Adefovir Group Research Articles

Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in patients with chronic hepatitis B: a prospective cohort study in China.

Chronic hepatitis B therapy with nucleos(t)ide analogues, particularly tenofovir or adefovir, may affect renal function. To date, there has not been a head-to-head controlled study to assess estimated glomerular filtration rate (eGFR) fluctuations in nucleos(t)ide-treated CHB patients. We aimed to evaluate the long-term effects of nucleos(t)ide on eGFR in Chinese patients with chronic hepatitis B. This prospective cohort study included 275 patients. Patient subgroups included those treated with lamivudine (n = 50), adefovir (n = 60), telbivudine (n = 68) and entecavir (n = 61); untreated patients (n = 36) served as control. After an average follow-up duration of 23 months, eGFR calculated by Cockcroft-Gault and Modification of Diet in Renal Disease formulas increased by 18.35 mL/min and 19.34 mL/min (P < 0.0001) in the telbivudine group, respectively, and decreased by 10.95 mL/min and 12.17 mL/min (P = 0.0001) in the adefovir group, respectively. Even if renal function was normal or mildly impaired at baseline, eGFR increased significantly more in the telbivudine group than in the other groups (P < 0.001). More patients in the adefovir group (23%) had a ≥20% decrease in eGFR than the other groups (P < 0.0001). More patients in the telbivudine group (31%) had a ≥20% increase in eGFR than the other groups (P < 0.0001). In conclusion, prolonged telbivudine therapy resulted in improved eGFR, while adefovir therapy was associated with decreased eGFR. Lamivudine and entecavir therapy did not significantly influence eGFR.

Efficacy of Adefovir-Based Combination Therapy for Patients with Lamivudine- and Entecavir-Resistant Chronic Hepatitis B Virus Infection

Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB) patients are not yet well established. The aim of this study was to evaluate overall antiviral efficacy and to compare the efficacy of combination therapy with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus (HBV) variants. Virologic, biochemical, and serologic responses during combination therapy with ADV plus nucleoside analogues were assessed. Propensity score analysis was used to select a matched group of patients for the comparison of rescue therapy regimens. A total of 67 consecutive patients were analyzed. Complete virologic suppression was achieved in 27 patients. The overall cumulative incidence of complete virologic suppression at month 24 was 47.4%: 44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV. There was no significant difference between these two groups (P = 0.234). The cumulative incidences of complete virologic suppression were still comparable between the two groups selected and matched using the propensity score model (P = 0.419). Virologic breakthrough was observed in 9 patients, and rtA181V substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg) negativity and lower baseline HBV DNA level were associated with complete virologic suppression in univariate analysis. In multivariate analysis, lower baseline HBV DNA level remained an independent predictor. In conclusion, combination therapy with ADV plus nucleoside analogues fails to show sufficient antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further study is warranted to evaluate the efficacy of a more potent tenofovir-based regimen in such patients.

English

The aim of this study was to compare the safety, efficacy, and pharmacoeconomics of the diminishing type antiviral combination of lamivudine and adefovir group (LA group) and entecavir monotherapy group (E group) in HBeAg-positive chronic hepatitis B.&nbsp;One hundred (100)&nbsp;patients were randomized equally to LA group,&nbsp;and&nbsp;E group in a multi-center randomized clinical trial. In the LA group, the earliest time for lamivudine discontinuation was 12 weeks and adefovir monotherapy continued until 96 weeks. Group E received entecavir monotherapy for 96 weeks. At 12 weeks, the&nbsp;hepatitis B virus (HBV)DNA suppression and ALT normalization rates in LA group were both comparable to E group. At weeks 24 and 48 of treatment, the difference in virological response (VR) and HBeAg seroconversion between LA group and E group was not significant, while&nbsp;similar results were observed for the biochemical response (BR). At 96 weeks, HBeAg seroconversion of LA group were higher than that of the E group, but the difference was still not&nbsp;statistically significant, while BR and VR in LA and E group were similar. At the same time, no virological breakthrough or drug resistance occurred in either of the two treatment groups by week 96 of the study. Both treatment strategies were well tolerated, with a low incidence of adverse reaction. The costs of all items related to LA group were lower than those related to E group (RMB&nbsp;ï¿¥14,480.13 vs. RMB&nbsp;ï¿¥28,818.47; t=164.78, p&lt;0.001). This study demonstrates that diminishing type antiviral combination of lamivudine and adefovir is economical, safe, and effective in HBeAg-positive chronic hepatitis B. &nbsp; Key words:&nbsp;Chronic hepatitis B, HBeAg-positive, lamivudine, adefovir dipivoxil, combination treatment, entecavir, monotherapy, pharmacoeconomic.

