Lamivudine Group Research Articles

HIV-1 Drug Resistance and Second-Line Treatment in Children Randomized to Switch at Low Versus Higher RNA Thresholds.

The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. PENPACT-1 had a 2 × 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples ≥1000 copies/mL before switch, resuppression, and at 4-years/trial end. Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were <400 copies/mL 24 weeks later. Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet resuppressed on second-line. An abacavir + lamivudine NRTI combination seemed protective against development of NRTI resistance.

Effect of echinacoside on replication and antigen expression of hepatitis B virus

To verify the effect of echinacoside on replication and antigen expression of hepatitis B virus (HBV) by using HBV-transfected HepG2. 2. 15 cells as the in vitro model. The ELISA method was used to determine HBeAg and HBsAg levels in cellular supernatants. The effect of echinacoside on HBV replication was studied by using HBV transgenic mice as the in vivo model. First of all, the HBV DNA level in hepatic tissues was quantified with PCR method. Meanwhile, the serum transaminase levels and hepatic pathological changes were also evaluated. Subsequently, HBV transgenic mice were divided into five groups: the control group, the lamivudine group (50 mg · kg(-1)) and echinacoside high, medium and low dose group (50, 25 and 12.5 mg · kg(-1)). The mice were orally administered with drugs once per day for 30 days. At the 31st day, the mice serum was separated to measure HBsAg, HBeAg and HBV DNA. Additionally, the liver HBV DNA level and histopathological change were detected. The results indicated that echinacoside at 50 and 100 mg · L(-1) suppressed significantly HBsAg and HBeAg expressions on the sixth day, with the maximum inhibition ratios of 42.68% and 46.29%; And echinacoside at 100 mg · L(-1) also showed an inhibitory effect on HBV DNA. Besides, echinacoside at 50 mg · kg(-1) inhibited significantly HBsAg and HBeAg expressions of HBV transgenic mice, with the inhibition ratios of 42.82% and 29.12%, and reduced markedly the serum HBV DNA level in HBV transgenic mice. In conclusion, the study suggested that echinacoside has a strong effect against HBV replication and antigen expression.

Antiviral therapy improves the survival rate and decreases recurrences and fatalities in liver cancer patients following curative resection: A meta-analysis.

The present study aimed to investigate the impact of postoperative antiviral treatment on tumor recurrence, fatalities and survival of patients with chronic hepatitis B virus (HBV) infection-related primary hepatocellular carcinoma (HCC). A systematic meta-analysis was performed. All the studies comparing nucleos(t)ide analogues (NAs) versus placebo or no treatment were considered. The results were expressed as relative ratio (RR) for 1-, 3- and 5-year recurrence-free survival (RFS) and overall survival (OS), recurrence HCC and fatalities with 95% confidence intervals (CI) using STATA 11.0. In total, 15 trials with 7,619 patients were included. There were significant improvements for 1-, 3- and 5-year RFS (RR, 1.09; P=0.003; RR, 1.202; P<0.001; and RR, 1.219; P=0.02; respectively) and in 3- and 5-year OS (RR, 1.087, P=0.006; and RR, 1.186; P<0.001) in the NAs group compared with the control group. Sensitivity analyses confirmed the robustness of the results. In addition, the significantly high rate of recurrence HCC and fatalities existed in the control group (RR, 1.301; P=0.002; and RR, 1.816, P<0.001). One study was for an entecavir (ETV)-treated group compared with an adefovir (ADV)-treated group and lamivudine (LAM)-treated group. The 3-year disease-free survival rate for the ETV group was significantly better compared with the ADV and LAM groups [hazard ratio (HR), 0.810; P=0.049; and HR, 0.737; P=0.007]. The present study demonstrated the beneficial effects of NAs therapy following curative treatment of HBV-related HCC. ETV may be the superior choice compared to ADV or LAM for the antiviral treatment.

Long-term lamivudine for chronic hepatitis B and cirrhosis: A real-life cohort study.

To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM). This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups. Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five-year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group. Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths.

