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1
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Radcliffe C, Kotton CN. Vaccination strategies for solid organ transplant candidates and recipients: insights and recommendations. Expert Rev Vaccines 2025; 24:313-323. [PMID: 40184037 DOI: 10.1080/14760584.2025.2489659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 03/04/2025] [Accepted: 04/02/2025] [Indexed: 04/05/2025]
Abstract
INTRODUCTION Vaccines save lives. They are integral to reducing the morbidity and mortality of vaccine-preventable infections in solid organ transplant recipients. Pre-transplant vaccination provides a unique opportunity for administration of live, viral vaccines, and enhanced vaccine efficacy, compared to the post-transplant period with decreased vaccine response due to immunosuppression. AREAS COVERED We discuss a general approach to pre- and post-transplant vaccination in solid organ transplant candidates and recipients. We then review guideline statements and recent literature related to individual vaccines, including the recently developed respiratory syncytial virus vaccine. Travel and occupation-related vaccines are also discussed. EXPERT OPINION The challenge of vaccination for immunocompromised patients expands as the prevalence of immunocompromised adults rises, and immunocompromised patients are frequently excluded from vaccine trials. In an age of vaccine hesitancy and reemerging vaccine-preventable infections, well-powered, prospective studies are needed to evaluate the clinical effectiveness of vaccines in solid organ transplant candidates and recipients.
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Affiliation(s)
| | - Camille N Kotton
- Transplant Infectious Disease and Compromised Host Program, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
- Travelers' Advice and Immunization Center, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
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2
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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Samuel D, De Martin E, Berg T, Berenguer M, Burra P, Fondevila C, Heimbach JK, Pageaux GP, Sanchez-Fueyo A, Toso C. EASL Clinical Practice Guidelines on liver transplantation. J Hepatol 2024; 81:1040-1086. [PMID: 39487043 DOI: 10.1016/j.jhep.2024.07.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 07/30/2024] [Indexed: 11/04/2024]
Abstract
Liver transplantation (LT) is an established life-saving procedure. The field of LT has changed in the past 10 years from several perspectives, with the expansion of indications, transplantation of patients with acute-on-chronic liver failure, evolution of transplant oncology, the use of donations after cardiac death, new surgical techniques, and prioritisation of recipients on the waiting list. In addition, the advent of organ perfusion machines, the recognition of new forms of rejection, and the attention paid to the transition from paediatric to adult patients, have all improved the management of LT recipients. The purpose of the EASL guidelines presented here is not to cover all aspects of LT but to focus on developments since the previous EASL guidelines published in 2016.
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4
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Yong CC, Lin YH, Espinosa WZ, Chen IH, Wang SH, Chan YC, Chen CL, Lin CC. Long-term outcomes of active vaccination against de novo hepatitis B among pediatric recipients of living donor liver transplantations with anti-HBc (+) grafts: a retrospective case-control study. Int J Surg 2024; 110:6702-6710. [PMID: 38870007 PMCID: PMC11486961 DOI: 10.1097/js9.0000000000001801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 05/30/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Active vaccination has been utilized to prevent de novo hepatitis B virus infection (DNHB) in anti-HBc (+) grafts after liver transplantation. However, the long-term efficacy of active vaccination and graft/patient outcomes of anti-HBc (+) grafts have yet to be comprehensively investigated. MATERIALS AND METHODS Among 204 pediatric patients enrolled in the study, 82 recipients received anti-HBc (+) grafts. For DNHB prevention, active vaccination was repeatedly administered prior to transplant. Antiviral therapy was given to patients with pretransplant anti-HBs <1000 IU/ml (nonrobust response) for 2 years and discontinued when post-transplant patients achieved anti-HBs >1000 IU/ml, while antiviral therapy was not given in patients with an anti-HBs titer over 1000 IU/ml. The primary outcome was to investigate the long-term efficacy of active vaccination, while the secondary outcomes included the graft and patient survival rates. RESULTS Among the 82 anti-HBc (+) transplant patients, 68% of recipients achieved a robust immune response, thus not requiring antiviral therapy. Two patients (2.4%) developed DNHB infection, one of which was due to an escape mutant. With a median follow-up of 150 months, the overall 10-year patient and graft survival rates were significantly worse in recipients of anti-HBc (+) grafts than those of anti-HBc (-) grafts (85.2 vs 93.4%, P =0.026; 85.1 vs 93.4%, P =0.034, respectively). Additionally, the 10-year patient and graft outcomes of the anti-HBc (+) graft recipients were significantly worse than those of the anti-HBc (-) graft recipients after excluding early mortality and nongraft mortality values (90.8 vs 96.6%, P =0.036; 93.0 vs 98.3%, P =0.011, respectively). CONCLUSION Our long-term follow-up study demonstrates that active vaccination is a simple, cost-effective strategy against DNHB infection in anti-HBc (+) graft patients, whereby the need for life-long antiviral therapy is removed. Notably, both the anti-HBc (+) grafts and patients exhibited inferior long-term survival rates, although the exact mechanisms remain unclear.
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Affiliation(s)
- Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
| | - Yu-Hung Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
| | - Wendell Z. Espinosa
- Department of Internal Medicine, College of Medicine, University of St. La Salle, Philippines
| | - I-Hsuan Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
| | - Shih-Ho Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
| | - Yi-Chia Chan
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
- Chang Gung University College of Medicine, Taiwan
- Kaohsiung Municipal Feng Shan Hospital-Under the management of Chang Gung Medical Foundation, Kaohsiung, Taiwan
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5
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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.
