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Huang Y, Liu N, Ning Q, Zhou M, Zang N, Liang T, Wei W. Design, synthesis, and biological evaluation of novel (E)-1-arylethan-1-one O-((3-arylisoxazol-5-yl) methyl) oxime derivatives as potent non-nucleoside HBV inhibitors. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.132789] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
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Fabrizi F, Bunnapradist S, Lunghi G, Villa M, Martin P. Transplanting Solid Organs from HBsAg Negative Donors Positive for Antibody to Hepatitis B Core Antigen: The Implications. Int J Artif Organs 2018; 26:972-83. [PMID: 14708825 DOI: 10.1177/039139880302601102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- F Fabrizi
- Division of Nephrology, Dialysis and Transplantation, Institute of Hygiene and Preventive Medicine, Policlinico IRCCS, Milan, Italy.
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Fung J, Wong T, Chok K, Chan A, Cheung TT, Dai JWC, Sin SL, Ma KW, Ng K, Ng KTP, Seto WK, Lai CL, Yuen MF, Lo CM. Long-term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years. Hepatology 2017; 66:1036-1044. [PMID: 28370215 DOI: 10.1002/hep.29191] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2017] [Revised: 02/28/2017] [Accepted: 03/21/2017] [Indexed: 12/17/2022]
Abstract
UNLABELLED Long-term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long-term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. The median duration of follow-up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg-positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P = 0.52). The overall 9-year survival was 85%. There were 37 deaths during the follow-up period, of which none were due to hepatitis B recurrence. CONCLUSION Long-term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long-term survival of 85% at 9 years. (Hepatology 2017;66:1036-1044).
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Affiliation(s)
- James Fung
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Gastroenterology and Hepatology, Department of Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
| | - Tiffany Wong
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Kenneth Chok
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Albert Chan
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Tan-To Cheung
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Jeff Wing-Chiu Dai
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Sui-Ling Sin
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Ka-Wing Ma
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Kelvin Ng
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Kevin Tak-Pan Ng
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Division of Gastroenterology and Hepatology, Department of Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
| | - Ching-Lung Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
| | - Man-Fung Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, The University of Hong Kong, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
| | - Chung-Mau Lo
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.,Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong
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Yu Y, Ai J, Zhang W. Current clinical evidence for nucleos(t)ide analogues in patients with HBV-related hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2017; 11:925-937. [PMID: 28661190 DOI: 10.1080/17474124.2017.1343665] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of death globally and is frequently seen following Hepatitis B virus (HBV) or Hepatitis C virus infection. Areas with high HBV infection rates, such as Asia and sub-Saharan Africa, are therefore also high-risk areas for HCC. Areas covered: This review identifies and discusses the current evidence from robust clinical trials which have investigated the benefits of Nucleos(t)ide analogue (NA) antiviral therapy in HBV-related HCC patients, including HCC patients that underwent liver transplantation and HCC patients with or without curative treatment. In addition, we assess how this evidence has influenced current clinical practice, with a particular focus on those areas of high HBV infection rates. Expert commentary: A number of studies have assessed whether NA antiviral treatment can improve the prognosis of HBV-related HCC patients. In this review we evaluate the current evidence, including that from trials in Asia, for antiviral NA treatments in HBV-related HCC patients. We also focus on those NAs with a high genetic barrier to resistance (i.e. ETV or TDF), on different therapeutic approaches, and on the future evidence that is required in this field.
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Affiliation(s)
- Yiqi Yu
- a Department of Infectious Diseases , Huashan Hospital, Fudan University , Shanghai , China
| | - Jingwen Ai
- a Department of Infectious Diseases , Huashan Hospital, Fudan University , Shanghai , China
| | - Wenhong Zhang
- a Department of Infectious Diseases , Huashan Hospital, Fudan University , Shanghai , China
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Zheng JN, Zou TT, Zou H, Zhu GQ, Ruan LY, Cheng Z, Van Poucke S, Zheng MH. Comparative efficacy of oral nucleotide analogues for the prophylaxis of hepatitis B virus recurrence after liver transplantation: a network meta-analysis. Expert Rev Anti Infect Ther 2016; 14:979-87. [PMID: 27491868 DOI: 10.1080/14787210.2016.1220831] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Prophylactic nucleos(t)ide anologues against hepatitis B virus (HBV) recurrence after liver transplantation (LT) include lamivudine, entecavir, tenofovir, adefovir. Since the most effective strategies for post-LT remain inconclusive, we aimed to compare 6 different treatment options (lamivudine, entecavir, tenofovir, adefovir, lamivudine plus adefovir, lamivudine plus tenofovir) in terms of HBV recurrence after LT using network meta-analysis. METHODS The search identified seventeen studies involving 6 different prophylactic regimens covering 7274 patients. RESULTS Compared with entecavir, lamivudine plus tenofovir (OR 2.00, 95%CI 0.02-183.29), lamivudine plus adefovir, (OR 2.83, 95%CI 0.18-33.57), tenofovir (OR 1.11, 95%CI 0.22-5.80), adefovir (OR 3.78, 95%CI 0.59-22.16), lamivudine (OR 4.62, 95%CI 1.75-11.39) were associated with an increased risk of HBV recurrence. CONCLUSION Entecavir resulted with the highest probability (31%) as the best prophylactic option on reducing the risk of HBV recurrence. Entecavir is the preferred oral NAs treatment compared to other five different prophylactic regimens in the prevention of HBV recurrence after LT.
