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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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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [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: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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Abstract
Abnormal liver tests are common after liver transplantation. The differential diagnosis depends on the clinical context, particularly the time course, pattern and degree of elevation, and donor and recipient factors. The perioperative period has distinct causes compared with months and years after transplant, including ischemia-reperfusion injury, vascular thrombosis, and primary graft nonfunction. Etiologies seen beyond the perioperative period include biliary complications, rejection, infection, recurrent disease, and non-transplant-specific causes. The evaluation begins with a liver ultrasound with Doppler as well as appropriate laboratory testing and culminates in a liver biopsy if the imaging and laboratory testing is unrevealing.
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Affiliation(s)
- Jacqueline B Henson
- Division of Gastroenterology, Department of Medicine, Duke University, DUMC Box 3913, Durham, NC 27710, USA. https://twitter.com/jackie_henson
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University, DUMC Box 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, Duke University, DUMC Box 3913, Durham, NC 27710, USA.
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Yu X, Wei B, Su R, Yao J, Feng X, Jiang G, Xie H, Wu J, Xu X, Zhang M, Zheng S, Zhou L. A risk assessment model of acute liver allograft rejection by genetic polymorphism of CD276. Mol Genet Genomic Med 2019; 7:e689. [PMID: 31044564 PMCID: PMC6603397 DOI: 10.1002/mgg3.689] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 03/01/2019] [Accepted: 03/01/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Liver transplantation is an effective therapy for end-stage liver diseases and acute liver failure. After the operation, however, recipients may suffer grafts loss induced by alloimmune reaction, which is termed as acute allograft rejection. The interaction between costimulatory molecules, CD276, and its ligand, TREML2, promotes T cell-mediated immune response, as well as acute or chronic allograft rejection. Our research aimed at correlating genetic polymorphisms of CD276/TREML2 with acute rejection, and evaluating its prognostic value of acute rejection after liver transplantation. METHODS The study enrolled a total of 388 recipients. Among them, acute allograft rejection was observed in 54 cases. We performed single nucleotide polymorphism genotyping of CD276, including rs11072431, rs11574495, rs12593558, rs12594627, rs2127015, rs3816661 and rs7176654, and TREML2, including rs4714431, rs6915083, rs7754593, and rs9394767 from preoperative peripheral blood genome DNA. RESULTS We found rs2127015 of CD276, rs6915083 and rs7754593 of TREML2, and HBV infection as well were associated with acute rejection. And, rs2127015 influences CD276 expression. Moreover, we established a risk assessment model, composited by statistically proved risk factors. CONCLUSION By integrating both clinical and genetic variables, liver transplant recipients can be categorized into different risk groups, and might benefit from individualized therapies.
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Entecavir and other nucleos(t)ide analogs prophylaxis in hepatitis B virus-related liver transplantation: long-term efficacy and safety. Eur J Gastroenterol Hepatol 2019; 31:607-612. [PMID: 30724767 DOI: 10.1097/meg.0000000000001377] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIM Although hepatitis B virus (HBV) recurrence after liver transplantation (LTx) has been reduced since the application of the combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogs (NUCs), the optimum regimen to prevent HBV recurrence with LTx favorable outcome is still not clear. AIM The aim was to evaluate the efficacy and safety of NUCs prophylaxis (±HBIG) against HBV recurrence after LTx. PATIENTS AND METHODS This was a retrospective cohort-longitudinal study on 44 HBV-related post-LTx patients on anti-HBV prophylactic therapy. They included the entecavir (ETV)-based (n=34, 30 males) and the other NUC-based (n=10, 7 males) groups±HBIG. RESULTS The median age was 63.5 (60-70) years in ETV and 62.5 (55-65) years in other NUCs groups. The mean follow-up duration was 6.09±1.83 years in ETV-based group and 6.3±1.89 years in other NUCs-based group. The mean ETV duration was 3.47±3.04 years. In ETV+HBIG patients, none of them developed HBV recurrence throughout the ±8 years. In the 14 patients on ETV+other NUC+HBIG, four developed HBsAg positive and then transformed to HbsAb positive at the end of ±8 years without hepatitis or detectable HBV-DNA. Liver graft function showed nonsignificant difference for ETV-based patients, in comparison with other NUC groups (P=0.09). With subdivision, the graft function was maintained significantly better in ETV+HBIG or other NUCs+HBIG (P=0.04) groups. None of our patients reported NUCs-related complications or adverse effects. CONCLUSION ETV and other NUCs were effective and safe as a long-term prophylaxis of HBV recurrence after LTx, leading to a good graft function. HBsAg temporally reappeared in a minority of patients, where all showed HBsAb seroconversion without detectable HBV-DNA or clinical hepatitis.