Influence of Chongcao Yigan Capsule on function of intestinal flora and chemoprevention for patients with chronic hepatitis B-induced liver fibrosis.

Hapatitis B visus (CHB)-induced fibrosis is a precancerous condition of liver. To explore the influence of Chongcao Preparation (Chongcao Yigan Capsule) on the function of intestinal flora and chemoprevention for patients with CHB-induced liver fibrosis. A total of 136 patients with CHB-induced liver fibrosis were randomly divided into control group treated with lamivudine (LAM) and research group added with Chongcao Yigan Capsule for totally 48 weeks. The changes of intestinal flora, secretory immunoglobin A (SIgA), serum albumin (ALB), prealbumin (PALB), IgA and IgG at different time points in both groups were observed. Before treatment, there was no significant difference between two groups in each index (P>0.05). After treatment, the intestinal flora were evidently optimized in research group than treatment before (P<0.05 or P<0.01), and were apparently better than those in control group (P<0.05 or P<0.01); SIgA was obviously increased and ALB, PALB, IgA and IgG were markedly improved in research group than treatment before (P<0.05 or P<0.01), and were significantly better than those in control group (P<0.05 or P<0.01). Chongcao Yigan Capsule could regulate the intestinal flora, increase SIgA, serum ALB and PALB concentrations and significantly improve serum IgA and IgG as well as strengthen the immunological function and autologous repair capacity of patients with CHB-induced liver fibrosis.

Prediction of prognosis to lamivudine in patients with spontaneous reactivation of hepatitis B virus-related acute-on-chronic liver failure: Using virologic response at week 4

Background/aimsCurrent results had demonstrated lamivudine (LAM) contributed to improve liver function and short-term prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure (ACLF), but data concerning the outcome of long-term prognosis are limited. Our objective was to explore the prediction value of early viral response for prognosis and LAM resistance in ACLF patients with lamivudine treatment within 96weeks. MethodsOne hundred and forty consecutive subjects were recruited, 76 patients were treated with LAM and supportive treatment (LAM group) and 64 patients only received supportive treatment (non-NAs group). All the patients were followed up until death or 96weeks. The primary end point was overall survival rate at 96weeks, as well as the relationship between the virologic response at weeks 4 or 12 and prognosis and resistance at 96weeks. ResultsAt 96weeks, the cumulative survival was higher in the LAM group than that in the non-NA group (43/76 (56.58%) vs 9/64 (14.06%), respectively, p=0.000). The survival rate of patients achieved complete viral response (CVR) at week 4 was higher than that of those with partial virologic response (PVR) during the 96-week follow-up (27/29 [93.10%] vs 16/45 [35.56%], p=0.000). In CVR patients, there was a significant improvement in model for end-stage liver failure (MELD) scores compared to PVR. Logistic recurrence indicated that both 4-week CVR and MELD scores were an independent predictor of the 96-week survival. Twelve patients developed LAM resistance (22.22%); all of them came from the PVR at 4weeks. ConclusionLAM can significantly improve the long-term survival rate, and 4weeks CVR can predict the long-term clinical outcome and LAM-resistant in patients with HBV-related ACLF.

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?

Efficiency and safety of lamivudine and adefovir dipivoxil combination therapy for ninety-six weeks in patients with chronic hepatitis B associated compensated liver cirrhosis