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Affiliation(s)
- Naveen Kumar
- Hepatology and Gastroenterology, Narayana Hospital Delhi, India
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Busebee B, Myhre L, Mara K, Aqel B, Taner T, Watt KD. De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis. Clin Transplant 2024; 38:e15263. [PMID: 38375953 DOI: 10.1111/ctr.15263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 01/13/2024] [Accepted: 01/28/2024] [Indexed: 02/21/2024]
Abstract
Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.
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Affiliation(s)
- Brad Busebee
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Laura Myhre
- Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA
| | - Kristin Mara
- Department of Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar Aqel
- Department of Internal Medicine, Division of Gastroenterology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Timucin Taner
- Department of Surgery, Division of Transplant Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Kymberly D Watt
- Department of Internal Medicine, Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA
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7
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Battistella S, Zanetto A, Gambato M, Germani G, Senzolo M, Burra P, Russo FP. The Role of Antiviral Prophylaxis in Preventing HBV and HDV Recurrence in the Setting of Liver Transplantation. Viruses 2023; 15:1037. [PMID: 37243124 PMCID: PMC10224456 DOI: 10.3390/v15051037] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/15/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatitis B virus (HBV) is a prevalent underlying disease, leading to liver transplantation (LT) for both decompensated cirrhosis and hepatocellular carcinoma (HCC). The hepatitis delta virus (HDV) affects approximately 5-10% of HBsAg carriers, accelerating the progression of liver injury and HCC. The initial introduction of HBV immunoglobulins (HBIG), and then of nucleos(t)ide analogues (NUCs), considerably improved the survival of HBV/HDV patients post-transplantation, as they helped prevent re-infection of the graft and recurrence of liver disease. Combination therapy with HBIG and NUCs is the primary post-transplant prophylaxis strategy in patients transplanted for HBV- and HDV-related liver disease. However, monotherapy with high-barrier NUCs, such as entecavir and tenofovir, is safe and also effective in some individuals who are at low risk of HBV reactivation. To address the problems of organ shortage, last-generation NUCs have facilitated the use of anti-HBc and HBsAg-positive grafts to meet the ever-increasing demand for grafts.
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Affiliation(s)
- Sara Battistella
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, 35128 Padova, Italy
| | - Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, 35128 Padova, Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
| | - Giacomo Germani
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy; (S.B.); (A.Z.); (M.G.); (M.S.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, 35128 Padova, Italy
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Dong C, Song Z, Sun C, Wang K, Chen J, Zhang W, Wu D, Zheng W, Yang Y, Qin H, Han C, Zhang F, Wang Z, Xu M, Zhang G, Xie E, Jiao J, Cao S, Gao W, Shen Z. HBsAg seroconversion in de novo hepatitis B virus-infected paediatric liver transplant recipients with anti-viral therapy. J Viral Hepat 2022; 29:1099-1106. [PMID: 36094676 DOI: 10.1111/jvh.13749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 08/02/2022] [Accepted: 09/07/2022] [Indexed: 12/29/2022]
Abstract
We investigated the clinical characteristics and therapeutic strategies for paediatric liver transplant (PLT) recipients who experienced de novo hepatitis B virus infection and the features of HBsAg seroconversion. A total of 821 PLT were performed in HBV-free recipients between January 2013 and January 2019 in Paediatric Organ Transplant Center, Tianjin First Central Hospital. Twenty-one recipients developed de novo HBV infection, the clinical data were analysed. The overall incidence of de novo HBV infection was 2.5%. Only one recipient received an HBcAb-negative graft, 20 recipients received HBcAb-positive grafts. The incidence of de novo HBV infection in HBcAb-negative and HBcAb-positive graft recipients were 0.2% and 6.3%, respectively. Fifteen de novo HBV-infected recipients showed HBsAg seroconversion, the incidence of HBsAg seroconversion was 71.4%. The median time from the diagnosis of de novo HBV infection to HBsAg seroconversion was 15 (1, 73) months. Recipients with hepatitis B surface antigen (HBsAg) titre <1000 IU/L and negative hepatitis B e antigen (HBeAg) at the time of de novo HBV infection diagnosis were more likely to achieve HBsAg seroconversion. Nucleotide analogues were effective in treating recipients with de novo HBV infection. De novo HBV infection does not impact liver graft function as well as recipient and graft survival rate. De novo HBV infection does not impact PLT recipient outcomes under close monitoring and appropriate treatment. High incidence of HBsAg seroconversion can be achieved after anti-viral therapy.
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Affiliation(s)
- Chong Dong
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Zhuolun Song
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Chao Sun
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Kai Wang
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Jing Chen
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Wei Zhang
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Di Wu
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Weiping Zheng
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Yang Yang
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Hong Qin
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Chao Han
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Fubo Zhang
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Zhen Wang
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Min Xu
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Guofeng Zhang
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Enbo Xie
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Junli Jiao
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Shunqi Cao
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Wei Gao
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
| | - Zhongyang Shen
- Department of Paediatric Transplantation, Tianjin First Central Hospital, Tianjin, China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, China
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9
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Russo FP, Viganò M, Stock P, Ferrarese A, Pugliese N, Burra P, Aghemo A. HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist. J Hepatol 2022; 77:503-515. [PMID: 35398460 DOI: 10.1016/j.jhep.2022.03.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 02/08/2022] [Accepted: 03/02/2022] [Indexed: 12/04/2022]
Abstract
Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.