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Affiliation(s)
- Ji-Na Zheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Tian-Tian Zou
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,c School of the Second Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Hai Zou
- d Department of Infection Diseases , Zhejiang Provincial People's Hospital , Hangzhou , China
| | - Gui-Qi Zhu
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Lu-Yi Ruan
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Zhang Cheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,b School of the First Clinical Medical Sciences , Wenzhou Medical University , Wenzhou , China
| | - Sven Van Poucke
- e Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy , Ziekenhuis Oost-Limburg , Genk , Belgium
| | - Ming-Hua Zheng
- a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.,f Institute of Hepatology , Wenzhou Medical University , Wenzhou , China
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Malik MU, Ucbilek E, Trilianos P, Cameron AM, Gurakar A. Prophylaxis Among Hepatitis B Core Antibody-positive Deceased-donor Liver Transplant Recipients: Hepatitis B Immunoglobulin Plus Oral Antiviral Agents Versus Antiviral Agents Alone: A Single-center Experience. EXP CLIN TRANSPLANT 2016; 15:183-188. [PMID: 27212251 DOI: 10.6002/ect.2015.0277] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Hepatitis B core antibody immunoglobulin G seropositivity is evidence of past exposure to hepatitis B virus. Donor or recipient hepatitis B core antibody positivity may pose a risk of reactivation, especially early after liver transplant. Although most centers advocate using antiviral agents plus hepatitis B immunoglobulin, some have recently relied on antivirals only as prophylaxis after liver transplant. Here, we retrospectively investigated patient survival in hepatitis B core antibody-positive recipients, comparing those treated with antivirals plus hepatitis B immunoglobulin versus antivirals alone. MATERIALS AND METHODS After Internal Review Board approval, we reviewed medical records of deceased-donor liver transplant recipients between 1995 and 2013. Demographic characteristics, transplant indication, hepatitis B core antibody status, time to death, and type of posttransplant prophylaxis were recorded. We also recorded whether donors showed hepatitis B core antibody positivity. Patients who died within 30 days of liver transplant were excluded. RESULTS There were 148 hepatitis B core antibody-positive recipients. Prophylaxis was given to 75 recipients after transplant: 8 (5%) received hepatitis B immunoglobulin, 22 (15%) received antivirals, and 45 (30%) received the combination. There were 34 deaths: 3 (38%) in hepatitis B immunoglobulin only, 3 (14%) in antiviral only, 8 (18%) in the combination, and 20 (27%) in no prophylaxis groups. One- and 5-year survival rates were similar for binary comparisons among prophylaxis groups (P > .05). CONCLUSIONS Preliminary results support the current practice of using hepatitis B immunoglobulin plus antivirals for prophylaxis after liver transplant. The similar survival benefit with the combination versus antiviral agents alone suggests equal effectivity for prophylaxis posttransplant. However, a clear benefit of antivirals was not evident in our analysis. Future larger prospective studies are warranted to identify potential benefits of using antivirals alone as prophylaxis after liver transplant and to further clarify their role as the sole prophylactic regimen.
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Affiliation(s)
- Mohammad U Malik
- >From the Division of Gastroenterology and Hepatology, Transplant Hepatology, Johns Hopkins Hospital School of Medicine, Baltimore, Maryland, USA
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Rational Basis for Optimizing Short and Long-term Hepatitis B Virus Prophylaxis Post Liver Transplantation: Role of Hepatitis B Immune Globulin. Transplantation 2016; 99:1321-34. [PMID: 26038873 PMCID: PMC4539198 DOI: 10.1097/tp.0000000000000777] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates, such as entecavir or tenofovir, suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, and delay or obviate the need for liver transplantation in some patients. After liver transplantation, the combination of long-term antiviral and low-dose hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in greater than 90% of transplant recipients. Some forms of HBV prophylaxis need to be continued indefinitely after transplantation but, in patients with a low-risk of HBV recurrence (i.e., HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain only long-term nucleos(t)ide analogue(s) therapy. A more cautious approach is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e., HIV or hepatitis D virus coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those at risk of noncompliance with antiviral therapy. In this group, HBIG-free prophylaxis cannot be recommended. The combination of long-term antiviral and low-dose Hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in > 90% of liver transplant recipients. In patients with low HBV DNA levels, nucleos(t)ide analogue(s) treatment without HBIG is possible.
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Aoki J, Kimura K, Kakihana K, Ohashi K, Sakamaki H. Efficacy and tolerability of Entecavir for hepatitis B virus infection after hematopoietic stem cell transplantation. SPRINGERPLUS 2014; 3:450. [PMID: 25184113 PMCID: PMC4149683 DOI: 10.1186/2193-1801-3-450] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Accepted: 08/06/2014] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatitis B virus (HBV) flare is a serious problem following hematopoietic stem cell transplantation (HSCT), and the mortality rate is high if severe hepatitis occurs. CASE DESCRIPTION Although Entecavir (ETV) is a standard antiviral drug for HBV infection, the efficacy and safety of ETV therapy in HSCT are still unclear. DISCUSSION AND EVALUATION To examine the efficacy and tolerability of ETV treatment in HSCT, we retrospectively identified 5 patients who received ETV for treatment of HBsAg carrier among patients undergoing HSCT in our institute. We reviewed their clinical information such as clinical course of serum HBV DNA levels, administration period and dose of ETV, and adverse events. There were no episodes of HBV flare or reactivation after HSCT in all patients during the observation period, as a 10-fold rise in HBV DNA levels or positive conversion of HBsAg were not observed. CONCLUSION ETV monotherapy is effective and safe for HBsAg carrier patients following HSCT.
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Affiliation(s)
- Jun Aoki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Kiminori Kimura
- Hepatology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Kazuhiko Kakihana
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Kazuteru Ohashi
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Hisashi Sakamaki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
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Kasraianfard A, Watt KD, Lindberg L, Alexopoulos S, Rezaei N. HBIG Remains Significant in the Era of New Potent Nucleoside Analogues for Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation. Int Rev Immunol 2014; 35:312-324. [PMID: 24911598 DOI: 10.3109/08830185.2014.921160] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Gao YJ, Zhang M, Jin B, Meng FP, Ma XM, Liu ZW, Su HB, Zhao JM, Li HW. Clinical-pathological analysis of hepatitis B virus recurrence after liver transplantation in Chinese patients. J Gastroenterol Hepatol 2014; 29:554-60. [PMID: 24117714 DOI: 10.1111/jgh.12404] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Liver transplantation (LT) for hepatitis B virus (HBV)-related disease can be complicated by HBV recurrence. The aim of this study was to evaluate the risk factors, prophylaxis treatment, and histological characteristics of HBV recurrence after LT when using long-term, low-dose hepatitis B immunoglobulin (HBIG) plus nucleoside analog (lamivudine [LAM] or entecavir [ETV]). METHODS Retrospective data from 253 adult LT patients using long-term, low-dose HBIG plus nucleoside analog after LT, for a mean treatment duration of 1-72 months, were collected from a single center in Beijing, China. Univariate analyses were conducted to determine the association among gender, age, hepatocellular carcinoma, hepatitis B e antigen-positive status, HBV-DNA level and tyrosine-methionine-aspartate-aspartate (YMDD) mutations on HBV recurrence in these patients. RESULTS Overall, the HBV recurrence rate was 6.32% (16/253). There was no significant difference in the survival rate between the HBV recurrence and non-recurrence groups. Risk factors for HBV recurrence were: hepatitis B e antigen positivity, HBV-DNA > 10(5) copies/mL, hepatocellular carcinoma, and YMDD mutation. Sixteen patients receiving LAM had HBV recurrence (16/169; mean treatment duration: 61.8 ± 18.3 months). No HBV recurrence occurred in patients receiving ETV after LT (0/84; mean treatment duration: 57.1 ± 15.9 months). Differences in rate of mortality and HBV recurrence were not significant between the two groups. CONCLUSIONS LT is an effective treatment for HBV-related end-stage liver disease. The combination of ETV and intramuscular HBIG for HBV recurrence prophylaxis after LT was more effective than LAM, especially in Chinese patients with HBV recurrence risk factors.
