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
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
BACKGROUND: Patients with decompensated hepatitis B vires (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective ...BACKGROUND: Patients with decompensated hepatitis B vires (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective suppression of HBV replication with antiviral agents may potentially decrease hepatic necroinflammation and improve or stabilize liver function. This review was to under stand the efficacy and safety of lamivudine in the treatment of decompensated HBV cirrhosis. DATA SOURCES: An English-language literature search (MEDLINE January 1988-July 2005) was performed, and a total of 52 articles/abstracts relevant to the issue were selected. After review of the selected papers, the meaningful results and conclusions were extracted using scientific crite ria. The papers reviewed pertained mainly to the efficacy and safety profiles of lamivudine treatment for decompensated HBV cirrhosis. RESULTS: The ultimate treatment of decompensated HBV cirrhosis is liver transplantation, but lamivudine treatment may lead to rapid suppression of viral replication and improvement of biochemical and clinical parameters, reduced morbidity and hospitalization for complications of liver disease, increased pre-transplant survival as well as reduced need for transplantation. However, viral resistance can develop after prolonged treatment with lamivudine, and breakthrough hepatitis may be fatal in few patients. Adefovir is effective for lamivudine-resistant HBV mutants. CONCLUSIONS: Antiviral therapy with lamivudine for decompensated HBV cirrhosis can be effective. However, some patients may experience a hepatitis flare with the emergence of YMDD mutants resulting in progressive worsening of liver disease, and should be referred for 'rescue' therapy with other nucleoside/nucleotide analogues such as adefovir dipivoxil.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
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
AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into thre...AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.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
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.
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.
文摘BACKGROUND: Patients with decompensated hepatitis B vires (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective suppression of HBV replication with antiviral agents may potentially decrease hepatic necroinflammation and improve or stabilize liver function. This review was to under stand the efficacy and safety of lamivudine in the treatment of decompensated HBV cirrhosis. DATA SOURCES: An English-language literature search (MEDLINE January 1988-July 2005) was performed, and a total of 52 articles/abstracts relevant to the issue were selected. After review of the selected papers, the meaningful results and conclusions were extracted using scientific crite ria. The papers reviewed pertained mainly to the efficacy and safety profiles of lamivudine treatment for decompensated HBV cirrhosis. RESULTS: The ultimate treatment of decompensated HBV cirrhosis is liver transplantation, but lamivudine treatment may lead to rapid suppression of viral replication and improvement of biochemical and clinical parameters, reduced morbidity and hospitalization for complications of liver disease, increased pre-transplant survival as well as reduced need for transplantation. However, viral resistance can develop after prolonged treatment with lamivudine, and breakthrough hepatitis may be fatal in few patients. Adefovir is effective for lamivudine-resistant HBV mutants. CONCLUSIONS: Antiviral therapy with lamivudine for decompensated HBV cirrhosis can be effective. However, some patients may experience a hepatitis flare with the emergence of YMDD mutants resulting in progressive worsening of liver disease, and should be referred for 'rescue' therapy with other nucleoside/nucleotide analogues such as adefovir dipivoxil.
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.
基金Supported by Grants from Key Medical Specialties Fund of Shanghai Municipal Health Bureau(partially),No.05II 011 2-1Glaxo Smith Kline(China)Investment Co,Ltd,Project 110353
文摘AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.
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