|
1
|
Mak LY, Boettler T, Gill US. HBV Biomarkers and Their Role in Guiding Treatment Decisions. Semin Liver Dis 2024; 44:474-491. [PMID: 39442530 DOI: 10.1055/a-2448-4157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
Over 300 million individuals worldwide are chronically infected with hepatitis B virus and at risk for progressive liver disease. Due to the lack of a therapy that reliably achieves viral elimination and the variability of liver disease progression, treatment decisions are guided by the degree of liver disease and viral biomarkers as the viral life-cycle is well characterized and largely conserved between individuals. In contrast, the immunological landscape is much more heterogeneous and diverse and the measurement of its components is less well standardized. Due to the lack of a universal and easily measurable set of biomarkers, clinical practice guidelines remain controversial, aiming for a balance between simplifying treatment decisions by reducing biomarker requirements and using all available biomarkers to avoid overtreatment of patients with low risk for disease progression. While approved therapies such as nucleos(t)ide analogs improve patient outcomes, the inability to achieve a complete cure highlights the need for novel therapies. Since no treatment candidate has demonstrated universal efficacy, biomarkers will remain important for treatment stratification. Here, we summarize the current knowledge on virological and immunological biomarkers with a specific focus on how they might be beneficial in guiding treatment decisions in chronic hepatitis B.
Collapse
Affiliation(s)
- Lung-Yi Mak
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Department of Medicine, Queen Mary Hospital, School of Clinical Medicine, The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tobias Boettler
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Upkar S Gill
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| |
Collapse
|
|
2
|
Rizza G, Glynou K, Eletskaya M. Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey. World J Transplant 2024; 14:90949. [PMID: 39295979 PMCID: PMC11317858 DOI: 10.5500/wjt.v14.i3.90949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 05/02/2024] [Accepted: 06/07/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Hepatitis B immunoglobulin (HBIG) in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation for HBV-associated disease. AIM To evaluate patients' satisfaction, preferences, and requirements for subcutaneous (SC), intramuscular (IM), and intravenous (IV) HBIG treatments. METHODS A self-completion, cross-sectional, online, 22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France, Italy, and Turkey. Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint (trade-off) exercise. RESULTS Ninety patients were enrolled; 32%, 17%, and 51% were SC, IM, and IV HBIG users, respectively. Mean duration of treatment was 36.2 months. SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient, easiest to administer, least painful, and had the highest self-rating of treatment compliance. More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive (67%, 28%, and 28%, respectively). In the target product profile assessment, 76% of patients were likely to use hypothetical SC HBIG. In the conjoint exercise, administration route, frequency, and duration were key drivers of treatment preferences. CONCLUSION Ease, frequency, duration, and side effects of HBIG treatment administration were key drivers of treatment preferences, and SC HBIG appeared advantageous over IM and IV HBIG for administration ease, convenience, and pain. A hypothetical SC HBIG product elicited a favorable response. Patient demographics, personal preferences, and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.
Collapse
Affiliation(s)
- Giorgia Rizza
- General Surgery and Liver Transplant Center, S. Giovanni Battista Hospital, Turin I-10126, Italy
| | | | - Masha Eletskaya
- Lumanity Insight (Cello Health Insight), London SE1 1PP, United Kingdom
| |
Collapse
|
|
3
|
Kumar N, Choudhary NS. Managing HBV and HCV Infection Pre- and Post-liver Transplant. J Clin Exp Hepatol 2024; 14:101287. [PMID: 38076445 PMCID: PMC10709521 DOI: 10.1016/j.jceh.2023.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 09/19/2023] [Indexed: 03/03/2025] Open
Abstract
Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation.
Collapse
Affiliation(s)
- Naveen Kumar
- Hepatology and Gastroenterology, Narayana Hospital Delhi, India
| | | |
Collapse
|
|
4
|
Zheng H, Zhu Z, Wang N, Qin J, Guo Y, Xu Z, Li X, Qi C, Yuan X, Wu W, Wang J, Liu L, Nashan B. Entecavir Combined With Short-term Hepatitis B Immunoglobulin in Preventing Hepatitis B Virus Recurrence in Liver Transplant Recipients. Transplant Proc 2023; 55:408-412. [PMID: 36907782 DOI: 10.1016/j.transproceed.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/02/2023] [Indexed: 03/12/2023]
Abstract
BACKGROUND The combination of nucleoside analogs and long-term hepatitis B immunoglobulin (HBIG) is considered to be the standard regimen for preventing hepatitis B virus (HBV) recurrence after liver transplant (LT). However, long-term use of HBIG causes many adverse effects. The aim of this study was to evaluate the effect of nucleoside analogs entecavir combined with short-term HBIG in preventing HBV recurrence after LT. METHODS This retrospective study assessed the effect a combination of entecavir and short-term HBIG in prophylaxis of HBV recurrence among 56 LT recipients who had undergone the procedure because of HBV-associated liver disease at our center between December 2017 and December 2021. All patients received entecavir treatment combined with HBIG for the prevention of hepatitis B recurrence, and HBIG treatment was withdrawn within 1 month. The patients were followed up to determine levels of hepatitis B surface antigen, antibody to hepatitis B surface antigen (HBsAb), and HBV-DNA and the recurrence rate of HBV. RESULTS Only 1 patient appeared positive for hepatitis B surface antigen at 2 months post-LT. The overall HBV recurrence rate was 1.8%. The HBsAb titers of all patients gradually decreased over time, with a median of 376.6 IU/L at 1 month post-LT and a median of 13.47 IU/L at 12 months post-LT. During the follow-up period, the HBsAb titer of the preoperative HBV-DNA-positive patients remained at a lower level than that of HBV-DNA-negative patients. CONCLUSIONS Entecavir combined with short-term HBIG can exert a good effect for the prevention of HBV reinfection post-LT.
Collapse
Affiliation(s)
- Hao Zheng
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Zebin Zhu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Ning Wang
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Jiwei Qin
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Yafei Guo
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Zhijun Xu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Xuefeng Li
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Can Qi
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Xiaodong Yuan
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Wei Wu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Jizhou Wang
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Lianxin Liu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Björn Nashan
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China.
| |
Collapse
|
|
5
|
Burm R, Van Houtte F, Verhoye L, Mesalam AA, Ciesek S, Roingeard P, Wedemeyer H, Leroux-Roels G, Meuleman P. A human monoclonal antibody against HBsAg for the prevention and treatment of chronic HBV and HDV infection. JHEP Rep 2023; 5:100646. [PMID: 36748051 PMCID: PMC9898450 DOI: 10.1016/j.jhepr.2022.100646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/17/2022] [Accepted: 11/21/2022] [Indexed: 12/12/2022] Open
Abstract
Background & Aims Elimination of chronic HBV/HDV infection remains a major global health challenge. Targeting excessive hepatitis B surface antigen (HBsAg) release may provide an interesting window of opportunity to break immune tolerance and to achieve a functional cure using additional antivirals. Methods We evaluated a HBsAg-specific human monoclonal antibody, as part of either a prophylactic or therapeutic strategy, against HBV/HDV infection in cell culture models and in human-liver chimeric mice. To assess prophylactic efficacy, mice were passively immunized prior to infection with HBV or HBV/HDV (coinfection and superinfection setting). Therapeutic efficacy was assessed in HBV and HBV/HDV-coinfected mice receiving 4 weeks of treatment. Viral parameters (HBV DNA, HDV RNA and HBsAg) were assessed in mouse plasma. Results The antibody could effectively prevent HBV/HDV infection in a dose-dependent manner with IC50 values of ∼3.5 ng/ml. Passive immunization showed complete protection of mice from both HBV and HBV/HDV coinfection. Moreover, HDV superinfection was either completely prevented or at least attenuated in HBV-infected mice. Finally, antibody treatment in mice with established HBV/HDV infection resulted in a significant decline in viremia and a concomitant drop in on-treatment HBsAg, with a moderate viral rebound following treatment cessation. Conclusion We present data on a valuable antibody candidate that could complement other antivirals in strategies aimed at achieving functional cure of chronic HBV and HDV infection. Impact and implications Patients chronically infected with HBV may eventually develop liver cancer and are at great risk of being superinfected with HDV, which worsens and accelerates disease progression. Unfortunately, current treatments can rarely eliminate both viruses from chronically infected patients. In this study, we present data on a novel antibody that is able to prevent chronic HBV/HDV infection in a mouse model with a humanized liver. Moreover, antibody treatment of HBV/HDV-infected mice strongly diminishes viral loads during therapy. This antibody is a valuable candidate for further clinical development.