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Affiliation(s)
- Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy
| | - Mauro Viganò
- Division of Hepatology, San Giuseppe Hospital, MultiMedica IRCCS, Milan, Italy
| | - Peter Stock
- Department of Surgery, University of California at San Francisco, San Francisco, California, USA
| | - Alberto Ferrarese
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, Verona, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale Università-Padova, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Milan, Italy
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10
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An Update on Usage of High-Risk Donors in Liver Transplantation. J Clin Med 2021; 11:jcm11010215. [PMID: 35011956 PMCID: PMC8746244 DOI: 10.3390/jcm11010215] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/01/2021] [Accepted: 12/28/2021] [Indexed: 12/13/2022] Open
Abstract
The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.
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11
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Kreitman KR, Kothadia JP, Nair SP, Maliakkal BJ. Unexpected hepatitis B virus transmission after liver transplant from nucleic acid testing- and serology-negative liver donors who are hepatitis C viremic. Hepatol Res 2021; 51:1242-1246. [PMID: 34114715 DOI: 10.1111/hepr.13680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 06/02/2021] [Accepted: 06/06/2021] [Indexed: 01/15/2023]
Abstract
The opioid epidemic has led to increased availability of organs for liver transplantation. The success of direct-acting antiviral therapy for hepatitis C (HCV) has led to the acceptance of HCV viremic donor organs. Nucleic acid testing (NAT) has led to increased detection of HCV and hepatitis B (HBV) in potential donors. A total of 36 patients underwent liver transplantation from donation after brain death donors who were HCV NAT-positive, and three of them were diagnosed with HBV several months after. All three recipients received livers from HCV viremic donors who were negative for HBV by serology and NAT. Soon after liver transplantation, HCV was treated, and all achieved sustained virologic response. They became HBV DNA-positive shortly thereafter. To date, there have been no reported cases of unexpected HBV transmission since universal donor NAT was implemented in 2013. We postulate that the inhibitory effect of HCV viremia on HBV may have prolonged the "NAT window period" in these donors beyond the 20-22 days quoted for solitary HBV infection. These cases highlight the need for more intensive and prolonged screening for HBV in recipients of livers from HCV viremic donors.
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Affiliation(s)
- Kyle R Kreitman
- MUH James D. Eason Transplant Institute, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
| | - Jiten P Kothadia
- MUH James D. Eason Transplant Institute, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
| | - Satheesh P Nair
- MUH James D. Eason Transplant Institute, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
| | - Benedict J Maliakkal
- MUH James D. Eason Transplant Institute, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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12
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Dooghaie Moghadam A, Eslami P, Dowlati Beirami A, Iravani S, Farokhi E, Mansour-Ghanaei A, Hashemi MR, Aghajanpoor Pasha M, Mehrvar A, Nassiri-Toosi M. An Overview of the Current Hepatitis B Treatment Strategies after Liver Transplantation. Middle East J Dig Dis 2021; 13:5-14. [PMID: 34712432 PMCID: PMC8531931 DOI: 10.34172/mejdd.2021.197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 10/11/2020] [Indexed: 12/15/2022] Open
Abstract
Currently, liver transplantation (LT) is considered as the only option for the treatment of patients with various causes of liver failure, including patients with chronic hepatitis B virus (HBV) infections. Overall, patients with HBV who undergo LT are at increased risk of hepatitis B infection recurrence. Although the current knowledge regarding the pathophysiology of this infection has been dramatically increased over the past few decades, it is still considered a complex disease process with varying degrees of clinical characteristics and changing patterns over time. There are various treatment strategies for preventing HBV recurrence in the LT setting. Generally, these regimens include oral nucleoside/ nucleotide analogues (NAs), hepatitis B immune globulin (HBIG), and vaccines or the combination of these drugs. The treatment strategy of choice should be based on cost-effectiveness, along with other patients underlying conditions. In this case, studies indicate that potent NAs are more cost-effective than HBIG in most case scenarios. In this article, we aimed to review the general medications used in the prophylaxis of the recurrence of HBV infection after LT.
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Affiliation(s)
- Arash Dooghaie Moghadam
- Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pegah Eslami
- Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amirreza Dowlati Beirami
- Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahrokh Iravani
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran
| | - Ermia Farokhi
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center (GLDRC), Guilan University of Medical Sciences, Guilan, Iran
| | - Mahmood Reza Hashemi
- Gastroenterology and Hepatobiliary Research Center, AJA University of Medical Sciences, Tehran, Iran
| | - Morteza Aghajanpoor Pasha
- Gastroenterology and Hepatobiliary Research Center, AJA University of Medical Sciences, Tehran, Iran
| | - Azim Mehrvar
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran
| | - Mohssen Nassiri-Toosi
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
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13
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Bhaimia E, Jung JH, Chan EL, Shah NN, Santos CAQ. Breakthrough Hepatitis B Virus Infection in a Liver Transplant Recipient on Lamivudine Prophylaxis for Donor Hepatitis B Core Antibody Seropositivity: A Review of Practices to Prevent De Novo Hepatitis B Virus Infection After Transplant. Clin Liver Dis (Hoboken) 2021; 18:22-25. [PMID: 34484700 PMCID: PMC8405053 DOI: 10.1002/cld.1102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/28/2021] [Accepted: 02/12/2021] [Indexed: 02/04/2023] Open
Affiliation(s)
- Eric Bhaimia
- Division of Infectious DiseasesDepartment of Internal MedicineRush University Medical CenterChicagoIL
| | - Jae Hyung Jung
- Department of Internal MedicineRush University Medical CenterChicagoIL
| | - Edie L. Chan
- Division of Abdominal TransplantationDepartment of SurgeryRush University Medical CenterChicagoIL
| | - Nikunj N. Shah
- Department of Internal MedicineSection of HepatologyRush University Medical CenterChicagoIL
| | - Carlos A. Q. Santos
- Division of Infectious DiseasesDepartment of Internal MedicineRush University Medical CenterChicagoIL
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14
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Cornberg M, Sandmann L, Protzer U, Niederau C, Tacke F, Berg T, Glebe D, Jilg W, Wedemeyer H, Wirth S, Höner Zu Siederdissen C, Lynen-Jansen P, van Leeuwen P, Petersen J. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:691-776. [PMID: 34255317 DOI: 10.1055/a-1498-2512] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Markus Cornberg
- Deutsches Zentrum für Infektionsforschung (DZIF), Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover; Centre for individualised infection Medicine (CiiM), Hannover.,Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Ulrike Protzer
- Institut für Virologie, Technische Universität München/Helmholtz Zentrum München, München
| | | | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig
| | - Dieter Glebe
- Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Gießen
| | - Wolfgang Jilg
- Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensberg, Regensburg
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Stefan Wirth
- Zentrum für Kinder- und Jugendmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal
| | | | - Petra Lynen-Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Pia van Leeuwen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg
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15
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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.
