throughout the Entire Pregnancy

OZ Objective: Women of childbearing potential treated for chronic hepatitis B virus (HBV) infection may experience exacerbations during or after pregnancy. Infants may also acquire HBV infection through perinatal route. Currently, there is no antiviral agent approved for use in pregnancy. This makes it difficult to decide whether treatment should be withdrawn immediately or continued in women who become pregnant while on HBV antiviral therapy. The present study aims to establish the safety and, as a second measure, the efficacy of telbivudine in patients who became pregnant while they were on telbivudine treatment for chronic HBV infections and were maintained on the treatment throughout pregnancy. Materials and Methods: Between 2010 and 2013, twentyone patients, who became pregnant while receiving telbivudine treatment for chronic HBV infection and continued the treatment, were evaluated retrospectively. Results: The mean age of the patients was 28.9±6.3 years (range: 18-41 years). All patients were hepatitis B envelope antigen-negative. The mean pre-treatment hepatic activity index was 9.4±1.6 (range: 7-13), and fibrosis and serum HBV, DNA measurements were 3.2±0.8 (range: 2-5) and 3.5x105±2.8x105 IU/mL, respectively. No drug-related side effects were seen in any of the patients. All infants had normal birth weights and no abnormalities were observed in any of them. At the end of week 28, none of the infants was hepatitis B surface antigen-positive. Conclusion: The use of telbivudine from the first trimester of pregnancy appears to be safe both for the mother and fetus and Amac: Kronik hepatit B virusu (HBV) nedeni ile takip edilen dogurganlik cagindaki kadin hastalarda kronik karaciger hastaligi gelisebilir, gebelik doneminde veya sonrasinda alevlenmelere neden olabilir, bununla birlikte perinatal donemde HBV bulasi ile bebek infekte olabilir. Gebelik doneminde HBV enfeksiyonu icin kullanimi onaylanmis bir antiviral ilac yoktur. Bu nedenle, antiviral ilac kullanirken gebe kalan kadinlarda tedaviyi sonlandirma ya da devam etme kararini vermek zordur. Bu calismada kronik HBV enfeksiyonu nedeniyle telbivudin tedavisi almakta iken gebe kalan ve tum gebelik donemi boyunca tedavi alan hastalarda telbivudinin ilk etapta guvenilirligini daha sonra ise etkinligini degerlendirmeyi amacladik. Gerec ve Yontemler: 2010-2013 yillari arasinda kronik HBV enfeksiyonu nedeniyle telbivudine tedavisi kullanirken gebe kalan ve tedaviye devam karari verilen 21 hasta retrospektif olarak degerlendirildi. Tum hastalarin tedavi baslandigi andaki serum hepatit B yuzey antijeni, hepatit B zarf antijen, anti-HBe, HBV DNA, alanin aminotransferaz (ALT), aspartat aminotransferaz (AST) seviyeleri, hepatik aktivite indeksi ve fibrozis degerleri kaydedildi. Daha sonra hastalarin gebelik baslangici, gebelik donemi boyunca ve dogum sonrasi 6. aya kadar 3’er ay ara ile serum hepatit B yuzey antijeni, hepatit B zarf antijen, anti-HBe, HBV, DNA, ALT, AST seviyeleri olculdu. Bulgular: Hastalarin yas ortalamasi 28,9±6,3 (yas araligi: 18-41) idi. Tum hastalar hepatit B zarf antijen negatif idi. Tedavi oncesi hepatik aktivite indeksi ortalama 9,4±1,6 (yas araligi: 7-13), fibrozis 3,2±0,8 (yas araligi: 2-5), serum HBV DNA duzeyi 3,5x105±2,8x105 IU/mL idi.