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

To examine the efficacy of telbivudine (LdT) + adefovir (ADV) vs continuation of lamivudine (LAM) + ADV in patients with LAM-resistant chronic hepatitis B (CHB) who show a suboptimal response to LAM + ADV. This was a randomized, active-control, open-label, single-center, parallel trial. All eligible patients were enrolled in this study in Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea, between March 2010 and March 2011. Hepatitis Be antigen (HBeAg)-positive CHB patients whose serum hepatitis B virus (HBV) DNA remained detectable despite at least 6 mo of LAM + ADV therapy were included. Enrolled patients were randomized to either switching to LdT (600 mg/d orally) plus ADV (10 mg/d orally) (LdT + ADV group) or to continuation with LAM (100 mg/d orally) plus ADV (10 mg/d orally) (LAM + ADV group), and were followed for 48 wk. One hundred and six patients completed the 48-wk treatment period. Serum HBV DNA, HBeAg status, liver biochemistry and safety were monitored at baseline and week 12, 24, 36 and 48. The duration of prior LAM + ADV treatment was 18.3 (LdT + ADV) and 14.9 mo (LAM + ADV), respectively (P = 0.131). No difference was seen in baseline serum HBV DNA between the two groups [3.66 (LdT + ADV) vs 3.76 (LAM + ADV) log10 IU/mL, P = 0.729]. At week 48, although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT + ADV group and LAM + ADV group (-0.81 vs -0.47 log10 IU/mL, P = 0.167), more patients in the LdT + ADV group had undetectable HBV DNA levels compared to those in the LAM + ADV group (30.2% vs 11.5%, P = 0.019). Three patients with LdT + ADV treatment and 2 patients with LAM + ADV treatment achieved HBeAg loss. The patients in both groups tolerated the treatment well without serious adverse events. The proportion of patients with estimated glomerular filtration rate ≥ 90 mL/min per 1.73 m(2) in the LdT + ADV group increased from 49.1% (26/53) at baseline to 58.5% (31/53) at week 48, while that in the LAM + ADV group decreased from 37.7% (20/53) at baseline to 30.2% (16/53) at week 48. The switch to LdT + ADV in suboptimal responders to LAM + ADV showed a significantly higher rate of virologic response at week 48. These results suggest that LdT + ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.

Antiviral therapy delays esophageal variceal bleeding in hepatitis B virus-related cirrhosis

To investigate the effect of antiviral therapy with nucleoside analogs in hepatitis B virus (HBV)-related cirrhosis and esophageal varices. Eligible patients with HBV-related cirrhosis and esophageal varices who consulted two tertiary hospitals in Beijing, China, the Chinese Second Artillery General Hospital and Chinese PLA General Hospital, were enrolled in the study from January 2005 to December 2009. Of 117 patients, 79 received treatment with different nucleoside analogs and 38 served as controls. Bleeding rate, change in variceal grade and non-bleeding duration were analyzed. Multivariate Cox proportional hazard regression was used to identify factors related to esophageal variceal bleeding. The bleeding rate was decreased in the antiviral group compared to the control group (29.1% vs 65.8%, P < 0.001). Antiviral therapy was an independent factor related to esophageal bleeding in multivariate analysis (HR = 11.3, P < 0.001). The mean increase in variceal grade per year was lower in the antiviral group (1.0 ± 1.3 vs 1.7 ± 1.2, P = 0.003). Non-bleeding duration in the antiviral group was prolonged in the Kaplan-Meier model. Viral load rebound was observed in 3 cases in the lamivudine group and in 1 case in the adefovir group, all of whom experienced bleeding. Entecavir and adefovir resulted in lower bleeding rates (17.2% and 28.6%, respectively) than the control (P < 0.001 and P = 0.006, respectively), whereas lamivudine (53.3%) did not (P = 0.531). Antiviral therapy delays the progression of esophageal varices and reduces bleeding risk in HBV-related cirrhosis, however, high-resistance agents tend to be ineffective for long-term treatment.