Objective To evaluate the efficiency and safety of lamivudine (LAM) and adefovir dipivoxil (ADV) combination therapy in patients with chronic hepatitis B (CHB) associated compensated liver cirrhosis.Methods From June 2007 to February 2009,patients vith CHB associated compensated liver cirrhosis of eight hospitals were enrolled.According to random code table,these patients were divided into initial LAM group and initial ADV group in 1:1 ratio.Patients of the two groups received ADV or LAM monotherapy initially.At week 24 or week 36 of treatment,if the serum hepatitis B virus (HBV) DNA level of patients exceeded 3.30 lglU/mL or virological breakthrough (VBT) occurred,the other medicine was added for combination therapy.At week 48,the treatment of all the patients was changed to two medicine combination therapy till week 96.During follow-up period,the occurrences of complications of liver cirrhosis or hepatocellular carcinoma,virological and biochemical responses,VBT,HBV drug resistance gene mutations and adverse reactions were observed.Fisher' s exact test was performed for statistical analyses.Results Among the 206 patients and in 96 weeks' follow-up,a total of 17 cases developed complications of liver cirrhosis or hepatocellular carcinoma and in which eight cases were hepatocellular carcinoma (3.88％).At week 96 of treatment,HBV DNA negative convertion rate of initial ADV group was 80.9％ (76/94) and that of initial LAM group was 70.5％ (67/95).The alanine aminotransferase (ALT) levd normalization rate of initial ADV group was 95.7 ％ (90/94) and that of initial LAM group was 87.4％ (83/95).Compared with the baseline,the serum albumin level increased 2.5 and 3.3 g/L,respectively,and the prothrombin time shortened 0.6 and 0.7 seconds,respectively.The accumulated VBT rate of initial ADV group was 7.84％ (8/102) and that of initial LAM group was 23.08％ (24/104),the difference was statistically significant (Fisher's exact test,P=0.003).Among 14cases without virus negative convertion at week 96 of treatment,11 cases developed VBT during treatment and in which seven cases were with gene mutations and the other four cases were wild strains.During treatment,adverse reactions included abdominal discomfort,elevated fasting blood glucose,high blood pressure and dizziness,which improved after symptomatic treatments.Conclusion Both ADV and LAM initiated combination therapy can prevent the occurrences of complications of liver cirrhosis or hepatocellular carcinoma in patients with CHB associated compensated liver cirrhosis,and furthermore,it obtains sustained virological response and biochemical function improvement,with slight adverse reaction. Key words: Hepatitis B, chronic; Liver cirrhosis; Adefovir dipivoxil; Lamivudine; Combination therapy

Telbivudine or lamivudine use in late pregnancy safely reduces perinatal transmission of hepatitis B virus in real-life practice.

Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen–positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx = 252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx = 257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention-to-treat analysis indicated 2.2% (95% confidence [CI]: 0.6-3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9-10.3) in the NTx group (P = 0.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups (1.9% vs. 3.7%; P = 0.758). On-treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P = 0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. Conclusions: LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified.

Adefovir Dipivoxil, Tenofovir Disoproxil Fumarate or Lamivudine; Which is Suitable Monotherapy Medication in the Patients with Chronic Hepatitis B Virus Infection? One Year Experience

Introduction: The hepatitis B virus infection is responsible for more than one million deaths all over the world. This study design is to compare the efficacy of Lamivudine (LAM), Adefovir Dipivoxil (ADV) or Tenofovir Disoproxil Fumarate (TDF) monotherapy in chronically infected hepatitis B patients. Methods: We design a prospective cohort study and select patients who were under treatment with TDF (300mg/day), ADV (10mg/day) and LAM (100mg/day). After matching patient's primary data and on base of our inclusion and exclusion criteria; 19, 20 and 19 patients were enrolled in TDF, LAM and ADV groups, respectively. Then, we evaluated patients at 6 and 12 month after treatment. Results: Patents primary data was closely matched. After 6 month medication, ALT level in 7 patients (36.8%), 12 patients (60%) and 6 patients (31.6%) of TDF, LAM and ADV groups were back to normal range, respectively (P>0.05). All drugs significantly decrease ALT level after 6 month therapy (P 0.05). Finally, response to treatment was observed in 5 patients (45.5%), 7 patients (35%) and 2 patients (10.5%) of TDF, LAM and ADV group, respectively (P>0.05).