Long-Term Effects of Telbivudine for Treatment-Na飗e Chronic Hepatitis B-Associated Decompensated Cirrhosis

AIM: To compare the effects of telbivudine (TBV) with entecavir (ETV) on hepatitis B virus (HBV)-infected decompensated cirrhosis. METHODS: A total of 94 consecutive chronic hepatitis B patients with decompensated cirrhosis were recruited and retrospectively studied. Forty five patients were assigned to TBV group (600 mg/day) and 49 to ETV group (0.5mg/day), none of whom undertook antiviral treatment before. RESULTS: At 2 years, TBV and ETV groups had comparable cumulative rates of undetectable viremia (74.4% vs 88.0%, p = 0.083, by log-rank test) despite higher reduction of HBV-DNA levels in ETV group (-3.93 ± 0.22 vs -3.72 ± 0.24, p < 0.001). TBV and ETV groups showed comparable HBeAg clearance or seroconvertion rates, normalized alanine aminotransferase (ALT) proportions, Child-Turcotte-Pugh (CTP) and Model for end-stage liver disease (MELD) scores, cumulative rates of survival and hepatocellualr carcinoma (HCC), and proportions of cirrhosis-associated complications. TBV group had significantly higher rates of drug-resistance (15.9% vs 0%, p < 0.05) and elevated creatine kinase (CK, 18.2% vs 4.0%, p < 0.05). Cox proportional hazard regression model revealed that pretreatment HBV DNA level was the only independent predictive factor for 2-year undetectable viremia [Hazard Ratio (HR): 0.627; 95% Confidence Interval (CI): 0.432-910, p = 0.014]. CONCLUSIONS: For hepatitis B-associated decompensated cirrhosis, TBV was comparable to ETV in viral suppression, biochemical and immunological responses, and clinical outcomes. However, TBV was associated with higher rates of drug-resistance and increased CK.

Clinical effect of telbivudine in pregnant patients with e antigen-negative chronic hepatitis B

Objective To investigate clinical effect of telbivudine used in e antigen-negative chronic hepatitis B pregnant patients, to provide a reference for clinical treatment. Methods 90 pregnant patients with chronic hepatitis B e antigen-negative were selected, they were divided into two groups, 50 patients in the control group and 40 patients in the observation group.The observation group used telbivudine treatment, the control group used the compound glycyrrhizin treatment.Before and after treatment, HBV DNA levels, negative rate, serum ALT levels, pregnancy outcome were compared between the two groups. Results After treatment, HBV-DNA in the two groups was significantly decreased compared with before treatment, before treatment, the HBV-DNA of the control group was (6.37±1.18)mL, 6 weeks after delivery was (5.49±1.21)mL; before treatment, the HBV-DNA of the observation group was (6.31±1.21)mL, 6 weeks after delivery was (0.23±0.04)mL.The difference was statistically significant (t=8.154, P<0.01). In the observation group, before birth, six weeks after childbirth HBV-DNA were (0.21±0.05)lg copy/mL, (0.23±0.04)lg copy/mL, which were significantly lower than those of the control group, the differences were significant (t=19.257, P=0.000; t=8.154, P=0.000).4 weeks, 8 weeks after treatment, six weeks after childbirth, the HBV-DNA negative conversion rates of the control group were 52.00%, 60.00%, 88.00%, which were significantly lower than the observation group (χ2=177.61, 142.41, 184.58, P<0.01). Compared with before treatment, ALT levels after treatment were significantly decreased in the two groups (t=29.665, P<0.01). Before birth, six weeks after birth, ALT levels in the observation group were (12.58±2.58)U/L, (18.44±3.43)U/L, which were significantly lower than the control group (t=54.251, P=0.000; t=29.665, P=0.000). The incidence rate of adverse pregnancy of the observation group was 14.00%, compared with the control group the difference was not statistically significant (χ2=0.524, P=0.493). Conclusion Telbivudine in the treatment of gestational e antigen-negative chronic hepatitis B pregnant patients has good clinical effect, it can help to control hepatitis activity and reduce virus levels, which is worthy of clinical application. Key words: Hepatitis B, chronic; Telbivudine; Pregnancy; E antigen

NEW METHOD FOR DETERMINING HEPATITIS B VIRUS RESISTANCE MUTATIONS M204I/V TO NUCLEOS(T)IDE ANALOGUES IN PATIENTS WITH CHRONIC HEPATITIS B

