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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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Vutien P, Nguyen MH. HBV Reactivation in Immunosuppressed Patients: Screening, Prevention, and Management Including Solid Organ Transplant Recipients. Viruses 2025; 17:388. [PMID: 40143316 PMCID: PMC11945625 DOI: 10.3390/v17030388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/05/2025] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
Hepatitis B virus (HBV) infection remains a global health challenge, affecting over 254 million individuals chronically and contributing significantly to cirrhosis, liver failure, and hepatocellular carcinoma. Despite advancements in antiviral therapy, HBV reactivation remains a critical concern, particularly in immunosuppressed individuals, including non-transplant patients undergoing immunosuppressive therapy and solid organ transplant recipients. This review provides screening and management strategies for HBV reactivation in these populations.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356175, Seattle, WA 98195, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA 94305, USA;
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA 94305, USA
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Angelico R, Trapani S, Manzia TM, Lenci I, Grossi P, Ricci A, Burra P, Andorno E, Agnes S, Bhoori S, Baccarani U, Belli LS, Carrai P, Caccamo L, Carraro A, Cescon M, Colledan M, Cillo U, De Carlis L, De Maria N, De Simone P, di Benedetto F, Donato MF, Maria Ettorre G, Ferri F, Lanza AG, Ghinolfi D, Grieco A, Gruttadauria S, Marenco S, Martini S, Mazzaferro V, Pellicelli A, Pinelli D, Rendina M, Rizzetto M, Romagnoli R, Rossi M, Russo FP, Schiadà L, Tandoi F, Toniutto P, Turco L, Vennarecci G, Viganò M, Vivarelli M, Tisone G, Feltrin G, Nardi A, Angelico M. Liver transplantation for hepatitis D virus/hepatitis B virus coinfection in Italy: an intention-to-treat analysis of long-term outcomes. Am J Transplant 2025:S1600-6135(25)00106-6. [PMID: 40057194 DOI: 10.1016/j.ajt.2025.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 03/02/2025] [Accepted: 03/03/2025] [Indexed: 04/11/2025]
Abstract
Patients with hepatitis D virus (HDV)/hepatitis B virus (HBV)-related end-stage liver disease candidates for liver transplantation (LT) have traditionally been regarded as a special population, although their outcomes are controversial. An intention-to-treat (ITT) analysis of long-term outcomes of HDV/HBV-coinfected patients waitlisted for LT in Italy, between 2011 and 2020, was performed and compared with HBV-monoinfected LT candidates. Of 1731 HBV-infected LT candidates, 1237 (71.5%) had HBV monoinfection and 494 (28.5%) HDV/HBV coinfection. At listing, HDV/HBV-coinfected patients were significantly younger, listed mainly for decompensated cirrhosis, and with fewer hepatocellular carcinoma (HCC) cases; (26% vs 65.8%; P <.0001) compared with HBV-monoinfected patients. HDV/HBV-coinfected patients showed better 5-year ITT survival (83.2%; 95% CI: 79.4%-83.4%, vs 71.6%; 95% CI: 68.8%-74.2%; P < .0001). ITT-multivariable analysis identified the presence of HCC, advanced recipient age, and high model for end-stage liver disease-Na scores as mortality risk factors. Five years after LT, 99.1% of HDV/HBV-coinfected patients received oral nucleos(t)ide analogs, with immunoglobulins against antigen of the hepatitis B virus in 91.8% of cases. HBV and HDV viral recurrences were 1.1% and 0.2%, respectively, whereas recurrent or de novo HCC were 8.9% and 0.3%, respectively. In Italy, HDV/HBV-coinfected patients waitlisted for LT showed more favorable outcomes compared with HBV-monoinfected patients, both before and after LT. These excellent results, from the largest cohort reported so far, suggest that HDV/HBV-coinfected LT recipients do not represent a risky population and may be considered for simpler long-term antiviral prophylactic strategies.
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Affiliation(s)
- Roberta Angelico
- Department of Surgical Sciences, HPB and Transplant Unit, University of Rome Tor Vergata, Rome, Italy
| | - Silvia Trapani
- Italian National Transplant Center, National Institute of Health, Rome, Italy
| | - Tommaso Maria Manzia
- Department of Surgical Sciences, HPB and Transplant Unit, University of Rome Tor Vergata, Rome, Italy.
| | - Ilaria Lenci
- Hepatology Unit, University of Rome Tor Vergata, Rome, Italy
| | - Paolo Grossi
- Department of Medicine and Surgery, University of Insubria-ASST Sette Laghi, Varese, Italy
| | - Andrea Ricci
- Italian National Transplant Center, National Institute of Health, Rome, Italy
| | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Italy
| | - Enzo Andorno
- Department of Hepatobiliary-Pancreatic Surgery and Liver Transplantation Unit, A.O.U.S. Martino, Genova, Italy
| | - Salvatore Agnes
- Department of Surgery, Transplantation Service, Catholic University of the Sacred Heart, Foundation A. Gemelli Hospital, Rome, Italy
| | - Sherrie Bhoori
- Gastroenterology, Surgery and Liver Transplantation Unit, Fondazione Istituto Nazionale Tumori IRCCS, National Cancer Institute. Milan, Italy
| | | | - Luca S Belli
- Division of General Surgery and Abdominal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, University of Milano-Bicocca, Milan, Italy
| | - Paola Carrai
- Hepatobiliary Surgery and Liver Transplant, Faculty of Medicine Hospital of the University of Pisa, Pisa, Italy
| | - Lucio Caccamo
- Division of General Surgery and Liver Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Amedeo Carraro
- Liver Transplant Unit, Department of General Surgery and Oncology, University Hospital of Verona, Verona, Italy
| | - Matteo Cescon
- General Surgery and Transplantation Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria-Policlinico S.Orsola-Malpighi, Bologna, Italy
| | - Michele Colledan
- Department of Organ Failure and Transplantation-ASST Papa Giovanni XXIII, Bergamo, Italy; Università Milano-Bicocca, Milan, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplant Unit, University Hospital of Padua, Padua, Italy
| | - Luciano De Carlis
- Division of General Surgery and Abdominal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, University of Milano-Bicocca, Milan, Italy
| | - Nicola De Maria
- Gastroenterology-OHBP Surgery and Liver Transplant, AOU Policlinico di Modena, Italy
| | - Paolo De Simone
- Division of Hepatic Surgery and Liver transplantation, University Hospital of Pisa, Pisa, Italy
| | - Fabrizio di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Azienda-Ospedaliera-Policlinico, University of Modena-Reggio Emilia, Modena, Italy
| | - Maria Francesca Donato
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuseppe Maria Ettorre
- Division of General Surgery and Liver Transplantation, Azienda-Ospedaliera San Camillo-Forlanini, Rome, Italy
| | - Flaminia Ferri
- Division of Gastroenterology, Department of Translational and Precision Medicine, La Sapienza University, Rome, Italy
| | | | - Davide Ghinolfi
- Division of Hepatic Surgery and Liver transplantation, University Hospital of Pisa, Pisa, Italy
| | - Antonio Grieco
- University Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, Rome, Italy; Internal Medicine, Gastroenterology and Medical Oncology Area, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy
| | - Salvatore Gruttadauria
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT, UPMC, Palermo, Italy; University of Catania, Catania, Italy
| | - Simona Marenco
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Silvia Martini
- Division of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery and Liver Transplantation Unit, Department of Oncology, University of Milan, Istituto Nazionale Tumori, IRCCS, Milan, Italy
| | - Adriano Pellicelli
- Liver Unit, Department of Liver Transplant, Azienda-Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Domenico Pinelli
- Chirurgia Generale 3-Trapianti Addominali, Department of Surgery, ASST Papa Giovanni XXIII, Piazza OMS 1, Bergamo, Italy
| | - Maria Rendina
- U.O.C. Gastroenterologia Universitaria, Azienda Ospedaliero-Universitaria-Policlinico di Bari, Bari, Italy
| | - Mario Rizzetto
- Department of Medical Sciences, University of Torino, Turin, Italy
| | - Renato Romagnoli
- General Surgery 2U, Liver Transplantation Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation, Sapienza University of Rome, Umberto I Policlinic, Rome, Italy
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Italy
| | - Laura Schiadà
- Liver Injury and Transplant Unit, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
| | - Francesco Tandoi
- General Surgery and Liver Transplantation Unit, University of Bari, Bari, Italy
| | - Pierluigi Toniutto
- Liver Transplant Unit, Department of Medicine University of Udine, Udine, Italy
| | - Laura Turco
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Vennarecci
- Laparoscopic, Hepatic, and Liver Transplant Unit, AORN A. Cardarelli, Naples, Italy
| | - Mauro Viganò
- Gastroenterology Hepatology and Transplantation Unit Department of Medical Area, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Marco Vivarelli
- Hepatobiliary and Abdominal Transplantation Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Giuseppe Tisone
- Department of Surgical Sciences, HPB and Transplant Unit, University of Rome Tor Vergata, Rome, Italy
| | - Giuseppe Feltrin
- Italian National Transplant Center, National Institute of Health, Rome, Italy
| | - Alessandra Nardi
- Department of Mathematics, University of Rome Tor Vergata, Rome, Italy
| | - Mario Angelico
- Hepatology Unit, University of Rome Tor Vergata, Rome, Italy
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4
