BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in many medical centers. Before the use of effective measures...BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in many medical centers. Before the use of effective measures, hepatitis B recurrence and the existence of HBsAg(+) donors, patients with hepatitis B-related diseases are contraindicated for liver transplantation. Application of interferon, hepatitis B immunoglobulin (HBIG), and nucleotide analogues (e.g., lamivudine) has made great progress in the clinical care of HBV. However, there are still many shortcomings such as low viral suppression rate, rising expense, and the induction of HBV tyrosine-methionine-aspartate-aspartate (YMDD) mutation. This article systematically reviews the current evidence that immunotherapy, conventional drug combinations, and some special fields of HBV infection correlate with liver transplantation. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords 'hepatitis B virus', 'hepatitis B vaccination', 'lamivudine', 'adefovir', 'entecavir', 'tenofovir', 'HBV genotype', and 'liver transplantation' up to October 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Hepatitis B vaccine and human monoclonal antibody have very good clinical prospects. Compared with traditional therapies, the new medical regimens have many benefits such as boosting viral suppression rate and decreasing medical expenses. The triple therapy for YMDD mutation also has an excellent therapeutic effect and a low barrier to resistance. New nucleos(t)ide analogues (entecavir and tenofovir) eliminate virus more effectively with few adverse reactions, and may replace lamivudine or HBIG in future. CONCLUSIONS: Hepatitis B vaccine needs further large-scale and rigorous randomized controlled trials to confirm its effective dose and injection frequency. Monoclonal antibody is still experimental, and the next step is to carry out the relevant animal and human studies. A consensus standard regimen for the treatment of hepatitis B should be developed.展开更多
The progress in treatment against hepatitis B virus(HBV)with the development of effective and well tolerated nucleotide analogues(NAs)has improved the outcome of patients with HBV decompensated cirrhosis and has preve...The progress in treatment against hepatitis B virus(HBV)with the development of effective and well tolerated nucleotide analogues(NAs)has improved the outcome of patients with HBV decompensated cirrhosis and has prevented post-transplant HBV recurrence.This review summarizes updated issues related to the management of patients with HBV infection before and after liver transplantation(LT).A literature search using the PubMed/Medline databases and consensus documents was performed.Pre-transplant therapy has been initially based on lamivudine,but entecavir and tenofovir represent the currently recommended first-line NAs for the treatment of patients with HBV decompensated cirrhosis.After LT,the combination of HBV immunoglobulin(HBIG)and NA is considered as the standard of care for prophylaxis against HBV recurrence.The combination of HBIG and lamivudine is related to higher rates of HBV recurrence,compared to the HBIG and entecavir or tenofovir combination.In HBIG-free prophylactic regimens,entecavir and tenofovir should be the first-line options.The choice of treatment for HBV recurrence depends on prior prophylactic therapy,but entecavir and tenofovir seem to be the most attractive options.Finally,liver grafts from hepatitis B core antibody(anti-HBc)positive donors can be safely used in hepatitis B surface antigen negative,preferentially anti-HBc/anti-hepatitis B surface antibody positive recipients.展开更多
BACKGROUND: Hepatitis B virus reinfection is an impor-tant problem after liver transplantation. The aim of thisstudy was to discuss the prevention of hepatitis B virus rein-fection following orthotopic liver transplan...BACKGROUND: Hepatitis B virus reinfection is an impor-tant problem after liver transplantation. The aim of thisstudy was to discuss the prevention of hepatitis B virus rein-fection following orthotopic liver transplantation.METHODS: Sixty-eight cases of chronic fulminant hepatitisB, end-stage liver cirrhosis, and liver carcinoma complicat-ed with HBV cirrhosis were given anti-viral drugs beforeand after transplantation to prevent hepatitis B virus rein-fection. Lamivudine