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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
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16
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Ohta T, Ito K, Sugiura T, Koyama N, Saitoh S, Murakami S, Tanaka Y. Breakthrough HBV infection in a vaccinated child due to vaccine escape mutant. KANZO 2021; 62:403-412. [DOI: 10.2957/kanzo.62.403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2023]
Affiliation(s)
- Takanori Ohta
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University
| | - Koichi Ito
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University
| | - Tokio Sugiura
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University
- Sugiura Kids Clinic, Hekinan
| | | | - Shinji Saitoh
- Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University
| | - Shuko Murakami
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University
- Department of Gastroenterology and Hepatology, Kumamoto University
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17
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Risk of disease transmission in an expanded donor population: the potential of hepatitis B virus donors. Curr Opin Organ Transplant 2021; 25:631-639. [PMID: 33027191 DOI: 10.1097/mot.0000000000000810] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW Lack of availability of donor organs is a constant challenge that patients and providers face in transplantation. To address this shortage, donors that test positive for hepatitis B, in particular those with resolved infection, have been increasingly utilized in clinical practice. We review here the potential risks for the recipient and the advances in hepatitis B management that have made use of these donors a well tolerated and advisable proposition. RECENT FINDINGS As routine administration of antiviral prophylaxis in the posttransplant setting among those deemed high risk for transmission, outcomes for recipients of hepatitis B donors, including liver transplant recipients, have been comparable to uninfected donors. Universal hepatitis B nucleic acid testing of donors has also enhanced our ability to accurately inform recipients regarding transmission risk. Appropriate use of prophylaxis and careful monitoring for transmission posttransplant is key to ensuring no adverse outcomes occur. SUMMARY Treatment of hepatitis B has evolved over the past two decades. Expanding the donor pool with hepatitis B donors is now well tolerated, ethical, and advantageous to the transplant community at large. A clear discussion with recipients on the substantial benefit and low harm of using hepatitis B donors will lead to greater acceptance and utilization of these organs.
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18
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Song Z, Dong C, Meng X, Sun C, Wang K, Qin H, Han C, Yang Y, Zhang F, Zheng W, Chen J, Duan K, Bi B, Gao W. Prophylactic Strategy Against De Novo Hepatitis B Virus Infection for Pediatric Recipients Who Receive Hepatitis B Core Antibody-Positive Liver Grafts. Liver Transpl 2021; 27:96-105. [PMID: 32511854 DOI: 10.1002/lt.25813] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 05/20/2020] [Accepted: 06/01/2020] [Indexed: 12/12/2022]
Abstract
The goal of this study was to evaluate the efficacy of a perioperative prophylactic strategy against de novo hepatitis B virus (HBV) infection in pediatric liver transplantation (LT) recipients with hepatitis B core antibody (HBcAb)-positive grafts. A total of 482 pediatric recipients transplanted between 2013 and 2017 were enrolled, and 170 recipients received HBcAb-positive liver grafts. The overall graft and recipient survival rates in HBcAb-positive and HBcAb-negative graft recipients were 91.8% versus 91.3% and 95.3% versus 94.2% at the end of follow-up. Preoperative hepatitis B surface antibody (HBsAb) titer ≥ 1000 IU/L and postoperative HBsAb titer ≥200 IU/L were our prophylactic targets for recipients receiving HBcAb-positive grafts. While 11 recipients developed de novo HBV infection, 10 received HBcAb-positive grafts. Both the preoperative and postoperative HBsAb targets were achieved in 78 recipients, the infection rate of de novo HBV was 1.3%; 24 recipients met the preoperative target, the infection rate was 4.2%; 52 recipients met the postoperative target, the infection rate was 1.9%; and 16 recipients met neither the preoperative nor postoperative HBsAb target, 43.8% of the recipients were infected with de novo HBV, which was significantly higher than the recipients who met both or either of the preoperative and postoperative targets. Split-liver grafts positive for HBcAb showed higher risk of de novo HBV infection. Postoperative application of lamivudine to recipients whose preoperative HBsAb titer < 1000 IU/L did not show preventive effect. Out of 11 infected recipients, 3 showed seroconversion under entecavir treatment. In conclusion, the graft and recipient survival rates were similar in pediatric LT recipients receiving HBcAb-positive or HBcAb-negative grafts. Our prophylactic strategy was effective for preventing de novo HBV infection in HBcAb-positive liver graft recipients.