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Affiliation(s)
- Yin-Jie Gao
- Medical School of Chinese PLA, Beijing, China; Department of Infectious Diseases, 302 Military Hospital, Beijing, China
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Cholongitas E, Papatheodoridis GV. Review of the pharmacological management of hepatitis B viral infection before and after liver transplantation. World J Gastroenterol 2013; 19:9189-9197. [PMID: 24409047 PMCID: PMC3882393 DOI: 10.3748/wjg.v19.i48.9189] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2013] [Revised: 10/29/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023] Open
Abstract
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.
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Wong TCL, Fung JYY, Lo CM. Prevention of recurrent hepatitis B infection after liver transplantation. Hepatobiliary Pancreat Dis Int 2013; 12:465-72. [PMID: 24103275 DOI: 10.1016/s1499-3872(13)60074-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recurrence of hepatitis B virus (HBV) infection after liver transplantation can lead to graft loss and a reduction in long-term survival. The purpose of this review is to summarize the current therapeutic options for preventing HBV recurrence in liver transplant recipients. DATA SOURCES Up to January 2013, studies that were published in MEDLINE and EMBASE on prevention of HBV recurrence after liver transplantation were reviewed. RESULTS There have been remarkable advancements in the past two decades on the prevention of HBV recurrence after liver transplantation, from the discovery of hepatitis B immune globulin (HBIG) and lamivudine monotherapy to the combination therapy using HBIG and lamivudine. With the development of newer and stronger antiviral agents, the need for life-long HBIG is doubtful. With their low resistance profile, oral antiviral prophylaxis using these new agents alone is sufficient and is associated with excellent outcome. CONCLUSIONS Restoration of host HBV immunity with adoptive immunity transfer and vaccination may represent the ultimate strategy to withdraw prophylactic treatment and to achieve a drug free regimen against HBV recurrence after liver transplantation.
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Affiliation(s)
- Tiffany C L Wong
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
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Villamil FG, Cairo FM. Hepatitis B virus: Prevention of recurrent infection. Clin Liver Dis (Hoboken) 2013; 2:169-172. [PMID: 30992855 PMCID: PMC6448646 DOI: 10.1002/cld.224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 04/04/2013] [Accepted: 05/27/2013] [Indexed: 02/04/2023] Open
Affiliation(s)
| | - Fernando M. Cairo
- Liver Transplantation Unit, British Hospital, Buenos Aires, Argentina
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Roche B, Samuel D. Treatment of patients with HBV-related decompensated cirrhosis and liver transplanted patients. Clin Liver Dis 2013; 17:451-73. [PMID: 23905816 DOI: 10.1016/j.cld.2013.05.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.
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Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif F-94800, France
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Fung J, Chan SC, Cheung C, Yuen MF, Chok KSH, Sharr W, Chan ACY, Cheung TT, Seto WK, Fan ST, Lai CL, Lo CM. Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B. Am J Gastroenterol 2013; 108:942-8. [PMID: 23629601 DOI: 10.1038/ajg.2013.111] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone. METHODS A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. RESULTS Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients. CONCLUSIONS Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.
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Affiliation(s)
- James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
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Perrakis A, Förtsch T, Del Medico A, Croner R, Vassos N, Yedibela S, Lohmüller C, Zopf S, Hohenberger W, Müller V. Liver Transplantation for Hepatitis B-Induced Liver Disease: Long-Term Outcome and Effectiveness of Antiviral Therapy for Prevention of Recurrent Hepatitis B Infection. Transplant Proc 2013; 45:1953-6. [DOI: 10.1016/j.transproceed.2012.11.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2012] [Accepted: 11/19/2012] [Indexed: 01/11/2023]
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Tanaka T, Benmousa A, Marquez M, Therapondos G, Renner EL, Lilly LB. The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver transplantation. Clin Transplant 2013; 26:E561-9. [PMID: 23061767 DOI: 10.1111/ctr.12022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long-term nucleos(t)ide analog in combination with one yr of low-dose HBIG. One hundred and fifty-two adults with HBV-related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long-term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow-up post-transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long-term follow-up, demonstrates that short course of low-dose HBIG (without anti-HBs monitoring) combined with the use of long-term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.
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Affiliation(s)
- Tomohiro Tanaka
- Liver Transplant Unit, Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
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20
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Abstract
UNLABELLED The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion. TARGET POPULATION The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.