Collapse
Affiliation(s)
- Rani Burm
- Laboratory of Liver Infectious Diseases (LLID), Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Freya Van Houtte
- Laboratory of Liver Infectious Diseases (LLID), Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Lieven Verhoye
- Laboratory of Liver Infectious Diseases (LLID), Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Ahmed Atef Mesalam
- Laboratory of Liver Infectious Diseases (LLID), Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre (NRC), Dokki, Cairo 12622, Egypt
| | - Sandra Ciesek
- Institute for Medical Virology, University Hospital, Goethe University, Frankfurt am Main, Germany
- German Center for Infection Research, DZIF, External Partner Site, Frankfurt am Main, Germany
- Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor Stern Kai 7, Frankfurt am Main, Germany
| | - Philippe Roingeard
- INSERM U966, Université François Rabelais and CHRU de Tours, Tours, France
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Geert Leroux-Roels
- Center for Vaccinology, Faculty of Medicine and Health Sciences, Ghent University and University Hospital, Ghent, Belgium
| | - Philip Meuleman
- Laboratory of Liver Infectious Diseases (LLID), Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| |
Collapse
|
|
6
|
Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
7
|
Duvoux C, Belli LS, Fung J, Angelico M, Buti M, Coilly A, Cortesi P, Durand F, Féray C, Fondevila C, Lebray P, Martini S, Nevens F, Polak WG, Rizzetto M, Volpes R, Zoulim F, Samuel D, Berenguer M. 2020 position statement and recommendations of the European Liver and Intestine Transplantation Association (ELITA): management of hepatitis B virus-related infection before and after liver transplantation. Aliment Pharmacol Ther 2021; 54:583-605. [PMID: 34287994 DOI: 10.1111/apt.16374] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/25/2020] [Accepted: 04/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prophylaxis of HBV recurrence is critical after liver transplantation in HBV patients. Despite new prophylactic schemes, most European LT centres persist on a conservative approach combining hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogues (NA). AIM This setting prompted the European Liver Intestine Transplantation Association (ELITA) to look for a consensus on the prevention of HBV recurrence. METHODS Based on a 4-round Delphi process, ELITA investigated 16 research questions and established 50 recommendations. RESULTS Prophylaxis should be driven according to 3 simplified risk groups: Low and high virological risk patients, with undetectable and detectable HBV DNA pre-LT, respectively, and special populations (HDV, HCC, poorly adherent patients). In low-risk patients, short-term (4 weeks) combination of third-generation NA+ HBIG, or third generation NA monotherapy can be considered as prophylactic options. In high-risk patients, HBIG can be discontinued once HBV DNA undetectable. Combined therapy for 1 year is advised. HBV-HCC patients should be treated according to their virological risk. In HDV/HBV patients, indefinite dual prophylaxis remains the gold standard. Full withdrawal of HBV prophylaxis following or not HBV vaccination should only be attempted in the setting of clinical trials. Organs from HBsAg+ve donors may be considered after assessment of risks, benefits, and patient consent. They should not be used if HDV is present. In poorly adherent patients, dual long-term prophylaxis is recommended. Budget impact analysis should be taken into account to drive prophylactic regimen. CONCLUSIONS These ELITA recommendations should stimulate a more rational and homogeneous approach to HBV prophylaxis across LT programs.
Collapse
|
|
8
|
Orfanidou A, Papatheodoridis GV, Cholongitas E. Antiviral prophylaxis against hepatitis B recurrence after liver transplantation: Current concepts. Liver Int 2021; 41:1448-1461. [PMID: 33656809 DOI: 10.1111/liv.14860] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/20/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022]
Abstract
The advance in treatment against hepatitis B virus (HBV) infection with the development of nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, including entecavir and tenofovir, has improved clinical outcomes of patients transplanted for HBV infection, by preventing HBV recurrence after liver transplantation (LT) effectively. Currently, after LT, the combination of hepatitis B immunoglobulin (HBIG) and a high-barrier NA is considered as the standard of care for prophylaxis against HBV recurrence. However, because of the high cost of intravenous high-dose HBIG, other routes of HBIG administration, such as intramuscular or subcutaneous, have come to the foreground. In addition, several transplant centres tend to use a NA as monoprophylaxis, following a short post-LT period of HBIG and NA combination. Lately, studies using HBIG-free prophylactic regimens with entecavir or tenofovir have shown promising outcomes in preventing HBV recurrence, mostly regarding patients with undetectable HBV DNA at the time of LT. Although vaccination against HBV has been an attractive prophylactic approach, its efficacy has been controversial. Moreover, further studies are needed regarding long-term outcomes of complete withdrawal anti-HBV prophylaxis. For patients transplanted for HBV/HDV co-infection, combined regimen should be administered for a longer period post-LT. Finally, the use of grafts from hepatitis B core antibody-positive donors is safe for HBV-negative recipients, with the administration of lifelong antiviral prophylaxis.
Collapse
Affiliation(s)
- Afroditi Orfanidou
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
9
|
Li MS, Hou ZH, Yao GZ, Tan DM. The strategy and efficacy of prophylaxis against hepatitis B virus recurrence after liver transplantation for HBV-related diseases in the era of potent nucleos(t)ide analogues: A meta-analysis. J Dig Dis 2021; 22:91-101. [PMID: 33128339 DOI: 10.1111/1751-2980.12959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/04/2020] [Accepted: 10/27/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This meta-analysis aimed to evaluate the clinical outcome of liver transplant (LT) recipients under potent nucleoside or nucleotide analogue (NA)-based regimens and investigate different prophylactic schemes. METHODS We followed PRISMA statement to conduct this study. Two reviewers independently searched relevant literature via PubMed, Embase, Ovid MEDLINE, Web of Science and Insightmeme. Studies were included if they evaluated hepatitis B virus (HBV) recurrence under potent NA-based regimens in patients who received HBV-related LT. Primary and secondary outcomes were HBV recurrence, hepatocellular carcinoma (HCC) recurrence, all-cause and HBV recurrence-related mortality. Incidences with 95% confidence intervals were calculated and assessed by fixed and random effects models. Subgroup analyses were used to examine the impact of different treatment strategies. RESULTS Altogether 25 studies (N = 2327) were included, with a pooled HBV recurrence rate of 1.01% (95% CI 0.53%-1.59%). HBV viremia or hepatitis D virus superinfection did not influence HBV recurrence significantly (P = 0.23 and 0.71, respectively). The recurrence rate under an indefinite combination of potent NA and hepatitis B immunoglobulin (HBIG) was lower than that under potent NA monotherapy (P = 0.000) and similar to that under NA plus a finite course of HBIG (P = 0.48). The pooled HCC recurrence rate was 5.34% (95% CI 0.78%-12.48%). HBV recurrence-related mortality and all-cause mortality were 0% and 6.95% (95% CI 4.30%-10.08%), respectively. CONCLUSIONS Potent NA-based regimens provide satisfactory HBV antiviral prophylaxis and improve long-term outcomes for LT recipients. A finite combination of potent NA and HBIG is an alternative to life-long dual therapy.
Collapse
Affiliation(s)
- Ming Shu Li
- Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China
| | - Zhou Hua Hou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Guo Zhu Yao
- School of Mathematics and Statistics, Changsha University of Science and Technology, Changsha, Hunan Province, China
| | - De Ming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| |
Collapse
|
|
10
|
Park JS, Gayam V, Pan CQ. Review article: preventing hepatitis B graft infection in hepatitis B patients after liver transplantation: immunoglobulin vs anti-virals. Aliment Pharmacol Ther 2020; 52:944-954. [PMID: 32743822 DOI: 10.1111/apt.15999] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 03/10/2020] [Accepted: 07/05/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND A critical aspect of liver transplantation in hepatitis B patients is to prevent graft reinfection with hepatitis B virus. The use of hepatitis B immune globulin after transplant was a significant milestone, which allowed prolonged graft and patient survival by controlling hepatitis B reinfection in liver grafts. The development of anti-viral treatments with oral nucleos(t)ide analogues, led to a further reduction in graft reinfection and improvement in patient survival. The combination of the aforementioned two therapies has been widely used in hepatitis B-associated liver transplants. AIMS To address the post-transplant management of hepatitis B and provide updates on preventing graft reinfection. METHODS We performed a literature search on Ovid and PubMed for randomised controlled trials or cohort studies in English, which investigated the effectiveness of hepatitis B immune globulin and anti-viral therapy on hepatitis B-associated transplants (1/2000-1/2020). Studies that met pre-established criteria were reviewed. RESULTS Based on currently available evidence, an algorithm for post-transplant management with anti-viral therapy is proposed. Also, the management of recipients who received grafts from hepatitis B core antibody-positive donors is discussed. CONCLUSIONS The development of hepatitis B immune globulin and anti-viral treatments led to substantial improvement in graft and patient survival. The prevention of hepatitis B graft reinfection is complex and involves a broad interdisciplinary team.