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Burra P, Battistella S, Turco L, Morelli MC, Frassanito G, De Maria N, Pasulo L, Fagiuoli S, Di Benedetto C, Donato MF, Magro B, Pagano D, Bhoori S, Mazzaferro V, Lauterio A, De Carlis L, Forastiere D, Rendina M, Angrisani D, Lanza AG, Scandali G, Svegliati Baroni G, Piano S, Angeli P, Manuli C, Martini S, De Simone P, Vacca PG, Ghinolfi D, Lionetti R, Giannelli V, Mameli L, Fornasiere E, Toniutto P, Biolato M, Ponziani FR, Lenci I, Ferrarese A, Passigato N, Marenco S, Giannini E, Ferri F, Trapani S, Grossi P, Aghemo A, Zanetto A, Russo FP. Liver transplantation for HBV-related liver disease: Impact of prophylaxis for HBV on HCC recurrence. JHEP Rep 2025; 7:101278. [PMID: 40041120 PMCID: PMC11876922 DOI: 10.1016/j.jhepr.2024.101278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 11/14/2024] [Accepted: 11/14/2024] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND & AIMS Conflicting data exist regarding optimal prophylaxis for HBV recurrence (HBV-R) after liver transplantation (LT), particularly in patients with hepatocellular carcinoma (HCC). We assessed current practices for HBV-R prophylaxis in Italy, evaluating rates, risk factors, and the clinical impact of HBV-R and HCC-R. METHODS We performed a multicentric, retrospective study involving 20 Italian LT centers. All patients who underwent LT for HBV-related liver diseases between 2010 and 2021 were included. Logistic regression was used to identify predictors of HBV-R and HCC-R. Survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS We included 1,205 LT recipients (60.8% with HCC). HBV prophylaxis was prescribed in 99.7% of recipients, mostly with lifelong hepatitis B immunoglobulin+nucleos(t)ide analogues (HBIG+NUCs) (83.9%). Rates of HBV-R were 2.1% and 3.1% in patients transplanted without and with HCC, respectively. Median times from LT were 60 [9.5-77.5] and 5.5 [1-13] months, respectively. Recipients on lifelong HBIG+NUCs experienced lower rates of HBV-R than those in whom HBIG was withdrawn, used only during LT, or in those who received NUCs alone (2.3% vs. 6.2% vs. 1.9% vs. 8%, respectively; p = 0.042). In recipients with HCC, HCC-R rate was 10.8% (median time from LT: 18 months). At multivariate analysis, HBV-R (odds ratio [OR] 10.329; 95% CI 3.665-29.110), Child-Pugh C (OR 3.519; 95% CI 1.305-9.484), and microvascular invasion (OR 3.088; 95% CI 1.692-5.634) were independently associated with HCC-R. Five-year survival was lower in recipients who experienced HCC-R (32.5% vs. 92.4% in those who did not; p <0.001). CONCLUSION In Italy, HBV prophylaxis is mostly based on lifelong HBIG+NUCs. HBV-R was rare and not associated with survival in patients transplanted for decompensated cirrhosis. In patients transplanted for HCC, HBV-R was independently associated with HCC-R. The clinical implications of these findings deserve further investigation. IMPACT AND IMPLICATIONS In Italy, the combination of high-barrier nucleos(t)ide analogues and hepatitis B immunoglobulins remains the most widely used regimen for antiviral prophylaxis following liver transplantation for HBV-related liver disease. Hepatitis B recurrence after liver transplantation is a rare event and not associated with reduced survival. In transplant recipients with hepatocellular carcinoma, HBV recurrence was independently associated with hepatocellular carcinoma recurrence, though this may simply reflect an epiphenomenon without any causal relationship.
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Affiliation(s)
- Patrizia Burra
- Department of Surgery, Oncology, and Gastroenterology, University of Padova, Italy; Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Italy
| | - Sara Battistella
- Department of Surgery, Oncology, and Gastroenterology, University of Padova, Italy; Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Italy
| | - Laura Turco
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Maria Cristina Morelli
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Gabriella Frassanito
- Gastroenterology - OHBP Surgery & Liver Transplant, AOU Policlinico di Modena, Italy
| | - Nicola De Maria
- Gastroenterology - OHBP Surgery & Liver Transplant, AOU Policlinico di Modena, Italy
| | - Luisa Pasulo
- Gastroenterology, Department of Medicine – University of Milan Bicocca & Gastroenterology Hepatology & Liver Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, Bergamo 24127, Italy
| | - Stefano Fagiuoli
- Gastroenterology, Department of Medicine – University of Milan Bicocca & Gastroenterology Hepatology & Liver Transplantation Unit, ASST Papa Giovanni XXIII, Piazza OMS 1, Bergamo 24127, Italy
| | - Clara Di Benedetto
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Maria Francesca Donato
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Bianca Magro
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, University of Pittsburgh Medical Center Italy, Palermo, Italy
| | - Duilio Pagano
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, University of Pittsburgh Medical Center Italy, Palermo, Italy
| | - Sherrie Bhoori
- Hepatology, HPB Surgery and Liver Transplantation, Fondazione Istituto Nazionale Tumori IRCCS. Milan, and Department of Oncology and Hemato-oncology, University of Milan, Italy
| | - Vincenzo Mazzaferro
- Hepatology, HPB Surgery and Liver Transplantation, Fondazione Istituto Nazionale Tumori IRCCS. Milan, and Department of Oncology and Hemato-oncology, University of Milan, Italy
| | - Andrea Lauterio
- ASST Grande Ospedale Metropolitano Niguarda. Piazza Ospedale Maggiore, 3. 20162 Milano, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Luciano De Carlis
- ASST Grande Ospedale Metropolitano Niguarda. Piazza Ospedale Maggiore, 3. 20162 Milano, Italy
| | - Domenico Forastiere
- U.O.C. Gastroenterologia Universitaria, Azienda Ospedaliero-Universitaria - Policlinico di Bari, Italy
| | - Maria Rendina
- U.O.C. Gastroenterologia Universitaria, Azienda Ospedaliero-Universitaria - Policlinico di Bari, Italy
| | - Debora Angrisani
- Hepatology Unit, Cardarelli Hospital, Via A. Cardarelli 9, Naples 80131, Italy
| | | | - Giulia Scandali
- Liver Injury and Transplant Unit, Polytechnic University of Marche, Ancona, Italy
| | | | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Chiara Manuli
- Division of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Silvia Martini
- Division of Gastroenterology, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy
| | - Paolo De Simone
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Hospital, Pisa, Italy
| | - Pier Giuseppe Vacca
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Hospital, Pisa, Italy
| | - Davide Ghinolfi
- Division of Hepatic Surgery and Liver Transplantation, University of Pisa Hospital, Pisa, Italy
| | - Raffaella Lionetti
- UOC Malattie infettive-epatologia, Dipartimento POIT, Lazzaro Spallanzani, Roma, Italy
| | - Valerio Giannelli
- Liver Unit, Department of Liver Transplant, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Laura Mameli
- Liver and Pancreas Transplant Center, Azienda Ospedaliera Brotzu Piazzale Ricchi 1, Cagliari 09134, Italy
| | - Ezio Fornasiere
- Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, University of Udine, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, University of Udine, Italy
| | - Marco Biolato
- UOC Medicina Interna e del Trapianto di Fegato, Fondazione Policlinico Universitario Gemelli IRCCS, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Francesca Romana Ponziani
- Liver Unit - CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Ilaria Lenci
- Hepatology Unit, Tor Vergata University, Rome, Italy
| | - Alberto Ferrarese
- Gastroenterology, Azienda Universitaria Integrata Verona. Verona, Italy
| | - Nicola Passigato
- Gastroenterology, Azienda Universitaria Integrata Verona. Verona, Italy
| | - Simona Marenco
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Edoardo Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Flaminia Ferri
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Silvia Trapani
- Italian National Transplant Center, National Institute of Health, Rome, Italy
| | - Paolo Grossi
- Department of Medicine and Surgery, University of Insubria-ASST Sette Laghi, Varese, Italy
| | - Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Alberto Zanetto
- Department of Surgery, Oncology, and Gastroenterology, University of Padova, Italy; Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology, and Gastroenterology, University of Padova, Italy; Gastroenterology and Multivisceral Transplant Unit, Padova University Hospital, Italy
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Chiang CM, Lin YJ, Liu WC, Chou TC, Tsai CH, Chang TT, Wu IC. HBV Recurrence Detected by HBV-Related Serum Markers and Immune Escape Mutations in Chronic Hepatitis B Patients Following Liver Transplantation. J Med Virol 2025; 97:e70306. [PMID: 40108993 DOI: 10.1002/jmv.70306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 03/01/2025] [Accepted: 03/09/2025] [Indexed: 03/22/2025]
Abstract
The posttransplantation recurrence rate of hepatitis B virus (HBV) infection in patients with chronic hepatitis B (CHB) is underestimated and linked with unfavorable outcomes. We investigated HBV recurrence by serum assays in patients with CHB following liver transplantation. We enrolled patients with CHB who underwent liver transplantation between March 2001 and July 2021 to participate in cross-sectional testing for HBV-related serum markers, including biochemical analysis for HBsAg and hepatitis B core-related antigen (HBcrAg) and real-time RT-PCR/PCR for HBV RNA and HBV DNA, in 2022. HBV recurrence in this study was defined as positive results of at least one posttransplantation HBV-related serum markers. Next-generation sequencing was performed for those with posttransplantation virological breakthroughs. Ninety-six patients with CHB who underwent liver transplantation were enrolled. Among 84 patients who received grafts negative for HBsAg, 41 (48.8%) exhibited HBV recurrence, and they tested positive for either HBsAg or HBcrAg, or both. High-risk patients, identified using a risk stratification model, had a higher likelihood of recurrence than low-risk patients (odds ratio: 2.59, 95% confidence interval: 1.06-6.35, p = 0.038). In 51 patients who tested negative for HBsAg after receiving HBsAg-negative grafts, 8 (15.7%) had positive HBcrAg, indicating occult HBV infection (OBI). We identified immune escape mutations and altered N-glycosylation patterns on the surface protein in patients experiencing virological breakthroughs following lamivudine resistance. HBsAg plus HBcrAg levels can be used to detect posttransplantation HBV recurrence. The OBI prevalence was higher in patients transplanted with HBsAg-negative liver grafts compared to blood donors, vaccinated young population, and community-based populations reported in literatures, possibly because of immune escape mutations or altered N-glycosylation patterns of surface proteins.