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MESH Headings
- Acute Disease
- Adolescent
- Adult
- Aged
- Alanine Transaminase/blood
- Antiviral Agents/therapeutic use
- Asian People
- Aspartate Aminotransferases/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/etiology
- Child
- Child, Preschool
- Coinfection/drug therapy
- DNA, Viral/blood
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Immunosuppression Therapy
- Infectious Disease Transmission, Vertical/prevention & control
- Liver/pathology
- Liver/physiology
- Liver Cirrhosis/physiopathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/etiology
- Liver Transplantation
- Male
- Middle Aged
- Pregnancy
- Renal Dialysis
- Republic of Korea
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Samuel D, Roche B. Combined prophylaxis might still be better than monoprophylaxis with entecavir following liver transplantation for hepatitis B. Gastroenterology 2012; 142:e34; author reply e34-5. [PMID: 22115628 DOI: 10.1053/j.gastro.2011.09.052] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 09/28/2011] [Indexed: 12/02/2022]
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Fung J, Cheung C, Chan SC, Yuen MF, Chok KSH, Sharr W, Dai WC, Chan ACY, Cheung TT, Tsang S, Lam B, Lai CL, Lo CM. Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation. Gastroenterology 2011; 141:1212-9. [PMID: 21762659 DOI: 10.1053/j.gastro.2011.06.083] [Citation(s) in RCA: 153] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 06/27/2011] [Accepted: 06/30/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS We investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis B who received a liver transplant. METHODS We studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis B-related disease and entecavir monotherapy as prophylaxis. None of the patients received hepatitis B immunoglobulin. Indications for transplant included decompensation from cirrhosis (27.5%), acute-on-chronic hepatitis B (47.5%), and hepatocellular carcinoma (25%). The median follow-up time was 26 months (range, 5-40 months). Before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). RESULTS At the time of transplant, the median log HBV DNA level was 3.5 copies/mL (range, 1.54-8.81); 21 patients (26%) had undetectable levels of HBV DNA. The cumulative rate of hepatitis B surface antigen (HBsAg) loss was 86% and 91% after 1 and 2 years, respectively. Ten patients had reappearance of HBsAg. Eighteen patients (22.5%) were HBsAg positive at the time of their last examination; 17 of these had undetectable levels of HBV DNA, and the remaining patient had a low level of HBV DNA (217 copies/mL). There was no evidence of mutations at sites that confer resistance to entecavir among patients who were HBsAg positive. CONCLUSIONS Although only 26% of patients had complete viral suppression at the time of transplant, 91% lost HBsAg, with 98.8% achieving undetectable levels of HBV DNA. A hepatitis B immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis B.
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Affiliation(s)
- James Fung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
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23
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Successful switch to tenofovir after suboptimal response to entecavir in an immunocompromised patient with chronic hepatitis B and without genotypic hepatitis B virus resistance. Infection 2011; 39:367-70. [PMID: 21674358 DOI: 10.1007/s15010-011-0127-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2010] [Accepted: 05/31/2011] [Indexed: 01/07/2023]
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25
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Ishigami M, Kamei H, Nakamura T, Katano Y, Ando H, Kiuchi T, Goto H. Different effect of HBV vaccine after liver transplantation between chronic HBV carriers and non-HBV patients who received HBcAb-positive grafts. J Gastroenterol 2011; 46:367-77. [PMID: 20835733 DOI: 10.1007/s00535-010-0313-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2009] [Accepted: 08/09/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND Combination of nucleos(t)ide analogue and anti-HBs immunoglobulin (HBIg) is the standard protocol for prevention of HBV reactivation after liver transplantation, but because of the extremely high cost of HBIg, HBV vaccine is tried as a much cheaper and potentially safer substitute. Here we show the different effect of HBV vaccine between chronic HBV carrier and non-HBV patients who received grafts from HBc antibody-positive donors. METHODS Fifteen chronic HBV carriers and 6 non-HBV patients who received grafts from HBc antibody-positive donors were included in this study. These patients received double dose of pre-S-containing HBV vaccine every month from later than 12 months after liver transplantation. Successful vaccination was defined as HBsAb >100 IU/l without HBIg administration for 3 months. RESULTS None of the 15 chronic HBV carriers succeeded in maintaining high enough HBsAb titers. In contrast, 5 of 6 non-HBV patients with HBcAb-positive donors achieved HBsAb >100 IU/l without HBIg coadministration. Recipient HBV status (HBV carrier/non-HBV) was considered to have a stronger effect on vaccine success (p < 0.001) though recipient age (p = 0.006) was also selected as a significant factor. CONCLUSIONS Recipient HBV status seems to be the most important factor affecting success of HBV vaccine after liver transplantation. In non-HBV patients who received grafts from HBcAb-positive donors, HBV vaccination is an effective, cost-saving, and safe method for prevention of HBV reactivations. In contrast in chronic HBV patients, response rate was quite poor, so some modifications such as combination with adjuvant or modification of administration schedules should be considered.
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Affiliation(s)
- Masatoshi Ishigami
- Department of Gastroenterology, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
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26
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Mutimer D. Hepatitis B after transplantation: competition between the recipient virus and the donor virus. Liver Transpl 2010; 16:1225-7. [PMID: 21031536 DOI: 10.1002/lt.22185] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Prevention and Risk Factors of the HBV Recurrence After Orthotopic Liver Transplantation: 160 Cases Follow-Up Study. Transplantation 2010; 90:786-90. [DOI: 10.1097/tp.0b013e3181f09c89] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Cholongitas E, Papatheodoridis GV. Management of HBV Infection and Liver Transplantation. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 2010:748-761. [DOI: 10.1002/9781444314403.ch45] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Katz LH, Tur-Kaspa R, Guy DG, Paul M. Lamivudine or adefovir dipivoxil alone or combined with immunoglobulin for preventing hepatitis B recurrence after liver transplantation. Cochrane Database Syst Rev 2010:CD006005. [PMID: 20614442 DOI: 10.1002/14651858.cd006005.pub2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Recurrence of hepatitis B virus (HBV) infection in the liver graft is a grave complication following liver transplantation for HBV cirrhosis. Hepatitis B immunoglobulin (HBIg) seems effective in increasing survival after liver transplantation. HBIg and anti-viral drugs are given alone or in combination for its prevention. OBJECTIVES To assess the benefits and harms of different regimens for preventing HBV reactivation following liver transplantation. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2010. We attempted to identify further trials by reviewing the reference lists and contacting the principal authors of identified trials. SELECTION CRITERIA Randomised clinical trials addressing benefits and harms of lamivudine or adefovir dipivoxil alone or in combination with hepatitis B immunoglobulins (HBIg) for preventing recurrent HBV infection in patients who are liver transplanted due to HBV infection with or without hepatocellular carcinoma. DATA COLLECTION AND ANALYSIS Two authors independently assessed the trials for risk of bias and extracted data. We contacted study authors whenever information was lacking. We collected information on adverse events. The primary outcomes were all-cause mortality and reappearance of hepatitis B surface antigen in serum after liver transplantation. Relative risks were calculated from individual trials. MAIN RESULTS Four trials, recruiting 136 participants, were included. Two trials compared lamivudine alone versus HBIg alone. Randomisation was performed one week after transplantation in one of the trials and after six months after transplantation in another; from transplantation until randomisation, HBIg alone was given to all patients in the two trials. A third trial compared combination treatment with lamivudine and HBIg versus lamivudine alone after one month of combination treatment, and a fourth trial compared the combination of lamivudine and HBIg versus a combination of lamivudine and adefovir dipivoxil after at least 12-month of lamivudine and HBIg combination treatment. Statistically significant differences were not detected in any of the comparisons and outcomes. All trials were open-labelled, and none of the trials were adequately powered to show a difference in HBV recurrence. No meta-analyses were performed since the identified trials assessed different comparisons. AUTHORS' CONCLUSIONS This review could not derive clear evidence from randomised clinical trials for the treatment of patients with chronic HBV following liver transplantation for preventing recurrence of HBV infection. Large randomised clinical trials comparing long-term combination treatment to each of the monotherapy alone, including the newer antiviral drugs, are needed.