Collapse
Affiliation(s)
- James S Park
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU School of Medicine, NYU Langone Health, New York, NY, USA.,NYU Langone Transplant Institute, NYU Langone Health, New York, NY, USA
| | - Vijay Gayam
- Interfaith Medical Center, SUNY Downstate University Hospital, Brooklyn, NY, USA
| | - Calvin Q Pan
- Division of Gastroenterology and Hepatology, Department of Medicine, NYU School of Medicine, NYU Langone Health, New York, NY, USA.,Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
11
|
Nasir M, Wu GY. Prevention of HBV Recurrence after Liver Transplant: A Review. J Clin Transl Hepatol 2020; 8:150-160. [PMID: 32832395 PMCID: PMC7438351 DOI: 10.14218/jcth.2020.00003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/16/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022] Open
Abstract
Globally, hepatitis B virus (HBV) infection is recognized as a major risk factor for the development of hepatocellular carcinoma, and HBV-induced liver failure is one of the leading indications for liver transplantation. Until about two decades ago, liver transplantation in patients with chronic HBV infection was a relative contraindication, due to high risk of viral replication with the use of immunosuppressants which could result in graft infection. In the 1990s, hepatitis B immunoglobulin (HBIg) use significantly reduced the risk of graft infection, improving outcomes of liver transplant in patients with chronic HBV infection. However, very high costs, especially with the need for long-term use, became a major concern. With the advent of nucleos(t)ide analogs (NAs), there was less need for high-dose, long-term HBIg use to prevent HBV recurrence. Lamivudine was initially used but resistance soon became a major issue. This was followed by more potent NAs, such as entecavir and tenofovir, emerging as the more preferred agents. Additionally, the use of these antiviral agents (HBIg and/or NAs) have made it possible to use the grafts from donors with positivity for hepatitis B core antibody, allowing for expansion of the donor pool. Nevertheless, there is no consensus on management protocols, which vary significantly amongst centers. In this review, we appraise studies on management strategies used and the role of active vaccination in the prevention of HBV recurrence in post-liver transplant patients.
Collapse
Affiliation(s)
- Myra Nasir
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| |
Collapse
|
|
12
|
Dobrindt EM, Keshi E, Salim Y, Gillespie A, Saipbaev A, Schöning W, Öllinger R, Pratschke J, Eurich D. Hepatitis B Immunoglobulin discontinuation in long-term liver transplant patients. Transpl Infect Dis 2020; 22:e13303. [PMID: 32367631 DOI: 10.1111/tid.13303] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 03/16/2020] [Accepted: 04/25/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatitis B immunoglobulin (HBIG)-as a monotherapy or combined with nucleos(t)ide analogs (NUCs)-has effectively lowered Hepatitis B virus (HBV) reinfection after liver transplantation. However, it is associated with high costs and viral resistance. HBIG-free prophylaxis with novel NUCs (tenofovir, entecavir) composes a viable alternative. We evaluated reinfection rate, histological changes, and outcome associated with HBIG discontinuation. METHODS A retrospective analysis was performed of patients undergoing liver transplantation due to HBV-induced liver disease at our center since 1988. A controlled HBIG discontinuation was conducted between 2015 and 2017 in 65 patients. Recurrent infection was determined by HbsAg values. Fibrosis and inflammation were evaluated by routine biopsy. The survival of patients after HBIG discontinuation was compared to a control population on HBIG for prophylaxis. RESULTS From 1988 to 2013, 352 patients underwent liver transplantation due to HBV-induced liver disease. 169 patients could be included for analysis. 104 (51.5%) patients continued a prophylaxis containing HBIG. HBIG was discontinued in 65 (38.5%) patients in a controlled manner, maintaining an oral NUC. None of those patients showed HBV reinfection or graft dysfunction. No significant changes of inflammation grades (P = .067) or fibrosis stages (P = .051) were detected. The survival of patients after HBIG discontinuation was comparable to the control (P = .95). CONCLUSION HBIG withdrawal under continuation of oral NUC therapy is safe and not related to graft dysfunction, based on blood tests and histology. HBIG-free prophylaxis is not associated with a worse outcome and displays a financial relief as well as a logistic simplification during long-term follow-up.
Collapse
Affiliation(s)
- Eva Maria Dobrindt
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Eriselda Keshi
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Yones Salim
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Allan Gillespie
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Akylbek Saipbaev
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Robert Öllinger
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Dennis Eurich
- Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| |
Collapse
|
|
13
|
Chen T, Liu J, Yu Q, Yao N, Yang Y, Wu Y, Ren D, Tian Z, Zhao Y, Wang J. Tenofovir plus hepatitis B immunoglobulin treatment resulted in a rapid HBV DNA load decline in high-risk pregnant women who missed the optimal time window of antiviral prophylaxis. Antivir Ther 2020; 24:125-131. [PMID: 30570488 DOI: 10.3851/imp3284] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) administration in the third trimester for pregnant women with high HBV DNA load has been accepted as a wise practice to prevent mother-to-infant transmission (MTIT). However, for those women who missed the optimal time window of antiviral prophylaxis, this treatment is lacking in the current clinical guidelines. METHODS Forty-eight pregnant women who did not receive antiviral prophylaxis before 28 weeks of gestation were screened and were administrated with TDF plus hepatitis B immunoglobulin (HBIG; TDF+HBIG group) or TDF alone (TDF group). HBV DNA inhibition and the safety profile were compared between two groups. RESULTS A decline of HBV DNA load was observed in both groups after a short period of treatment, and no infant had MTIT. However, compared with the TDF group, the speed of HBV DNA load decline was more rapid (P=0.002) and a much more striking HBV DNA load decline in the first 4 weeks of treatment was exhibited in the TDF+HBIG group (P=0.001). The percentages of mothers with HBV DNA <4 log10 IU/ml and 3 log10 IU/ml at delivery were both much higher in the TDF+HBIG group than the TDF group (P=0.034 and 0.024, respectively). TDF and HBIG were found to be well-tolerated with no safety concerns in the mothers and their infants. CONCLUSIONS TDF plus HBIG treatment resulted in a rapid HBV DNA load decline in high-risk women who missed the optimal time window of antiviral prophylaxis in pregnancy, which potentially protected infants from HBV infection.
Collapse
Affiliation(s)
- Tianyan Chen
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Jinfeng Liu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Qiang Yu
- Department of Pediatric Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Naijuan Yao
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yuan Yang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yuchao Wu
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Danfeng Ren
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Zhen Tian
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| | - Jing Wang
- Department of Infectious Diseases, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China.,Department of Rheumatology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an City, China
| |
Collapse
|
|
14
|
Volpes R, Burra P, Germani G, Manini MA, Caccamo L, Strignano P, Rizza G, Tamè M, Pinna AD, Calise F, Migliaccio C, Carrai P, De Simone P, Valentini MF, Lupo LG, Cordone G, Picciotto FP, Nicolucci A. Switch from intravenous or intramuscular to subcutaneous hepatitis B immunoglobulin: effect on quality of life after liver transplantation. Health Qual Life Outcomes 2020; 18:99. [PMID: 32276633 PMCID: PMC7149917 DOI: 10.1186/s12955-020-01349-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 04/02/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Hepatitis B immunoglobulin (HBIG) therapy is available in intravenous (IV) or intra-muscular (IM) formulations. Recently, a subcutaneous (SC) formulation was introduced. This study evaluated changes in quality of life when liver transplant (LT) recipients were switched from IV or IM HBIG to the SC formulation. METHODS This multicentre, observational study involved adults who had undergone LT at least 1 year prior to study entry. Quality of life was evaluated using the ITaLi-Q questionnaire, assessing the impact of HBIG therapy on daily activities and patient satisfaction, and the SF-36 Health Survey. Patients completed the questionnaires prior to switching from IV or IM HBIG to SC HBIG and 6 months later. RESULTS Eighty-six patients were enrolled; before the switch, 68.6% were receiving IM HBIG and 31.4% IV HBIG. After 6 months, significant improvements in 7 of the 8 ITaLi-Q domains were found, particularly side effects, need for support to adhere to the therapy and satisfaction with the HBIG therapy. Significant improvements in several SF-36 domains were documented, including physical functioning, physical and emotional role limitations, pain, social functioning, physical and mental summary scores. CONCLUSIONS The SC route of administration reduces side effects and their interference with daily life, ameliorates negative feelings, and increases patient autonomy.