was administered in 2 patients, lami-vudine + hepatitis B immunoglobulin ( HBIG ) in 63, andadefovir + HBIG in 3. The measurement of serum HBV,HBV DNA, liver biopsy immunohistochemistry and clini-cal study were performed.RESULTS: In 1 of the 2 patients who developed reinfectionafter lamivudine administration, serum HBsAg, HBeAb,HBcAb, HBV DNA were positive and liver biopsy immu-nohistochemistry showed HBsAg phenotype. In 2 of 63 pa-tients who developed reinfection after use of lamivudine +HBIG, serum HBsAg, HBeAb, HBcAb were positive andliver biopsy immunohistochemistry showed HBsAg pheno-type. Serum HBV DNA was positive in one of them.Three patients developed no reinfection with HBV after useof adefovir.CONCLUSIONS: Orthotopic liver transplantation is effectivein the treatment of HBV-infected diseases. Lamivudine +HBIG or adefovir + HBIG could effectively prevent hepatitisB virus reinfection.展开更多
Hepatitis B virus(HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people wil...Hepatitis B virus(HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin(HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV(entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of "hepatitis B virus AND liver transplantation". We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.展开更多
BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was und...BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was undertaken to evaluate the effect of combined therapy on patients with hepatitis B recurrence after liver transplantation. METHODS: Twenty-two patients with hepatitis B recurrence after liver transplantation from August 2000 to October 2011 were enrolled in this study. Of these patients, 16 received lamivudine plus HBIG (combination therapy group) and 6 were treated with lamivudine alone (lamivudine-treated group) The clinical features were matched in the two groups. HBV recurrence parameters, HBsAg clearance rate, patient survival rate, and survival time were compared. RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant difference was noted in the HBsAg clearance rate in the lamivudine-treated and combination therapy groups (50% vs 93.8%, P【0.05). There was no significant difference in the time of HBV recurrence, patient survival rate and survival time between lamivudine-treated and combination therapy groups (P】0.05). CONCLUSION: Compared with lamivudine monotherapy combination therapy significantly increased the HBsAg clearance rate in patients with HBV recurrence after liver transplantation.展开更多
目的观察联合应用拉米呋定和小剂量乙肝免疫球蛋白预防肝移植术后乙肝复发的临床疗效。方法回顾性分析35例乙肝病毒(hepatitis B virus,HBV)相关终末期肝病患者行肝移植术后联合应用拉咪夫定和小剂量乙肝免疫球蛋白的临床资料,观察此方...目的观察联合应用拉米呋定和小剂量乙肝免疫球蛋白预防肝移植术后乙肝复发的临床疗效。方法回顾性分析35例乙肝病毒(hepatitis B virus,HBV)相关终末期肝病患者行肝移植术后联合应用拉咪夫定和小剂量乙肝免疫球蛋白的临床资料,观察此方案对预防肝移植术后乙肝病毒再感染的疗效。结果4例肝移植术后发生乙肝复发,复发率11%,其余31例病毒标志物均为阴性。结论联合应用拉米呋定和小剂量乙肝免疫球蛋白可以有效地预防乙肝病毒相关终末期肝病肝移植术后乙肝复发,小样本短期随访效果满意,有待于进一步大样本长期观察。展开更多
目的评价拉米夫定(lamivudine,LAM)联合乙型肝炎免疫球蛋白(hepatitis B immunoglobulin,HBIG)预防肝移植后乙肝病毒复发的价值。方法计算机检索MEDLINE(Ovid)、PubMed、EMbase、CENTRAL(Cochrane Central Register of Controlled Tria...目的评价拉米夫定(lamivudine,LAM)联合乙型肝炎免疫球蛋白(hepatitis B immunoglobulin,HBIG)预防肝移植后乙肝病毒复发的价值。方法计算机检索MEDLINE(Ovid)、PubMed、EMbase、CENTRAL(Cochrane Central Register of Controlled Trials)、CBM、CNKI、VIP关于LAM联合HBIG与LAM单用预防肝移植后乙肝病毒复发的随机双盲对照、非随机同期对照及病例对照研究。检索时间截至2008年12月。两名研究者独立按Cochrane系统评价方法选择试验、提取资料,并采用RevMan 5.0.18软件进行Meta分析。结果共纳入11项研究,均为非随机同期对照试验,共1 421例患者,其中LAM联合HBIG组1 035例,LAM单用组386例。结果显示,LAM联合HBIG治疗组较单用LAM治疗组:①减少乙肝病毒复发风险达73%[RR=0.27,95%CI(0.20,0.37),P<0.000 01];②减少乙肝病毒YMDD变异风险达72%[RR=0.28,95%CI(0.15,0.53),P=0.000 01];③减少乙肝病毒复发所致的死亡风险达79%[RR=0.21,95%CI(0.09,0.49),P=0.000 3];④受者和移植物总的生存率两组相似[RR=1.03,95%CI(0.95,1.11),P=0.51;RR=1.04,95%CI(0.97,1.12),P=0.26]。结论现有研究显示LAM联合HBIG治疗比LAM单用可明显减少肝移植后乙肝病毒复发、发生YMDD变异及乙肝病毒复发所致的死亡风险。LAM联合HBIG是预防肝移植后乙肝病毒复发的有效措施。展开更多
基金supported by grants from the Key Program of National Natural Science Foundation of China(30730085)the National High Technology Research and Development Program of China (863 Program2006AA 02A412)
