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Ortiz-López N, Acevedo M, Vergara T, Roblero JP, Urzúa Á, Cattaneo M, Poniachik J. Dual therapy with nucleos(t)ide analogues in the prevention of hepatitis B virus recurrence after liver transplantation: Two case reports. World J Hepatol 2025; 17:98660. [PMID: 40308816 PMCID: PMC12038423 DOI: 10.4254/wjh.v17.i4.98660] [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: 07/02/2024] [Revised: 08/31/2024] [Accepted: 09/14/2024] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Infection by the hepatitis B virus (HBV) represents a significant global socio-sanitary burden. While liver transplantation (LT) is an important therapeutic option, treatments that prevent HBV reinfection are necessary. The combination of anti-hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogs (NA) is the standard post-transplant treatment; however, there are limitations in using HBIG, particularly its cost. We present two illustrative clinical cases as examples of post-transplant management using dual NA therapy, unaccompanied by HBIG. CASE SUMMARY The first case involves a 42-year-old man with HBV-related cirrhosis, who, in the context of a diagnosis of hepatocellular carcinoma and hepatopulmonary syndrome, underwent LT without viremia at the time of transplantation. A lack of availability of HBIG led to the combined use of two NAs, entecavir, and tenofovir alafenamide-resulting in the negativization of hepatitis B surface antigen (HBsAg) and maintenance of a negative viral load in the post-transplant period. In the second case, a 63-year-old woman presented with acute hepatic failure due to HBV with viremia during transplantation. Combined therapy with entecavir and tenofovir alafenamide, again due to the unavailability of HBIG, ultimately led to the negativization of HBsAg and viral load. CONCLUSION These cases suggest the efficacy of dual NA therapy in post-transplant HBV management, emphasizing the need to reconsider traditional treatment approaches.
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Affiliation(s)
- Nicolás Ortiz-López
- Sección de Medicina Interna, Hospital Clínico Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile
| | - Maximiliano Acevedo
- Escuela de Medicina, Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile
| | - Tamara Vergara
- Escuela de Medicina, Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile
| | - Juan Pablo Roblero
- Sección de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile
| | - Álvaro Urzúa
- Sección de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile
| | - Máximo Cattaneo
- Sección de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile
| | - Jaime Poniachik
- Sección de Gastroenterología, Hospital Clínico Universidad de Chile, Santiago 8380453, Región Metropolitana, Chile.
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Lopez-Soler RI, Joyce C, Cotiguala L, Aguirre O, Samra M, Trotter C, Zingraf G, Sorensen J, Sodhi R, Thorndyke A. Utilization of Hepatitis B viremic donors (NAT+) leads to improved kidney transplant access for older adult recipients with little to no wait time. Transpl Infect Dis 2024; 26:e14295. [PMID: 38761060 DOI: 10.1111/tid.14295] [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: 04/28/2024] [Accepted: 05/03/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND Though the use of Hepatitis B viremic (HBV) donor kidneys may be a safe alternative to improve access to transplantation, there has not been wide acceptance of this practice. In this study, we determined the safety and effectiveness of HBV NAT (+) donor kidneys in a protocolized manner in an older adult population. METHODS Over a 3-year period, 16 decreased donor kidney transplants were performed with HBV NAT+ kidneys. Recipients of HBV NAT+ kidneys were treated with entecavir started pre-operatively and continued for 52 weeks. RESULTS HBV NAT+ kidneys were preferentially used in older (68 ± 5 vs. 64 ± 9 years; p = .01) recipients with less dialysis time (93.8% < 5 years vs. 67% <5 years; p = .03). In this cohort, 3/16 had detectable HBV PCR 1-week post-transplant, but all were negative at 9- and 12-months. Calculated estimated glomerular filtration rate (eGFR) was slightly decreased 12-months post-transplant. Post-transplant outcomes in an age-matched cohort showed no difference in rates of delayed graft function, readmission within 30 days, and graft loss or death within 6 months of transplant (p > .05). CONCLUSION Transplants with HBV NAT+ donor kidneys in a pre-emptive treatment protocol allow for increased safe access to transplantation in older adult recipients with little or no dialysis time.
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Affiliation(s)
- Reynold I Lopez-Soler
- Section of Transplantation, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
- Department of Surgery, Division of Intra-Abdominal Transplantation, Stritch School of Medicine, Maywood, Illinois, USA
| | - Cara Joyce
- Department of Pharmacy, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
| | - Laura Cotiguala
- Department of Medicine, Stritch School of Medicine, Maywood, Illinois, USA
| | - Oswaldo Aguirre
- Section of Transplantation, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
- Department of Surgery, Division of Intra-Abdominal Transplantation, Stritch School of Medicine, Maywood, Illinois, USA
| | - Manpreet Samra
- Department of Medicine, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
| | - Chrsitine Trotter
- Section of Transplantation, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
| | - Geraldine Zingraf
- Section of Transplantation, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
| | - Jeffrey Sorensen
- Section of Transplantation, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
| | - Rupinder Sodhi
- Department of Medicine, Stritch School of Medicine, Maywood, Illinois, USA
- Department of Medicine, Edward Hines VA Jr. Hospital Hines, Hines, Illinois, USA
| | - Anne Thorndyke
- Department of Medicine, Stritch School of Medicine, Maywood, Illinois, USA
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Pati I, Cruciani M, Candura F, Massari MS, Piccinini V, Masiello F, Profili S, De Fulvio L, Pupella S, De Angelis V. Hyperimmune Globulins for the Management of Infectious Diseases. Viruses 2023; 15:1543. [PMID: 37515229 PMCID: PMC10385259 DOI: 10.3390/v15071543] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/10/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, Clostridium tetani, Clostridium botulinum. The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.