Аnalogues of nucleos(t)ides (AN) such as lamivudine (LAM), telbivudine (TBV), adefovir (ADP), entecavir (ENT) are widely used for the treatment of chronic hepatitis B (CHB). However, the prolonged treatment using these drugs often leads to the development of drug resistance. The most common substitutions in the reverse transcriptase are methionine for valine (rtM204V), or methionine for isoleucine (rtM204I) at position 204. Early AN-resistant mutations detection is of great importance to determine the treatment strategy of patients with CHB. Currently there are many highly sensitive methods for detection of drug resistance mutations, such as next-generation sequencing, reverse hybridizationbased line probe assay (LiPA), mass spectrometry. However, these methods require expensive equipment and reagents, and they are not widely used in clinical laboratories. The aim of this study was to develop a simple and accurate real-time PCR method for detection of rtM204I/V mutation. This method showed high specificity and sensitivity (1000 copies/ml), it is less laborious and does not require additional equipment, fast and cost effective compared to other methods. HBV mutations of resistance to AN were determined in 5 groups of patients with CHB. Patients of the first group received monotherapy with pegylated interferon (n = 12), the second group — lamivudine (n = 10), the third group — telbivudine (n = 7), the fourth group — entecavir (n = 15). The fifth group consisted of patients who did not receive antiviral therapy (n = 3). The frequency of mutations in HBV polymerase YMDD-motif was determined among 47 patients with CHB: it was 10% for lamivudine treated patients, 20% — for entecavir, 28% — for telbivudine. YIDD/YVDD motifs were identified in two patients and YMDD/YIDD — in one patient. Real-time PCR method for the detection of AN-resistant rtM204I/V mutations in HBV polymerase can be used in routine diagnostics for primary screening of patients not responding to AN treatment. The application of this method can reduce the number of samples for in-depth study of primary and compensatory mutations of resistance to AN by sequencing method. The developed method versus Sanger-sequencing is fast, economical, and provides the detection of minor variants of HBV populations.

Clinical features and individualized treatment of 39 cases of adefovir dipivoxil-induced renal hypophosphatemia and osteomalacia

Objective To investigate the clinical features, early diagnosis and individualized treatment of renal hypophosphatemia and osteomalacia induced by adefovir dipivoxil (ADV) in patients with chronic hepatitis B (CHB). Methods Thirty-nine CHB or hepatitis B virus (HBV)-related cirrhosis patients of renal hypophosphatemia and osteomalacia induced by ADV were consecutively collected. The clinical features were analyzed and treatment outcome was followed up. Results The mean age of the 39 patients was 54 (27-71) years old. There were 26 male and 13 female patients, and 19 patients with cirrhosis. The mean ADV treatment duration was 69 (range 18-116) months, and 31 patients were treated for 36-96 months. The mean serum phosphate was 0.68 (0.42-0.79) mmol/L. Twenty-six cases developed renal hypophosphatemic osteomaolacia, of which 14 had bone pain and 19 had abnormally elevated alkaline phosphatase (ALP). Three patients had increased serum creatinine and 24 patients had decreased estimated glomerular filtration rate (eGFR). After individualized treatment, patients gained normal serum phosphate in mean of 2.0 (range 0.5-6.0) months, and had bone pain remission in the mean of 0.8 (range 0.2-1.0) month and bone pain disappeared in the mean of 1.5 (range 0.5-5.0) months. Function indices of liver and kidney were improved gradually, and the bone mineral density examination improved slowly. Conclusions CHB and HBV-related cirrhosis patients treated with long-term ADV could develop renal hypophosphatemia and hypophosphatemic osteomalacia, which is partially reversible. Monitoring serum phosphate, creatinine and cystatin C is necessary during long-term ADV therapy. After confirmed diagnosis, withdrawal or dosage reduction of ADV, and switch to telbivudine or entecavir should be considered. Meanwhile, serum phosphate and HBV DNA level should be monitored. Key words: Adefovir dipivoxil; Hypophosphatemia; Osteomalacia; Hepatitis B, chronic