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Affiliation(s)
- Zhuolun Song
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Chong Dong
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Xingchu Meng
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Chao Sun
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Kai Wang
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Hong Qin
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Chao Han
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Yang Yang
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Fubo Zhang
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Weiping Zheng
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Jing Chen
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
| | - Keran Duan
- Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin, People's Republic of China
| | - Bowen Bi
- Biological Sample Resource Sharing Center, Tianjin First Central Hospital, Tianjin, People's Republic of China
| | - Wei Gao
- Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, People's Republic of China.,Tianjin Key Laboratory for Organ Transplantation, Tianjin, People's Republic of China
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19
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Outcome and risk of de novo Hepatitis B after liver transplantation: Are all anti-HBc-positive grafts the same? Clin Res Hepatol Gastroenterol 2020; 44:791-793. [PMID: 32586783 DOI: 10.1016/j.clinre.2020.05.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 05/20/2020] [Indexed: 02/04/2023]
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20
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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.
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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
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21
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Nair AP, Sasi S, Al-Maslamani MS, Chandra P, Hashim SA, Abu Jarir S, Derbala M. Epidemiological characteristics of de novo hepatitis B infection in liver transplant recipients-An experience from a tertiary care centre in Qatar. Transpl Infect Dis 2020; 22:e13444. [PMID: 32790961 DOI: 10.1111/tid.13444] [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: 05/17/2020] [Revised: 07/17/2020] [Accepted: 08/04/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The emergence of hepatitis B surface antigen in a patient with previously negative hepatitis B virus (HBV) serology post-orthotropic liver transplant (OTLX) is known as de novo hepatitis B (DNHB). As there are no data on patients with DNHB available from Qatar, we aim to do a pioneer study indexing their clinical profile and epidemiology of patients with DNHB in Qatar. MATERIALS AND METHODS This descriptive epidemiological study was done by retrospectively reviewing records of 159 post-OTLX patients. HBV serology of these patients post-OTLX was reviewed, and 17 were identified as DNHB cases. Baseline epidemiological characteristics were defined and compared between DNHB cases and the rest. DNHB cases were analyzed statistically using the chi-square test and Kaplan-Meier curve. RESULTS The majority of the subjects were men (65%) and Qataris (40%). Mean age was 57.4 ± 12.5 years. Bulk of them underwent OTLX in China (44%). The overall incidence of DNHB was 10.7%, with transplants in China having significantly higher incidence than transplants from all other countries. The mortality rate was 23.5% in DNHB cases compared to 2.8% in non-DNHB. 67% of patients survived at least 64 months after the diagnosis of DNHB. Five-year survival did not vary significantly between those with DNHB and those without. CONCLUSION Orthotropic liver transplant in centers selecting donors liberally without screening for HBV poses the risk of DNHB. We recommend having protective levels of HBs antibodies before OTLX. Prophylactic antiviral treatment should be considered until peri-operative HBV transmission has been excluded by screening hepatic tissue for HBV DNA.
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Affiliation(s)
- Arun P Nair
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Sreethish Sasi
- Department of Internal Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Muna S Al-Maslamani
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Prem Chandra
- Medical Research Center, Hamad Medical Corporation, Doha, Qatar
| | - Samar A Hashim
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Sulieman Abu Jarir
- Department of Infectious Diseases, Communicable Diseases Center, Hamad Medical Corporation, Doha, Qatar
| | - Moutaz Derbala
- Department of Medical Gastroenterology, Hamad Medical Corporation, Doha, Qatar
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22
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Rodríguez M, Buti M, Esteban R, Lens S, Prieto M, Suárez E, García-Samaniego J. Consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B virus infection (2020). GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:559-587. [PMID: 32778356 DOI: 10.1016/j.gastrohep.2020.03.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.
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Affiliation(s)
- Manuel Rodríguez
- Sección de Hepatología, Servicio de Digestivo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España.
| | - María Buti
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Rafael Esteban
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Sabela Lens
- Servicio de Hepatología, Hospital Clínic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Universidad de Barcelona, Barcelona, España
| | - Martín Prieto
- Sección de Hepatología, Servicio de Medicina Digestiva, Hospital Universitari ì Politècnic La Fe, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Valencia, España
| | - Emilio Suárez
- Unidad de Enfermedades Digestivas, Hospital Universitario Virgen de Valme, Sevilla, España
| | - Javier García-Samaniego
- Unidad de Hepatología, Hospital Universitario La Paz, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, España.
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23
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Xie R, Huang S, Sun C, Zhu Z, Tang Y, Zhao Q, Guo Z, He X, Ju W. Deceased Donor Predictors for Pediatric Liver Allograft Utilization. Transplant Proc 2020; 52:2901-2908. [PMID: 32718748 DOI: 10.1016/j.transproceed.2020.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 02/23/2020] [Accepted: 05/12/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND The number of pediatric deceased organ donors has recently declined, and the nonutilization of pediatric liver allografts has limited the development of liver transplantation. We determined the utilization rate of pediatric livers and identified risk factors for graft discard. METHODS We used data from the Scientific Registry of Transplant Recipients database from January 1, 2000, to December 31, 2012. The trends of pediatric liver donors and utilization rates were analyzed. Donor risk factors that impacted the graft use of pediatric livers were measured. Logistic regression modelling was performed to evaluate graft utilization and risk factors. RESULTS A total of 11,934 eligible pediatric liver donors were identified during this period. A total of 1191 authorized liver grafts did not recover or recovered without transplantation. Factors including pediatric donors >1 year of age (odds ratio [OR] = 2.956, 95% confidence interval [CI] 2.494-3.503, P < .001), nonhead trauma (OR = 2.243, 95% CI 1.903-2.642, P < .001), lack of heartbeat (OR = 7.534, 95% CI 5.899-9.623, P < .001), hepatitis B surface antigen positivity (OR = 4.588, 95% CI 1.021-20.625, P = .047), anti-hepatitis C virus positivity (OR = 4.691, 95% CI 1.352-16.280, P = .015), total bilirubin >1 mg/dL (OR = 1.743, 95% CI 1.469-2.068, P < .001), and blood urea nitrogen >21 mg/dL (OR = 1.941, 95% CI 1.546-2.436, P < .001) were significantly related to graft nonutilization. Steroids or diuretics administered prerecovery were significantly related to graft utilization (OR = 0.684, 95% CI 0.581-0.806, P < .001; OR = 0.744, 95% CI 0.634-0.874, P < .001; respectively). CONCLUSIONS The pediatric liver allograft utilization rate and risk factors for nonutilization of grafts were determined.