Sustained efficacy of adefovir add-on therapy in chronic hepatitis B patient with a poor virological response to peginterferon alfa

Background. Currently, there is no consensus on the recommendation of peginterferon alfa (pegIFNα) to chronic hepatitis B (CHB) patients with poor viral response (EVR). This study aimed to assess the sustained curative efficacy of adefovir (ADV) add-on therapy in optimizing pegIFNα monotherapy. Methods. A total of 85 hepatitis B e antigen (HBeAg)-positive CHB patients with poor virological response at month 6 after starting pegIFNα-2a were enrolled, and received either pegIFNα-2a continuing monotherapy (group A, n = 51) or add-on therapy with ADV (group B, n = 34). The treatment duration for all patients was 6 months, and the sustained responses after the end of treatment were evaluated between two groups. Results. The baseline characteristics were comparable between two groups. At months 6 after treatment completion, the sustained virological response (SVR) rates were 31.4% and 73.5%, the sustained biochemical response (SBR) rates were 39.2% and 85.3% in group A and group B respectively, and the difference in either SVR or SBR was statistically significant (both p < 0.001). As compared to patients in group A, significantly more patients in group B obtained HBeAg loss (19.6% vs. 55.9%, p = 0.001) and seroconversion (13.7% vs. 41.2%, p = 0.004). Conclusion: ADV add-on therapy could significantly improve and sustain the curative efficacy of CHB patient with poor virological response to pegIFNα-2a monotherapy, but further large well-designed randomized controlled trials are needed to confirm our findings.

Virologic Responses to Add‐on Adefovir Dipivoxil Treatment Versus Entecavir Monotherapy in Children With Lamivudine‐resistant Chronic Hepatitis B

The aim of the study was to compare the virologic response to adefovir (ADV) add-on therapy with switching to entecavir (ETV) monotherapy in children and adolescents with chronic hepatitis B (CHB) who have developed lamivudine (LAM) resistance during LAM treatment. Twenty-seven consecutive patients with CHB who had developed LAM resistance during LAM treatment were included. Of these 27 patients, 8 patients were treated with the addition of ADV to ongoing LAM and 8 patients were treated by switching to ETV monotherapy and each of these 16 patients were compared with the 11 patients who were treated by switching to ADV alone, as a historical control. Therapeutic responses to treatment were evaluated at 12, 24, 36, and 48 weeks from the initiation of therapy by measuring the decrement of hepatitis B virus (HBV)-DNA titers. The therapeutic period for HBV-DNA titer decrement (>2 log(10) IU/mL) was significantly shorter in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.008); however, there was no significant difference between the LAM+ADV group and the ETV group. The rate of virologic response, defined as decrement in HBV-DNA titer to undetectable levels at 24 weeks, was significantly higher in both the LAM+ADV group and the ETV group than in the ADV group (P = 0.029). Both the LAM+ADV combination therapy and ETV monotherapy exhibited significantly more effective virologic responses compared to the ADV monotherapy in children and adolescents with LAM-resistant CHB, although there was no significant difference between the LAM+ADV group and the ETV group.