Collapse
Affiliation(s)
- Riccardo Volpes
- Mediterranean Institute for Transplantation and High Specialization Therapies, Palermo, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit (Gastroenterology), Department of Surgery, Oncology and Gastroenterology,Surgical and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit (Gastroenterology), Department of Surgery, Oncology and Gastroenterology,Surgical and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Matteo Angelo Manini
- 1st Division of Gastroenterology and Hepatology, Ca' Granda-Maggiore Polyclinic Hospital, Scientific Institute for Research, Hospitalization, and Health Care, Milan, Italy
| | - Lucio Caccamo
- 1st Division of Gastroenterology and Hepatology, Ca' Granda-Maggiore Polyclinic Hospital, Scientific Institute for Research, Hospitalization, and Health Care, Milan, Italy
| | - Paolo Strignano
- General Surgery and Liver Transplant Center, S. Giovanni Battista Hospital, Turin, Italy
| | - Giorgia Rizza
- General Surgery and Liver Transplant Center, S. Giovanni Battista Hospital, Turin, Italy
| | - Mariarosa Tamè
- Liver and Multiorgan Transplantation, Department of General Surgery, Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - Antonio Daniele Pinna
- Liver and Multiorgan Transplantation, Department of General Surgery, Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - Fulvio Calise
- Hepatobiliary Surgery and Transplant Unit, Cardarelli Hospital, Naples, Italy
| | - Carla Migliaccio
- Hepatobiliary Surgery and Transplant Unit, Cardarelli Hospital, Naples, Italy
| | - Paola Carrai
- Department of General Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Paolo De Simone
- Department of General Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
| | - Maria Filippa Valentini
- General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Luigi Giovanni Lupo
- General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | | | | | - Antonio Nicolucci
- Center for Outcomes Research and Clinical Epidemiology, Via Tiziano Vecellio, 2, 65124, Pescara, Italy.
| |
Collapse
|
|
15
|
Maini MK, Burton AR. Restoring, releasing or replacing adaptive immunity in chronic hepatitis B. Nat Rev Gastroenterol Hepatol 2019; 16:662-675. [PMID: 31548710 DOI: 10.1038/s41575-019-0196-9] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2019] [Indexed: 02/06/2023]
Abstract
Multiple new therapeutic approaches are currently being developed to achieve sustained, off-treatment suppression of HBV, a persistent hepatotropic infection that kills ~2,000 people a day. A fundamental therapeutic goal is the restoration of robust HBV-specific adaptive immune responses that are able to maintain prolonged immunosurveillance of residual infection. Here, we provide insight into key components of successful T cell and B cell responses to HBV, discussing the importance of different specificities and effector functions, local intrahepatic immunity and pathogenic potential. We focus on the parallels and interactions between T cell and B cell responses, highlighting emerging areas for future investigation. We review the potential for different immunotherapies in development to restore or release endogenous adaptive immunity by direct or indirect approaches, including limitations and risks. Finally, we consider an alternative HBV treatment strategy of replacing failed endogenous immunity with infusions of highly targeted T cells or antibodies.
Collapse
Affiliation(s)
- Mala K Maini
- Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK.
| | - Alice R Burton
- Division of Infection and Immunity, Institute of Immunity and Transplantation, University College London, London, UK
| |
Collapse
|
|
16
|
Ma Z, Zhang E, Gao S, Xiong Y, Lu M. Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response. Front Immunol 2019; 10:2308. [PMID: 31608073 PMCID: PMC6769125 DOI: 10.3389/fimmu.2019.02308] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 09/12/2019] [Indexed: 12/13/2022] Open
Abstract
The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.
Collapse
Affiliation(s)
- Zhiyong Ma
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ejuan Zhang
- Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Shicheng Gao
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yong Xiong
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Mengji Lu
- Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| |
Collapse
|
|
17
|
Vatansever S, Farajov R, Yılmaz HC, Zeytunlu M, Kılıç M. The efficiency of low-dose hepatitis B immunoglobulin plus nucleos(t)ide analogs in preventing posttransplant hepatitis B virus recurrence. Turk J Med Sci 2019; 49:1019-1024. [PMID: 31385669 PMCID: PMC7018359 DOI: 10.3906/sag-1808-86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background/aim In this study, the efficiency of using low-dose hepatitis B immunoglobulin (HBIG) plus antiviral treatment according to individual needs has been evaluated in posttransplant hepatitis B virus (HBV) patients. Materials and methods We retrospectively evaluated 179 patients who were admitted between 2009 and 2014. Five thousand IU intravenous HBIG was given in the anhepatic phase, and 400 IU/day intramuscular (IM) HBIG was given in the posttransplant period. After HBsAg seroconversion, 400 IU IM HBIG was continued as prophylaxis every two weeks. Results The average follow-up period was 26 (2–65) months. Seventy patients had hepatocellular carcinoma (HCC). The HBV recurrence was 4.5% in the first year, and 5.8% in the third year. The HBsAg became negative in 11 (2–63) days, and anti-HBs became positive in 9 (1–31) days. HBsAg positivity occurred in 6 patients during the follow-up period. Five of these patients were those who underwent transplantation due to HCC. In 5 of the HCC patients, in whom HBsAg became positive, tumor recurrence was observed after 0.3–9.9 months. HBsAg positivity was more frequently detected in patients with HCC (P = 0.009). Conclusion The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who were transplanted due to HCC.
Collapse
Affiliation(s)
- Sezgin Vatansever
- Department of Gastroenterology, Atatürk Training and Research Hospital, İzmir Katip Çelebi University, İzmir, Turkey
| | - Rasim Farajov
- Department of Liver Transplantation, Kent Hospital, İzmir, Turkey
| | | | - Murat Zeytunlu
- Department of Liver Transplantation, Kent Hospital, İzmir, Turkey
| | - Murat Kılıç
- Department of Liver Transplantation, Kent Hospital, İzmir, Turkey
| |
Collapse
|
|
18
|
Chen Y, Kong Y, Shi L, Zhang X, Yang X, Liu X, Lin S, Ye F. Study of the distribution of hepatitis B immunoglobulin in pregnant mice using small-animal imaging technology. J Med Virol 2019; 91:1811-1817. [PMID: 31209906 DOI: 10.1002/jmv.25521] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 06/09/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND The safety and necessity of hepatitis B immunoglobulin (HBIG) in preventing the mother-to-child transmission of hepatitis B virus (HBV) are still controversial because of its unclear mechanism of action and the inconsistent injection programs used during gestation. OBJECTIVES This study aimed to show the dynamic transportation and distribution of HBIG in the maternal body and to provide evidence for its clinical efficacy in preventing mother-to-child HBV transmission. STUDY DESIGN Pregnant mice were injected with Cy7-labeled mouse anti-human monoclonal hepatitis B surface antibodies through the tail vein. In vivo imaging technology was used to observe the dynamic transportation and distribution of HBIG in the pregnant mice. RESULTS HBIG fluorescence signals were higher in the uterus than in the liver, spleen, and kidneys. Fluorescence signals in the uterine region were obviously higher at the third trimester than at early and mid pregnancy. CONCLUSIONS HBIG is gradually deposited in the mouse placenta during pregnancy, with the phenomenon being more significant in the third trimester.
Collapse
Affiliation(s)
- Yunru Chen
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ying Kong
- Department of Endocrinology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Lei Shi
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xi Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xueliang Yang
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaojing Liu
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shumei Lin
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Feng Ye
- Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| |
Collapse
|
|
19
|
De Simone P, Salizzoni M, Cillo U, Benedetto FD, Woodward MK, Barceló M, Páez A. Efficacy and safety of Niuliva ® immune globulin to prevent hepatitis B reinfection in de novo orthotopic liver transplant. Future Virol 2019. [DOI: 10.2217/fvl-2018-0139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aims: To determine efficacy and safety of intravenous hepatitis B immune globulin (Niuliva®, Grifols) to prevent reinfection in de novo orthotopic liver transplantation. Patients & methods: In a nonrandomized, noncontrolled and Phase III clinical trial, 15 adult patients (12 men) were treated with Niuliva from the anhepatic phase (10,000 IU/daily 1 week postsurgery) up to 6 or 12 months (5000 IU/weekly 1 month; 5000 IU/monthly thereafter). Results: No patients showed reinfection throughout the study. Niuliva was effective in maintaining antibody titers above the thresholds recommended by the European Medicines Agency (EMA) to prevent reinfection (100–150 IU/l). Four serious adverse events were reported in three patients (none related to the study product). There were no seroconversions and no deaths. Conclusion: Long-term, high-dose Niuliva administration was safe and effective to prevent graft reinfection in the tested patients.
Collapse
Affiliation(s)
- Paolo De Simone
- UO Chirurgia Epatica e Trapianto di Fegato, Az. Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Mauro Salizzoni
- Chirurgia Generale 2 – Centro Trapianto di Fegato A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Umberto Cillo
- U.O. Chirurgia Epatobiliare e dei Trapianti Epatici. Az. Ospedaliera Universitaria di Padova, Padova, Italy
| | - Fabrizio Di Benedetto
- Chirurgia Oncologica, Epatobiliopancreatica e dei Trapianti di Fegato. A.O.U. Policlinico Università di Modena e Reggio Emilia, Modena, Italy
| | | | - Miquel Barceló
- Clinical Development, Instituto Grifols S.A., Barcelona, Spain
| | - Antonio Páez
- Clinical Development, Instituto Grifols S.A., Barcelona, Spain
| |
Collapse
|
|
20
|
Lens S, García-Eliz M, Fernández I, Castells L, Bonacci M, Mas A, Crespo G, Buti M, Prieto M, Forns X. Shorter hepatitis B immunoglobulin administration is not associated to hepatitis B virus recurrence when receiving combined prophylaxis after liver transplantation. Liver Int 2018; 38:1940-1950. [PMID: 29660249 DOI: 10.1111/liv.13858] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 03/29/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS The combination of hepatitis B immunoglobulin and a nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus recurrence after liver transplantation; however, the optimal duration of hepatitis B immunoglobulin has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to hepatitis B virus recurrence after liver transplantation in a large cohort of patients under different hepatitis B immunoglobulin regimens. METHODS Retrospective multicentre analysis of hepatitis B virus-related liver transplantation recipients receiving combined prophylaxis (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short-term hepatitis B immunoglobulin was compared to lifelong administration. Hepatitis B virus recurrence was defined as positive HBsAg after liver transplantation. RESULTS Three hundred and thirty-eight patients were analysed. After a median follow-up period of 72 months, 37 patients (11%) developed hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine resistance after liver transplantation were the only factors independently associated to hepatitis B virus recurrence (HR 5.4 [2.3-12] and 9.3 [4.2-20] respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was transient (16 patients), persistent (15) or alternant (6). The hepatitis B immunoglobulin regimen did not have an impact on the rate or evolution of hepatitis B virus recurrence. Overall, patient survival was good and not influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or hepatocellular carcinoma at liver transplantation were independent risk factors for lower survival. CONCLUSIONS Liver transplantation is an effective treatment for hepatitis B virus-related liver disease. Since the introduction of combined prophylaxis the rate of hepatitis B virus recurrence is very low. However, lifelong hepatitis B immunoglobulin administration does not seem necessary to reduce hepatitis B virus recurrence.