文摘BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in many medical centers. Before the use of effective measures, hepatitis B recurrence and the existence of HBsAg(+) donors, patients with hepatitis B-related diseases are contraindicated for liver transplantation. Application of interferon, hepatitis B immunoglobulin (HBIG), and nucleotide analogues (e.g., lamivudine) has made great progress in the clinical care of HBV. However, there are still many shortcomings such as low viral suppression rate, rising expense, and the induction of HBV tyrosine-methionine-aspartate-aspartate (YMDD) mutation. This article systematically reviews the current evidence that immunotherapy, conventional drug combinations, and some special fields of HBV infection correlate with liver transplantation. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords 'hepatitis B virus', 'hepatitis B vaccination', 'lamivudine', 'adefovir', 'entecavir', 'tenofovir', 'HBV genotype', and 'liver transplantation' up to October 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Hepatitis B vaccine and human monoclonal antibody have very good clinical prospects. Compared with traditional therapies, the new medical regimens have many benefits such as boosting viral suppression rate and decreasing medical expenses. The triple therapy for YMDD mutation also has an excellent therapeutic effect and a low barrier to resistance. New nucleos(t)ide analogues (entecavir and tenofovir) eliminate virus more effectively with few adverse reactions, and may replace lamivudine or HBIG in future. CONCLUSIONS: Hepatitis B vaccine needs further large-scale and rigorous randomized controlled trials to confirm its effective dose and injection frequency. Monoclonal antibody is still experimental, and the next step is to carry out the relevant animal and human studies. A consensus standard regimen for the treatment of hepatitis B should be developed.
文摘The progress in treatment against hepatitis B virus(HBV)with the development of effective and well tolerated nucleotide analogues(NAs)has improved the outcome of patients with HBV decompensated cirrhosis and has prevented post-transplant HBV recurrence.This review summarizes updated issues related to the management of patients with HBV infection before and after liver transplantation(LT).A literature search using the PubMed/Medline databases and consensus documents was performed.Pre-transplant therapy has been initially based on lamivudine,but entecavir and tenofovir represent the currently recommended first-line NAs for the treatment of patients with HBV decompensated cirrhosis.After LT,the combination of HBV immunoglobulin(HBIG)and NA is considered as the standard of care for prophylaxis against HBV recurrence.The combination of HBIG and lamivudine is related to higher rates of HBV recurrence,compared to the HBIG and entecavir or tenofovir combination.In HBIG-free prophylactic regimens,entecavir and tenofovir should be the first-line options.The choice of treatment for HBV recurrence depends on prior prophylactic therapy,but entecavir and tenofovir seem to be the most attractive options.Finally,liver grafts from hepatitis B core antibody(anti-HBc)positive donors can be safely used in hepatitis B surface antigen negative,preferentially anti-HBc/anti-hepatitis B surface antibody positive recipients.
文摘BACKGROUND: Hepatitis B virus reinfection is an impor-tant problem after liver transplantation. The aim of thisstudy was to discuss the prevention of hepatitis B virus rein-fection following orthotopic liver transplantation.METHODS: Sixty-eight cases of chronic fulminant hepatitisB, end-stage liver cirrhosis, and liver carcinoma complicat-ed with HBV cirrhosis were given anti-viral drugs beforeand after transplantation to prevent hepatitis B virus rein-fection. Lamivudine was administered in 2 patients, lami-vudine + hepatitis B immunoglobulin ( HBIG ) in 63, andadefovir + HBIG in 3. The measurement of serum HBV,HBV DNA, liver biopsy immunohistochemistry and clini-cal study were performed.RESULTS: In 1 of the 2 patients who developed reinfectionafter lamivudine administration, serum HBsAg, HBeAb,HBcAb, HBV DNA were positive and liver biopsy immu-nohistochemistry showed HBsAg phenotype. In 2 of 63 pa-tients who developed reinfection after use of lamivudine +HBIG, serum HBsAg, HBeAb, HBcAb were positive andliver biopsy immunohistochemistry showed HBsAg pheno-type. Serum HBV DNA was positive in one of them.Three patients developed no reinfection with HBV after useof adefovir.CONCLUSIONS: Orthotopic liver transplantation is effectivein the treatment of HBV-infected diseases. Lamivudine +HBIG or adefovir + HBIG could effectively prevent hepatitisB virus reinfection.