The Efficacy of Adefovir Plus Entecavir Combination Therapy in Patients with Chronic Hepatitis B Refractory to Both Lamivudine and Adefovir

The efficacy of adefovir (ADV) plus entecavir (ETV) combination in patients with chronic hepatitis B (CHB) who developed multidrug refractoriness had not been fully evaluated. We aimed to evaluate the efficacy of ADV plus ETV as compared to that of lamivudine (LAM) plus ADV in the patients with antiviral refractoriness to sequential LAM monotherapy and then ADV monotherapy. Twenty-seven patients were treated with a combination of ADV plus ETV and 63 patients were treated with a combination of LAM plus ADV. The virological and biochemical parameters were compared between the two groups, retrospectively. Treatment with a combination of ADV plus ETV produced significantly superior virological response than that of a combination of LAM plus ADV. At 12 months, the HBV DNA declined more in the ADV plus ETV group than in the LAM plus ADV (-4.52 ± 1.956 vs. -2.65 ± 1.723 log 10 IU/mL; p = 0.001). The rate of a complete response at 12 months was greater in the ADV plus ETV group than that in the LAM plus ADV group (63.16 vs. 14.81 %, p < 0.001). In the patients with CHB refractory to both LAM and ADV, the response to ADV plus ETV was significantly superior compared to that of the LAM plus ADV in suppressing HBV DNA. The result indicates that ADV plus ETV can be used as a bridging therapy in the patients with refractoriness to both LAM and ADV, especially in the areas where tenofovir is not yet available.

Lamivudine plus Adefovir or Telbivudine plus Adefovir for Chronic Hepatitis B Patients with Suboptimal Response to Adefovir

There is no standard management of chronic hepatitis B (CHB) patients with suboptimal response to nucleoside/nucleotide analogues (NAs). This study aimed to evaluate two different NA combination therapies in patients with suboptimal response to adefovir (ADV). In this study, 72 CHB patients with suboptimal response to ADV were assessed, with 37 patients receiving lamivudine plus ADV (group A) and 35 patients receiving telbivudine plus ADV (group B). Baseline characteristics between two groups were similar. At month 12, rates of biochemical response (BR) and virological response (VR) were similar between groups A and B (17/19 versus 18/20 for BR, [P=0.269] and 30/37 versus 31/35 for VR [P=0.377]), and cumulative rates of serological response were greater in group B than in group A (10/26 versus 2/28 in hepatitis B e antigen [HBeAg] loss [P=0.006] and 7/26 versus 1/28 in HBeAg/hepatitis B e antibody seroconversion [P=0.022]). After 12-month treatment, 8.1% (3/37) of patients in group A and 5.7% (2/35) of patients in group B had VR; among patients in group A, two had rtM204V/I and rtL180M and one had rtN236T, whereas the two patients in group B had rtM204I+rtL180M. Both combination therapies led to a significant decrease in HBV DNA. HBeAg serological outcomes were higher with telbivudine plus ADV combination therapy.

Efficacy of lamivudine and adefovir de novo combination therapy or after mono-therapy in chronic hepatitis B patients

To investigate the efficacy of 104 weeks of lamivudine (LAM) and adefovir (ADV) de novo combination therapy, as compared to optimized combination therapy administered after 48 weeks of treatment with lamivudine or adefovir mono-therapy, in chronic hepatitis B (CHB) patients. A total of 174 patients with CHB were equally divided among three treatment groups: LAM mono-therapy; ADV mono-therapy; and LAM + ADV combination therapy. The patients in the LAM + ADV group were treated with LAM plus ADV for 104 consecutive weeks. The patients in the LAM or the ADV groups were first treated for 48 weeks with LAM or ADV, respectively, after which the patient's virological response was assessed. According to the results, the patient was continued on mono-therapy or switched to combination therapy for the subsequent 56 weeks. Virological and biochemical examinations were carried out at weeks 48 and 104. The rates of undetectable HBV DNA in the LAM mono-therapy, ADV mono-therapy, and LAM-ADV combination therapy groups at week 48 were 68%, 50%, and 84%, and at week 104 were 80%, 72%, and 95%, respectively. For the same groups, the virus breakthrough rates at week 48 were 15%, 0%, and 0%, and at week 104 were 18%, 2%, and 0%, respectively. Statistical analysis showed significant differences for the rate of undetectable HBV DNA between LAM + ADV group and LAM group at week 48 (x2 = 4.473, P= 0.034) and at week 104 (x2 = 5.795, P = 0.016), LAM + ADV group and ADM group at week 48 (x2 = 14.802, P less than 0.001) and week 104 (x2 = 5.547, P = 0.001). The hepatitis B e antigen (HBeAg) seroconversion rates at week 48 were 15% (x2 = 4.543, P = 0.033), 13% (x2 = 4.035, P = 0.045) and 38%, and at week 104 were 21% (x2 = 4.438, P = 0.035), 17% (x2 = 4.223, P = 0.04) and 44%, respectively, among patients positive for HBeAg. Statistical analysis showed that the differences among the three groups for each of these parameters were statistically significant (all, P less than 0.05). When compared with LAM or ADV mono-therapy followed by LAM+ADV at week 48, the LAM plus ADV de novo combination therapy for 104 weeks provided CHB patients with better virological and serological responses and a lower drug resistance rate.