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Affiliation(s)
- Lior H Katz
- Gastroenterology Department, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel, 52621
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30
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Chun J, Kim W, Kim BG, Lee KL, Suh KS, Yi NJ, Park KU, Kim YJ, Yoon JH, Lee HS. High viremia, prolonged Lamivudine therapy and recurrent hepatocellular carcinoma predict posttransplant hepatitis B recurrence. Am J Transplant 2010; 10:1649-59. [PMID: 20642687 DOI: 10.1111/j.1600-6143.2010.03162.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Hepatitis B virus (HBV) recurrence following orthotopic liver transplantation (OLT) is generally preventable by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM). However, HBV recurrence sometimes develops despite prophylaxis. This study assessed posttransplant outcomes and identified predictors of HBV recurrence. We analyzed the outcomes of 209 consecutive patients positive for hepatitis B surface antigen who underwent OLT, who received either combination prophylaxis with HBIG and LAM (89.0%) or HBIG monoprophylaxis (11.0%). The median follow-up was 36.8 months (range, 1.0-84.4). Posttransplant HBV recurrence occurred in 22 patients (10.5%), including 13 patients with drug-resistant mutations. HBV recurrence was observed in six patients after hepatocellular carcinoma (HCC) recurrence. Independent predictors of HBV recurrence were recurrent HCC (p < 0.001), LAM therapy >1.5 years (p = 0.001) and high HBV DNA titers (> or =10(5) copies/mL) at OLT (p = 0.036). In conclusion, high viremia at OLT and prolonged exposure to LAM should be further stressed as main predictors of HBV recurrence.
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Affiliation(s)
- J Chun
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea
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Chen J, Yi L, Jia JD, Ma H, You H. Hepatitis B immunoglobulins and/or lamivudine for preventing hepatitis B recurrence after liver transplantation: a systematic review. J Gastroenterol Hepatol 2010; 25:872-9. [PMID: 20546440 DOI: 10.1111/j.1440-1746.2009.06151.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Currently, hepatitis B immunoglobulins (HBIg) and/or lamivudine have become the main options for prevention of hepatitis B recurrence after liver transplantation. AIM To assess the benefits of HBIg and/or lamivudine for prevention of hepatitis B recurrence after liver transplantation. METHODS We conducted a search of electronic databases and a manual search of bibliographical lists of relevant articles. All randomized clinical trials and non-randomized studies that meet the pre-specified criteria were included. However, results of non-randomized studies were reported under 'exploratory analyses' in the result section. The outcome measure was hepatitis B recurrence. RESULTS Two randomized and 44 non-randomized studies were included. Meta-analysis of two randomized studies shows one week HBIg combined with lamivudine regimen had equivalent effect compared with long-term high-dose HBIg regimen for preventing hepatitis B recurrence (RR 1.23; 95% CI 0.38-4.03; P = 0.73). For 44 non-randomized studies, only qualitative systematic review was performed. With long-term HBIg prophylaxis, hepatitis B recurrence rate ranged from 3.7% to 65%; with lamivudine prophylaxis, hepatitis B recurrence rate varied from 3.8% to 40.4%; Long-term high-dose HBIg plus lamivudine prophylaxis can reduce the risk of HBV recurrence to less than 10%. CONCLUSIONS Long-term HBIg prophylaxis or lamivudine prophylaxis can reduce the risk for hepatitis B virus recurrence. Long-term high-dose HBIg combined with lamivudine can further reduce HBV recurrence to less than 10%.
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Affiliation(s)
- Jie Chen
- Beijing Friendship Hospital, Capital Medical University; Municipal Key Laboratory of Beijing for Regulation of Liver Protection and Regeneration. Beijing, China
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Tolkoff-Rubin NE, Rubin RH. Infection in solid organ transplantation. Infect Dis (Lond) 2010. [DOI: 10.1016/b978-0-323-04579-7.00075-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Management of HBV infection during immunosuppressive treatment. Mediterr J Hematol Infect Dis 2009; 1:e2009025. [PMID: 21415959 PMCID: PMC3033125 DOI: 10.4084/mjhid.2009.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Accepted: 12/21/2009] [Indexed: 12/21/2022] Open
Abstract
The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and refers mainly to the pre-antivirals era. Currently, a rational approach to the problem of hepatitis B in these patients provides for: a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), b) the treatment with antivirals (therapy) of active carriers, c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, d) the biochemical and HBsAg monitoring (or universal prophylaxis in case of high risk immunosuppression, as in onco-haematologic patients and bone marrow transplantation) in subjects with markers of previous contact with HBV (HBsAg-negative and antiHBc-positive), in order to prevent reverse seroconversion. Moreover in solid organ transplants it is suggested a strict adherence to the criteria of allocation based on the virological characteristics of both recipients and donors and the universal prophylaxis or therapy with nucleos(t)ides analogs
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Dusheiko G, Burney T. Current treatment of chronic HBV infection: A European perspective. CURRENT HEPATITIS REPORTS 2009; 8:141-147. [DOI: 10.1007/s11901-009-0020-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Papatheodoridis GV, Cholongitas E, Archimandritis AJ, Burroughs AK. Current management of hepatitis B virus infection before and after liver transplantation. Liver Int 2009; 29:1294-305. [PMID: 19619264 DOI: 10.1111/j.1478-3231.2009.02085.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
The progress in treatment against hepatitis B virus (HBV) has substantially improved the outcome of all HBV-infected patients. We systematically reviewed the existing data in the management of HBV transplant patients in order to assess the optimal regimen in the pretransplant setting, for post-transplant prophylaxis and for therapy of HBV recurrent infection. All data suggest that an effective pretransplant anti-HBV therapy prevents post-transplant HBV recurrence. Pretransplant therapy has been based on lamivudine with addition of adefovir upon lamivudine resistance, but the use of newer, potent high-genetic barrier agents is expected to improve long-term efficacy. Moreover, it may lead to improvement of liver function, which sometimes removes the need for transplantation, although more objective criteria for removal from waiting lists are required. After liver transplantation, the combination of HBV immunoglobulin and one nucleos(t)ide analogue, mostly lamivudine, is currently the best approach, almost eliminating the probability of HBV recurrence. Treatment of post-transplant HBV recurrence has been mainly studied with lamivudine, but it will be most effective with entecavir and tenofovir, which have a low risk of resistance. In conclusion, the newer anti-HBV agents improve the treatment of HBV both pretransplant and post-transplant. HBV immunoglobulin is still used in combination with an anti-HBV agent for post-transplant prophylaxis. Monoprophylaxis with one of the new anti-HBV agents might be possible, particularly in patients preselected as having a low risk of HBV recurrence, but further data are needed and strategies to ensure compliance must be used.