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Affiliation(s)
- Chien-Ming Chiang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Chun Liu
- Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan
| | - Tsung-Ching Chou
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chih-Hsuan Tsai
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - I-Chin Wu
- Medical Department, Ministry of Health and Welfare Hengchun Tourism Hospital, Pingtung, Taiwan
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6
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Cerutti E, D'Arcangelo F, Becchetti C, Cilla M, Cossiga V, Guarino M, Invernizzi F, Lapenna L, Lavezzo B, Marra F, Merli M, Morelli MC, Toniutto P, Burra P, Zanetto A. Sex disparities in acute-on-chronic liver failure: From admission to the intensive care unit to liver transplantation. Dig Liver Dis 2025; 57:355-361. [PMID: 39164168 DOI: 10.1016/j.dld.2024.08.002] [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: 06/14/2024] [Revised: 07/01/2024] [Accepted: 08/04/2024] [Indexed: 08/22/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by acute liver decompensation in patients with chronic liver disease, marked by systemic inflammation and systemic organ failure. In this review, we discussed sex-related disparities in the incidence, prognosis, and access to liver transplantation (LT) for patients with ACLF, particularly during Intensive Care Unit (ICU) management. Some studies have suggested that ACLF is more prevalent among male patients admitted to the ICU, and they have higher mortality rates than females. Available prognostic scores, such as CLIF-C or TAM-score, lack sex-specific adjustments. Sarcopenia seems to enhance the accuracy of these scores though this is observed only in male individuals. LT is the only effective treatment for patients with ACLF grade 2-3 who do not respond to medical therapies. Sex-related disparities occur in both access to LT and post-transplant outcomes, although the influence of sex on the prevalence, clinical course, and listing for LT in ACLF remains largely undetermined. A sex-orientated analysis of ICU outcomes in ACLF would facilitate the development of sex-orientated management strategies, thereby improving patients' outcomes.
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Affiliation(s)
- Elisabetta Cerutti
- Department of Anesthesia, Transplant and Surgical Intensive Care, Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy
| | - Francesca D'Arcangelo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Chiara Becchetti
- Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marta Cilla
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Valentina Cossiga
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | - Maria Guarino
- Diseases of the Liver and Biliary System Unit, Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy
| | - Federica Invernizzi
- Center for Liver Disease, Division of Internal Medicine and Hepatology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
| | - Lucia Lapenna
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Bruna Lavezzo
- Emergency Department, Anesthesia and Intensive Care Unit, SS Annunziata Hospital, Savigliano ASL Cuneo, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Manuela Merli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Maria Cristina Morelli
- Internal Medicine Unit for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Academic Hospital, University of Udine, Udine, Italy
| | - Patrizia Burra
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy.
| | - Alberto Zanetto
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology and Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
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7
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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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8
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Cardoso MF, Machado MV. The Changing Face of Hepatitis Delta Virus Associated Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:3723. [PMID: 39594679 PMCID: PMC11591730 DOI: 10.3390/cancers16223723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/22/2024] [Accepted: 11/01/2024] [Indexed: 11/28/2024] Open
Abstract
Hepatitis delta virus (HDV) infection requires the presence of hepatitis B virus (HBV), and chronic HBV-HDV coinfection is considered the most severe form of viral hepatitis. When compared with HBV mono-infection, HBV-HDV coinfection is associated with higher rates of liver cirrhosis and hepatocellular carcinoma (HCC). In this review, we aim to elucidate the complex relationship between HDV infection and the development of HCC. The exact mechanisms underlying the carcinogenic potential of HDV remain to be fully elucidated. Evidence suggests that HDV has both indirect and direct oncogenic effects. Indirect effects promote accelerated progression to liver cirrhosis, which results in a different tumor microenvironment. Direct oncogenic effects are suggested by a distinct molecular signature. The recent epidemiological data regarding HBV-HDV coinfection should make us reconsider the HCC screening strategy, with special focus in younger non-cirrhotic patients. Finally, treating HCC in patients with chronic HDV poses unique challenges due to the complex interplay between HBV and HDV and the severity of liver disease. An in-depth understanding of the epidemiology and pathophysiology of HDV infection and carcinogenesis is essential to improve disease management in this high-risk population.
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Affiliation(s)
- Mariana Ferreira Cardoso
- Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal;
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
| | - Mariana Verdelho Machado
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
- Gastroenterology Department, Hospital de Vila Franca de Xira, 2600-009 Vila Franca de Xira, Portugal
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9
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Vinaixa C, DiMaira T, Russo FP, Goldberg D, Mazzola A, Walabh P, Price J, Sagal S, Kirchner V, Shaker T, Krag A, Pruett T, Coilly A, Terrault N, Berenguer M. Use of HBsAg-positive donors in liver transplantation: An ILTS-EASL-AASLD multisociety survey. Liver Transpl 2024; 30:1116-1122. [PMID: 39018028 DOI: 10.1097/lvt.0000000000000432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/21/2024] [Indexed: 07/18/2024]
Abstract
The gap between organ supply and demand in liver transplantation remains large in most parts of the world. One strategy to increase the donor pool is to use grafts infected with HCV, HBV, and/or HIV viruses. We aimed to explore the current use of HBsAg-positive liver grafts worldwide. A prospective cross-sectional web-based survey was designed, with a total of 28 queries, assessing national and local regulations, center experience, and center-specific experience related to the topic, and sent to all members of International Liver Transplantation Society, European Association for the Study of the Liver, and American Association for the Study of the Liver, and promoted on social media. A total of 135 liver transplant centers answered the survey: 38% from WHO European Regions, 39% from American regions, and 9.7% from South-East Asian regions. Most of the participating centers (67.3%) had been performing liver transplantation for over 15 years, with a mean of 66.5 liver transplants per year, and 54% also performed living-donor liver transplants. HBV-related disease was the indication for liver transplantation in an average of 15% of all liver transplantation cases. Regarding national and/or regional regulations, 40% of the centers reported that the use of HBsAg-positive donors was permitted, and an additional 20% could use them under special circumstances. Thirty-two centers (31%) had previously used HBsAg-positive donors. Among these centers, 62.5% conducted living-donor liver transplants and showed an increased inclination toward the use of HBsAg-positive grafts in centers with elevated waitlist mortality. HBsAg-positive donors are underutilized worldwide. The use of HBsAg-positive liver grafts could help to increase the donor pool, particularly in highly endemic areas.