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Rogers W, Robertson MP, Ballantyne A, Blakely B, Catsanos R, Clay-Williams R, Fiatarone Singh M. Compliance with ethical standards in the reporting of donor sources and ethics review in peer-reviewed publications involving organ transplantation in China: a scoping review. BMJ Open 2019; 9:e024473. [PMID: 30723071 PMCID: PMC6377532 DOI: 10.1136/bmjopen-2018-024473] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 09/28/2018] [Accepted: 11/13/2018] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES The objective of this study is to investigate whether papers reporting research on Chinese transplant recipients comply with international professional standards aimed at excluding publication of research that: (1) involves any biological material from executed prisoners; (2) lacks Institutional Review Board (IRB) approval and (3) lacks consent of donors. DESIGN Scoping review based on Arksey and O'Mallee's methodological framework. DATA SOURCES Medline, Scopus and Embase were searched from January 2000 to April 2017. ELIGIBILITY CRITERIA We included research papers published in peer-reviewed English-language journals reporting on outcomes of research involving recipients of transplanted hearts, livers or lungs in mainland China. DATA EXTRACTION AND SYNTHESIS Data were extracted by individual authors working independently following training and benchmarking. Descriptive statistics were compiled using Excel. RESULTS 445 included studies reported on outcomes of 85 477 transplants. 412 (92.5%) failed to report whether or not organs were sourced from executed prisoners; and 439 (99%) failed to report that organ sources gave consent for transplantation. In contrast, 324 (73%) reported approval from an IRB. Of the papers claiming that no prisoners' organs were involved in the transplants, 19 of them involved 2688 transplants that took place prior to 2010, when there was no volunteer donor programme in China. DISCUSSION The transplant research community has failed to implement ethical standards banning publication of research using material from executed prisoners. As a result, a large body of unethical research now exists, raising issues of complicity and moral hazard to the extent that the transplant community uses and benefits from the results of this research. We call for retraction of this literature pending investigation of individual papers.
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Affiliation(s)
- Wendy Rogers
- Department of Clinical Medicine and Department of Philosophy, Macquarie University, Sydney, New South Wales, Australia
- Department of Philosophy, Macquarie University, Sydney, New South Wales, Australia
| | | | - Angela Ballantyne
- Department of Primary Health Care and General Practice, University of Otago, Wellington, New Zealand
| | - Brette Blakely
- Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia
| | | | - Robyn Clay-Williams
- Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia
| | - Maria Fiatarone Singh
- Faculty of Health Sciences, University of Sydney, Sydney, New South Wales, Australia
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Lens S, García-Eliz M, Fernández I, Castells L, Bonacci M, Mas A, Crespo G, Buti M, Prieto M, Forns X. Shorter hepatitis B immunoglobulin administration is not associated to hepatitis B virus recurrence when receiving combined prophylaxis after liver transplantation. Liver Int 2018; 38:1940-1950. [PMID: 29660249 DOI: 10.1111/liv.13858] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 03/29/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS The combination of hepatitis B immunoglobulin and a nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus recurrence after liver transplantation; however, the optimal duration of hepatitis B immunoglobulin has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to hepatitis B virus recurrence after liver transplantation in a large cohort of patients under different hepatitis B immunoglobulin regimens. METHODS Retrospective multicentre analysis of hepatitis B virus-related liver transplantation recipients receiving combined prophylaxis (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short-term hepatitis B immunoglobulin was compared to lifelong administration. Hepatitis B virus recurrence was defined as positive HBsAg after liver transplantation. RESULTS Three hundred and thirty-eight patients were analysed. After a median follow-up period of 72 months, 37 patients (11%) developed hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine resistance after liver transplantation were the only factors independently associated to hepatitis B virus recurrence (HR 5.4 [2.3-12] and 9.3 [4.2-20] respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was transient (16 patients), persistent (15) or alternant (6). The hepatitis B immunoglobulin regimen did not have an impact on the rate or evolution of hepatitis B virus recurrence. Overall, patient survival was good and not influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or hepatocellular carcinoma at liver transplantation were independent risk factors for lower survival. CONCLUSIONS Liver transplantation is an effective treatment for hepatitis B virus-related liver disease. Since the introduction of combined prophylaxis the rate of hepatitis B virus recurrence is very low. However, lifelong hepatitis B immunoglobulin administration does not seem necessary to reduce hepatitis B virus recurrence.
