Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. For...Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.展开更多
AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na v...AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.展开更多
AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepati...AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.展开更多
We report the case of a patient treated with living donor-related liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)-containing antiviral therapy for lamivudine-resistant hepatitis B ...We report the case of a patient treated with living donor-related liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)-containing antiviral therapy for lamivudine-resistant hepatitis B virus infection. The patient had generalized bone pain,with severe hypophosphatemia after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV at 10mg/day. It was also found that ADV affected the metabolism of tacrolimus,a calcineurin-inhibitor,and caused an increase in the plasma levels of tacrolimus. The disability was reversed with the withdrawal of ADV and with mineral supplementation. ADV can cause an elevation of plasma tacrolimus levels,which may be associated with renal dysfunction. High levels of ADV and tacrolimus can cause nephrotoxicity and osteomalacia. This case highlights the importance of considering a diagnosis of osteomalacia in liver transplantation recipients treated with both ADV and tacrolimus.展开更多
We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved a...We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.展开更多
AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.
Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the ...Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.展开更多
Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, accor...Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Results Several findings were demonstrated with the increase of serum HBV DNA： 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly（P〈0.05）, while the plasma level of albumin decreased significantly（P〈0.05）; The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group（P〈0.01）. Conclusion With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.展开更多
AIM： To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those rece...AIM： To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS： Eighty patients who had received lamivudine treatment for various periods and had a lamivudineo resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus （HBV） DNA at 0, 12 and 48 wk and serum alanine aminotransferase （ALT） levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS： We found serum ALT became normalized in 72 （87.5%） of the 80 patients, and HBV DNA decreased by ≥ 2 Ioglo copies/mL in 60 （75%） of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION： These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.展开更多
AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis ...AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.展开更多
BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic he...BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.展开更多
Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to b...Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced.展开更多
Objective:To explore the effect of adefovir dipivoxil in combined with lamivudine on the liver function in patients with hepatitis B cirrhosis and the antiviral efficacy.Methods:A total of 156 patients with hepatitis ...Objective:To explore the effect of adefovir dipivoxil in combined with lamivudine on the liver function in patients with hepatitis B cirrhosis and the antiviral efficacy.Methods:A total of 156 patients with hepatitis B cirrhosis who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 78 cases in each group. The patients in the treatment group were given adefovir dipivoxil in combined with lamivudine, while the patients in the control group were given entecavir. After 12-month treatment, the efficacy was evaluated. The liver function, serum virology indicators, and AFP before and after treatment in the two groups were compared. The adverse reactions during the treatment process were recorded.Results: The serum GTP, ALT, AST, and TBIL levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05);moreover, ALT and TBIL levels in the treatment group were significantly lower than those in the control group (P<0.05). HBeAg, HBV-DNA, and AFP levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05), HBeAg and AFP levels in the treatment group were significantly lower than those in the control group (P<0.05), and the comparison of HBV-DNA between the two groups was not statistically significant (P>0.05). ALT normalization rate and HBeAg negative conversion rate after treatment in the treatment group were significantly higher than those in the control group (P<0.05). The comparison of HBV-DNA negative conversion rate and HBeAg conversion rate between the two groups was not statistically significant (P>0.05). No obvious drug adverse reactions and liver function damage occurred during the treatment process in the two groups. Conclusions:Adefovir dipivoxil in combined with lamivudine can significantly improve the liver function and serum virology indicators in patients with hepatitis B cirrhosis, with antiviral efficacy significantly superior to that by entecavir.展开更多
Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e ...Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e antigen(HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group(EG,received ADV plus CM)and control group(CG,received ADV plus CM-placebo)for 48 weeks.The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12,24,36,48,respectively.Secondary endpoints including liver functions(enzymes and bilirubin readings)were evaluated every 4 weeks at the beginning of week 24,36,and 48.Routine blood,urine,and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations.Adverse events(AEs)were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks,without additional AEs.The full analysis population was 560 and 280 in each group.In the EG,population achieved HBeAg loss on week 12,24,36,and 48 were 25(8.90%),34(12.14%),52(18.57%),and 83(29.64%),respectively;the equivalent numbers in the CG were 20(7.14%),41(14.64%),54(19.29%),and 50(17.86%),respectively.There was a statistically significant difference between two groups on week 48(P<0.01).No additional AEs were found in EG.Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy.The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile(ChiCTR-TRC-11001263).展开更多
Background Knowledge on Hepatitis B surface antigen （HBsAg） kinetics in chronic hepatitis B （CHB） patients with longterm adefovir dipivoxil （ADV） treatment is limited.The aims of this study were to investigate H...Background Knowledge on Hepatitis B surface antigen （HBsAg） kinetics in chronic hepatitis B （CHB） patients with longterm adefovir dipivoxil （ADV） treatment is limited.The aims of this study were to investigate HBsAg kinetics in patients with chronic hepatitis B virus （HBV） infection treated with long-term ADV and to evaluate different characteristics between patients with and without HBsAg loss.Methods We retrospectively evaluated HBsAg kinetics in 24 Chinese patients with chronic HBV infection who achieved continuous virologic suppression during ADV therapy.HBV genotype was determined at baseline.Liver biochemistry,hepatitis B e antigen status,serum HBV DNA,and HBsAg levels were measured at baseline,6 months,and once every year thereafter.Results Of these 24 patients,3,1,and 20 patients were followed up for 3,5,and 6 years,respectively.Baseline serum HBsAg level had a moderate correlation with baseline HBV DNA level （r=0.52,P=0.01）.The median rate of HBsAg reduction during the therapy period was 0.08 Ig IU·ml-1·y-1.Baseline serum HBsAg level was significantly higher than other time points （P ranges from 0.046 to 0.002）.The HBsAg reduction rate during the first year was similar to that in other years （P〉0.05）.The HBsAg reduction rate during the first year in patients with eventual HBsAg loss was significantly faster than that in patients without HBsAg loss （P=0.005）.Conclusions Serum HBsAg levels in Chinese CHB patients receiving long-term ADV demonstrated a gradual reduction.Patients with eventual HBsAg loss had a significantly faster HBsAg reduction rate during the first year than those without HBsAg loss.展开更多
Objective To explore clinical efficacy of Yiguanjian Decoction(YD)combined Adefovir Dipivoxil Tablet(ADT)in treating HBe Ag negative chronic viral hepatitis B(CVHB)active compensated liver cirrhosis(LC)patients.Method...Objective To explore clinical efficacy of Yiguanjian Decoction(YD)combined Adefovir Dipivoxil Tablet(ADT)in treating HBe Ag negative chronic viral hepatitis B(CVHB)active compensated liver cirrhosis(LC)patients.Methods Totally 68 HBe Ag negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group展开更多
文摘Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.
基金Supported by the National Key Program for Infectious Diseases of China to Yang YD,2013ZX1000200112th Five-Year Significant New Drugs Creation Plan of the Ministry of Science and Technology of China toYangYD,2011ZX09302-003-03
文摘AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.
基金Supported by National Key Program for Infectious Diseases of China(to Yang YD),No.2013ZX1000200112th FiveYear Significant New Drugs Creation Plan of the Ministry of Science and Technology of China(to Yang YD),No.2011ZX09302-003-03
文摘AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.
文摘We report the case of a patient treated with living donor-related liver transplantation who suffered from osteomalacia during adefovir dipivoxil (ADV)-containing antiviral therapy for lamivudine-resistant hepatitis B virus infection. The patient had generalized bone pain,with severe hypophosphatemia after 20 mo of ADV therapy. Radiographic studies demonstrated the presence of osteomalacia. The peak plasma ADV level was 38 ng/mL after administration of ADV at 10mg/day. It was also found that ADV affected the metabolism of tacrolimus,a calcineurin-inhibitor,and caused an increase in the plasma levels of tacrolimus. The disability was reversed with the withdrawal of ADV and with mineral supplementation. ADV can cause an elevation of plasma tacrolimus levels,which may be associated with renal dysfunction. High levels of ADV and tacrolimus can cause nephrotoxicity and osteomalacia. This case highlights the importance of considering a diagnosis of osteomalacia in liver transplantation recipients treated with both ADV and tacrolimus.
文摘We describe a 77-year-old woman with chronic hepatitis B who became resistant to lamivudine.She was started on adefovir(10 mg daily)while still continuing lamivudine therapy.Four mo later her liver function improved and serum Hepatitis B virus(HBV)-DNA level became undetectable.Three years after the start of additional adefovir treatment,hepatocellular carcinoma (HCC)was detected and the patient underwent a successful hepa-tectomy.Our findings suggest tha-t the addition of adefovir to ongoing lamivudine therapy cannot completely suppress hepatocarcinogenesis,but is useful for improving liver function in patients with lamivudine-resistant HBV-related cirrhosis,allowing HCC surgery.