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Affiliation(s)
- George V Papatheodoridis
- 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, 114 Vas. Sophias avenue, Athens, Greece.
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Jiang L, Jiang LS, Cheng NS, Yan LN. Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation. World J Gastroenterol 2009; 15:2489-99. [PMID: 19468999 PMCID: PMC2686907 DOI: 10.3748/wjg.15.2489] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Prophylactic strategies against hepatitis B virus (HBV) recurrence after liver transplantation (LT) are essential for patients with HBV-related disease. Before LT, lamivudine (LAM) was proposed to be down-graded from first- to second-line therapy. In contrast, adefovir dipivoxil (ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance. Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy. Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT. After LT, low-dose intramuscular hepatitis B immunoglobulin (HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers. With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.
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Abstract
In the past, reinfection of the graft by hepatitis B virus (HBV) after liver transplantation for HBV-related liver disease was often followed by severe liver damage and reduced survival. The long-term administration of hepatitis B immunoglobulin (HBIG) dramatically reduced this risk. However, this procedure was ineffective in most patients with active viral replication pre-transplant. The use of lamivudine in the pre-transplant setting partially solved this problem. The emergence of resistant mutants to lamivudine was also solved by the addition of adefovir. At present, combination therapy by oral antivirals pre-transplant and HBIG plus the same drugs post-transplant achieves nearly 100% of protection against graft reinfection. In a recent study, a new intravenous HBIG, Niuliva has shown high efficacy in achieving protective anti-HBs levels after liver transplantation for HBV-related liver diseases, as well as a good safety profile. Using combination therapies, the doses of HBIG can be reduced or even stopped after several weeks or months post-transplant, continuing with oral antivirals alone. The recently introduced antivirals achieve a very high antiviral potency and low risk of resistance. This may further increase the efficacy in preventing graft reinfection in the post-liver transplantation setting.
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Affiliation(s)
- A Mas
- ICU for Digestive & Metabolic Diseases, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain.
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Abstract
The transplantation outcome depends largely on the prevention of hepatitis B recurrence. The spontaneous risk of HBV reinfection exceeds 75%, but major advances in prophylaxis during the last 15 years have led to the control of post-transplant hepatitis B reinfection in more than 90% of HBV transplants. Treatment with hepatitis B immune globulins (HBIG) plays a major role in prophylaxis, either as monotherapy in non-replicating patients or in combination with antiviral drugs in replicating subjects. Although no standardized therapeutic protocols have been defined, at present the prevailing approach is to use high-dose intravenous HBIG in the immediate perioperative period (first week, induction phase) and to administer over the long term monthly fixed or on-demand doses of intravenous or intramuscular HBIG (maintenance therapy), in association with antiviral(s). Results have been excellent, yet different strategies of long-term prophylaxis have been proposed in order to simplify therapy and reduce costs. Long-term prophylaxis with antiviral(s) and low-dose intramuscular HBIG seems to be the most promising option; in stable patients, the combination with antiviral agents reduces the need of HBIG, in particular when using on-demand administration protocols and intramuscular HBIG has proven as effective and safe as intravenous preparations during the maintenance phase.
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Yamashiki N, Sugawara Y, Tamura S, Kaneko J, Matsui Y, Togashi J, Kokudo N, Omata M, Makuuchi M. Double-dose double-phase use of second generation hepatitis B virus vaccine in patients after living donor liver transplantation: Not an effective measure in transplant recipients. Hepatol Res 2009; 39:7-13. [PMID: 18761679 DOI: 10.1111/j.1872-034x.2008.00412.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
AIMS Post-transplant active immunization for chronic hepatitis B patients has been attempted in several studies with controversial results. We assessed the effect of a double-dose double-phase vaccination regimen among partial living donor liver recipients. METHODS Eighteen patients who underwent liver transplantation (LT) for chronic hepatitis B and two non-hepatitis B virus (HBV)-infected patients who received hepatitis B core antibody (HBcAb)-positive donor organs were recruited 18-78 months after LT. All were on hepatitis B immunoglobulin (HBIG) mono-prophylaxis before and throughout vaccination, to maintain hepatitis B surface antibody (HBsAb) titers of more than 100 IU/mL. Recombinant hepatitis B surface antigen vaccine (40 microg) was administered intramuscularly during weeks 0, 4, 8, 24, 28 and 32. RESULTS The patients consisted of 15 males and five females with a median age of 52 (39-59) years. None developed a sufficient HBsAb titer above 500 IU/mL by week 48. In two patients whose maximum HBsAb titer increased to above 300 IU/mL, we attempted to skip HBIG, but shortly thereafter the titer dropped below 100 IU/mL and HBIG administration was resumed. Although the HBIG dose was reduced during and after vaccination, cessation of administration was not achieved. CONCLUSION Double-dose double-phase use of second generation recombinant vaccine was not effective in this study population. The selected population should be targeted for a conventional vaccine regimen, and different approaches, such as strong adjuvant or pre-S containing protein, should be further tested in a larger number of patients after LT for chronic hepatitis B.