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Affiliation(s)
- Sabela Lens
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | | | | | - Lluis Castells
- Internal Medicine, Hepatology Section, Hospital Vall Hebron, CIBERehd, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Martin Bonacci
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - Antoni Mas
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - María Buti
- Internal Medicine, Hepatology Section, Hospital Vall Hebron, CIBERehd, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Martín Prieto
- Liver Unit, CIBERehd, Hospital La Fe, Valencia, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clínic, IDIBAPS and CIBERehd, Universitat de Barcelona, Barcelona, Spain
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8
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Lu D, Zhuo J, Yang M, Wang C, Pan L, Xie H, Xu X, Zheng S. The association between donor genetic variations in one-carbon metabolism pathway genes and hepatitis B recurrence after liver transplantation. Gene 2018; 663:121-125. [PMID: 29627528 DOI: 10.1016/j.gene.2018.03.071] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/12/2018] [Accepted: 03/21/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUNDS AND AIM Hepatitis B recurrence adversely affects patients' survival after liver transplantation. This study aims to find association between donor gene variations of one carbon metabolism and post-transplant hepatitis B recurrence. METHODS This study enrolled 196 patients undergoing liver transplantation for HBV related end-stage liver diseases. We detected 11 single nucleotide polymorphisms (SNP) of 7 one-carbon metabolism pathway genes (including MTHFR, MTR, MTRR, ALDH1L1, GART, SHMT1 and CBS) in donor livers and analyzed their association with HBV reinfection after liver transplantation. RESULTS Hepatitis B recurrence was observed in 19 of the 196 patients (9.7%) undergoing liver transplantation. Hepatitis B recurrence significantly affected post-transplant survival in the 196 patients (p = 0.018), and correlate with tumor recurrence in the subgroup of HCC patients (n = 99, p = 0.006). Among the 11 SNPs, donor liver mutation in rs1979277 (G > A) was adversely associated with post-transplant hepatitis B recurrence (p = 0.042). In the subgroup of HCC patients, survival analysis showed donor liver mutations in rs1801133 (G > A) and rs1979277 (G > A) were risk factors for hepatitis B recurrence (p < 0.05). None of the 11 SNPs was related to hepatitis B recurrence in non-HCC patients (n = 97, p > 0.05). CONCLUSION Hepatitis B recurrence impaired post-transplant survival. Donor liver genetic variations in one-carbon metabolism pathway genes were significantly associated with post-transplant hepatitis B recurrence.
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Affiliation(s)
- Di Lu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Jianyong Zhuo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Modan Yang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Chao Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Linhui Pan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Haiyang Xie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Abstract
The goal in patients with immune active hepatitis B virus (HBV) infection is to significantly suppress viral replication and prevent progression of fibrosis to cirrhosis and liver decompensation and decrease the incidence of hepatocellular carcinoma. This is achievable by the highly active antivirals, entecavir and tenofovir, which are considered first-line therapy in most patients with immune active hepatitis C virus and after liver transplantation to prevent HBV recurrence. Patients with decompensated cirrhosis should be referred for liver transplantation and treated with first-line antivirals as early as possible, with the goal of achieving complete viral suppression in the shortest time possible.
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Affiliation(s)
| | - Tarek I Hassanein
- Southern California Research Center, Coronado, CA 92118, USA; University of California, San Diego School of Medicine, San Diego, CA, USA.