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Affiliation(s)
- Carmen Vinaixa
- Department of Digestive Diseases, Hepatology, and Liver Transplantation, Hospital Universitario y Politécnico La Fe, Valencia, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Tommaso DiMaira
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università Padova, Padova, Italy
| | - David Goldberg
- Division of Digestive Health and Liver Diseases, University of Miller, Miller School of Medicine, Miami, Florida, USA
| | - Alessandra Mazzola
- Unité Médicale de Transplantation Hépatique, Service d'hépato-gastroentérologie. Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France
| | - Priya Walabh
- Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Paediatric Gastroenterology, Hepatology, and Nutrition, Charlotte Maxeke Johannesburg Academic Hospital, University of Witwatersrand, Johannesburg, South Africa
| | - Jennifer Price
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, University of San Francisco, California, USA
| | - Sanjiv Sagal
- Hepatology and Liver Transplant, Centre of Liver and Biliary Sciences, Centre of Gastroenterology, Hepatology, and Endoscopy, Max Saket Hospital, New Delhi, India
| | - Varvara Kirchner
- Division of Abdominal Transplantation, Department of Surgery, Stanford University, California, USA
| | - Tamer Shaker
- Division of Abdominal Transplantation, Methodist Transplant Institute- San Antonio, Texas Transplant Institute, San Antonio, Texas, USA
| | - Aleksander Krag
- Department of Clinical Research, University of Southern Denmark and Head of Hepatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Timothy Pruett
- Department of Solid Organ Transplantation, University of Minnesota, Minnesota, USA
| | - Audrey Coilly
- Centre Hepato-Biliaire, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Norah Terrault
- Department of Gastrointestinal Liver Diseases, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
| | - Marina Berenguer
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, School of Medicine of Valencia, Spain
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10
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Rizza G, Glynou K, Eletskaya M. Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey. World J Transplant 2024; 14:90949. [PMID: 39295979 PMCID: PMC11317858 DOI: 10.5500/wjt.v14.i3.90949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 05/02/2024] [Accepted: 06/07/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Hepatitis B immunoglobulin (HBIG) in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation for HBV-associated disease. AIM To evaluate patients' satisfaction, preferences, and requirements for subcutaneous (SC), intramuscular (IM), and intravenous (IV) HBIG treatments. METHODS A self-completion, cross-sectional, online, 22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France, Italy, and Turkey. Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint (trade-off) exercise. RESULTS Ninety patients were enrolled; 32%, 17%, and 51% were SC, IM, and IV HBIG users, respectively. Mean duration of treatment was 36.2 months. SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient, easiest to administer, least painful, and had the highest self-rating of treatment compliance. More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive (67%, 28%, and 28%, respectively). In the target product profile assessment, 76% of patients were likely to use hypothetical SC HBIG. In the conjoint exercise, administration route, frequency, and duration were key drivers of treatment preferences. CONCLUSION Ease, frequency, duration, and side effects of HBIG treatment administration were key drivers of treatment preferences, and SC HBIG appeared advantageous over IM and IV HBIG for administration ease, convenience, and pain. A hypothetical SC HBIG product elicited a favorable response. Patient demographics, personal preferences, and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.
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Affiliation(s)
- Giorgia Rizza
- General Surgery and Liver Transplant Center, S. Giovanni Battista Hospital, Turin I-10126, Italy
| | | | - Masha Eletskaya
- Lumanity Insight (Cello Health Insight), London SE1 1PP, United Kingdom
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11
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De Nicola S, Aghemo A. Are We Ready to Discontinue Hepatitis B Immunoglobulins to Prevent Hepatitis B and D Recurrence in Liver Transplant Recipients? Transplantation 2024; 108:1828-1829. [PMID: 38867348 DOI: 10.1097/tp.0000000000005099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2024]
Affiliation(s)
- Stella De Nicola
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano MI, Italy
| | - Alessio Aghemo
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano MI, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele MI, Italy
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12
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Cholongitas E, Oikonomou T, Bafa K, Sinakos E, Papatheodoridis GV, Goulis I. Efficacy of Newer Nucleos(t)ide Analogs After Hepatitis B Immunoglobulin Discontinuation Against Hepatitis B and D Recurrence in Liver Transplant Recipients. Transplantation 2024; 108:e239-e244. [PMID: 38557857 DOI: 10.1097/tp.0000000000005027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
BACKGROUND The use of nucleos(t)ide analogs (NAs) with a high genetic barrier to resistance, namely entecavir and tenofovir, has improved the efficacy of antiviral prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the optimal duration and dosage of hepatitis B immunoglobulin (HBIG) administration, particularly in patients transplanted for HBV and hepatitis D virus (HDV) coinfection, remains controversial. METHODS We evaluated 28 patients transplanted for HBV/HDV cirrhosis. After LT, each patient received a fixed scheme of low-dose HBIG plus NA for 6 mo post-LT and then continued with long-term NA prophylaxis (entecavir: 8, tenofovir: 20 patients). RESULTS During 72 mo of follow-up, reappearance of hepatitis B surface antigen at low titers was observed in 1 (3.6%) patient at 33 mo after HBIG discontinuation, which became negative after a single dose of HBIG 1000 IU/L, whereas both serum HBV DNA and HDV RNA remained persistently undetectable and without any clinical or biochemical evidence of HBV/HDV recurrence. CONCLUSIONS We showed for the first time the efficacy of a short, fixed scheme of low-dose HBIG plus NA followed by long-term NA monoprophylaxis against HBV/HDV recurrence after LT, although careful follow-up is needed after HBIG discontinuation, whereas further larger studies are needed to confirm these findings.
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Affiliation(s)
- Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Theodora Oikonomou
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantina Bafa
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko," Athens, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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13
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Marzano A, Canali B, De Carlis L, De Simone P, Fiorentino F, Rendina M, Vassallo C, Fagiuoli S. Estimation of lifetime costs for patients receiving a transplant: the case of liver transplantation related to hepatitis B in Italy. Front Public Health 2024; 12:1328782. [PMID: 39026594 PMCID: PMC11256195 DOI: 10.3389/fpubh.2024.1328782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 05/29/2024] [Indexed: 07/20/2024] Open
Abstract
Introduction In Italy, post-liver transplant (LT) hepatitis B virus (HBV) reinfection prophylaxis is frequently based on a combined regimen of anti-HBV immunoglobulin (HBIG) and oral antivirals. However, little information is available at the national level on the cost of LT and the contribution of HBV prophylaxis. This study aimed to quantify the direct healthcare cost for adult patients undergoing LT for HBV-related disease over a lifetime horizon and from the perspective of a National Healthcare Service. Methods A pharmaco-economic model was implemented with a 4-tiered approach consisting of 1) preliminary literature research to define the research question; 2) pragmatic literature review to retrieve existing information and inform the model; 3) micro-simulated patient cycles; and 4) validation from a panel of national experts. Results The average lifetime healthcare cost of LT for HBV-related disease was €395,986. The greatest cost drivers were post-transplant end-stage renal failure (31.9% of the total), immunosuppression (20.6%), and acute transplant phase (15.8%). HBV reinfection prophylaxis with HBIG and antivirals accounted for 12.4% and 6.4% of the total cost, respectively; however, lifetime HBIG prophylaxis was only associated with a 6.6% increase (~€422 k). Various sensitivity analyses have shown that discount rates have the greatest impact on total costs. Conclusion This analysis showed that the burden of LT due to HBV is not only clinical but also economic.
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Affiliation(s)
- Alfredo Marzano
- Gastroenterology and Hepatology Unit, San Giovanni Battista Hospital, Turin, Italy
| | - Beatrice Canali
- Real World Solutions, IQVIA Solutions Italy S.R.L., Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Hospital, Milan, Italy
| | - Paolo De Simone
- Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, Pisa, Italy
| | | | - Maria Rendina
- Gastroenterology Department of Emergency and Organ Transplantation, University Hospital Policlinico di Bari, Bari, Italy
| | - Chiara Vassallo
- Real World Solutions, IQVIA Solutions Italy S.R.L., Milan, Italy
| | - Stefano Fagiuoli
- Department of Medicine, University of Milan Bicocca and Gastroenterology Hepatology and Transplantation Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy
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14
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Chiu CY, Brumble LM, Vikram HR, Watt KD, Beam E. Hepatitis B Virus Reactivation in Non-Liver Solid Organ Transplantation: Incidence and Risk Analysis. Clin Transplant 2024; 38:e15389. [PMID: 38952185 DOI: 10.1111/ctr.15389] [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: 03/06/2024] [Revised: 06/05/2024] [Accepted: 06/08/2024] [Indexed: 07/03/2024]
Abstract
INTRODUCTION Hepatitis B virus reactivation (HBVr) can occur in solid organ transplant (SOT) recipients with previously inactive hepatitis B virus (HBV) infection. Previous studies have reported that HBVr is generally less than 10% in nonliver SOT recipients with past HBV infection. METHODS We conducted a retrospective study from January 2018 to August 2023 at Mayo Clinic sites in Arizona, Florida, and Minnesota. We examined the antiviral prophylaxis strategy used and the characteristics of HBVr in hepatitis B core antibody-positive (HBcAb +) nonliver SOT adult recipients. Past HBV infection was defined as HBcAb + / hepatitis B surface antigen (HBsAg) -. Chronic HBV infection was defined as HBcAb + / HBsAg +. RESULTS A total of 180 nonliver SOT recipients were identified during the study period. Indefinite antiviral prophylaxis was utilized in 77 recipients, and none developed HBVr after transplantation. In 103 recipients without antiviral prophylaxis, the incidence of HBVr was 12% (12/97) and 33% (2/6) in those with past HBV infection and chronic HBV infection. The incidence of HBVr in patients with past HBV infection is 16% (8/50), 15% (3/20), and 5% (1/22) in kidney, heart, and lungs, respectively. HBVr was more frequent in those who received alemtuzumab. Among 14 recipients with HBVr, none had HBV-associated liver failure or death. CONCLUSIONS Our study observed a higher rate of HBVr (12%) in nonliver SOT recipients with past HBV infection compared to the previous studies. Further studies are needed to identify predictors of HBVr in nonliver SOT recipients and optimize antiviral prophylaxis guidance.