The effects of Telbivudine for the prevention of perinatal transmission of hepatitis B virus infection from pregnant women to newborn on the expression of IL-17A,IL-10,IL-6 in the maternal plasma,umbilical plasma,neonatal plasma

Objective To explore the expression of interleukin-17A(IL-17A),interleukin-10(IL-10),interleukin-6(IL-6)in the maternal plasma,umbilical plasma,neonatal plasma from the pregnant women who accepted the Telbivudine for the prevention of perinatal transmission of hepatitis B virus infection. Methods 85 pregnant women who were delivered in the hospital were chosen[Telbivudine group 25 cases,HBVDNA high viral level group,HBVDNA negative group,non-infection group(health pregnant),each group included 20 cases].The level of the serum of IL-17A,IL-10,IL-6 in the maternal plasma,umbilical plasma,neonatal plasma from the different group was prospectively analyzed by the CBA method. Results The levels of IL-17A in the maternal plasma,umbilical plasma,neonatal plasma of the Telbivudine group[(15.29±4.80)pg/ m L,(19.45±4.80)pg/m L,(17.32±4.18)pg/m L]were lower than the HBVDNA high viral level group[(26.03±4.88)pg/m L,(34.07±5.59)pg/m L,(24.12±4.76)pg/m L],there were significant differences(P= 0.000, 0.001,0.019);The level of IL-10 in the maternal plasma,umbilical plasma,neonatal plasma of the Telbivudine group[(6.08±1.32)pg/m L,(2.33±0.68)pg/m L,(3.74±0.61)pg/m L]were higher than the HBVDNA high viral level group[(3.95±1.21)pg/m L,(1.71±0.53)pg/m L,(2.22±0.55)pg/m L],there were significant differences(P= 0.023,0.015,0.012);The level of IL-6 in the maternal plasma,umbilical plasma,neonatal plasma of the Telbivudine group were lower than the HBVDNA high viral level group,there were significant differences(all P<0.05). Conclusion Telbivudine can cause the inhibition of the replication of HBV virus,partially reverse the immunologic dissonance of the pregnant women with HBV virus,which is conducive to maintaining pregnancy. Key words: Hepatitis Brirus; Interleukins; Telbivudine

Genetic variation of Hepatitis B Virus Polymerase gene from chronic hepatitis B infected patient with telbivudine therapy

Infection caused by hepatitis B virus (HBV) is still a major global health problem and can cause liver cirrhosis and hepatocellular carcinoma as well. Telbivudine is one among the drugs used to treat the disease routinely. However, using this drug in a long term therapy might cause mutations in HBV polymerase gene that decreases the effectiveness of the therapy. Here with the researchers report the genetic variations of the gene isolated from telbivudine-which is used treated chronic hepatitis B patients in Surabaya, Indonesia. The blood sera were collected at Dr. Soetomo hospital from 10 telbivudine-treated and 10 untreated chronic hepatitis B patients. The DNA viral was isolated and purified from each serum. Sequence polymerase gene at nucleotides 455 to 796 was amplified by PCR, and then analyzed bio informatically to determine their mutation profile. This study revealed a point mutation in HBV25 sample at nucleotide A1525G that gives rise to I509V modification. Such mutation is also observed in a sequence that is available in Gen Bank with an accession number AY641562. Additionally, the researchers found point mutations A1554G, T1593C, and C1629T in HBV25 sample and a point mutation A1554G in HBV20 sample. However, these mutations are silent. To conclude, the mutation in HBV polymerase gene among telbivudinetreated chronic hepatitis B patients in Surabaya is known as A1525G.