Collapse
Affiliation(s)
- Sabela Lens
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | | | | | - Lluis Castells
- Internal Medicine, Hepatology Section, Hospital Vall Hebron, CIBERehd, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Martin Bonacci
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - Antoni Mas
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - María Buti
- Internal Medicine, Hepatology Section, Hospital Vall Hebron, CIBERehd, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Martín Prieto
- Liver Unit, CIBERehd, Hospital La Fe, Valencia, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| |
Collapse
|
|
21
|
Teegen EM, Maurer MM, Globke B, Pratschke J, Eurich D. Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience. Transpl Infect Dis 2018; 21:e12997. [PMID: 30203903 DOI: 10.1111/tid.12997] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/24/2018] [Accepted: 09/02/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.
Collapse
Affiliation(s)
- Eva Maria Teegen
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Max Magnus Maurer
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Brigitta Globke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Dennis Eurich
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| |
Collapse
|
|
22
|
Corti D, Benigni F, Shouval D. Viral envelope-specific antibodies in chronic hepatitis B virus infection. Curr Opin Virol 2018; 30:48-57. [PMID: 29738926 DOI: 10.1016/j.coviro.2018.04.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 03/26/2018] [Accepted: 04/02/2018] [Indexed: 12/20/2022]
Abstract
While the cellular immune response associated with acute and chronic HBV infection has been thoroughly studied, the B cell response in chronic hepatitis B and the role of antibodies raised against the HBV envelope antigens in controlling and prevention of infection requires further investigation. The detection of anti-HBs antibodies is considered as one of the biomarkers for functional cure of chronic hepatitis B virus infection, as well as for protective immunity. Indeed, vaccine-induced neutralizing anti-HBs antibodies have been shown to protect against HBV challenge. Yet, the therapeutic potential of viral envelope-specific antibodies and the mechanism involved in protection and prevention of cell-to-cell transmission warrants additional investigative efforts. In this review, we will provide a critical overview of the available preclinical and clinical literature supporting the putative role of active and passive vaccination and neutralizing envelope-specific antibodies for therapeutic intervention in combination regimens intended to cure persistent HBV infection.
Collapse
Affiliation(s)
- Davide Corti
- Humabs BioMed SA, A Subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
| | - Fabio Benigni
- Humabs BioMed SA, A Subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
| | - Daniel Shouval
- Liver Unit, Institute for Gastroenterology and Hepatology, Hadassah-Hebrew University Hospital, P.O. Box 12000, 91120 Jerusalem, Israel.
| |
Collapse
|
|
23
|
|
|
24
|
Young K, Liu B, Bhuket T, Younossi Z, Saab S, Ahmed A, Wong RJ. Long-term trends in chronic hepatitis B virus infection associated liver transplantation outcomes in the United States. J Viral Hepat 2017; 24:789-796. [PMID: 28273387 DOI: 10.1111/jvh.12703] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 02/02/2017] [Indexed: 12/19/2022]
Abstract
With effective antiviral therapies, rates of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and decompensated liver disease requiring liver transplantation (LT) are expected to decrease. We aim to evaluate overall trends in LT waitlist registrations, waitlist survival and likelihood of receiving LT among chronic HBV patients in the United States. Using the United Network for Organ Sharing database, we retrospectively evaluated adults (age≥18) with chronic HBV (with and without HCC) listed for LT from 1992 to 1996 (Era 1) vs 1997 to 2004 (Era 2) vs 2005-2015 (Era 3). Multivariate Cox-regression models evaluated probability of waitlist survival and receiving LT. Overall, 6797 chronic HBV adults were listed for LT. While the total number of HBV patients listed for LT remained stable, the proportion of HBV patients with HCC increased from 5.4% in Era 1 to 39.0% in Era 3. Compared to Era 1, waitlist mortality was higher in Era 2 (HR: 4.55, P<.001) and Era 3 (HR: 3.63, P<.001). However, in the most recent era, waitlist mortality significantly improved (compared to 2005-2007: 2008-2011: HR: 0.74, P=.05, 95% CI: 0.55-0.99; 2012-2015: HR: 0.53, P<.001, 95% CI: 0.38-0.75). Probability of receiving LT was also lower with latter time periods (compared to 2005-2007: 2008-2011: HR: 0.77, P<.001 95% CI: 0.68-0.86; 2012-2015: HR: 0.61, P<.001, 95% CI: 0.54-0.69). Although the number of HBV patients requiring LT remained stable, the proportion of HBV patients with HCC continues to rise. The decrease in waitlist mortality and lower likelihood of LT among HBV patients may reflect the effectiveness of antiviral therapies in delaying disease progression in the current era.
Collapse
Affiliation(s)
- K Young
- Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA
| | - B Liu
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - T Bhuket
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| | - Z Younossi
- Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA.,Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - S Saab
- Departments of Medicine and Surgery, David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, CA, USA
| | - A Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - R J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA
| |
Collapse
|
|
25
|
Han S, Na GH, Kim DG. A 6-month mixed-effect pharmacokinetic model for post-transplant intravenous anti-hepatitis B immunoglobulin prophylaxis. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2099-2107. [PMID: 28744101 PMCID: PMC5513836 DOI: 10.2147/dddt.s134711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Background Although individualized dosage regimens for anti-hepatitis B immunoglobulin (HBIG) therapy have been suggested, the pharmacokinetic profile and factors influencing the basis for individualization have not been sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics of anti-HBIG quantitatively during the first 6 months after liver transplantation. Methods Identical doses of 10,000 IU HBIG were administered to adult liver transplant recipients daily during the first week, weekly thereafter until 28 postoperative days, and monthly thereafter. Blood samples were obtained at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was quantified using 4 different immunoassay methods. The titer determined by each analytical method was used for mixed-effect modeling, and the most precise results were chosen. Simulations were performed to predict the plausible immunoglobulin maintenance dose. Results HBIG was eliminated from the body most rapidly in the immediate post-transplant period, and the elimination rate gradually decreased thereafter. In the early post-transplant period, patients with higher DNA titer tend to have lower plasma HBIG concentrations. The maintenance doses required to attain targets in 90%, 95%, and 99% of patients were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough level (in IU/L). Conclusion The variability (explained and unexplained) in HBIG pharmacokinetics was relatively larger in the early post-transplant period. Dose individualization based upon patient characteristics should be adjusted focusing quantitatively on the early post-transplant period.
Collapse
Affiliation(s)
- Seunghoon Han
- Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea.,Pharmacometrics Institute for Practical Education and Training, The Catholic University of Korea, Seocho-gu, Seoul, South Korea
| | - Gun Hyung Na
- Department of Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea
| | - Dong-Goo Kim
- Department of Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea
| |
Collapse
|
|
26
|
Urabe A, Imamura M, Tsuge M, Kan H, Fujino H, Fukuhara T, Masaki K, Kobayashi T, Ono A, Nakahara T, Kawaoka T, Hiramatsu A, Kawakami Y, Aikata H, Hayes CN, Maki N, Ohdan H, Chayama K. The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients. J Gastroenterol 2017; 52:366-375. [PMID: 27422771 DOI: 10.1007/s00535-016-1240-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2015] [Accepted: 07/02/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases. METHODS Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed. RESULTS Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325). CONCLUSIONS HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.