Antiviral Treatment Alters the Frequency of Activating and Inhibitory Receptor-Expressing Natural Killer Cells in Chronic Hepatitis B Virus Infected Patients

Natural killer (NK) cells play a critical role in innate antiviral immunity, but little is known about the impact of antiviral therapy on the frequency of NK cell subsets. To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. We found that NK cell numbers and subset distribution differ between CHB patients and normal subjects; furthermore, the association was found between ALT level and CD158b+ NK cell in HBV patients. In tenofovir group, the frequency of NK cells increased during the treatment accompanied by downregulated expression of NKG2A and KIR2DL3. In adefovir group, NK cell numbers did not differ during the treatment, but also accompanied by downregulated expression of NKG2A and KIR2DL3. Our results demonstrate that treatment with tenofovir leads to viral load reduction, and correlated with NK cell frequencies in peripheral blood of chronic hepatitis B virus infection. In addition, treatments with both tenofovir and adefovir in chronic HBV infected patients induce a decrease of the frequency of inhibitory receptor+ NK cells, which may account for the partial restoration of the function of NK cells in peripheral blood following treatment.

Risk Factors of Gene-Resistant Mutations in Different Nucleosides

To explore the risk factors of gene-resistant mutations during nucleotide treatment. A total of 320 patients with CHB were randomly divided into lamivudine (LAM, 107 cases), adefovir (ADV, 106 cases) and entecavir (ETV, 107 cases) groups, and P gene mutations of HBV were regularly detected. Kaplan-Meier and Cox regression analysis were performed. There was no statistical significance in baseline data between the three groups. The gene-resistant mutation rates were 20.0%, 0.0% and 0.0% one year later, 37.1%, 3.8% and 0.0% two years later, 42.8%, 9.5% and 0.9% three years later, and 64.7%, 25.7% and 0.9% four years later in LAM, ADV and ETV groups, respectively. In LAM group, rtL180M combined with rtM204V mutations accounted for 32.7% and in ADV group, rtN236T mutation accounted for 12.3%. The gene-resistant mutation rate was the most strong in LAM group. With an extension of time, gene-resistant mutation rates are increased, but it is the highest in LAM group and the lowest in ETV group. Family history, the negative conversion time of HBV DNA and different nucleosides are independent risk factors of gene-resistant mutations.

Adefovir‐based combination therapy with entecavir or lamivudine for patients with entecavir‐refractory chronic hepatitis B