Effects of Dahuang-Zhechong capsule combined with nucleos(t)ide analogues on liver function and serum markers of hepatic fibrosis in hepatic fibrosis patients with chronic hepatitis B

Objective To investigate the effects of Dahuang-Zhechong capsule combined with nucleos(t)ide analogues on the liver function and serum markers of hepatic fibrosis in hepatic fibrosis patients with chronic hepatitis B. Methods A total of 82 hepatic fibrosis patients with chronic hepatitis B were enrolled and randomly allocated to either a nucleos(t)ide analogues group (control group) and a nucleos(t)ide analogues plus Dahuang-Zhechong capsule group (treatment group) using the table of random digits, 41 patients in each group. The patients in the control group were treated with lamivudine, telbivudine, entecavir and adefovir dipivoxil, and those in the treatment group were administred with Dahuang-Zhechong capsule on the basis of the treatment in the control group for 4 courses of treatment, 3 months in a course of treatment. Liver function and serum markers of hepatic fibrosis were measured. Results The serum levels of alanine aminotransferase, total bilirubin, albumin, globulin in the treatment group have shown significantly improvement than those in the control group (t were 2.021, 3.811, 5.027, and 4.107, respectively; P<0.01 or P<0.05). The serum markers of hepatic fibrosis including hyaluronidase, procollagen type Ⅲ, collagen type Ⅳ, laminin were significantly decreaed than those in the control group (t were 11.441, 2.097, 6.589, and 2.102, respectively; P<0.01 or P<0.05). Conclusion Dahuang-Zhechong capsule combined with nucleos(t)ide analogues can improve the liver function and the serum markers of hepatic fibrosis in hepatic fibrosis patients with chronic hepatitis B. Key words: Nucleos(t)ide analog; Hepatitis B, chronic; Hepatic fibrosis; Dahuang-Zhechong capsule

Kushenin Combined with Nucleos(t)ide Analogues for Chronic Hepatitis B: A Systematic Review and Meta-Analysis.

Objective. To evaluate the efficacy and safety of Kushenin (KS) combined with nucleoside analogues (NAs) for chronic hepatitis B (CHB). Methods. Randomized controlled trials (RCTs) of KS combined with NAs for CHB were identified through 7 databases. Frequencies of loss of serum HBeAg, HBeAg seroconversion, undetectable serum HBV-DNA, ALT normalization, and adverse events at 48 weeks were abstracted by two reviewers. The Cochrane software was performed to assess the risk of bias in the included trials. Data were analyzed with Review Manager 5.3 software. Results. 18 RCTs involving 1684 subjects with CHB were included in the analysis. KS combined with NAs including lamivudine (LAM), entecavir (ETV), adefovir dipivoxil (ADV), and telbivudine (TLV) showed different degree of improvement in CHB indices. KS combined with NAs increased the frequency of loss of serum HBeAg, HBeAg seroconversion, undetectable HBV-DNA levels, and ALT normalization compared with single agents. It also decreased serum ALT and AST level after one-year treatment. However, KS combined with TLV did not show a significant difference in CHB indices. The side-effects of KS combined with NAs were light and of low frequency. Conclusion. KS combined with NAs improves the efficacy of NAs in CHB.

Influence of telbivudine on CD4+CD25+ regulatory T cells in pregnant women with chronic HBV infection

Objective To explore the mechanism of intrauterine Hepatitis B Virus infection observing the influence of telbivudine on CD4+CD25+ regulatory T cells in the peripheral blood of pregnant women with chronic HBV infection.Methods 100 pregnant women with chronic HPV infection were selected and divided into a treatment group,treated with telbivudine,and a control group,treated without telbivudine,50 for each group.Before and 1 and 3 months after the treatment and before delivery,the Tregs ratios were detected by flowcytometry and HBVDNA loads were detected by PCR.The 5 indicators of HBV in the infants were detected by enzyme-linked immunosorbent assay and the HBVDNA loads in the infants were detected by PCR after their birth.Results Among the 49 infants given birth by the control group,5 (11.2％) were positive in HBsAg; among the 50 infants given birth by the treatment group,none was positive in HBsAg; with a statistical difference (x 2=5.373,P ＜ 0.05).Before and 1 and 3 months after the treatment and before delivery,the Tregs ratio was (4.85 ± 1.83) ％,(3.26 ± 1.39) ％,(2.24 ± 1.47) ％,and (1.78 ± 0.56) ％ in the treatment group,respectively,and was (4.62 ± 2.01) ％,(4.59 ± 2.51) ％,(3.42 ± 2.90) ％,and (1.99 ± 1.64) ％ in the control group,respectively.There was interaction between pregnant time and antivirus treatment by telbivudine(F=3.88,P ＜ 0.05).There were statistical differences in the expression of CD4+CD25+ regulatory T cells between the 2 groups (F=10.56,P ＜ 0.05) and between before and different times after the treatment (F=42.39,P ＜ 0.001).Conclusion Telbivudine treatment reduce parental HBV transmission rate and decrease the Tregs ratio of pregnant women. Key words: Chronic hepatitis B; CD4+CD25+ regulatory T cells; Telbivudine; Immunoglobulin block