Collapse
Affiliation(s)
- Ayako Urabe
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiromi Kan
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takayuki Fukuhara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Keiichi Masaki
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomoki Kobayashi
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Atsushi Ono
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Noboru Maki
- Advanced Life Science Institute, Inc., Wako, Japan
| | - Hideaki Ohdan
- Division of Frontier Medical Science, Department of Surgery, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| |
Collapse
|
|
27
|
Postoperative Care of the Liver Transplant Recipient. ANESTHESIA AND PERIOPERATIVE CARE FOR ORGAN TRANSPLANTATION 2017. [PMCID: PMC7120127 DOI: 10.1007/978-1-4939-6377-5_29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
28
|
Saab S, Chen PY, Saab CE, Tong MJ. The Management of Hepatitis B in Liver Transplant Recipients. Clin Liver Dis 2016; 20:721-736. [PMID: 27742010 DOI: 10.1016/j.cld.2016.06.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver transplant (LT) is now an established indication for patients with chronic hepatitis B, mainly because of the development and use of hepatitis B immunoglobulin (HBIG) and oral antivirals for prophylaxis. The combination of low-dose HBIG and antivirals has been considered the standard prophylaxis regimen to prevent post-LT recurrence of hepatitis B. The important remaining issues are related to the long-term cost of HBIG and the risk of escape hepatitis B virus (HBV) mutants. Strategies for prevention of HBV after LT are constantly improving. With the availability of new nucleoside/nucleotide analogues, new post-LT strategies also should emerge.
Collapse
Affiliation(s)
- Sammy Saab
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA; Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
| | - Ping-Yu Chen
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Clara E Saab
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Myron J Tong
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA; Huntington Medical Research Institutes, Pasadena, CA, USA
| |
Collapse
|
|
29
|
Hara Y, Tokodai K, Nakanishi C, Miyagi S, Kawagishi N. Spontaneous resolution of de novo hepatitis B after living donor liver transplantation with hepatitis B core antibody positive graft: a case report. Surg Case Rep 2016; 2:118. [PMID: 27797067 PMCID: PMC5083705 DOI: 10.1186/s40792-016-0246-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 10/22/2016] [Indexed: 02/08/2023] Open
Abstract
Background Hepatitis B core antibody (HBcAb)-positive graft is reported to cause de novo hepatitis B after liver transplantation with a probability of 38–100 % without prophylaxis. Hepatitis B surface antigen loss is reported to be achieved with a probability of only 3–8 % in the patients treated by antiviral agents. We present an extremely rare case of spontaneous resolution of de novo hepatitis B after living donor liver transplantation (LDLT) with HBcAb-positive graft. Case presentation An 8-year-old female patient underwent LDLT for end-stage biliary atresia using an HBcAb-positive left lobe graft. After transplantation, she did not receive any prophylactic agents for hepatitis B. Two years after LDLT, she was diagnosed with chronic hepatitis B. Six years after LDLT, liver fibrosis and hepatitis activity were advanced and lamivudine was started. Two years after lamivudine administration, emergence of a lamivudine-resistant YMDD mutant was detected and adefovir dipivoxil was combined with lamivudine. Hepatitis B virus deoxyribonucleic acid (HBV-DNA) became undetectable soon after the addition of adefovir dipivoxil. Twelve years after transplantation, acute rejection occurred and steroid pulse therapy was performed, but hepatitis B did not become severe and HBV-DNA continued to be undetectable. Fifteen years after LDLT, she voluntarily discontinued medication of all drugs, including immunosuppressive agents and antiviral drugs for 1 year because of mental instability. After an interval of 1 year, liver function was normal and her serological HBV status was as follows: HBsAg(−), HBsAb(+), HBeAb(−), HBeAb(+), HBcAb(+) and HBV-DNA(−). From these results, we diagnosed her condition as spontaneous clearance of de novo hepatitis B. The patient is free of antiviral therapies and continues to take a low dose of immunosuppressive drugs and is leading a normal life. Conclusions In this case, HBsAg loss is finally achieved but we need to follow carefully for HBV reactivation with the fibrosis of the graft in mind.
Collapse
Affiliation(s)
- Yasuyuki Hara
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
| | - Kazuaki Tokodai
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Chikashi Nakanishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Shigehito Miyagi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Naoki Kawagishi
- The Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| |
Collapse
|
|
30
|
Liver transplantation and hepatitis B virus infection: towards an immunoglobulin-free antiviral treatment after transplantation. Curr Opin Organ Transplant 2016; 21:219-23. [PMID: 26859222 DOI: 10.1097/mot.0000000000000293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW This article provides an update on the latest development on deploying oral nucleosides in an immunoglobulin-free regime against hepatitis B virus (HBV) recurrence after liver transplantation. RECENT FINDINGS Entecavir and tenofovir are the two newer oral nucleosides that are associated with a low virological rebound rate at less than 2% at 5 years. As a result, they have been applied as standalone treatment against HBV recurrence after liver transplantation without immunoglobulin. Recent evidence has shown that a hepatitis B surface antigen seroclearance rate of 86% and 91% after 1 and 2 years was achievable with entecavir monotherapy. Moreover, none of the patients had histological graft damage because of HBV recurrence and an overall survival over 80% at 7 years has been reported. SUMMARY With newer and more potent oral nucleos(t)ide (NA) available, a hepatitis B immune globulin-free regimen after liver transplantation has become safe and feasible for suppression of HBV recurrence after liver transplantation, and for avoidance of HBV-related graft complications.
Collapse
|
|
31
|
Lenci I, Baiocchi L, Tariciotti L, Di Paolo D, Milana M, Santopaolo F, Manzia TM, Toti L, Svicher V, Tisone G, Perno CF, Angelico M. Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression. Liver Transpl 2016; 22:1205-1213. [PMID: 27272189 DOI: 10.1002/lt.24493] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 05/03/2016] [Accepted: 05/05/2016] [Indexed: 02/05/2023]
Abstract
Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.
Collapse
Affiliation(s)
- Ilaria Lenci
- Hepatology Unit, Tor Vergata University, Rome, Italy
| | | | | | | | | | | | | | - Luca Toti
- Liver Transplant Unit, Tor Vergata University, Rome, Italy
| | - Valentina Svicher
- Laboratory of Molecular Virology, Tor Vergata University, Rome, Italy
| | | | | | | |
Collapse
|
|
32
|
Lepelletier C, Salmona M, Berçot B, Maylin S, Sellier PO. First description of past Hepatitis B Virus infection acute reactivation occurring in a Human Immunodeficiency Virus infected patient as manifestation of immune reconstitution inflammatory syndrome. J Infect Chemother 2016; 22:490-4. [DOI: 10.1016/j.jiac.2016.01.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 12/04/2015] [Accepted: 01/06/2016] [Indexed: 01/05/2023]
|
|
33
|
De Simone P, Romagnoli R, Tandoi F, Carrai P, Ercolani G, Peri E, Zamboni F, Mameli L, Di Benedetto F, Cillo U, De Carlis L, Lauterio A, Lupo L, Tisone G, Prieto M, Loinaz C, Mas A, Suddle A, Mutimer D, Roche B, Wartenberg-Demand A, Niemann G, Böhm H, Samuel D. Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study. Transplantation 2016; 100:1507-1512. [PMID: 27023394 DOI: 10.1097/tp.0000000000001171] [Citation(s) in RCA: 21] [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
BACKGROUND Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. METHODS In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. CONCLUSIONS Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.
Collapse
Affiliation(s)
- Paolo De Simone
- 1 Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 2 Liver Transplantation Center and General Surgery 2U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy. 3 Unità Operativa di Chirurgia Generale e dei Trapianti di Fegato e Multiorgano, Bologna, Italy. 4 Centro Trapianti di Fegato e Pancreas, Cagliari, Italy. 5 Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 6 Chirurgia Epatobiliare e Trapianto Epatico Azienda Ospedaliera Universitaria di Padova-Unità Operativa di Chirurgia, Padova, Italy. 7 Struttura Complessa di Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milan, Italy. 8 Chirurgia Generale e Trapianto di Fegato, Bari, Italy. 9 Experimental Medicine and Surgery, Fondazione Policlinico Tor Vergata, Rome, Italy. 10 Unidad de Hepatología, Servicio de Medicina Digestiva, Hospital Universitari i Politècnic La Fe, Valencia, Spain. 11 Servicio de Cirugía General, Aparato Digestivo y Trasplante de Organos Abdominales, Hospital Universitario Doce de Octubre, Madrid, Spain. 12 Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain. 13 Institute of Liver Studies, King's College Hospital, London, United Kingdom. 14 NIHR Liver BRU, QE Hospital and Birmingham University, Birmingham, United Kingdom. 15 AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France. 16 University Paris-Sud, UMR-S 1193, Villejuif, France. 17 Biotest AG, Dreieich, Germany
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Usui M, Sugimoto K, Kato H, Murata Y, Tanemura A, Kuriyama N, Azumi Y, Kishiwada M, Mizuno S, Sakurai H, Takei Y, Isaji S. Discontinuation of Hepatitis B Immunoglobulin by Long-term Hepatitis B Vaccine Inoculation in Preventing Hepatitis B Recurrence After Liver Transplantation. Transplant Proc 2016; 48:1179-1183. [PMID: 27320582 DOI: 10.1016/j.transproceed.2015.12.110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/30/2015] [Indexed: 12/13/2022]
Abstract
INTRODUCTION For the patients undergoing liver transplantation for hepatitis B virus (HBV)-related diseases, hepatitis B immunoglobulin (HBIG) should be administered to prevent reinfection. Because HBIG is highly expensive and a blood product, an alternative strategy using HBV vaccination has been made in an attempt to discontinue use of HBIG. The aim of this study was to evaluate the impact of long-term HBV vaccination for discontinuation of HBIG, paying attention to the status of active immunization using T-cell proliferation assay. PATIENTS AND METHODS Among the 144 recipients who underwent liver transplantation in our hospital, 16 had HBV-related liver diseases; the 14 patients who had received vaccination were subjects in our study. To evaluate the status of active immunization, T-cell proliferation was examined by counting the number of T cells after adding HBV vaccine to the culture supernatant of T cells, and tumor necrosis factor α and interferon γ were measured in the culture supernatant. RESULTS The ratio of male/female was 13/1 (median age: 55 years; range: 37 years to 67 years). The median follow-up time was 102 months (range: approximately 14 months to 148 months). All 14 patients were free of HBV recurrence. HBIG-free status could be achieved in 9 patients (64.3%) during the treatment period for more than 50 months after beginning of HBV vaccination, of whom 5 (35.7%) became HBV vaccine-free. T-cell proliferation was confirmed by fact that the stimulation index ranged from 2.34 to 5.2 in the patients who were HBIG-free. CONCLUSION Long-term HBV vaccination after LT is a useful and effective treatment in preventing HBV recurrence, allowing the discontinuation of HBIG treatment.