This study evaluated the efficacy of adefovir (ADV) plus lamivudine (LAM) or ADV add-on therapy for patients with entecavir (ETV)-refractory hepatitis B infection. Twenty-nine ETV-resistant and 8 patients with suboptimal response to ETV were enrolled. Twenty-seven patients received ADV + LAM therapy and 10 patients received ADV + ETV therapy for >24 weeks. In 29 patients who were ETV-resistant, the mean reduction in HBV DNA levels at 24 weeks was not different between the ADV + LAM and ADV + ETV groups (-1.98 log(10) IU/ml vs. -2.16 log(10) IU/ml; P = 0.792). Primary non-response was observed in 52.2% (12/23) of ADV + LAM group and 33.3% (2/6) of ADV + ETV group (P = 0.651). Initial virologic response (IVR) was observed in 17.4% (4/23) of ADV + LAM group and 33.3% (2/6) of ETV + ADV group (P = 0.362). In eight patients with suboptimal response to ETV, the ADV + ETV group had a greater reduction in HBV DNA at 24 and 48 weeks than the ADV + LAM group (-2.29 log(10) IU/ml vs. -0.09 log(10) IU/ml and -2.04 log(10) IU/ml vs. -0.72 log(10) IU/ml; P = 0.020 and P = 0.012, respectively). Primary non-response and IVR did not significantly differ between the two groups [100% (4/4) vs. 50% (2/4) and 0% (0/4) vs. 50% (2/4); P = 0.429 and P = 0.429, respectively]. The antiviral efficacies of ADV-based therapy with ETV or LAM for patients with ETV-resistant hepatitis B were limited and did not differ between the two groups. However, adding ADV to ETV may be more effective than ADV + LAM therapy in patients with suboptimal virologic response to ETV.

Comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B: A Systematic Review

Chronic viral hepatitis B remains a global public health concern. Currently, several drugs, such as tenofovir and adefovir, are recommended for treatment of patients with chronic hepatitis B. tenofovir is a nucleoside analog with selective activity against hepatitis b virus and has been shown to be more potent in vitro than adefovir. But the results of trials comparing tenofovir and adefovir in the treatment of chronic hepatitis B were inconsistent. However, there was no systematic review on the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B. To evaluate the comparison of the efficacy of tenofovir and adefovir in the treatment of chronic hepatitis B we conducted a systematic review and meta-analysis of clinical trials. We searched PUBMED, Web of Science, EMBASE, CNKI, VIP database, WANFANG database, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review. Finally six studies were left for analysis which involved 910 patients in total, of whom 576 were included in tenofovir groups and 334 were included in adefovir groups. At the end of 48-week treatment, tenofovir was superior to adefovir at the HBV-DNA suppression in patients[RR = 2.59; 95%CI(1.01-6.67), P = 0.05]. While there was no significant difference in the ALT normalization[RR = 1.15; 95%CI(0.96-1.37), P = 0.14], HBeAg seroconversion[RR = 1.32; 95%CI(1.00-1.75), P = 0.05] and HBsAg loss rate[RR = 1.19; 95%CI(0.74-1.91), P = 0.48]. More high-quality, well-designed, randomized controlled, multi-center trails are clearly needed to guide evolving standards of care for chronic hepatitis B.

Comparison of the 48-week efficacy between entecavir and adefovir in HBeAg-positive nucleos(t)ide-naïve Asian patients with chronic hepatitis B: a meta-analysis

BackgroundAlthough entacavir and adefovir were widely used in most Asian countries, there were few conclusions drawn from a meta-analysis for comparing the efficacy between entecavir and adefovir in nucleos(t)ide-naïve Asian patients with chronic hepatitis B (CHB). The aim of this study was to evaluate the 48-week efficacy between the two drugs in HBeAg-positive nucleos(t)ide-naïve Asian CHB patients with the method of Meta analysis, which was generally accepted by the international as the best evidence for evaluating the efficacy of drugs.MethodsWe searched all data documented in Pubmed, Embase, Wanfang Database and CNKI (China National Knowledge Infrastructure) before November 30, 2010. Heterogeneity was examined by Chi-square test, the relative risk calculated and forest plot drawn. Rates of undetected serum HBV DNA, serum alanine aminotransferase (ALT) normalization, HBeAg clearance and HBeAg seroconversion were analyzed. A total of 6 articles was included. Meta analysis showed that the rate of undetected serum HBV DNA (relative risk, 1.73; 95% confidence interval, 1.38-2.17; P < 0.00001) and that of serum ALT normalization (relative risk, 1.25; 95% confidence interval, 1.06-1.49; P = 0.009) in the entecavir group were higher than those in the adefovir group. However, no statistic significance existed between the two groups in the rate of HBeAg clearance (relative risk, 0.77; 95% confidence interval, 0.44-1.35; P = 0.36), or the rate of HBeAg seroconversion (relative risk, 0.74; 95% confidence interval, 0.28-1.94; P = 0.53).ConclusionsEntecavir is superior to adefovir in decreasing serum HBV DNA and normalizing ALT but similar with adefovir in clearing HBeAg and encouraging HBeAg seroconversion for the HBeAg-positive nucleos(t)ide-naive Asian patients with chronic hepatitis B. Adefovir can be still used for first-line therapy in these patients.