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Affiliation(s)
- Chia-Yu Chiu
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Lisa M Brumble
- Division of Infectious Diseases, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Elena Beam
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
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15
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Xu M, Mayemura CT, Kong N, Genyk YS, Kahn JA, Terrault NA. Low frequency of HBsAg reemergence in liver transplant recipients after stopping hepatitis B immune globulin: Implications for prophylaxis protocols. Liver Transpl 2024; 30:668-671. [PMID: 38079257 DOI: 10.1097/lvt.0000000000000311] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 11/27/2023] [Indexed: 01/12/2024]
Affiliation(s)
- Mimi Xu
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Collin T Mayemura
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Niwen Kong
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Yuri S Genyk
- Division of Hepatobiliary/Pancreatic and Abdominal Organ Transplant Surgery, University of Southern California, Los Angeles, California, USA
| | - Jeffrey A Kahn
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
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16
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Li H, Lu D, Chen J, Zhang J, Zhuo J, Lin Z, Cao C, Shen W, He C, Chen H, Hu Z, Sun Y, Wei X, Zhuang L, Zheng S, Xu X. Post-transplant hepatitis B virus reactivation impacts the prognosis of patients with hepatitis B-related hepatocellular carcinoma: a dual-centre retrospective cohort study in China. Int J Surg 2024; 110:2263-2274. [PMID: 38348848 PMCID: PMC11019990 DOI: 10.1097/js9.0000000000001141] [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: 11/20/2023] [Accepted: 01/25/2024] [Indexed: 04/18/2024]
Abstract
BACKGROUND Highly active hepatitis B virus (HBV) is known to be associated with poor outcomes in patients with hepatocellular carcinoma (HCC). This study aims to investigate the relationship between HBV status and HCC recurrence after liver transplantation. METHODS The study retrospectively analyzed HCC patients undergoing liver transplantation in two centres between January 2015 and December 2020. The authors reviewed post-transplant HBV status and its association with outcomes. RESULTS The prognosis of recipients with hepatitis B surface antigen (HBsAg) reappearance ( n =58) was poorer than those with HBsAg persistent negative ( n =351) and positive ( n =53). In HBsAg persistent positive group, recipients with HBV DNA reappearance or greater than 10-fold increase above baseline had worse outcomes than those without ( P <0.01). HBV reactivation was defined as (a) HBsAg reappearance or (b) HBV DNA reappearance or greater than 10-fold increase above baseline. After propensity score matching, the 5-year overall survival rate and recurrence-free survival rate after liver transplantation in recipients with HBV reactivation were significantly lower than those without (32.0% vs. 62.3%; P <0.01, and 16.4% vs. 63.1%; P <0.01, respectively). Moreover, HBV reactivation was significantly related to post-transplant HCC recurrence, especially lung metastasis. Cox regression analysis revealed that beyond Milan criteria, microvascular invasion and HBsAg-positive graft were independent risk factors for post-transplant HBV reactivation, and a novel nomogram was established accordingly with a good predictive efficacy (area under the time-dependent receiver operating characteristic curve=0.78, C-index =0.73). CONCLUSIONS Recipients with HBV reactivation had worse outcomes and higher tumour recurrence rates than those without. The nomogram could be used to evaluate the risk of post-transplant HBV reactivation effectively.
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Affiliation(s)
- Huigang Li
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Di Lu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Jinyan Chen
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | | | - Jianyong Zhuo
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Zuyuan Lin
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Chenghao Cao
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Wei Shen
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Chiyu He
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Hao Chen
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Zhihang Hu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Yiyang Sun
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou
| | - Xuyong Wei
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
| | - Li Zhuang
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou China
| | - Xiao Xu
- Zhejiang University School of Medicine
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou
- National Center for Healthcare Quality Management in Liver Transplant, Hangzhou China
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17
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Vutien P, Nguyen MH. Expanding the Donor Pool for Liver Transplantation: Assessing the Potential Use of HBV-Positive Allografts. CURRENT HEPATOLOGY REPORTS 2024; 23:227-240. [DOI: 10.1007/s11901-024-00653-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/24/2024] [Indexed: 01/02/2025]
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18
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Gopalakrishna H, Mironova M, Dahari H, Koh C, Heller T. Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies. CURRENT HEPATOLOGY REPORTS 2024; 23:32-44. [PMID: 38533303 PMCID: PMC10965034 DOI: 10.1007/s11901-024-00643-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/14/2024] [Indexed: 03/28/2024]
Abstract
Purpose of Review Hepatitis D Virus (HDV), although a small defective virus, poses a substantial public health challenge due to lack of awareness, underrecognized prevalence, and limited treatment options. Universal HDV screening within hepatitis B virus (HBV) cohorts is essential to address this issue. Despite its aggressive nature, effective HDV therapies have remained elusive for over four decades. Recent Findings Advances in understanding HDV's biology and clinical behavior offer potential therapeutic breakthroughs, fostering optimism. As insights grow, effective and targeted therapies are being developed to improve HDV management. Summary This review delves into HDV's intricate structure and biology, highlighting formidable hurdles in antiviral development. It emphasizes the importance of widespread screening, exploring noninvasive diagnostics, and examining current and emerging innovative therapeutic strategies. Moreover, the review explores models for monitoring treatment response. In essence, this review simplifies the complexities of effectively combating HDV.
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Affiliation(s)
- Harish Gopalakrishna
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Maria Mironova
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Harel Dahari
- The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA
| | - Christopher Koh
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Theo Heller
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
- Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Building 10, Room 4-5722, Bethesda, MD 20892-1800, USA
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19
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Rodríguez-Tajes S, García-Eliz M, Marcos AC, Campos-Varela I, Ros AC, Loinaz C, Gómez Bravo MÁ, Rodríguez-Perálvarez M, Fabrega E, González Diéguez ML, Vinaixa C, Pascasio JM, Vázquez IF, Baliellas C, Castells L, Salcedo M, Prieto M, Crespo G, Lens S, Forns X. The role of HBIG in real life for patients undergoing liver transplantation due to HDV-related cirrhosis. Liver Int 2024; 44:279-285. [PMID: 38100141 DOI: 10.1111/liv.15777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 10/04/2023] [Accepted: 10/23/2023] [Indexed: 12/20/2023]
Abstract
Recommended post-liver transplant (LT) prophylaxis in patients with hepatitis delta includes a nucleos(t)ide analogue (NA) and anti-hepatitis B immunoglobulin (HBIG) indefinitely. We analysed the use of HBIG in real-life clinical practice and its impact on HBV/HDV recurrence in 174 HDV-related LT patients from 10 Spanish liver transplant centres (1988-2018). Median post-LT follow-up was 7.8 (2.3-15.1) years and patient survival at 5 years was 90%. Most patients (97%) received HBIG in the immediate post-LT, but only 42% were on HBIG at the last control. Among those discontinuing HBIG, the median time on treatment was 18 (7-52) months. Post-LT HBsAg+ was detected in 16 (9%) patients and HBV-DNA in 12 (7%). Despite HBsAg positivity, HDV recurrence was reported only in three patients (1.7%), all of whom were not receiving NA and had discontinued HBIG. Our data suggest that a finite HBIG prophylaxis in HDV-LT is feasible, especially if high-barrier NAs are used.
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Affiliation(s)
- Sergio Rodríguez-Tajes
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
| | - María García-Eliz
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
- Liver Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | | | | | - Alba Cachero Ros
- Liver Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain
| | - Carmelo Loinaz
- Liver Transplant Unit, University Hospital 12 de Octubre, Madrid, Spain
| | | | - Manuel Rodríguez-Perálvarez
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
- Liver Transplant Unit, Hospital Universitario Reina Sofia, Córdoba, Spain
| | - Emilio Fabrega
- Liver Unit, Marqués de Valdecilla University Hospital, Santander, Spain
| | | | - Carmen Vinaixa
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
- Liver Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | - José M Pascasio
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
- Liver Unit, Virgen del Rocio Hospital, Sevilla, Spain
| | | | - Carme Baliellas
- Liver Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, Spain
| | - Lluis Castells
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
- Liver Unit, Vall d'Hebron University Hospital, Barcelona, Spain
| | | | - Martín Prieto
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
- Liver Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, ISCIII, Madrid, Spain
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20
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Chen G, Hu X, Huang Y, Xiang X, Pan S, Chen R, Xu X. Role of the immune system in liver transplantation and its implications for therapeutic interventions. MedComm (Beijing) 2023; 4:e444. [PMID: 38098611 PMCID: PMC10719430 DOI: 10.1002/mco2.444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 12/17/2023] Open
Abstract
Liver transplantation (LT) stands as the gold standard for treating end-stage liver disease and hepatocellular carcinoma, yet postoperative complications continue to impact survival rates. The liver's unique immune system, governed by a microenvironment of diverse immune cells, is disrupted during processes like ischemia-reperfusion injury posttransplantation, leading to immune imbalance, inflammation, and subsequent complications. In the posttransplantation period, immune cells within the liver collaboratively foster a tolerant environment, crucial for immune tolerance and liver regeneration. While clinical trials exploring cell therapy for LT complications exist, a comprehensive summary is lacking. This review provides an insight into the intricacies of the liver's immune microenvironment, with a specific focus on macrophages and T cells as primary immune players. Delving into the immunological dynamics at different stages of LT, we explore the disruptions after LT and subsequent immune responses. Focusing on immune cell targeting for treating liver transplant complications, we provide a comprehensive summary of ongoing clinical trials in this domain, especially cell therapies. Furthermore, we offer innovative treatment strategies that leverage the opportunities and prospects identified in the therapeutic landscape. This review seeks to advance our understanding of LT immunology and steer the development of precise therapies for postoperative complications.