基金Supported by BaoenWang Liver Fibrosis Research Fund of the Chinese Foundation for Hepatitis Prevention and Control,No.20100009Zhejiang Medicine and Health Sciences Research Fund,No.2008B167 and No.2014PYA018+3 种基金Nanjing Military Area Command of the PLA Medical Technology Innovation,No.11MA019Ningbo Health Technology Project for Excellent Young and Middle-aged Talent,No.2011-145Ningbo Leader and Top Notch Person Training Project,No.2012-131Zhejiang Medicine and Health Project for Excellent Young Talent,No.2013-245
文摘AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.
文摘Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.
基金supported by the Education Department of Shandong Province,China,No.J11LF21
文摘Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Results Several findings were demonstrated with the increase of serum HBV DNA： 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly（P〈0.05）, while the plasma level of albumin decreased significantly（P〈0.05）; The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group（P〈0.01）. Conclusion With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.
基金Grants from Catholic Medical Center,The MedicalCollege of the Catholic University of Korea
文摘AIM： To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS： Eighty patients who had received lamivudine treatment for various periods and had a lamivudineo resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for ≥ 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus （HBV） DNA at 0, 12 and 48 wk and serum alanine aminotransferase （ALT） levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS： We found serum ALT became normalized in 72 （87.5%） of the 80 patients, and HBV DNA decreased by ≥ 2 Ioglo copies/mL in 60 （75%） of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION： These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.
基金Supported by Glorious Funds from Chinese foundation for hepatitis prevention and control,No.GHF2010205
文摘AIM:To investigate the appropriate time for combination therapy in HBeAg positive chronic hepatitis B(CHB) patients with decompensated cirrhosis.METHODS:Thirty HBeAg positive CHB patients with decompensated cirrhosis were enrolled in the study.All of the patients were given 48 wk combination therapy with lamivudine(LAM) and adefovir dipivoxil(ADV) .Briefly,10 patients were given the de novo combination therapy with LAM and ADV,whereas the other 20 patients received ADV in addition to LAM after hepatitis B virus(HBV) genetic mutation.RESULTS:Serum alanine aminotransferase and total bilirubin were both improved in the two groups at 4,12,24 and 48 wk after treatment.Serum albumin was also improved at 24 and 48 wk after combination therapy in both groups.The serum HBV DNA level wasstill detectable in every patient in the two groups at 4 and 12 wk after combination treatment.However,in the de novo combination group,serum HBV DNA levels in 4(40%) and 9(90%) patients was decreased to below 1×10 3 copies/mL at 24 and 48 wk after the combination treatment,respectively.In parallel,serum HBV DNA levels in 2(20%) and 8(40%) patients in the add-on combination group became undetectable at 24 and 48 wk after combination treatment,respectively.Furthermore,6(60%) patients in the de novo combination group achieved HBeAg seroconversion after 48 wk treatment,whereas only 4(20%) patients in the add-on combination group achieved seroconversion.Child-Pugh score of patients in the de novo combination group was better than that of patients in the add-on combination group after 48 wk treatment.Moreover,patients in the de novo combination group had a significantly decreased serum creatinine level and elevated red blood cell counts.CONCLUSION:De novo combination therapy with LAM and ADV was better than add-on combination therapy in terms of Child-Pugh score,virus inhibition and renal function.
文摘BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration. METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months. RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive. CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.
文摘Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced.