Comparison of telbivudine versus lamivudine in interrupting perinatal transmission of hepatitis B virus

BackgroundInfection with hepatitis B virus (HBV) during pregnancy may lead to perinatal transmission. ObjectivesTo compare the efficacy and safety of telbivudine versus lamivudine in interrupting perinatal transmission of hepatitis B virus. Study designAll pregnant women enrolled in this study were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Test patients underwent antiviral therapy with telbivudine or lamivudine while control patients received hepatitis B immune globulin (HBIG) injection. ResultsPatients in the telbivudine group had significantly lower HBV DNA and HBeAg levels and higher HBV DNA negative conversion rates compared to those in the lamivudine group before delivery. HBV DNA negative conversion rates in patients with abnormal alanine aminotransferase (ALT) levels were significantly higher than those in patients with normal ALT levels in the telbivudine and lamivudine groups before delivery. The intrauterine HBV infection rate and the percentage of immunization failure were both 0% in the telbivudine and lamivudine groups (χ2=0, 0; P=1, 1 respectively), compared to both 5% in the HBIG group (χ2=11.83, 7.86; P=0.002, 0.009 respectively). The side effects of three groups in mother and child were all unobvious. ConclusionsTelbivudine and lamivudine can reduce HBV DNA levels in pregnant women, interrupt the vertical transmission of HBV and be used safely in mothers and children.

Role of lamivudine with transarterial chemoembolization in the survival of patients with hepatocellular carcinoma.

The purpose of the present study was to determine whether lamivudine in combination with transarterial chemoembolization (TACE) could reduce hepatitis B virus (HBV) activation and improve the survival of patients with hepatocellular carcinoma (HCC). From July 2008 to October 2011, a total of 181 consecutive HBV-related HCC patients undergoing TACE were randomized to two groups (92: lamivudine, 89: control). Follow up was every 3 months. Primary and secondary end-points were time to progression (TTP) and overall survival (OS), respectively, both of which were evaluated by the Kaplan Meier technique and summarized by the hazard ratio. The level of HBV-DNA became undetectable in 42 (45.6%) patients in the lamivudine group, compared with 10 (11.2%) in the control group (P < 0.001). The median TTP was 8.2 months in lamivudine group and 4.3 months in control group (P = 0.005), and lamivudine therapy was an independent protective factor related to TTP (P = 0.006). Moreover, 1-, 2-, and 3-year survival rates were 83%, 69%, and 58% in lamivudine group and 60%, 48%, and 48% in control group, respectively (P = 0.002). With multivariate Cox regression model, lamivudine therapy (P = 0.002) and α-fetoprotein (AFP) level (P = 0.003) were two independent predictors for OS. Lamivudine therapy could reduce HBV activation and improve survival of HCC patients treated with TACE. Lamivudine therapy and AFP level are two independent factors affecting OS.

Research on HBV DNA inhibition of plasmid acute infection mouse with betulinic acid

Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with betulinic acid. Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the betulinic acid and lamivudine groups were inhibited compared with the control group. Taken together, these results reveal betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model.

Entecavir vs. lamivudine in chronic hepatitis B patients with severe acute exacerbation and hepatic decompensation

We compared the mortality and treatment response between lamivudine (LAM) and entecavir (ETV) in chronic hepatitis B (CHB) patients with severe acute exacerbation and hepatic decompensation. From 2003 to 2010 (the LAM group) and 2008 to 2010 (the ETV group), 215 and 107 consecutive CHB naïve patients with severe acute exacerbation and hepatic decompensation treated with LAM and ETV respectively, were recruited. At baseline, the LAM group had higher AST levels and end-stage liver disease (MELD) scores, and lower albumin levels than the ETV group. Univariate analysis showed that the LAM group had a higher rate of overall (p=0.02) and liver-related mortality (p=0.052) at week 24 than the ETV group, including in patients with acute-on-chronic liver failure. Multivariate analysis showed that MELD scores, ascites, and hepatic encephalopathy were independent factors for overall and liver-related mortality at week 24. ETV or LAM treatment was not an independent factor for mortality in all patients or patients with acute-on-chronic liver failure. The best cut-off value of MELD scores were 24 for 24-week liver-related mortality. The ETV group achieved better virological response (HBV DNA <300 copies/ml) than the LAM group at week 24 (p=0.043) and 48 (p=0.007). The T1753C/A mutation was also an independent predictor associated with overall and liver-related mortality at week 24. The choice between ETV and LAM was not an independent factor for mortality in CHB patients with acute exacerbation and hepatic decompensation. Patients with ascites, hepatic encephalopathy, and MELD scores ⩾24 were associated with poor outcome and should be considered for liver transplantation.