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Affiliation(s)
- Guanrong Chen
- The Fourth School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Xin Hu
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
| | - Yingchen Huang
- The Fourth School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Xiaonan Xiang
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
| | - Sheng Pan
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
| | - Ronggao Chen
- Department of Hepatobiliary and Pancreatic SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
| | - Xiao Xu
- Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang ProvinceHangzhouChina
- Zhejiang Chinese Medical UniversityHangzhouChina
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21
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Roche B, Samuel D. HBV prophylaxis after liver transplantation: close to the full success but at the price of long-term prophylaxis adapted to the risk of HBV recurrence. Hepatol Int 2023; 17:1072-1074. [PMID: 37353708 DOI: 10.1007/s12072-023-10508-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 02/25/2023] [Indexed: 06/25/2023]
Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Research Unit 1193, Université Paris-Saclay, 94800, Villejuif, France
- FHU Hepatinov, 94800, Villejuif, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm Research Unit 1193, Université Paris-Saclay, 94800, Villejuif, France.
- FHU Hepatinov, 94800, Villejuif, France.
- Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Centre Hépato-Biliaire, 12 av P.V. Couturier, 94804, Villejuif, France.
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22
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Giannini EG, Lai Q. HBV, antivirals, and immunoglobulins after liver transplantation: all that glitters is not gold. Hepatol Int 2023; 17:1324-1325. [PMID: 36862140 DOI: 10.1007/s12072-023-10499-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 02/04/2023] [Indexed: 03/03/2023]
Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of General and Specialty Surgery, Sapienza University of Rome, AOU Policlinico Umberto I of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
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23
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Sheng LP, Zhang JC, Zhong ZQ, Sheng XH, Ren J, Wang GQ. High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis. Hepatol Int 2023; 17:1113-1124. [PMID: 36592270 DOI: 10.1007/s12072-022-10466-w] [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: 10/10/2022] [Accepted: 12/01/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND The optimum prophylactic regimen against hepatitis B virus (HBV) recurrence after liver transplantation (LT) in HBV-infected patients is uncertain but of great clinical relevance. New evidence suggests that hepatitis B immunoglobulin (HBIG)-free approach would become a reasonable choice in the era of high-potency nucleos(t)ide analogues (HPNAs). We aimed to provide robust estimates for long-term survival and HBV recurrence in patients receiving different HBV-prophylaxis strategies after LT. METHODS We did a systematic review and meta-analysis using both pseudo-individual patient data recovered from included studies (IPDMA) and conventional trial-level aggregate data meta-analysis (ADMA). Hazard ratios (HRs) were calculated using different Cox proportional hazard models accounting for inter-study heterogeneity. ADMA was conducted to pool outcomes at specific time points. RESULTS A total of 16 studies involving 7897 patients and 41 studies involving 9435 were eligible for IPDMA and AMDA, respectively. Cumulative HBV recurrence rate and overall survival (OS) at 1, 3, 5 and 10 years post-LT were 0.3%, 0.9%, 1.2%, 1.7% and 95.6%, 89%, 86.4%, 86.4% in the HPNAs (i.e., entecavir and tenofovir) + HBIG combination group vs. 0.6%, 0.6%, 1.2%, 1.7% and 94.5%, 86.8%, 84.8%, 81.2% in the HPNAs monotherapy group (HR 1.20, 95% CI 0.56-2.60, p = 0.64; HR 1.09, 95% CI 0.70-1.69, p = 0.72), respectively. The results were compatible with AMDA. CONCLUSION A similar HBV recurrence and overall survival were found in patients who used HPNAs (mainly entecavir) monotherapy as in those who received a combination of HPNAs and HBIG. These findings address concerns regarding the safety and effectiveness of HPNAs monotherapy.
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Affiliation(s)
- Li-Ping Sheng
- Department of Infectious Diseases and Center for Liver Diseases, Peking University International Hospital, Life Park Road No.1, Chang Ping District, Beijing, 102206, China
| | - Jun-Chang Zhang
- Intensive Care Unit, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi-Qiang Zhong
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Shanghai, China
| | - Xue-Han Sheng
- The First Clinical Medical College of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jing Ren
- Department of Infectious Disease, The First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Gui-Qiang Wang
- Department of Infectious Diseases and Center for Liver Diseases, Peking University International Hospital, Life Park Road No.1, Chang Ping District, Beijing, 102206, China.
- Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
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24
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Lynch EN, Russo FP. Liver Transplantation in People Living with HIV: Still an Experimental Procedure or Standard of Care? Life (Basel) 2023; 13:1975. [PMID: 37895356 PMCID: PMC10608432 DOI: 10.3390/life13101975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/21/2023] [Accepted: 09/25/2023] [Indexed: 10/29/2023] Open
Abstract
Liver transplantation (LT) is the only curative treatment for various liver diseases, including acute liver failure, end-stage liver disease, and selected unresectable liver malignancies. Combination antiretroviral therapy has improved outcomes for people living with HIV (PLWH), transforming the status of acquired immune deficiency syndrome from a fatal disease to a chronic and manageable condition. These powerful antiviral therapies have not only increased the number of HIV+ enlisted patients by improving their survival but also made the use of HIV+ organs a viable option. In this review, we summarise current knowledge on the peculiarities of liver transplantation in PLWH. In particular, we focus on the indications, contraindications, specific considerations for treatment, and outcomes of LT in PLWH. Finally, we present available preliminary data on the use of HIV+ liver allografts.
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Affiliation(s)
- Erica Nicola Lynch
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Section, Padua University Hospital, 35128 Padua, Italy;
- Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
| | - Francesco Paolo Russo
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology/Multivisceral Transplant Section, Padua University Hospital, 35128 Padua, Italy;
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25
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Brunetto MR, Ricco G, Negro F, Wedemeyer H, Yurdaydin C, Asselah T, Papatheodoridis G, Gheorghe L, Agarwal K, Farci P, Buti M. EASL Clinical Practice Guidelines on hepatitis delta virus. J Hepatol 2023; 79:433-460. [PMID: 37364791 DOI: 10.1016/j.jhep.2023.05.001] [Citation(s) in RCA: 109] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 06/28/2023]
Abstract
Hepatitis D virus (HDV) is a defective virus that requires the hepatitis B virus to complete its life cycle and cause liver damage in humans. HDV is responsible for rare acute and chronic liver diseases and is considered the most aggressive hepatitis virus. Acute infection can cause acute liver failure, while persistent infection typically causes a severe form of chronic hepatitis which is associated with rapid and frequent progression to cirrhosis and its end-stage complications, hepatic decompensation and hepatocellular carcinoma. Major diagnostic and therapeutic innovations prompted the EASL Governing Board to commission specific Clinical Practice Guidelines on the identification, virologic and clinical characterisation, prognostic assessment, and appropriate clinical and therapeutic management of HDV-infected individuals.
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26
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Ferenci P, Reiberger T, Stadlbauer V, Zoller H. Transplantation of hepatitis D virus patients: Lifelong hepatitis B immunoglobulins? Liver Int 2023; 43 Suppl 1:96-100. [PMID: 35767373 DOI: 10.1111/liv.15352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 06/25/2022] [Accepted: 06/28/2022] [Indexed: 12/13/2022]
Abstract
The introduction of Hepatitis B Immunoglobulins (HBIg) prophylaxis at and after liver transplantation (LT) facilitated excellent long-term survival of transplant patients with chronic hepatitis B virus (HBV) infection. Several studies suggested that only short-term (i.e. 4-8 weeks) HBIg prophylaxis after LT followed by the long-term administration of HBV polymerase inhibitors prevents HBV recurrence. In hepatitis D virus (HDV)/HBV co-infected patients, the need for long-term HBIg prophylaxis on top of HBV polymerase inhibitors is unknown. HDV requires HBV surface antigen (HBsAg) for uptake into hepatocytes to subsequently establish HDV replication. Data on HDV recurrence and its impact on outcomes after LT are limited. In this review, we evaluated the available data on post-LT recurrence of HBV and/or HDV. Overall, HBIg prophylaxis was effective, but 10-13% of patients became HBsAg positive after LT. Only a single study from Turkey reported HDV recurrence, which was not observed in other LT centres. Since all studies administered continuous HBIg prophylaxis, the post-LT recurrence rates without HBIg prophylaxis remain unknown. In a German study, the clinical course and histopathological aspects of liver injury (inflammation, fibrosis and steatosis) were similar in post-LT patients on continuous HBIg and those who stopped HBIg after a median of 72 months. Discontinuation of HBIg in stable patients after LT for HBV/HDV co-infection did not lead to impaired overall survival or a higher recurrence rate in this long-term follow-up. In summary, discontinuation of HBIg after liver transplantation for HBV/HDV liver disease seems safe, but randomized controlled studies are needed before it can be generally recommended.