基金Supported by A grant(No.R15 HL 117199)contract No.U01 DK 065201 from the United States National Institutes of Health(to Bonkovsky HL)+1 种基金institutional funds from Carolinas HealthCare System(to Sendi H)Beth Israel Deaconess Medi-cal Center(to Ghaziani T)
文摘Hepatitis B virus(HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin(HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV(entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of "hepatitis B virus AND liver transplantation". We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.
基金supported by a grant from the National Natural Science Foundation of China (30872556)
文摘BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was undertaken to evaluate the effect of combined therapy on patients with hepatitis B recurrence after liver transplantation. METHODS: Twenty-two patients with hepatitis B recurrence after liver transplantation from August 2000 to October 2011 were enrolled in this study. Of these patients, 16 received lamivudine plus HBIG (combination therapy group) and 6 were treated with lamivudine alone (lamivudine-treated group) The clinical features were matched in the two groups. HBV recurrence parameters, HBsAg clearance rate, patient survival rate, and survival time were compared. RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant difference was noted in the HBsAg clearance rate in the lamivudine-treated and combination therapy groups (50% vs 93.8%, P【0.05). There was no significant difference in the time of HBV recurrence, patient survival rate and survival time between lamivudine-treated and combination therapy groups (P】0.05). CONCLUSION: Compared with lamivudine monotherapy combination therapy significantly increased the HBsAg clearance rate in patients with HBV recurrence after liver transplantation.
文摘目的观察联合应用拉米呋定和小剂量乙肝免疫球蛋白预防肝移植术后乙肝复发的临床疗效。方法回顾性分析35例乙肝病毒(hepatitis B virus,HBV)相关终末期肝病患者行肝移植术后联合应用拉咪夫定和小剂量乙肝免疫球蛋白的临床资料,观察此方案对预防肝移植术后乙肝病毒再感染的疗效。结果4例肝移植术后发生乙肝复发,复发率11%,其余31例病毒标志物均为阴性。结论联合应用拉米呋定和小剂量乙肝免疫球蛋白可以有效地预防乙肝病毒相关终末期肝病肝移植术后乙肝复发,小样本短期随访效果满意,有待于进一步大样本长期观察。
文摘目的评价拉米夫定(lamivudine,LAM)联合乙型肝炎免疫球蛋白(hepatitis B immunoglobulin,HBIG)预防肝移植后乙肝病毒复发的价值。方法计算机检索MEDLINE(Ovid)、PubMed、EMbase、CENTRAL(Cochrane Central Register of Controlled Trials)、CBM、CNKI、VIP关于LAM联合HBIG与LAM单用预防肝移植后乙肝病毒复发的随机双盲对照、非随机同期对照及病例对照研究。检索时间截至2008年12月。两名研究者独立按Cochrane系统评价方法选择试验、提取资料,并采用RevMan 5.0.18软件进行Meta分析。结果共纳入11项研究,均为非随机同期对照试验,共1 421例患者,其中LAM联合HBIG组1 035例,LAM单用组386例。结果显示,LAM联合HBIG治疗组较单用LAM治疗组:①减少乙肝病毒复发风险达73%[RR=0.27,95%CI(0.20,0.37),P<0.000 01];②减少乙肝病毒YMDD变异风险达72%[RR=0.28,95%CI(0.15,0.53),P=0.000 01];③减少乙肝病毒复发所致的死亡风险达79%[RR=0.21,95%CI(0.09,0.49),P=0.000 3];④受者和移植物总的生存率两组相似[RR=1.03,95%CI(0.95,1.11),P=0.51;RR=1.04,95%CI(0.97,1.12),P=0.26]。结论现有研究显示LAM联合HBIG治疗比LAM单用可明显减少肝移植后乙肝病毒复发、发生YMDD变异及乙肝病毒复发所致的死亡风险。LAM联合HBIG是预防肝移植后乙肝病毒复发的有效措施。