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Affiliation(s)
- Rongxing Xie
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Shanzhou Huang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chengjun Sun
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Zebin Zhu
- Organ Transplant Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Yunhua Tang
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Qiang Zhao
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Zhiyong Guo
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China
| | - Xiaoshun He
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
| | - Weiqiang Ju
- Organ Transplant Centre, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, China.
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Laws HJ, Baumann U, Bogdan C, Burchard G, Christopeit M, Hecht J, Heininger U, Hilgendorf I, Kern W, Kling K, Kobbe G, Külper W, Lehrnbecher T, Meisel R, Simon A, Ullmann A, de Wit M, Zepp F. Impfen bei Immundefizienz. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020; 63:588-644. [PMID: 32350583 PMCID: PMC7223132 DOI: 10.1007/s00103-020-03123-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Hans-Jürgen Laws
- Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Ulrich Baumann
- Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Christian Bogdan
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität FAU Erlangen-Nürnberg, Erlangen, Deutschland
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
| | - Gerd Burchard
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Deutschland
| | - Maximilian Christopeit
- Interdisziplinäre Klinik für Stammzelltransplantation, Universitätsklinikum Eppendorf, Hamburg, Deutschland
| | - Jane Hecht
- Abteilung für Infektionsepidemiologie, Fachgebiet Nosokomiale Infektionen, Surveillance von Antibiotikaresistenz und -verbrauch, Robert Koch-Institut, Berlin, Deutschland
| | - Ulrich Heininger
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Universitäts-Kinderspital beider Basel, Basel, Schweiz
| | - Inken Hilgendorf
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Deutschland
| | - Winfried Kern
- Klinik für Innere Medizin II, Abteilung Infektiologie, Universitätsklinikum Freiburg, Freiburg, Deutschland
| | - Kerstin Kling
- Abteilung für Infektionsepidemiologie, Fachgebiet Impfprävention, Robert Koch-Institut, Berlin, Deutschland.
| | - Guido Kobbe
- Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Wiebe Külper
- Abteilung für Infektionsepidemiologie, Fachgebiet Impfprävention, Robert Koch-Institut, Berlin, Deutschland
| | - Thomas Lehrnbecher
- Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
| | - Roland Meisel
- Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Arne Simon
- Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland
| | - Andrew Ullmann
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Maike de Wit
- Klinik für Innere Medizin - Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Deutschland
- Klinik für Innere Medizin - Onkologie, Vivantes Auguste-Viktoria-Klinikum, Berlin, Deutschland
| | - Fred Zepp
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz, Mainz, Deutschland
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25
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Yang Y, Huang A, Zhao Y. Effect of hepatitis B surface antibody in patients with core antibody-positive liver transplantation: a systematic review and meta-analysis. Hepatol Int 2020; 14:202-211. [PMID: 32100260 DOI: 10.1007/s12072-020-10021-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 01/28/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM There is an increased awareness of de novo hepatitis B virus (HBV) infection (DNH) in hepatitis B surface antigen (HBsAg)-negative recipients receiving hepatitis B core antibody (HBcAb)-positive liver organ. Whether hepatitis B surface antibody (HBsAb) has positive result on preventing the occurrence of DNH in HBcAb-positive liver graft recipients remains unknown. A meta-analysis was conducted to evaluate the effect of HBsAb on DNH in these patients. METHODS We sought published studies through August 29, 2019, in Medline and other sources that examined DNH in liver transplantation receptors with HBcAb-positive grafts. The rate of DNH was established in random-effects model meta-analyses. RESULTS In 36 studies involving 950 patients, the pooled incidence rate of DNH was 5% in patients with HBsAb positive versus 28.0% HBsAb negative. Prophylactic treatment has a significant impact on the occurrence of DNH in HBsAb-negative patients, no difference in hepatitis B immunoglobulin-combined and nucleos(t)ide analogues (NAs)-alone immunoprophylaxis. Unprotected HBV-naïve patients had the highest risk with DNH. CONCLUSION Immunoprophylaxis may need more consideration for HBsAb-positive patients receiving HBcAb-positive liver grafts. Active vaccination and mono-prophylaxis with NAs could be recommended in HBsAb-negative recipients against DNH. Further studies should examine the higher genetic barrier drugs for preventing DNH, and the association between DNH and HBV DNA-positive liver graft in this patient population.
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Affiliation(s)
- Yuting Yang
- Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China
| | - Ailong Huang
- Institute for Viral Hepatitis, Ministry of Education Key Laboratory of Molecular Biology On Infectious Diseases, Chongqing Medical University, Chongqing, People's Republic of China
| | - Yao Zhao
- Pediatric Research Institute, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.