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Affiliation(s)
- Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Vanessa Stadlbauer
- Department of Gastroenterology and Hepatology, Medial University of Graz, Austria; Center of Biomarker research in Medicine (CBmed), Austria
| | - Heinz Zoller
- Department of Medicine I and Christian Doppler Laboratory on Iron and Phosphate Biology, Medical University of Innsbruck, Innsbruck, Austria
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27
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Lenci I, Tariciotti L, Angelico R, Milana M, Signorello A, Manzia TM, Toti L, Tisone G, Angelico M, Baiocchi L. Successful clinical and virological outcomes of liver transplantation for HDV/HBV-related disease after long-term discontinuation of hepatitis B immunoglobulins. Clin Transplant 2023; 37:e14971. [PMID: 36928864 DOI: 10.1111/ctr.14971] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 03/05/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Indefinite, long-term administration of hepatitis B immunoglobulins (HBIg), together with a third generation nucleos(t)ide analog (NA), is the currently recommended prophylactic strategy to prevent viral recurrence after liver transplantation (LT) for Hepatitis Delta virus (HDV)/Hepatitis B virus (HBV)-related disease. METHODS We retrospectively analyzed the safety and long-term clinical and virological outcomes of a consecutive cohort of 16 patients (10 males, median age 64.5, range 41-75) transplanted for HDV/HBV-related cirrhosis at our Institution, who discontinued HBIg after a median of 24.5 months (range 15-116) after transplant. All patients continued prophylaxis with same NA used before LT. Recurrence of HDV/HBV infection was defined as reappearance of serum HDV-RNA with detectable serum HBsAg and/or HBV-DNA. RESULTS The median follow-up after LT was 138 months (range 73-316) and 110 months (range 52-200) after HBIg withdrawal. All patients were HBsAg-positive, HBV-DNA negative, and anti-HDV positive at the time of LT and without coinfections with HCV or HIV. Patients were followed with biochemical and virological tests every 3-6 months after HBIg withdrawal. No recurrences of HDV/HBV infection or disease were observed during monoprophylaxis with NA. In addition, eight patients (50%) spontaneously developed anti-HBs titers above 10 IU/L at a median of 74 months (range 58-140) following HBIG discontinuation. CONCLUSIONS HBIg withdrawal after LT is a safe and efficacious strategy in patients transplanted for HDV/HBV disease and is frequently associated with the spontaneous development of serological immunity against HBV. These data call for a revision of current prophylactic recommendations in this setting.
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Affiliation(s)
- Ilaria Lenci
- Hepatology Unit, Tor Vergata University, Rome, Italy
| | | | | | | | | | | | - Luca Toti
- Liver Transplant Unit, Tor Vergata University, Rome, Italy
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28
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Villeret F, Lebossé F, Radenne S, Samuel D, Roche B, Mabrut JY, Leroy V, Pageaux GP, Anty R, Thevenon S, Ahmed SS, Hamilton A, Heil M, Scholtès C, Levrero M, Testoni B, Zoulim F. Early intrahepatic recurrence of HBV infection in liver transplant recipients despite antiviral prophylaxis. JHEP Rep 2023; 5:100728. [PMID: 37122357 PMCID: PMC10131114 DOI: 10.1016/j.jhepr.2023.100728] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 02/01/2023] [Accepted: 02/20/2023] [Indexed: 05/02/2023] Open
Abstract
Background & Aims Prophylaxis with nucleos(t)ide analogues (NUCs) and hepatitis B immunoglobulin (HBIG) has decreased the rate of HBV recurrence after orthotopic liver transplantation (OLT), but the duration of this prophylaxis remains debated. Our aim was to investigate the recurrence of both intrahepatic and serum HBV markers after OLT in patients receiving long-term NUC and HBIG prophylaxis. Methods A total of 31 HBV-positive patients benefiting from OLT were prospectively enrolled in five French centres between 2012 and 2015. Tissue samples from the native liver, liver reperfusion biopsy, and 12-month post-OLT (M12) biopsy were collected. Intrahepatic HBV markers were quantified using Droplet Digital PCR. Serum hepatitis B core-related antigen (HBcrAg) and HBsAg were quantified using the Lumipulse platform. Results Among the 31 patients, 26 were HBeAg negative and 28 had undetectable serum HBV DNA at OLT. All patients received HBIG and NUC after OLT, and serum HBV DNA was undetectable at M12. Of the 27 available native livers, 26 had detectable total HBV DNA (median, 0.045 copies/cell), 21 were positive for cccDNA (0.001 copies/cell), and 19 were positive for 3.5-kb HBV RNA (0.0004 copies/cell). Among the 14 sequential reperfusion and M12 biopsies, seven were positive for HBV markers on the reperfusion sampling, and six of them were also positive at M12. Of the 27 patients with available serum samples at M12, eight were positive for HBcrAg and five were positive for HBsAg by ultrasensitive quantification, although they were negative by conventional techniques. Overall, among the 17 patients having a matched biopsy and serum sample at M12, only one had undetectable HBV markers in both the liver and serum. Conclusions Our results demonstrate a very early detection of viral genome in the graft and intrahepatic viral recurrence despite NUC and HBIG prophylaxis. Clinical Trials Registration This study is registered at ClinicalTrials.gov (NCT02602847). Impact and Implications In this work, we show that, despite the recommended prophylaxis based on NUC and HBIG, HBV can infect the new liver very rapidly after transplantation. Twelve months after transplantation, the majority of patients had at least one HBV marker detected in either serum or the liver. Therefore, our results demonstrate early intrahepatic viral recurrence despite NUC and HBIG therapy and underline the importance of an optimal patient compliance to the antiviral prophylaxis to prevent viral rebound.
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Affiliation(s)
- François Villeret
- Service d’Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
| | - Fanny Lebossé
- Service d’Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
| | - Sylvie Radenne
- Service d’Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Didier Samuel
- Centre Hépato-Biliaire, Université Paris-Saclay, Unité Inserm 1193, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris (AP-HP), Villejuif, France
| | - Bruno Roche
- Centre Hépato-Biliaire, Université Paris-Saclay, Unité Inserm 1193, Hôpital Paul-Brousse, Assistance Publique-Hôpitaux de Paris (AP-HP), Villejuif, France
| | - Jean-Yves Mabrut
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
- Service de Chirurgie Générale et Transplantation Hépatique, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Vincent Leroy
- Service d’Hépato-gastro-entérologie, Hôpital Grenoble-Alpes, Grenoble, France
| | | | - Rodolphe Anty
- Université Côte d’Azur, pôle digestif CHU de Nice, INSERM, U1065, C3M, Nice, France
| | - Sylvie Thevenon
- Centre de Recherche Clinique, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Sinafa Si Ahmed
- Service d’Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | | | | | - Caroline Scholtès
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
- Service de Virologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Massimo Levrero
- Service d’Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
| | - Barbara Testoni
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
- Corresponding authors. Address: INSERM U1052, 151, Cours Albert Thomas, 69008 Lyon, France. Tel.: +33-4-72-68-19-70; Fax: +33-4-72-68-19-71.
| | - Fabien Zoulim
- Service d’Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
- Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Université Claude Bernard Lyon 1, Lyon, France
- Corresponding authors. Address: INSERM U1052, 151, Cours Albert Thomas, 69008 Lyon, France. Tel.: +33-4-72-68-19-70; Fax: +33-4-72-68-19-71.
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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] [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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Blaney H, Khalid M, Heller T, Koh C. Epidemiology, presentation, and therapeutic approaches for hepatitis D infections. Expert Rev Anti Infect Ther 2023; 21:127-142. [PMID: 36519386 PMCID: PMC9905306 DOI: 10.1080/14787210.2023.2159379] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Chronic Hepatitis D virus (HDV) infection remains an important global public health problem, with a changing epidemiological landscape over the past decade along with widespread implementation of hepatitis B vaccination and human migration. The landscape of HDV treatments has been changing, with therapies that have been under development for the last decade now in late stage clinical trials. The anticipated availability of these new therapies will hopefully replace the current therapies which are minimally effective. AREAS COVERED This narrative review discusses the clinical course, screening and diagnosis, transmission risk factors, epidemiology, current and investigational therapies, and liver transplantation in HDV. Literature review was performed using PubMed and ClinicalTrials.gov and includes relevant articles from 1977 to 2022. EXPERT OPINION HDV infection is an important global public health issue with a true prevalence that is still unknown. The distribution of HDV infection has changed globally with the availability of HBV vaccination and patterns of human migration. As HDV infection is associated with accelerated disease courses and poor outcomes, the global community needs to agree upon a uniform HDV screening strategy to understand the truth of global prevalence such that new therapies can target appropriate individuals as they become available in the future.