Comparison of the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients

To compare the efficacy of 48 week-Entecavir therapy with that of Adefovir therapy for chronic hepatitis B patients. In this open-label study we randomly assigned 125 CHB patients to receive 0.5 mg of entecavir (n = 56) or 10mg of adefovir (n = 69) once daily for 48 weeks. HBV DNA, ALT and HBeAg were quantified at baseline and at 0, 24, 48 weeks. At week 24 and 48, more patients in entecavir group than in adefovir group achieved undetectable serum HBV DNA level (68% vs 35%, 84% vs 49%, P < 0.05). The percentage of patients with normal ALT level in the two groups at week 48 was similar (100% vs 94%, P > 0.05). Among the HBeAg positive patients, more patients in entecavir group than in adefovir group had HBeAg loss at week 24 and 48 (23% vs 7%, 44% vs 15%, P < 0.05). The ratio of HBeAg seroconversion was similar in the two groups at week 24 (18% vs 7%, P > 0.05), but more patients in entecavir group than in adefovir group achieved HBeAg seroconversion at week 48 (33% vs 12%, P < 0.05). The retreated patients in the entecavir group had a higher chance to achieve undetectable serum HBV DNA level (79% vs 34%, P < 0.05), HBeAg loss (42% vs 17%, P > 0.05), and seroconversion (26% vs 17%, P > 0.05), than these in the adefovir group. The safety profiles and adverse event profiles were similar in the two groups. Compared to adefovir, entecavir is more potent to suppress HBV replication.

Experience with Entecavir Therapy for Lamivudine-Resistant Chronic Hepatitis B in Korean Children and Adolescents

Purpose: To estimate the viral suppressive effect of entecavir monotherapy in Korean children and adolescents with lamivudine-resistant chronic hepatitis B (CHB). Methods: One milligram of entecavir was administered once daily to 6 patients (4 boys; mean age, 17.5 years; range, 15.10∼24.6 years) with lamivudine-resistant CHB for a mean duration of therapy of 13.4 months (range, 1∼21.1 months). The therapeutic results were compared with 11 patients who received adefovir (0.3 mg/kg/day [maximal dose 10 mg]) for at least 12 months (mean, 33.4 months; range, 12.4∼ 58.3 months). The serum HBV DNA level and serologic markers were measured every 2 months. Results: The interval to a HBV DNA titer decrement (>1 log10) was 1.2±0.2 and 4.4±5.2 months (p=0.185) for the entecavir and adefovir groups, respectively. The interval to a HBV DNA titer decrement (>2 log10) was 2.4±2.3 and 9.2±7.3 months (p=0.025), for the entecavir and adefovir groups, respectively. Conclusion: The therapeutic efficacy of entecavir was favorable in children and adolescents, especially in shortening the interval to a >2 log10 decrement in the HBV DNA titer. Long-term follow up is needed to determine the therapeutic efficacy of entecavir for lamivudine-resistant CHB in children and adolescents. (Korean J Pediatr Gastroenterol Nutr 2010; 13: 44∼50)

Efficacy and durability of generic adefovir dipivoxil in patients with HBeAg positive chronic hepatitis