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26
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Fernández I, Pascasio JM, Colmenero J. Prophylaxis and treatment in liver transplantation. VII Consensus Document of the Spanish Society of Liver Transplantation. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:169-177. [PMID: 32094045 DOI: 10.1016/j.gastrohep.2019.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 11/05/2019] [Accepted: 11/20/2019] [Indexed: 12/26/2022]
Abstract
Whilst prophylaxis of hepatitis B is universally accepted after liver transplantation (LT), national recommendations for the prophylaxis and treatment of hepatitis B virus (HBV) infection after LT are lacking in Spain. The aim of the VII consensus meeting organised by the Spanish Society of Liver Transplantation (SETH) was to set recommendations on the prophylaxis and treatment of hepatitis B after LT. The scientific evidence and strength of recommendations was evaluated by using the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) system. This document describes the recommendations and their level of evidence for: the definition and risk factors for hepatitis B recurrence after LT, monitoring and prophylaxis of hepatitis B recurrence at different periods after LT, treatment of hepatitis B before and after LT, and the prophylaxis of HBV infection by the recipients of LT with hepatitis B core antigen positive donors.
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Affiliation(s)
- Inmaculada Fernández
- Sociedad Española de Trasplante Hepático, Unidad de Hepatología y Trasplante Hepático, Hospital 12 de Octubre, Madrid, España
| | - Juan Manuel Pascasio
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Virgen del Rocío, Sevilla, España
| | - Jordi Colmenero
- Unidad de Trasplante Hepático, Hospital Clínic, IDIBAPS, CIBERehd, Univ. Barcelona, Barcelona, España.
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27
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Bae SK, Akamatsu N, Togashi J, Ichida A, Kawahara T, Maki H, Nishioka Y, Kokudo T, Mihara Y, Kawaguchi Y, Ishizawa T, Arita J, Kaneko J, Tamura S, Hasegawa K. Hepatitis B virus recurrence after living donor liver transplantation of anti-HBc-positive grafts: A 22-year experience at a single center. Biosci Trends 2019; 13:448-455. [PMID: 31666441 DOI: 10.5582/bst.2019.01283] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The use of hepatitis B core antibody (anti-HBc)-positive grafts is one strategy for expanding the donor pool for liver transplantation (LT). The aim of this study was to determine the risk factors associated with hepatitis B virus (HBV) recurrence after living donor LT (LDLT) of anti-HBc-positive grafts. From January 1996 to December 2018, a total of 609 LDLT procedures were performed at our center. A retrospective review was performed for 31 patients (23 males and 8 females; median age = 47 years) who underwent LDLT for HBV-unrelated liver disease from anti-HBc-positive donors. The factors associated with HBV recurrence were evaluated and compared between the HBV recurrence and non-recurrence groups. The median follow-up period after LT was 135 months (range, 6-273 months). Four of 31 patients (12.9%) developed post-LT HBV recurrence. All four cases were HBV-naïve patients (anti-HBc-negative and Hepatitis B surface antibody-negative). The median interval between LDLT and HBV recurrence was 42 months (range, 20-51). The overall actuarial rates of HBV recurrence at 1, 3, 5, 10, and 20 years were 0%, 7.2%, 15.7%, 15.7%, and 15.7%, respectively. Although there were no significant differences between the HBV recurrence and non-recurrence groups, HBV recurrence tended to occur in HBV-naïve recipients (P = 0.093). HBV-naïve status may contribute to HBV recurrence after LDLT for HBV-unrelated liver disease from anti-HBc-positive donors. Careful monitoring for serological HBV markers is needed, particularly in this group.
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Affiliation(s)
- Sung Kwan Bae
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Junichi Togashi
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Akihiko Ichida
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Takuya Kawahara
- Biostatistics Division, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan
| | - Harufumi Maki
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Yujiro Nishioka
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Takashi Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Yuichiro Mihara
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Takeaki Ishizawa
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Sumihito Tamura
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
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28
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Wong TCL, Fung JYY, Cui TYS, Lam AHK, Dai JWC, Chan ACY, Cheung TT, Chok KSH, Ng KKC, Lo CM. Liver transplantation using hepatitis B core positive grafts with antiviral monotherapy prophylaxis. J Hepatol 2019; 70:1114-1122. [PMID: 30871981 DOI: 10.1016/j.jhep.2019.03.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 02/20/2019] [Accepted: 03/04/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients. METHODS This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors. RESULTS A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT. CONCLUSIONS De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant. LAY SUMMARY The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.
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Affiliation(s)
- Tiffany Cho-Lam Wong
- Department of Surgery, The University of Hong Kong, Hong Kong; Department of Surgery, Queen Mary Hospital, Hong Kong; Department of Surgery, The University of Hong Kong-Shenzhen Hospital, China
| | - James Yan-Yue Fung
- Department of Medicine, The University of Hong Kong, Hong Kong; Department of Medicine, Queen Mary Hospital, Hong Kong.
| | | | | | - Jeff Wing-Chiu Dai
- Department of Surgery, The University of Hong Kong, Hong Kong; Department of Surgery, Queen Mary Hospital, Hong Kong
| | - Albert Chi-Yan Chan
- Department of Surgery, The University of Hong Kong, Hong Kong; Department of Surgery, Queen Mary Hospital, Hong Kong; Department of Surgery, The University of Hong Kong-Shenzhen Hospital, China
| | - Tan-To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong; Department of Surgery, Queen Mary Hospital, Hong Kong; Department of Surgery, The University of Hong Kong-Shenzhen Hospital, China
| | - Kenneth Siu-Ho Chok
- Department of Surgery, The University of Hong Kong, Hong Kong; Department of Surgery, Queen Mary Hospital, Hong Kong; Department of Surgery, The University of Hong Kong-Shenzhen Hospital, China
| | | | - Chung-Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong; Department of Surgery, Queen Mary Hospital, Hong Kong; Department of Surgery, The University of Hong Kong-Shenzhen Hospital, China
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29
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Lei M, Yan LN, Yang JY, Wen TF, Li B, Wang WT, Wu H, Xu MQ, Chen ZY, Wei YG. Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China. World J Gastroenterol 2018; 24:5525-5536. [PMID: 30622380 PMCID: PMC6319134 DOI: 10.3748/wjg.v24.i48.5525] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 12/08/2018] [Accepted: 12/13/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive (HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of mainland China. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal.