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Affiliation(s)
- Hanna Blaney
- Digestive Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Mian Khalid
- Digestive Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Theo Heller
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Christopher Koh
- Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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31
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Yao J, Lei YG, Yi HM, Yang Y. Clinical strategies to improve the survival rate of liver recipients with acute-on-chronic liver failure. Hepatobiliary Pancreat Dis Int 2023; 22:41-44. [PMID: 36464623 DOI: 10.1016/j.hbpd.2022.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/13/2022] [Indexed: 11/23/2022]
Affiliation(s)
- Jia Yao
- Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, China
| | - Yun-Guo Lei
- Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, China
| | - Hui-Min Yi
- Surgical Intensive Care Unit, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Yang Yang
- Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, China.
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32
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Cortesi PA, Viganò R, Conti S, Lenci I, Volpes R, Martini S, Angelico M, Fung J, Buti M, Coilly A, Durand F, Fondevila C, Lebray P, Nevens F, Polak WG, Rizzetto M, Zoulim F, Perricone G, Berenguer M, Mantovani LG, Duvoux C, Belli LS. Economic Impact of European Liver and Intestine Transplantation Association (ELITA) Recommendations for Hepatitis B Prophylaxis After Liver Transplantation. Transpl Int 2023; 36:10954. [PMID: 36793896 PMCID: PMC9922709 DOI: 10.3389/ti.2023.10954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 01/12/2023] [Indexed: 01/31/2023]
Abstract
The European Liver and Intestine Transplant Association, ELITA, promoted a Consensus Conference involving 20 experts across the world which generated updated guidelines on HBV prophylaxis in liver transplant candidates and recipients. This study explores the economic impact associated with the implementation of the new ELITA guidelines. To this aim, a condition-specific cohort simulation model has been developed to compare new and historical prophylaxis, including only pharmaceutical cost and using the European perspective. The target population simulated in the model included both prevalent and incident cases, and consisted of 6,133 patients after the first year, that increased to 7,442 and 8,743 patents after 5 and 10 years from its implementation. The ELITA protocols allowed a cost saving of around € 235.65 million after 5 years and € 540.73 million after 10 years; which was mainly due to early HIBG withdrawal either after the first 4 weeks or after the first year post Liver Transplantation (LT) depending on the virological risk at transplantation. Results were confirmed by sensitivity analyses. The money saved by the implementation of the ELITA guidelines would allow healthcare decision makers and budget holders to understand where costs could be reduced and resources re-allocated to different needs.
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Affiliation(s)
- Paolo Angelo Cortesi
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy,*Correspondence: Paolo Angelo Cortesi,
| | - Raffaella Viganò
- Hepatology and Gastroenterology Unit, ASST GOM Niguarda, Milan, Italy
| | - Sara Conti
- Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy
| | - Ilaria Lenci
- Unit of Hepatology and Liver Transplant Unit, Tor Vergata University, Rome, Italy
| | - Riccardo Volpes
- Hepatology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per I Trapianti e Terapia ad Alta Specializzazione), Palermo, Italy
| | - Silvia Martini
- Gastro-hepatology Unit, Azienda Ospedaliera Universitaria, Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy
| | - Mario Angelico
- Hepatology and Liver Transplant Unit, University of Tor Vergata, Rome, Italy
| | - James Fung
- Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Maria Buti
- Liver Unit, Hospital Universitario Valld’Hebron, Barcelona, Spain,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France,Unité INSERM 1193, Université Paris-Saclay, Paris, France
| | - Francois Durand
- Hepatology and Liver Intensive care, Hospital Beaujon, Clichy, France,Service d’Hépatologie et Transplantation Hépatique, APHP, Hôpital Beaujon, Université Paris Diderot, INSERM U1149, Clichy, France
| | - Constantino Fondevila
- HPB Surgery and Transplantation, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), CIBERehd, Madrid, Spain
| | - Pascal Lebray
- Médecine Sorbonne Université, Service d’Hépato-gastroentérologie, Hôpitaux Universitaires Pitié Salpêtrière—Charles Foix, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Frederik Nevens
- Division of Hepatology and Liver Transplantation, European Reference Network on Hepatological Diseases (ERN Rare-Liver), University Hospitals KU, Leuven, Belgium
| | - Wojciech G. Polak
- Erasmus MC, Transplant Institute, University Medical Center Rotterdam, Department of Surgery, Division of HPB and Transplant Surgery, Rotterdam, Netherlands
| | - Mario Rizzetto
- Department of Medical Sciences, School of Medicine, University of Turin, Turin, Italy
| | - Fabien Zoulim
- INSERM U1052—Cancer Research Center of Lyon (CRCL), Lyon University, Hospices Civils de Lyon, Lyon, France
| | | | - Marina Berenguer
- Hepatology and Liver Transplantation Unit, Ciberehd; Faculty of Medicine, La Fe University Hospital, Valencia, Spain
| | | | - Christophe Duvoux
- Service d'Hépatologie, Hôpitaux Universitaires Henri Mondor, Créteil, France
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Gang S, Choi Y, Lee B, Yoon KC, Hong SY, Suh S, Han ES, Hong SK, Lee HW, Cho JY, Yi NJ, Lee KW, Suh KS. Long-term outcomes of liver transplantation using grafts from donors with active hepatitis B virus replication: a multicenter cohort study. Ann Surg Treat Res 2023; 104:183-194. [PMID: 37051154 PMCID: PMC10083344 DOI: 10.4174/astr.2023.104.4.183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 03/06/2023] [Accepted: 03/08/2023] [Indexed: 04/07/2023] Open
Abstract
Purpose Liver grafts from donors with HBV infection contributed to expanding the donor pool under the hepatitis B immunoglobulin and antiviral agents (nucleos(t)ide analogues) in the HBV-endemic area. We report long-term outcomes of liver transplantations (LTs) using grafts from donors with active or chronic HBV infection. Methods Overall, 2,260 LTs performed in 3 major hospitals in Seoul from January 2000 to April 2019 were assessed for inclusion. Twenty-six grafts (1.2%) were obtained from HBsAg (+), HBeAb (+), or HBcAb (+) donors, and recipient outcomes were retrospectively reviewed. Donor and recipient demographics and transplantation outcomes were analyzed. Results Sixteen deceased donor LTs were performed using active HBsAg (+) grafts. Ten other LTs were sourced from 10 living donors. There was no significant difference in survival in patients who received deceased donor LTs compared with that in those who underwent LT with non-hepatitis virus-infected grafts. Fourteen patients who were followed up for >5 years were stable, and no difference in hepatocellular carcinoma recurrence rate was observed 5 years after transplantation between transplants from donors with and those without HBV. Conclusion Considering long-term outcomes, liver grafts from donors with active HBV replication can be safely used for LT.
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Affiliation(s)
- Sujin Gang
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Kyung Chul Yoon
- Department of Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Su young Hong
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Sanggyun Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Soo Han
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Nam-joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
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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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Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives. Biomedicines 2022; 10:biomedicines10071561. [PMID: 35884867 PMCID: PMC9313066 DOI: 10.3390/biomedicines10071561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 06/11/2022] [Accepted: 06/27/2022] [Indexed: 01/03/2023] Open
Abstract
End-stage liver disease patients undergoing liver transplantation are prone to develop numerous infectious complications because of immunosuppression, surgical interventions, and malnutrition. Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80%. The challenges faced in the early post-transplant period tend to be linked to transplant procedures and nosocomial infections commonly in bloodstream, surgical, and intra-abdominal sites. Viral infections represent an additional complication of immunosuppression; they can be donor-derived, reactivated from a latent virus, nosocomial or community-acquired. Bacterial and viral infections in solid organ transplantation are managed by prophylaxis, multi-drug resistant screening, risk assessment, vaccination, infection control and antimicrobial stewardship. The aim of this review was to discuss the epidemiology of bacterial and viral infections in liver transplants, infection control issues, as well as surgical frontiers of ex situ liver perfusion.
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36
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Goel A, Kwong A. CAQ Corner: Disease recurrence after liver transplantation. Liver Transpl 2022:1. [PMID: 37160054 DOI: 10.1002/lt.26492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 04/09/2022] [Accepted: 04/20/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Aparna Goel
- Division of Gastroenterology/Hepatology, Stanford University, Palo Alto, California, USA
| | - Allison Kwong
- Division of Gastroenterology/Hepatology, Stanford University, Palo Alto, California, USA
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37
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Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients. Transplantation 2022; 106:1935-1939. [DOI: 10.1097/tp.0000000000004138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Hepatitis B or Delta liver transplant patients at risk of recurrence: Long-term effectiveness and budget impact of low-dose subcutaneous anti-hepatitis B immunoglobulin plus patient education program. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2022.100088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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39
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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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