文摘Objective:To explore the effect of adefovir dipivoxil in combined with lamivudine on the liver function in patients with hepatitis B cirrhosis and the antiviral efficacy.Methods:A total of 156 patients with hepatitis B cirrhosis who were admitted in our hospital were included in the study and randomized into the treatment group and the control group with 78 cases in each group. The patients in the treatment group were given adefovir dipivoxil in combined with lamivudine, while the patients in the control group were given entecavir. After 12-month treatment, the efficacy was evaluated. The liver function, serum virology indicators, and AFP before and after treatment in the two groups were compared. The adverse reactions during the treatment process were recorded.Results: The serum GTP, ALT, AST, and TBIL levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05);moreover, ALT and TBIL levels in the treatment group were significantly lower than those in the control group (P<0.05). HBeAg, HBV-DNA, and AFP levels after treatment in the two groups were significantly reduced when compared with before treatment (P<0.05), HBeAg and AFP levels in the treatment group were significantly lower than those in the control group (P<0.05), and the comparison of HBV-DNA between the two groups was not statistically significant (P>0.05). ALT normalization rate and HBeAg negative conversion rate after treatment in the treatment group were significantly higher than those in the control group (P<0.05). The comparison of HBV-DNA negative conversion rate and HBeAg conversion rate between the two groups was not statistically significant (P>0.05). No obvious drug adverse reactions and liver function damage occurred during the treatment process in the two groups. Conclusions:Adefovir dipivoxil in combined with lamivudine can significantly improve the liver function and serum virology indicators in patients with hepatitis B cirrhosis, with antiviral efficacy significantly superior to that by entecavir.
基金Supported by the China National Science and Technology Major Projects,11th 5-year Project(No.2008ZX10005-006)。
文摘Objective:To evaluate the effects of a 48-week course of adefovir dipivoxil(ADV)plus Chinese medicine(CM)therapy,namely Tiaogan Jianpi Hexue(调肝健脾和血)and Tiaogan Jiedu Huashi(调肝解毒化湿)fomulae,in hepatitis B e antigen(HBeAg)-positive Chinese patients.Methods:A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group(EG,received ADV plus CM)and control group(CG,received ADV plus CM-placebo)for 48 weeks.The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12,24,36,48,respectively.Secondary endpoints including liver functions(enzymes and bilirubin readings)were evaluated every 4 weeks at the beginning of week 24,36,and 48.Routine blood,urine,and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations.Adverse events(AEs)were documented.Results:The combination therapy demonstrated superior HBeAg loss at 48 weeks,without additional AEs.The full analysis population was 560 and 280 in each group.In the EG,population achieved HBeAg loss on week 12,24,36,and 48 were 25(8.90%),34(12.14%),52(18.57%),and 83(29.64%),respectively;the equivalent numbers in the CG were 20(7.14%),41(14.64%),54(19.29%),and 50(17.86%),respectively.There was a statistically significant difference between two groups on week 48(P<0.01).No additional AEs were found in EG.Subgroup analysis suggested different outcomes among treatment patterns.Conclusion:Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy.The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile(ChiCTR-TRC-11001263).
文摘Background Knowledge on Hepatitis B surface antigen （HBsAg） kinetics in chronic hepatitis B （CHB） patients with longterm adefovir dipivoxil （ADV） treatment is limited.The aims of this study were to investigate HBsAg kinetics in patients with chronic hepatitis B virus （HBV） infection treated with long-term ADV and to evaluate different characteristics between patients with and without HBsAg loss.Methods We retrospectively evaluated HBsAg kinetics in 24 Chinese patients with chronic HBV infection who achieved continuous virologic suppression during ADV therapy.HBV genotype was determined at baseline.Liver biochemistry,hepatitis B e antigen status,serum HBV DNA,and HBsAg levels were measured at baseline,6 months,and once every year thereafter.Results Of these 24 patients,3,1,and 20 patients were followed up for 3,5,and 6 years,respectively.Baseline serum HBsAg level had a moderate correlation with baseline HBV DNA level （r=0.52,P=0.01）.The median rate of HBsAg reduction during the therapy period was 0.08 Ig IU·ml-1·y-1.Baseline serum HBsAg level was significantly higher than other time points （P ranges from 0.046 to 0.002）.The HBsAg reduction rate during the first year was similar to that in other years （P〉0.05）.The HBsAg reduction rate during the first year in patients with eventual HBsAg loss was significantly faster than that in patients without HBsAg loss （P=0.005）.Conclusions Serum HBsAg levels in Chinese CHB patients receiving long-term ADV demonstrated a gradual reduction.Patients with eventual HBsAg loss had a significantly faster HBsAg reduction rate during the first year than those without HBsAg loss.
文摘Objective To explore clinical efficacy of Yiguanjian Decoction(YD)combined Adefovir Dipivoxil Tablet(ADT)in treating HBe Ag negative chronic viral hepatitis B(CVHB)active compensated liver cirrhosis(LC)patients.Methods Totally 68 HBe Ag negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group