Clinical study on teibivudine combined with adefuvir dipivoxii in the treatment of Hepatitis B patients with decompensated cirrhosis

Objective To observe the effect of telbivudine combined with adefuvir dipivoxil in the treatment of Hepatitis B patients with decompensated cirrhosis.Methods 56 Hepatitis B patients with decompensated cirrhosis were divided into two groups:treatment group (30 cases) and control group (26 cases).During 24 weeks,the control group received adefuvir dipivoxil( 10mg daily),supportive and symptomatic treatments,while the treatment group received telbivudine therapy(600mg daily) combiled with adefuvir dipivoxil ( 10mg daily) based on the regular treatments.After 24 weeks,the effect was observed and compared between the two groups.Results After treatment,the biochemical markers,Child-Pugh score of the treatment group was (33.2 ± 13.8) μmol/L,(44.5 ± 16.4) U/L,(36.1 ±1.5) g/L,(6.1 ± 1.8) points,respectively,and was better than those of the control group[ (71.8 ±18.6) μ mol/L,(89.9 ±44.9) U/L,(29.7 ± 1.3)g/L,(8.1 ±2.2) points] (t=15.32,15.20,23.37,6.09,all P＜0.05) ;HBV-DNA negative rate,HBeAg seroconversion rates of the treatment group was 93.3％ (28/30),43.3％(13/30),and was higher than that of the control group[76.9％ (20/26),7.6％ (2/26) ] (x2 =4.87,9.08,all P＜0.05).Conclusion Telbivudine combined with adefuvir dipivoxil was effective and safe for the treatment of Hepatitis B patients with decompensated cirrhosis. Key words: Hepatitis B; Liver cirrhosis; Telbivudine; Adefuvir dipivoxil

Meta‐analysis: oral anti‐viral agents in adults with decompensated hepatitis B virus cirrhosis

The optimal oral anti-viral agent to use in patients with decompensated HBV cirrhosis remains unclear. We performed a meta-analysis of the oral nucleos(t)ide analogues in patients with decompensated HBV cirrhosis. One year efficacy and safety outcomes in 22 studies published in English between '95 and 2010 were analysed. Substantial heterogeneity was noted in the inclusion/exclusion criteria, controls, and sensitivity of the HBV DNA assay used. Pooled 1-year data showed benefit favouring lamivudine (LAM) vs. untreated controls for Child-Turcotte-Pugh (CTP) score improvement by ≥2 (OR: 117 (15 921), P ≤ 0.0001) and transplant-free survival (OR: 3.2 (1.2, 9), P = 0.022). Adefovir (ADV) led to undetectable HBV DNA at 1-year in 41% compared to 83% with LAM and 80% with entecavir (ETV). Overall, 1-year transplant-free survival rates varied from 78% with LAM to 95% and 94% with Tenofovir (TDF) and Telbivudine (TBV), respectively. The 1-year incidence of drug resistant HBV was 0% with ADV, ETV and TDF and 11% with LAM although TBV was associated with a 29% incidence at 2 years. Drug-related adverse events were infrequently reported. All the oral anti-viral agents were associated with improved virological, biochemical and clinical parameters at 1-year. However, the efficacy of lamivudine and telbivudine is limited by drug resistance, and adefovir is limited by its potency and slower onset of action. Additional studies of tenofovir and entecavir are needed to determine the optimal agent(s) for treatment naïve patients and in those with drug-resistant decompensated HBV cirrhosis.