To study the efficacy and durability of generic adefovir dipivoxil (ADV) in patients with HBeAg positive chronic hepatitis. 54 nucleosides-naïve patients with HBeAg positive chronic hepatitis were enrolled in this randomized, double-blinded, placebo-controlled, prospective study. 38 patients received ADV (10 mg once daily) and the others received placebo. Then all the patients were treated with ADV for 96 weeks and were followed up for 12 weeks. (1) At week 12, the level of ALT declined significantly in ADV group(135.84 +/- 10.63 U/L to 58.92 +/- 4.95 U/L, P < 0.001) compared with placebo group (145.56 +/- 17.19 U/L to 159.50 +/- 37.05 U/L) (P < 0.001). The HBV-DNA level also declined significantly in adefovir group compared with placebo group (2.51 vs. 1.04 log10 copies/ml, P < 0.001). (2) The rates of normal ALT, normal of AST and undetectable HBV-DNA at 48 and 96 weeks of therapy with ADV were 63.30%, 70.50%, 87.80%, 88.60%, 53.06%, 54.55%, respectively. (3) There were 17 patients discontinuated ADV after 96 weeks. The follow-up results showed that HBV-DNA became positive again in all these 17 patients and abnormal liver function developed in 88.24% (15/17) patients. Treatment of chronic hepatitis B with generic ADV was effective and well tolerated, but relapse may develop when treatment was discontinued.

Decrease in viral load at weeks 12 and 24 in patients with chronic hepatitis B treated with lamivudine or adefovir predicts virological response at week 48

The aim of our study was to evaluate the decrease in viral load (VL) that is able to predict antiviral treatment response at one year in patients with chronic hepatitis B. The clinical records of 66 patients, 31 treated with lamivudine (LAM) and 35 treated with adefovir (ADF), were retrospectively reviewed. We measured viral DNA at months 1, 3 and 6. The LAM group showed virological response (VR) in 51.6% of patients. Baseline VL was higher in non responders (5.37 +/- 1.16 vs. 7.01 +/- 1.05; p < 0.001). Responders showed a higher percentage of VL decrease at month 3 from baseline (49.2 vs. 38.3%; p = 0.03). We designed a ROC curve and established a cutoff point for decrease of 30% that had 80% of negative predictive value (NPV).The ADF group showed VR in 57.1% of patients. Baseline VL was higher in nonresponders (4.67 +/- 1.22 vs. 5.78 +/- 1.34; p = 0.01). We observed a significant decrease in VL (log) at months 3 (2.6 +/- 1.1 vs. 1.3 +/- 1.3; p = 0.03) and 6 (2.6 +/- 1.2 vs. 1.3 +/- 1.2; p = 0.006). The percentage of decrease of VL from baseline was also statistically significant. We created ROC curves at months 3 and 6, and established the best cutoff points. At month 6 a decrease of 1 log in VL had a NPV of 80%, and a decrease of 20% in VL from baseline had 100% NPV. The decrease in viral DNA at weeks 12 and 24 can predict VR at one year in patients with chronic hepatitis B treated with LAM or ADF. This could optimize treatment.

Investigation on perioperative Antivirus Treatment with adeforir on Chronic Hepatitis B Patients with Colon Cancer

Objective To study the activity of hepatitis B virus and therapeutic efficacy of adefovir in chron-ic hepatitis B patients with colon cancer during operation period. Methods 50 chronic hepatitis B patients with co-lon cancer to be underwent colon resection were divided two groups at random, one group was given adcfovir (adefovir group), the other group not (control group), and therapeutic measure except antivirus is the same. HBV-DNA con-centration and liver functon of the patients were detected. Results Serum HBV-DNA concentration and ALT level of the patients was increased significantly at 1 week and 1 month after operation compared with that before operation in control group. Serum HBV-DNA concentration of the patients was decreased significantly at 1 week and 1 month after operation compared with that before operation in adefovir group. The ALT level of patients in adefovir group is signifi-cantly lower than that in control group. Conclusions Surgical procedure may result in HBV replication and antivirus treatment should be done perioperatively. Adefovir can inhibite replication of HBV and also improve the liver function of the chronic hepatitis B patients with colon cancer during operation. Key words: Hepatitis B virus; Perioperative; Adefovir