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Affiliation(s)
- Ilaria Pati
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Mario Cruciani
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Fabio Candura
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | | | - Vanessa Piccinini
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Francesca Masiello
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Samantha Profili
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Lucia De Fulvio
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Simonetta Pupella
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
| | - Vincenzo De Angelis
- National Blood Centre, Italian National Institute of Health, 00161 Rome, Italy
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Zheng H, Zhu Z, Wang N, Qin J, Guo Y, Xu Z, Li X, Qi C, Yuan X, Wu W, Wang J, Liu L, Nashan B. Entecavir Combined With Short-term Hepatitis B Immunoglobulin in Preventing Hepatitis B Virus Recurrence in Liver Transplant Recipients. Transplant Proc 2023; 55:408-412. [PMID: 36907782 DOI: 10.1016/j.transproceed.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/02/2023] [Indexed: 03/12/2023]
Abstract
BACKGROUND The combination of nucleoside analogs and long-term hepatitis B immunoglobulin (HBIG) is considered to be the standard regimen for preventing hepatitis B virus (HBV) recurrence after liver transplant (LT). However, long-term use of HBIG causes many adverse effects. The aim of this study was to evaluate the effect of nucleoside analogs entecavir combined with short-term HBIG in preventing HBV recurrence after LT. METHODS This retrospective study assessed the effect a combination of entecavir and short-term HBIG in prophylaxis of HBV recurrence among 56 LT recipients who had undergone the procedure because of HBV-associated liver disease at our center between December 2017 and December 2021. All patients received entecavir treatment combined with HBIG for the prevention of hepatitis B recurrence, and HBIG treatment was withdrawn within 1 month. The patients were followed up to determine levels of hepatitis B surface antigen, antibody to hepatitis B surface antigen (HBsAb), and HBV-DNA and the recurrence rate of HBV. RESULTS Only 1 patient appeared positive for hepatitis B surface antigen at 2 months post-LT. The overall HBV recurrence rate was 1.8%. The HBsAb titers of all patients gradually decreased over time, with a median of 376.6 IU/L at 1 month post-LT and a median of 13.47 IU/L at 12 months post-LT. During the follow-up period, the HBsAb titer of the preoperative HBV-DNA-positive patients remained at a lower level than that of HBV-DNA-negative patients. CONCLUSIONS Entecavir combined with short-term HBIG can exert a good effect for the prevention of HBV reinfection post-LT.
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Affiliation(s)
- Hao Zheng
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Zebin Zhu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Ning Wang
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Jiwei Qin
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Yafei Guo
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Zhijun Xu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Xuefeng Li
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Can Qi
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Xiaodong Yuan
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Wei Wu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Jizhou Wang
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Lianxin Liu
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China
| | - Björn Nashan
- Department of Organ Transplantation Center, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China.
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Farshadpour F, Taherkhani R, Saberi F. Molecular evaluation of hepatitis B virus infection and predominant mutations of pre-core, basal core promoter and S regions in an Iranian population with type 2 diabetes mellitus: a case-control study. BMC Infect Dis 2022; 22:553. [PMID: 35715756 PMCID: PMC9206294 DOI: 10.1186/s12879-022-07528-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/06/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND This study was designed to evaluate the prevalence, genotypic patterns, and predominant mutations of hepatitis B virus (HBV) infection among diabetic patients. METHODS Serum samples were obtained from 733 patients with type 2 diabetes mellitus and 782 non-diabetic controls. The presence of HBsAg and HBcAb was determined by ELISA. Nested PCR, targeting S and pre-core regions of the HBV genome, followed by sequencing was carried out to determine HBV genotypes and predominant mutations in the S, basal core promoter (BCP), and pre-core regions of the HBV genome. RESULTS Of 733 diabetic patients, 94 cases (12.82%) were positive for HBcAb, 28 cases (3.82%) were positive for HBsAg, and 19 cases (2.59%) had HBV-DNA with genotype D, sub-genotype D1/D3 and subtype ayw2. An occult HBV infection was found in one of the HBV DNA-positive samples, which was positive for HBcAb but negative for HBsAg. P120T/G145R, G1896A/G1899A, and A1762T/G1764T were the most frequent point substitution mutations detected in the S, pre-core, and BCP regions of the HBV genome, respectively. P120T and G145R mutations were associated with low levels or undetectable levels of HBsAg in serum. Therefore, routine tests based on HBsAg detection cannot detect HBsAg-negative infected patients. CONCLUSIONS Relatively high prevalence of HBV infection was found in diabetic patients, while all of the HBV-infected patients were unaware of their infection. Therefore, screening for HBV infection should be included in the management program of diabetes for timely diagnosis and treatment of infected but asymptomatic patients.
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Affiliation(s)
- Fatemeh Farshadpour
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran
| | - Reza Taherkhani
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran.
| | - Fatemeh Saberi
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran
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