Early Entecavir Treatment for Chronic Hepatitis B with Severe Acute Exacerbation

A previous study found that lamivudine, if started early enough, may improve the chance of survival in chronic hepatitis B virus (HBV) with severe acute exacerbation (SAE). The aim of this study was to investigate the effect of early entecavir treatment before the bilirubin level exceeds 20 mg/dl for chronic HBV with SAE. Consecutive patients with chronic HBV with SAE and a serum bilirubin level of <20 mg/dl who received lamivudine or entecavir were enrolled. Short-term (4 months) survival was evaluated. One hundred fourteen patients received lamivudine, and 53 patients received entecavir. The baseline characteristics were similar for the two groups except that the entecavir group was older and had a lower alanine aminotransferase (ALT) level. Three patients (8.0%) in the entecavir group and 9 patients (7.9%) in the lamivudine group died (P=1.000). If only patients who started antiviral treatment before serum bilirubin level rose to more than 15 mg/dl were included, 3 patients (8.3%) in the entecavir group and 3 patients (3.0%) in the lamivudine group died (P=0.189). If only patients with an HBV DNA level higher than 10(5) copies/ml and a bilirubin level lower than 15 mg/dl were included, 5 out of 40 patients (12.5%) in the entecavir group died and 1 out of 59 patients (1.7%) in the lamivudine group died. Multivariate analysis found that entecavir treatment was associated with more mortality than lamivudine (P=0.035). Early entecavir treatment in patients with high viral load is associated with more short-term mortality than lamivudine for chronic HBV with severe acute exacerbation.

Higher adherence with 3‐year entecavir treatment than lamivudine or telbivudine in treatment‐naïve Taiwanese patients with chronic hepatitis B

Oral nucleos(t)ide analogs (NAs) are effective in suppressing hepatitis B virus (HBV) replication in treatment naïve chronic hepatitis B (CHB) patients. However, little is known about the treatment modification and adherence on such patients with prolonged NA treatment. In this multicenter observational study, a total of 600 NA-naïve Taiwanese CHB patients aged 16 years and older were enrolled. The 600 patients were retrospectively identified by their NA treatment history from August 2008 to July 2009; this cohort was prospectively followed up over 3 years. During the 3-year period, incidence of treatment modifications, reasons for modification, and rate of adherence were evaluated. Among the 583 evaluable patients, the initial NA treatment included entecavir (ETV) in 468 patients, telbivudine (LdT) in 67, and lamivudine (LVD) in 48. During the 3-year treatment, 9.0% of ETV-treated patients, 38.8% of LdT-treated patients, and 54.2% of LVD-treated patients had treatment modification. The main reasons for treatment modification were fulfilling stopping criteria in the ETV group (40.5%) and virological breakthrough in both the LdT (61.5%) and LVD (46.2%) groups. The proportion of patients with adherence rate (> 90%) at year 3 was 90.8% in the ETV group, 83.9% in the LdT group, and 83.9% in the LVD group. Treatment-naïve CHB patients with a 3-year ETV treatment in Taiwan have the lower likelihood of treatment modification and better rate of adherence compared with those with LdT or LVD treatment.