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Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 09/20/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
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12
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1928] [Impact Index Per Article: 214.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Xu X, Lu D, Zhuang R, Wei X, Xie H, Wang C, Zhu Y, Wang J, Zhong C, Zhang X, Wei Q, He Z, Zhou L, Zheng S. The phospholipase A2 activity of peroxiredoxin 6 promotes cancer cell death induced by tumor necrosis factor alpha in hepatocellular carcinoma. Mol Carcinog 2015; 55:1299-308. [PMID: 26293541 DOI: 10.1002/mc.22371] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 06/29/2015] [Accepted: 07/06/2015] [Indexed: 12/21/2022]
Abstract
In this study, we used proteomic profiling to compare hepatocellular carcinoma (HCC) and peri-tumoral tissues to identify potential tumor markers of HCC. We identified eight differentially expressed proteins (>3-fold), including Peroxiredoxin 6 (PRDX6). PRDX6 is a bifunctional enzyme with both peroxidase and calcium-independent phospholipase A2 (iPLA2) activity. We found that peri-tumoral tissues expressed higher levels of PRDX6 mRNA (n = 59, P = 0.018) and protein (n = 265, P < 0.001) than HCC tissues, and that decreased expression of PRDX6 in HCC tissues was an independent risk factor indicating a poor prognosis (n = 145, P = 0.007). Combining the examination of serum PRDX6 with α-fetoprotein improved the diagnostic sensitivity of tests for HCC compared to α-fetoprotein alone (85.0% vs 50.0%, n = 40). We found that PRDX6 induced S phase arrest in HCC cells and inhibited HCC tumorigenicity in mice injected with cancer cells. When treated with H2 O2 , PRDX6 inhibited apoptosis. When treated with tumor necrosis factor alpha (TNF-α), PRDX6 promoted apoptosis. Inhibition of iPLA2 activity of PRDX6 decreased the apoptosis induced by TNF-α. In conclusion, PRDX6 inhibited the carcinogenesis of HCC, and the iPLA2 activity of PRDX6 promoted cancer cell death induced by TNF-α. © 2015 Wiley Periodicals, Inc.
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Affiliation(s)
- Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Di Lu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Runzhou Zhuang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Xuyong Wei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Haiyang Xie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Chao Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Yangbo Zhu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Jianguo Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Cheng Zhong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Xuanyu Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Qiang Wei
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Zenglei He
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Lin Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China
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Shen S, Jiang L, Xiao GQ, Yan LN, Yang JY, Wen TF, Li B, Wang WT, Xu MQ, Wei YG. Prophylaxis against hepatitis B virus recurrence after liver transplantation: A registry study. World J Gastroenterol 2015; 21:584-592. [PMID: 25593480 PMCID: PMC4294170 DOI: 10.3748/wjg.v21.i2.584] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Revised: 08/04/2014] [Accepted: 11/11/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin (HBIG) in combination with different nucleos(t)ide analogues.
METHODS: A total of 5333 hepatitis B surface antigen-positive patients from the China Liver Transplant Registry database were enrolled between January 2000 and December 2009. Low-dose intramuscular (im) HBIG combined with one nucleos(t)ide analogue has been shown to be very cost-effective in recent reports. Hepatitis B virus (HBV) prophylactic outcomes were compared based on their posttransplant prophylactic protocols [group A (n = 4684): im HBIG plus lamivudine; group B (n = 491): im HBIG plus entecavir; group C (n = 158): im HBIG plus adefovir dipivoxil]. We compared the related baseline characteristics among the three groups, including the age, male sex, Meld score at the time of transplantation, Child-Pugh score at the time of transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre-transplantation HBV deoxyribonucleic acid (HBV DNA) positivity, HBV DNA at the time of transplantation, pre-transplantation antiviral therapy, and the duration of antiviral therapy before transplantation of the patients. We also calculated the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the different groups. All potential risk factors were analyzed using univariate and multivariate analyses.
RESULTS: The mean follow-up duration was 42.1 ± 30.3 mo. The 1-, 3- and 5-year survival rates were lower in group A than in groups B (86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P < 0.001) and C (86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P < 0.001). The 1-, 3- and 5-year posttransplant HBV recurrence rates were significantly higher in group A than in group B (1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively, P = 0.023). No significant difference existed between groups A and C and between groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates. Pretransplant hepatocellular carcinoma, high viral load and posttransplant prophylactic protocol (lamivudine and HBIG vs entecavir and HBIG) were associated with HBV recurrence.