Collapse
Affiliation(s)
- M Usui
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan.
| | - K Sugimoto
- Hepatogastroenterology, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - H Kato
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - Y Murata
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - A Tanemura
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - N Kuriyama
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - Y Azumi
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - M Kishiwada
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - S Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - H Sakurai
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - Y Takei
- Hepatogastroenterology, Mie Graduate School of Medicine, Tsu, Mie, Japan
| | - S Isaji
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie Graduate School of Medicine, Tsu, Mie, Japan
| |
Collapse
|
|
35
|
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: 40] [Impact Index Per Article: 4.4] [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.
Collapse
|
|
36
|
Lee EC, Kim SH, Lee SD, Park H, Lee SA, Park SJ. High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation. World J Gastroenterol 2016; 22:3803-3812. [PMID: 27076765 PMCID: PMC4814743 DOI: 10.3748/wjg.v22.i14.3803] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 12/13/2015] [Accepted: 01/11/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the impact of high-dose hepatitis B immunoglobulin (HBIG) on hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) recurrence and overall survival after living donor liver transplantation (LDLT).
METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen (HBeAg) -positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose.
RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively (P = 0.042). In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose (P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met (P = 0.317 and 0.190, respectively) and did not meet (P = 0.350 and 0.987, respectively) the Milan criteria.
CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBeAg-positive patients after LDLT.
Collapse
|
|
37
|
Abstract
BACKGROUND Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated liver cirrhosis is a major indication for liver transplantation. This concise review gives an overview about current interferon (IFN)-free treatment options before and after liver transplantation in HBV- or HCV-associated liver disease. METHODS A PubMed database search using the terms hepatitis B, hepatitis C, cirrhosis, and liver transplantation was performed to identify significant clinical studies as well as national and international guidelines. RESULTS Studies investigating IFN-free treatment in patients with decompensated HBV as well as in HCV-associated cirrhosis are scarce. Hepatic recompensation during antiviral therapy seems more frequent in patients with HBV than in those with HCV-associated cirrhosis. Graft hepatitis B or C is characterized by an accelerated and unfavorable course. Graft infection prophylaxis is safe and efficacious in HBV-related liver transplantation. Eradication of HCV prior to liver transplantation prevents HCV graft infection, and IFN-free treatment of established HCV graft infection is safe and associated with high sustained virologic response rates. CONCLUSION Patients with HBV-associated cirrhosis should be treated prior to liver transplantation, and receive a continuing graft infection prophylaxis thereafter. Patients with HCV-associated decompensated cirrhosis may be considered as candidates for antiviral therapy prior to liver transplantation or may be treated subsequently.
Collapse
Affiliation(s)
- Martin-Walter Welker
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
| | | |
Collapse
|
|
38
|
Maiwall R, Kumar M. Prevention and Treatment of Recurrent Hepatitis B after Liver Transplantation. J Clin Transl Hepatol 2016; 4:54-65. [PMID: 27047773 PMCID: PMC4807144 DOI: 10.14218/jcth.2015.00041] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 02/01/2016] [Accepted: 02/01/2016] [Indexed: 12/13/2022] Open
Abstract
Chronic hepatitis B is a global health problem that leads to development of various complications, such as cirrhosis, liver cancer, and liver failure requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction, cirrhosis of the allograft, and graft failure. Patients with high viral load at the time of transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation, while patients with low viral load, including HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation. Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and, therefore, all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence. Even, marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients. In this article, we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection.
Collapse
Affiliation(s)
- Rakhi Maiwall
- Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Kumar
- Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| |
Collapse
|
|
39
|
Jiménez-Pérez M, González-Grande R, Mostazo Torres J, González Arjona C, Rando-Muñoz FJ. Management of hepatitis B virus infection after liver transplantation. World J Gastroenterol 2015; 21:12083-12090. [PMID: 26576093 PMCID: PMC4641126 DOI: 10.3748/wjg.v21.i42.12083] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2015] [Revised: 07/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation (LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B (CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins (HBIG) during the 1990s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance (e.g., entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors (with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.
Collapse
|
|
40
|
Oh IS, Park SH. Immune-mediated Liver Injury in Hepatitis B Virus Infection. Immune Netw 2015; 15:191-8. [PMID: 26330805 PMCID: PMC4553257 DOI: 10.4110/in.2015.15.4.191] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Revised: 07/26/2015] [Accepted: 08/02/2015] [Indexed: 12/29/2022] Open
Abstract
Hepatitis B virus (HBV) is responsible for approximately 350 million chronic infections worldwide and is a leading cause of broad-spectrum liver diseases such as hepatitis, cirrhosis and liver cancer. Although it has been well established that adaptive immunity plays a critical role in viral clearance, the pathogenetic mechanisms that cause liver damage during acute and chronic HBV infection remain largely known. This review describes our current knowledge of the immune-mediated pathogenesis of HBV infection and the role of immune cells in the liver injury during hepatitis B.
Collapse
Affiliation(s)
- In Soo Oh
- Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea. ; Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 06973, Korea
| | - Su-Hyung Park
- Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea
| |
Collapse
|
|
41
|
Iwasawa K, Inui A, Tsunoda T, Kondo T, Kawamoto M, Sogo T, Komatsu H, Fujisawa T. Hepatitis B (HB) immunoglobulin plus HB vaccine for intrauterine HB virus infection. Pediatr Int 2015; 57:401-5. [PMID: 25331640 DOI: 10.1111/ped.12528] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 08/28/2014] [Accepted: 10/08/2014] [Indexed: 12/26/2022]
Abstract
BACKGROUND Vaccination against hepatitis B virus (HBV) infection in infants born to hepatitis B surface antigen (HBsAg)-positive mothers using HB immunoglobulin (HBIG) and hepatitis B (HB) vaccine was launched in Japan in 1985. Infants testing positive for HBsAg at 1 month of age are considered to have prenatally acquired the infection and are usually excluded from the prevention program. Infants born to HB e antigen (HBeAg)-positive mothers are at a high risk of perinatally acquiring the infection. In this study, long-term outcome was evaluated in children with prenatal HBV infection who received the HBIG and HB vaccine in Japan. METHODS Newborns of both HBsAg- and HBeAg-positive carrier mothers received HBIG within 48 h of birth and at 2 months of age. Subsequently, three doses of recombinant HB vaccine were given at 2, 3, and 5 months of age. Outcome was compared between the following two groups: infants who completed the vaccination program, even if they were HBsAg positive at 1 month of age (n = 15), and infants who did not (n = 51). RESULTS Seroconversion from HBeAg to anti-HBe antibody (HBeAb) before 3 years of age was observed in five children (33%) who completed the vaccination program and in two (4%) who did not (P = 0.005). In 2/5 children who completed the vaccination program and achieved HBeAb seroconversion, seroconversion from HBsAg to anti-HBs antibody was also noted. CONCLUSION This specific vaccination program for children with prenatal HBV infection has the potential to alter immune tolerance to HBV.