Telbivudine protects renal function in patients with chronic hepatitisBinfection in conjunction with adefovir‐based combination therapy

Previous studies have demonstrated that the treatment of chronic hepatitis B (CHB) infection with adefovir (ADV) can impair renal function. In contrast, treatment with telbivudine (LdT) improves renal function in CHB patients. The aim of this study was to evaluate the renoprotective effect of LdT in CHB patients receiving ADV-based combination therapy. The effects of treatment with ADV + LdT on renal function were compared to those resulting from treatment with ADV + entecavir (ETV), ADV + lamivudine (LAM), ADV alone and ETV alone. The consecutive cohort analysis included 831 CHB patients who received ADV + LdT, ADV + LAM, ADV + ETV, ADV alone or ETV alone for 96weeks. Alterations in estimated glomerular filtration rate (eGFR) were compared between the five groups using a linear mixed-effects model. HBV DNA levels were also compared between the five groups during the 96-week period. Among the five treatment groups, significant improvements in eGFR were observed in the ADV + LdT and ADV + LAM groups over time (P<0.001 for each group compared with baseline eGFR). In patients with a baseline eGFR between 50 and 90mL/min, the change in eGFR was the most significant in the ADV + LdT group (+0.641mL/min; P<0.001). Age, gender, baseline eGFR and treatment option were significant predictive factors for eGFR changes. In conclusion, our results suggest that the combination therapy of LdT and ADV is significantly associated with renoprotective effects in CHB patients when compared with other ADV-based combination or single therapies.

Efficacy and safety of telbivudine therapy in liver failure patients with chronic hepatitis B virus infection

The objective of this study was to evaluate the short-term efficacy and safety of telbivudine therapy as compared to lamivudine therapy in liver failure patients with chronic hepatitis B virus (HBV) infection. These data were collected from 38 liver failure patients with chronic HBV infection who were randomly enrolled to one of the two treatments. All patients received comprehensive treatments; 20 patients were treated with telbivudine, and the other 18 patients were treated with lamivudine. The serum levels of HBV DNA, alanine aminotransferase, total bilirubin, prothrombin time activity, and creatine kinase were determined every 7 days for 8 weeks. The results showed that the serum HBV DNA levels in patients treated with either telbivudine or with lamivudine declined gradually after the 2nd week of treatment. However, HBV DNA levels in the telbivudine group fell to the lower limit of detection (<5+E2 copies/ml) after the 5th week, which was more rapid than in the lamivudine group. In addition, the total bilirubin and prothrombin time activity of the patients with telbivudine treatment showed a more significant improvement as compared to the patients treated with lamivudine from the start of the 5th week. All patients tolerated telbivudine or lamivudine treatment well. The patients treated with telbivudine did not have elevated serum creatine kinase or myopathic symptoms during the 8-week treatment period. Thus, telbivudine treatment is superior to lamivudine treatment in improving the condition of patients with liver failure as a result of chronic HBV infection in the short term.

Influence of combination therapy of lamivudine and IFN on IL-8 level in chronic hepatitis B patients

Objective To explore the influence of combination therapy of IFN and lamivudine on IL-8 level in chronic hepatitis B patients.Methods 58 patients with chronic hepatitis B were selected and divided into control group and experiment group randomly and evenly.Based on regular treatments,control group received treatment of lamivudine and experiment group received combination treatment of lamivudine and IFN alpha-1 b.Restoring rate of ALT,serum conversion rate of HBeAg/anti-HBe,conversion rate of HBV-DNA and mutation rate of YMDD were observed and compared between two groups.Serum level of IL-8 was observed before and after treatment in two groups.Results Compared with control group,serum conversion rate of HBeAg/anti-HBe significantly increased,mutation rate of YMDD significantly decreased in experiment group(P ＜ 0.05).Serum level of IL-8 in two groups significantly decreased after treatment,but more significant in experiment group compared with control group (P ＜ 0.05).Conclusion Combination therapy of lamivudine and IFN shows positive effects to chronic hepatitis B,mainly via inhibiting activities of HBV and decreasing status of inflammation. Key words: Hepatitis, B Chronic ; IFN ; Lamivudine; Interleukin

Oral Nucleoside/Nucleotide Analogs Without Hepatitis B Immune Globulin After Liver Transplantation for Hepatitis B

The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone. A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients. Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.