AIM To evaluate the safety of using hepatitis B virus (HBV) core antibody-positive donors for liver transplantation in Chinese patients.
METHODS We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study.
RESULTS In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative (HBcAb-) liver grafts. The 1-, 3- and 5-year survival rates in patients and grafts between the two groups were similar (patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3- and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcAb+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive (HBsAg+) and HBsAg negative (HBsAg-) patients.
Newly diagnosed HBV infection had a relatively higher incidence in HBsAg- patients with HBcAb+ liver grafts (13.23%), in which HBV naive recipients suffered most (31.82%), although this difference did not affect patient and graft survival (P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody (anti-HBs) titer (more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks.
CONCLUSION HBcAb+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.
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Affiliation(s)
- Ming Lei
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lu-Nan Yan
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yin Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Tian-Fu Wen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Li
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Tao Wang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong Wu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ming-Qing Xu
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhe-Yu Chen
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yong-Gang Wei
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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30
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Badawy A, Kaido T, Uemoto S. Current Status of Liver Transplantation Using Marginal Grafts. J INVEST SURG 2018; 33:553-564. [PMID: 30457408 DOI: 10.1080/08941939.2018.1517197] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Amr Badawy
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of General Surgery, Alexandria University, Alexandria, Egypt
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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31
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Lan X, Zhang H, Li HY, Chen KF, Liu F, Wei YG, Li B. Feasibility of using marginal liver grafts in living donor liver transplantation. World J Gastroenterol 2018; 24:2441-2456. [PMID: 29930466 PMCID: PMC6010938 DOI: 10.3748/wjg.v24.i23.2441] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/04/2018] [Accepted: 05/18/2018] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is one of the most effective treatments for end-stage liver disease caused by related risk factors when liver resection is contraindicated. Additionally, despite the decrease in the prevalence of hepatitis B virus (HBV) over the past two decades, the absolute number of HBsAg-positive people has increased, leading to an increase in HBV-related liver cirrhosis and hepatocellular carcinoma. Consequently, a large demand exists for LT. While the wait time for patients on the donor list is, to some degree, shorter due to the development of living donor liver transplantation (LDLT), there is still a shortage of liver grafts. Furthermore, recipients often suffer from emergent conditions, such as liver dysfunction or even hepatic encephalopathy, which can lead to a limited choice in grafts. To expand the pool of available liver grafts, one option is the use of organs that were previously considered "unusable" by many, which are often labeled "marginal" organs. Many previous studies have reported on the possibilities of using marginal grafts in orthotopic LT; however, there is still a lack of discussion on this topic, especially regarding the feasibility of using marginal grafts in LDLT. Therefore, the present review aimed to summarize the feasibility of using marginal liver grafts for LDLT and discuss the possibility of expanding the application of these grafts.
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Affiliation(s)
- Xiang Lan
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hua Zhang
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong-Yu Li
- Department of Pancreatic Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ke-Fei Chen
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Fei Liu
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yong-Gang Wei
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bo Li
- Department of Liver Surgery and Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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32
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Verna EC. Updated Hepatitis B Guidance: Implications for liver transplant patients. Liver Transpl 2018; 24:465-469. [PMID: 29466838 DOI: 10.1002/lt.25037] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 02/20/2018] [Indexed: 12/31/2022]
Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Department of Medicine, Columbia University Medical Center, New York, NY
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33
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Chauhan R, Lingala S, Gadiparthi C, Lahiri N, Mohanty SR, Wu J, Michalak TI, Satapathy SK. Reactivation of hepatitis B after liver transplantation: Current knowledge, molecular mechanisms and implications in management. World J Hepatol 2018; 10:352-370. [PMID: 29599899 PMCID: PMC5871856 DOI: 10.4254/wjh.v10.i3.352] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 01/27/2018] [Accepted: 02/09/2018] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC). Liver transplantation (LT) is considered gold standard for treatment of hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival. The combination of lamivudine (LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA (cccDNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.
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Affiliation(s)
- Ranjit Chauhan
- Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Health Sciences Centre, Memorial University, St. John's, NL A1B 3V6, Canada
| | - Shilpa Lingala
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - Chiranjeevi Gadiparthi
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
| | - Nivedita Lahiri
- Division of Rheumatology, Immunology and Allergy, Brigham Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
| | - Smruti R Mohanty
- Division of Gastroenterology and Hepatobiliary Disease, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
| | - Jian Wu
- Department of Medical Microbiology, Key Laboratory of Molecular Virology, Fudan University School of Basic Medical Sciences, Shanghai 200032, China
| | - Tomasz I Michalak
- Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Health Sciences Centre, Memorial University, St. John's, NL A1B 3V6, Canada
| | - Sanjaya K Satapathy
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States.
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Verna EC. Vaccination to prevent de novo hepatitis B: Are there patients who do not need antiviral prophylaxis? Liver Transpl 2017; 23:1253-1254. [PMID: 28837749 DOI: 10.1002/lt.24858] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 08/22/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation,Division of Digestive and Liver Diseases, Columbia University, New York, NY
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