Collapse
Affiliation(s)
- Kentaro Iwasawa
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| | - Ayano Inui
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| | - Tomoyuki Tsunoda
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| | - Takeo Kondo
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| | - Manari Kawamoto
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| | - Tsuyoshi Sogo
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| | - Haruki Komatsu
- Department of Pediatrics, Sakura Hospital, Toho University Schowol of Medicine, Sakura, Chiba, Japan
| | - Tomoo Fujisawa
- Division of Hepatology and Gastroenterology, Children's Center for Health and Development, Saiseikai Yokohamashi Tobu Hospital, Sakura, Chiba, Japan
| |
Collapse
|
|
42
|
Choudhary NS, Saraf N, Saigal S, Mohanka R, Rastogi A, Goja S, Menon PB, Soin AS. Low-dose short-term hepatitis B immunoglobulin with high genetic barrier antivirals: the ideal post-transplant hepatitis B virus prophylaxis? Transpl Infect Dis 2015; 17:329-33. [PMID: 25682715 DOI: 10.1111/tid.12369] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 12/02/2014] [Accepted: 01/28/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Low-dose hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogs (lamivudine/adefovir) used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT) are associated with some risk of HBV recurrence and antiviral resistance. METHODS The study cohort included 176 patients (at least >12 months follow-up) with HBV cirrhosis/hepatocellular carcinoma who received secondary prophylaxis with indefinite entecavir/tenofovir after living-donor LT (LDLT). All patients received 10,000 IU intravenous HBIG in anhepatic phase followed by 600-1000 IU intramuscularly daily for 7 days, weekly for 3 weeks, and then monthly, to keep antiHBs levels >100 mIU/mL for 1 year. Hepatitis B surface antigen (HBsAg) and HBV DNA were tested every 6 months. RESULTS The study cohort is composed of 157 men and 19 women, mean age 47.9 ± 10.1 years, all HBsAg positive, 35 (19.8%) had HBV DNA >2000 IU/mL before LT. After LT, patients received entecavir (n = 126, 71.5%), tenofovir (n = 20, 11.3%), or a combination of entecavir and tenofovir (n = 30, 17% for 3 months), followed by entecavir alone. During follow-up of 43 (12-117) months, 2 patients (including 1 with non-compliance) had HBV recurrence. CONCLUSION In a large cohort of LDLT recipients for HBV-related liver disease, use of low-dose short-term HBIG with high genetic barrier drugs results in a substantially lower incidence of HBV recurrence, even in high-risk patients.
Collapse
Affiliation(s)
- N S Choudhary
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - N Saraf
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - S Saigal
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - R Mohanka
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - A Rastogi
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - S Goja
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - P B Menon
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| | - A S Soin
- Medanta Liver Institute, Medanta The Medicity, Gurgaon, Haryana, India
| |
Collapse
|
|
43
|
Cerino A, Bremer CM, Glebe D, Mondelli MU. A Human Monoclonal Antibody against Hepatitis B Surface Antigen with Potent Neutralizing Activity. PLoS One 2015; 10:e0125704. [PMID: 25923526 PMCID: PMC4414269 DOI: 10.1371/journal.pone.0125704] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 03/17/2015] [Indexed: 12/11/2022] Open
Abstract
We describe the production and characterization of human monoclonal antibodies (mAb) specific for the major hepatitis B virus (HBV) S protein. The mAbs, two IgG1κ and one IgG1λ, were secreted by B-cell clones obtained from peripheral blood mononuclear cells (PBMC) of one person convalescent from acute hepatitis B and one vaccinated individual. The former recognized a denaturation-insensitive epitope within the p24 protein whereas the latter recognized a denaturation-sensitive, conformational epitope located within the HBsAg common "a" determinant. This mAb, denominated ADRI-2F3, displayed a very high protective titer of over 43,000 IU/mg mAb and showed an extremely potent neutralizing activity in the in vitro model of HBV infection using primary hepatocytes from Tupaia belangeri as target. Recombinant variable heavy and light domain sequences derived from mAb ADRI-2F3 were cloned into eukaryotic expression vectors and showed identical fine specificity and 1 log10 higher titer than the original IgG1λ. It is envisaged that such mAb will be able to efficiently prevent HBV reinfection after liver transplantation for end-stage chronic HBV infection or infection after needle-stick exposure, providing an unlimited source of valuable protective anti-HBs antibody.
Collapse
Affiliation(s)
- Antonella Cerino
- Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Corinna M. Bremer
- Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Justus-Liebig University of Giessen, Giessen, Germany
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Centre for Hepatitis B and D Viruses, German Center for Infection Research, Justus-Liebig University of Giessen, Giessen, Germany
| | - Mario U. Mondelli
- Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
- * E-mail:
| |
Collapse
|
|
44
|
Wang C, Teng Z, Zhu Y, Zhao AZ, Sun C. Associations between pre-S deletion mutation of hepatitis B virus and risk of hepatocellular carcinoma in the Asian population: a meta-analysis. Med Sci Monit 2015; 21:1072-7. [PMID: 25868851 PMCID: PMC4410724 DOI: 10.12659/msm.894058] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the most common liver cancer, leading to many cancer-related deaths worldwide. Several studies have shown an association between pre-S deletion mutation of hepatitis B virus (HBV) and HCC risk, but the results remain conflicting. We aimed to verify HBV pre-S deletion mutations in relation to the risk of HCC. Material/Methods We searched the commonly used electronic databases for relevant studies of this association among the Asian population until September 30th, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to calculate the association. Results A total of 17 case-control studies were screened out, including 2837 HBV-infected patients, of whom 1246 had HCC. The results showed that the frequency of pre-S deletion of HBV in patients with HCC was higher than that in patients without HCC (35.7% vs. 11.5%), indicating the prevalence of this mutation in patients with HCC. Statistically significant correlations were observed for pre-S deletion mutation and risk of HCC in a random-effects model (OR=3.90, 95% CI=2.80–5.44, P<0.00001). This association was also found in Chinese populations (OR=4.84, 95% CI=2.86–8.20, P<0.00001). Conclusions Our data indicate that HBV pre-S deletion mutations might be associated with HCC risk. Their oncogenic role may be important in studying the potential mechanism of HBV hepatocarcinogenesis.
Collapse
Affiliation(s)
- Chao Wang
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
| | - Zhaowei Teng
- The People's Hospital of Yuxi City, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China (mainland)
| | - Yun Zhu
- The People's Hospital of Yuxi City, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China (mainland)
| | - Allan Z Zhao
- Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
| | - Chunhua Sun
- Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
| |
Collapse
|
|
45
|
EXP CLIN TRANSPLANTExp Clin Transplant 2015; 13. [DOI: 10.6002/ect.mesot2014.o78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
|
|
46
|
Affiliation(s)
- Jean-Michel Pawlotsky
- Department of Virology, National Reference Center for Viral Hepatitis B, C and D, Hôpital Henri Mondor, Université Paris-Est, Créteil, France INSERM U955, Créteil, France
| |
Collapse
|
|
47
|
Thio CL, Hawkins C. Hepatitis B Virus and Hepatitis Delta Virus. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:1815-1839.e7. [DOI: 10.1016/b978-1-4557-4801-3.00148-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
48
|
Jeong SW, Choi Y, Kim JW. Management of viral hepatitis in liver transplant recipients. Clin Mol Hepatol 2014; 20:338-44. [PMID: 25548738 PMCID: PMC4278063 DOI: 10.3350/cmh.2014.20.4.338] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 12/15/2014] [Indexed: 12/15/2022] Open
Abstract
Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.
Collapse
Affiliation(s)
- Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| |
Collapse
|
|
49
|
Harmancı Ö, Selçuk H, Haberal M. Prophylaxis against Recurrence in Liver Transplantation Patients with Hepatitis B Virus: What is New? J Clin Transl Hepatol 2014; 2:259-65. [PMID: 26356785 PMCID: PMC4521236 DOI: 10.14218/jcth.2014.00023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 09/17/2014] [Accepted: 09/18/2014] [Indexed: 12/18/2022] Open
Abstract
Hepatitis B virus (HBV) causes an endemic infection that affects nearly 2 billion patients worldwide. It is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). Recurrence of HBV infection after LT is due to specific HBV-host genome interactions. Although hepatitis B immunoglobulin treatment constituted the backbone of HBV recurrence, use of the nucleoside and nucleotide analogs (especially the ones with a higher genetic barrier to resistance), either alone or in combination, offer us new and powerful options in overcoming this serious issue.
Collapse
Affiliation(s)
- Özgür Harmancı
- Department of Gastroenterology, Başkent University Medical School, Ankara, Turkey
- Correspondence to: Özgür Harmancı, Department of Gastroenterology, Başkent University Medical School, Mareşal Fevzi çakmak Cad. No:45 Bahçelievler, 06490, Ankara, Turkey. Tel: +90-312-212-6868, Fax: +90-312-215-0835. E-mail:
| | - Haldun Selçuk
- Department of Gastroenterology, Başkent University Medical School, Ankara, Turkey
| | - Mehmet Haberal
- Department of General Surgery, Başkent University Medical School, Ankara, Turkey
| |
Collapse
|
|
50
|
Ghaziani T, Sendi H, Shahraz S, Zamor P, Bonkovsky HL. Hepatitis B and liver transplantation: molecular and clinical features that influence recurrence and outcome. World J Gastroenterol 2014; 20:14142-55. [PMID: 25339803 PMCID: PMC4202345 DOI: 10.3748/wjg.v20.i39.14142] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2014] [Revised: 04/29/2014] [Accepted: 05/25/2014] [Indexed: 02/07/2023] Open
Abstract
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.
Collapse
|