Clinical observation of telbivudine and lamivudine in treament of patients with chronic hepatitis B

Objective To investigate the efficacy and side effects of telbivudine and lamivudine for treatment of chronic hepatitis B for 1 year. Methods In this random and control study,the efficacy of telbivudine and lamivudine treatments were compared in 120 patients who consisted of 60 cases with HBeAg-negative and 60 cases with HBeAg-positive chronic hepatitis B.The patients were randomly assigned to a daily 600mug telhivudine treatment group or daily 100mg lamivudine group for 52 weeks.The clinical efficacy and adverse reactions of the two groups were observed in control after 52 weeks of therapy,and dynamics of serum HBsAg,HBeAg levels were monitored and compared. Results At week 52,mean reductions of serum HBV DNA from baseline and undetectable serum HBV DNA rates among patients with HBeAg-negative and HBeAg-positive chronic hepatitis B were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group(all P＜0.05).Viral resistance and viral breakthrough was significant common in lamivudine compared with telbivudine(all P＜0.05).Among patients with HBeAg-positive chronic hepatitis B,telbivudine was significant superior to lamivudine with respect to loss of HBeAg(P＜0.05).There was no significant difference in side effects between patients treated with tebivudine and Iamivudine. Conclusion Telbivudine was more effective than lamivudine in treatment of patients with chronic hepatitis B,and the drug was well tolerated. Key words: Chronic hepatitis B; Lamivudine; Telbivudine

Clinical study of telbivudine on HBeAg-positive chronic hepatitis B

Objective To investigate the curative effect of telbivudine versus lamivudine in chronic hepatic B with a therapy of 48 weeks. Methods 94 patients who were diagnosed chronic hepatitis B were investigated. The therapeutic group and the control group (n = 47) were respectively assigned to receive 600mg of telbivudine and 100mg of lamivudine in 48 weeks. Copies of HBV-DNA、serum markers、alanine transarninase(ALT) level were tested before therapy and 4 weeks、12 weeks、24 weeks、48 weeks in the the course of treatment. The HBV-DNA conversion、HBeAg conversion and the normal rate of the ALT were compared. Results The copies of HBV-DNA decreased as the treatment progressing,especially at the 4 thweek. Conversion rate of the HBV-DNA of the telbivudine group was 72.3% ,which was higher than the lamivudine group 42.6%. There is a significant difference between two groups (x2 = 8.530,P ＜ 0.05). 95.7% of ALT in the telbivudine group revived to normal level versus 91.5% of the lamivudine group became normal. There is no significant difference between two groups (P ＞ 0.05). At the end of treatment,the rate of the HBeAg converting to negative in the telbivudine group is 38.3% versus the lamivudine group 31.9%, but there is no significant statistical difference between two groups(x2 = 0.420 ,P ＞ 0.05). The frequence of seroconversion of HBeAg in the telbivudine group is 23.4% versus the lamivudine group 17.0%, but no statisticall difference between two groups (x2 = 0. 594, P ＞ 0.05). Conclusion It was more effective to treat the HBeAg positive chronic hepatitis with telbivudine than lamivudine,and lower frequence of seroconversion of the HBV-DNA、HBeAg. Key words: Hepatitis B,chronic; Telbivudine

Should We Continue Entecavir for HBV Infection Despite Partial Virologic Response

For patients with chronic hepatitis B virus (HBV) infection who achieve only partial virologic response (PVR) to initial therapy, current guidelines advise adding a second oral antiviral agent or switching to a more potent agent. However, this recommendation is based on studies that used retrospective data and evaluated less-potent antiviral agents such as lamivudine and telbivudine rather than more-potent, first-line agents such as tenofovir and entecavir. …