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Affiliation(s)
- Noriyo Yamashiki
- Organ Transplantation Service, University of Tokyo, Tokyo, Japan
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Beckebaum S, Sotiropoulos GC, Gerken G, Cicinnati VR. Hepatitis B and liver transplantation: 2008 update. Rev Med Virol 2009; 19:7-29. [DOI: 10.1002/rmv.595] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Abstract
Liver transplantation for hepatitis B represents 5-10 % of all liver transplantations performed in Europe. The prognosis after liver transplantation is related to the efficacy of prophylaxis of HBV graft reinfection. The risk of HBV reinfection is directly related to the HBV viral load at transplantation. HBV prophylaxis after transplantation with long-term administration of anti-HBS immune globulins (HBIG) or with monoprophylaxis with lamivudine can reduce significantly the risk of HBV recurrence mainly in patients without active HBV replication. Antivirals such as lamivudine, adefovir, entecavir or tenofovir can control HBV replication in patients with decompensated HBV cirrhosis waiting for transplantation. However, there is a risk of HBV viral breakthrough during nucleo (t) side antiviral treatment. The use of an antiviral alone or in combination should take into account the antiviral efficacy and the risk of viral resistance. The post-transplant combination of antiviral therapy and HBIG prophylaxis is very effective in reducing the rate of HBV reinfection to less than 10 % even in patients with HBV replication at transplantation. In the absence of active viral replication at transplantation, the possibilty to discontinue HBIG prophylaxis at long-term after transplantation with maintenance of antiviral treatment or HBV vaccination is in evaluation. The use of new antiviral therapies (nucleos(t)ide analogues) has dramatically improved the prognosis of patients with HBV reinfection of the graft. The current 5-year survival after liver transplantation for HBV related liver disease is 85 %. In conclusion, the prophylaxis of HBV reinfection combining antiviral therapy prior to transplantation, and combination of HBIG and antiviral therapy post-transplantation is effective in reducing the rate of HBV reinfection to less than 10 %.
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Liver Transplantation for Hepatitis B Virus Patients: Long-Term Results of Three Therapeutic Approaches. Transplant Proc 2008; 40:1961-4. [DOI: 10.1016/j.transproceed.2008.05.071] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Viral persistence after liver transplantation for hepatitis B virus: a cross-sectional study. Transplantation 2008; 85:1105-11. [PMID: 18431229 DOI: 10.1097/tp.0b013e31816a342a] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Prophylaxis to prevent recurrent HBV infection in liver transplant (LT) recipients has evolved over time, and we manage patients who receive lamivudine monoprophylaxis, lamivudine with HBV immunoglobulin (HBIg), and lamivudine and adefovir with HBIg. METHODS Serum was examined with sensitive assays to detect the persistence of HBV, and to identify mutations that might confer resistance to the antiviral prophylaxis. Forty patients were studied, and sera were collected 20 days to 13.3 years after LT. RESULTS Overall, HBV DNA was detected in serum of 67.5% of patients (8 of 10 of lamivudine monoprophylaxis patients, 15 of 24 of those receiving lamivudine and HBIg, and 4 of 6 of those receiving lamivudine, adefovir and HBIg). Thus, HBV infection persists for most of the patients despite successful prophylaxis after LT. Of those patients with detectable serum HBV DNA, three of eight of the lamivudine monoprophylaxis group had sequences associated with resistance to lamivudine (YMDD mutants), compared with only 1 of 15 of the lamivudine and HBIg cohort. Three of the lamivudine and HBIg cohort had the I126A Hepatitis B surface antigen escape variant. In those serum HBV DNA-positive patients who were receiving lamivudine, adefovir, and HBIg, only one of four had YMDD mutant, and none had Hepatitis B surface antigen escape variants. None of the 40 patients suffered clinical HBV recurrence. CONCLUSIONS Our observations imply that the selection of resistant virus may be essential, but is not sufficient to cause overt failure of prophylaxis with development of clinical disease. It seems likely that the patients' immune response contributes, at least partially, to the long-term control of infection in these patients.
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Selabe SG, Lukhwareni A, Song E, Leeuw YGM, Burnett RJ, Mphahlele MJ. Mutations associated with lamivudine-resistance in therapy-naïve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients. J Med Virol 2007; 79:1650-4. [PMID: 17854040 DOI: 10.1002/jmv.20974] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-naïve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-naïve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-naïve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.
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Affiliation(s)
- S Gloria Selabe
- HIV and Hepatitis Research Unit, Department of Virology, University of Limpopo, Medunsa Campus, Pretoria, South Africa
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46
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Anderson RD, Chinnakotla S, Guo L, Perrillo RP, Klintmalm GB, Davis GL. Intramuscular hepatitis B immunoglobulin (HBIG) and nucleosides for prevention of recurrent hepatitis B following liver transplantation: comparison with other HBIG regimens. Clin Transplant 2007; 21:510-7. [PMID: 17645711 DOI: 10.1111/j.1399-0012.2007.00678.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
UNLABELLED High titer hepatitis B immunoglobulin (HBIG) has significantly reduced the recurrence of hepatitis B virus (HBV) infection after liver transplantation. We compared our experience with intramuscular (IM) HBIG prophylaxis to our earlier outcomes with intravenous (IV) HBIG and other regimens. METHODS One hundred and twenty-three patients with acute or chronic hepatitis B underwent liver transplant at the Baylor Regional Transplant Center between July 1985 and July of 2005. Of these, 63 (43%) received long-term low-dose IM (n = 17) or high-dose IV (n = 46) HBIG. All patients in IM group also received a nucleoside before and after transplant. These patients were compared with those transplanted earlier who received either no prophylaxis (n = 16) or HBIG on day zero and one only (n = 44). RESULTS HBV recurrence was significantly lower in patients who received long-term HBIG [9/38 (23.7%) for IV and 1/17 (5.9%) for IM] compared with patients who received no treatment (8/11; 72.7%) or only two doses of HBIG (32/40; 80.0%). Two-yr actuarial survivals were 89%, 88%, 54%, and 64%, respectively. Patients on long-term HBIG by either parenteral route survived as well as patients transplanted for other indications. Post-transplant recurrence of hepatitis B in the long-term HBIG groups was usually controlled by intensifying antiviral therapy. CONCLUSION Long-term low-dose IM and high-dose IV HBIG are equally efficacious with similar survival and early hepatitis recurrence rates. Graft loss is usually avoidable when recurrence is discovered early and aggressively treated. The IM route is preferable to IV administration due to its ease of administration and lower cost.
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Affiliation(s)
- Robert D Anderson
- Department of Medicine, Baylor Uinversity Medical Center and the Baylor Regional Transplant Institute, Dallas, TX, USA
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47
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Marzano A, Angelucci E, Andreone P, Brunetto M, Bruno R, Burra P, Caraceni P, Daniele B, Di Marco V, Fabrizi F, Fagiuoli S, Grossi P, Lampertico P, Meliconi R, Mangia A, Puoti M, Raimondo G, Smedile A. Prophylaxis and treatment of hepatitis B in immunocompromised patients. Dig Liver Dis 2007; 39:397-408. [PMID: 17382608 DOI: 10.1016/j.dld.2006.12.017] [Citation(s) in RCA: 155] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2006] [Revised: 12/15/2006] [Accepted: 12/18/2006] [Indexed: 02/06/2023]
Abstract
The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and referred mainly to the pre-antivirals era. Today a rational approach to the problem of hepatitis B in these patients provides for: (a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), (b) the treatment with antivirals (therapy) of active carriers, (c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, (d) the biochemical and hepatitis B surface antigen (HBsAg) monitoring (or universal prophylaxis, in case of high risk immunosuppression) in subjects with markers of previous contact with HBV (HBsAg negative and anti-HBc positive), in order to prevent reverse seroconversion. Moreover it is suggested a strict adherence to criteria of allocation based on the virological characteristics of both recipients and donors in the general setting of transplants and in liver transplantation the universal prophylaxis with nucleos(t)ides analogues (frequently combined with specific anti-HBV immunoglobulins) in HBsAg positive candidates and in HBsAg negative recipients of anti-HBc positive grafts.
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Affiliation(s)
- A Marzano
- Division of Gastroenterology and Hepatology, AO San Giovanni Battista, Torino, Italy.
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Eisenbach C, Sauer P, Mehrabi A, Stremmel W, Encke J. Prevention of hepatitis B virus recurrence after liver transplantation. Clin Transplant 2007; 20 Suppl 17:111-6. [PMID: 17100710 DOI: 10.1111/j.1399-0012.2006.00609.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.
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Affiliation(s)
- Christoph Eisenbach
- Department of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany.
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Prada Lobato J, Garrido López S, Catalá Pindado MA, García Pajares F. [The prophylaxis against post-liver-transplant hepatitis B re-infection]. FARMACIA HOSPITALARIA 2007; 31:30-7. [PMID: 17439311 DOI: 10.1016/s1130-6343(07)75708-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE To review the prophylaxis against post-liver transplantation hepatitis B reinfection with anti-hepatitis B immunoglobulin and nucleoside analogues. METHOD A bibliographic search was carried out using Pubmed, entering the following key words: hepatitis B and liver transplantation and (hepatitis B hyperimmune globulin and lamivudine and adefovir dipivoxil) up to June 2006. The initial search was filtered using the terms clinical trial, randomized clinical trial and review. The data contained in selected studies were reviewed. RESULTS A total of 53 works were found. Prophylaxis with anti-HB immunoglobulin and lamivudine is the best strategy for avoiding recurrence of the hepatitis B virus in patients undergoing hepatic transplants; achieving very low reinfection rates (0-10%) with follow up periods of between 1-5 years. There is a great degree of variability (dose, duration and method of HBIg administration) in the prophylactic protocols reviewed. The use of low doses of anti-HB immunoglobulin (administered intravenously followed by intramuscular administration, or administered intramuscularly from the anhepatic stage), and lamivudine in patients who receive transplants with a low risk of recurrence, shows prophylactic efficacy comparable to the use of high doses of anti-HB immunoglobulin. Furthermore, it implies a considerable reduction in costs. CONCLUSIONS The availability of suitably designed clinical trials is required to design a more cost-effective protocol and reduce variability.
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Affiliation(s)
- J Prada Lobato
- Servicio de Farmacia, Hospital Universitario Río Hortega, Valladolid.
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50
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Rosenau J, Kreutz T, Kujawa M, Bahr MJ, Rifai K, Hooman N, Finger A, Michel G, Nashan B, Kuse ER, Klempnauer J, Tillmann HL, Manns MP. HBsAg level at time of liver transplantation determines HBsAg decrease and anti-HBs increase and affects HBV DNA decrease during early immunoglobulin administration. J Hepatol 2007; 46:635-44. [PMID: 17316869 DOI: 10.1016/j.jhep.2006.11.022] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2006] [Revised: 10/28/2006] [Accepted: 11/28/2006] [Indexed: 12/17/2022]
Abstract
BACKGROUND/AIMS Administration of hepatitis B immunoglobulin (HBIG) initially after liver transplantation of hepatitis B patients is considered important to prevent reinfection reliably. However, dosing schedules differ considerably between centers. We measured HBsAg, anti-HBs and HBV DNA kinetics to create a rational basis for dosing schemes. METHODS Thirteen patients (group A) received 10,000 IU HBIG in the anhepatic phase followed by 10,000 IU daily until HBsAg became negative, whereas five patients (group B) received 20,000 IU followed by 5000 IU every 30 min. RESULTS HBsAg levels at time of transplantation ranged from 0.12 to 12,990 IU/ml. Correlations between initial HBsAg and HBIG required to decrease HBsAg below 1 IU/ml were high in groups A and B (r=0.97, p<0.001; r=1.00, p<0.001), as were correlations between initial HBsAg and HBIG required to raise anti-HBs above 1000 IU/l (r=0.94, p<0.001; r=1.00, p<0.001). In 11 HBV DNA-positive patients, DNA levels became negative in seven, and dropped by 2.5 log10 (mean) in the other four patients during immunoglobulin administration. CONCLUSIONS In conclusion, required HBIG doses to decrease HBsAg and raise anti-HBs are determined by HBsAg levels at time of transplantation, not by HBV DNA levels. Shortened HBIG dosing intervals accelerate HBsAg decrease and anti-HBs increase. HBV DNA decreases rapidly during HBIG administration in most patients.
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Affiliation(s)
- Jens Rosenau
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
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