CONCLUSION: Low-dose intramuscular HBIG in combination with a nucleos(t)ide analogue provides effective prophylaxis against posttransplant HBV recurrence, especially for HBIG plus entecavir.
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Jiang L, Yan L, Wen T, Li B, Zhao J, Yang J, Xu M, Wang W. Hepatitis B prophylaxis using lamivudine and individualized low-dose hepatitis B immunoglobulin in living donor liver transplantation. Transplant Proc 2014; 45:2326-30. [PMID: 23953544 DOI: 10.1016/j.transproceed.2013.03.028] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Revised: 02/26/2013] [Accepted: 03/21/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Currently, most available experience concerning prophylaxis against hepatitis B virus (HBV) recurrence after living donor liver transplantation (LDLT) is limited to studies of small size and short follow-up. The objective of this study was to evaluate the efficacy of a prophylactic regimen using lamivudine and individualized low-dose intramuscular hepatitis B immunoglobulin (HBIG) in LDLT. METHODS We used a database of adult-to-adult right-lobe LDLT procedures performed from June 2002 to April 2012 at our center for HBV-related end-stage liver diseases. Patients were divided into 3 groups: group A, HBV-related decompensated liver cirrhosis; group B, fulminant hepatitis B; and group C, hepatocellular carcinoma (HCC). RESULTS During a mean follow-up of 38.3 ± 28.9 months, 8 of 165 (4.8%) recipients developed HBV recurrences. The mean time for HBV reinfection was 15.8 + 11.0 months after transplantation. The overall 1-, 3-, and 5-year HBV recurrence rates were 3%, 7%, and 8.2%, respectively. Both patients with fulminant hepatitis B or HCC seemed to have higher rates of HBV recurrence than those with decompensated liver cirrhosis, albeit not significantly. The independent predictor of HBV recurrence was high HBV DNA level (≥10(5) copies/mL) at LDLT. CONCLUSIONS Lamivudine and individualized low-dose intramuscular HBIG provides effective prophylaxis against HBV recurrence after LDLT. Pre-LDLT HBV DNA of ≥ 10(5) copies/mL was associated with HBV recurrence.
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Affiliation(s)
- L Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
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Jiang L, Yan LN, Wen TF, Li B, Yang JY. Comparison of hepatitis B prophylactic outcomes in living donor liver transplantation recipients who meet the Milan or UCSF criteria. Hepatobiliary Pancreat Dis Int 2013; 12:494-9. [PMID: 24103279 DOI: 10.1016/s1499-3872(13)60078-8] [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] [Indexed: 02/05/2023]
Abstract
BACKGROUND The tumor burden before liver transplantation indicates that hepatitis B virus (HBV) may hide in the extrahepatic and micrometastatic sites which serve as a source of HBV replication. Currently, many liver transplant centers, especially in Western countries, use the Milan or UCSF criteria to select patients with hepatocellular carcinoma for liver transplantation. This study was undertaken to compare the HBV prophylactic outcomes in two groups of living donor liver transplantation (LDLT) recipients. Patients in group A met the Milan criteria and those in group B exceeded the Milan criteria but were within the UCSF criteria. METHODS A database of adult-to-adult right-lobe LDLT performed at our institution for HBV-related hepatocellular carcinoma within the Milan or UCSF criteria between June 2002 and May 2012 was used to compare the HBV prophylactic outcomes between patients within the Milan criteria (group A, 41 patients) and those exceeding the Milan criteria but within the UCSF criteria (group B, 19 patients). RESULTS The 1-, 3-, and 5-year survival rates were similar between groups A and B (87.8%, 85.1% and 74.0% vs 73.3%, 61.1% and 61.1%, respectively, P=0.067). HBV recurred in 1 patient in 3.1 months after LDLT in group A and in 2 patients in group B (1 in 11.9 months and 1 in 24.1 months after LDLT). The 1-, 3-, and 5-year HBV recurrence rates were 2.6%, 2.6% and 2.6% in group A, and 7.3%, 17.9% and 17.9% in group B, respectively (P=0.118). CONCLUSION LDLT recipients who exceed the Milan criteria but remain within the UCSF criteria may have post-transplant HBV prophylactic outcomes similar to those who meet the Milan criteria.
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Affiliation(s)
- Li Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
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Tanaka T, Benmousa A, Marquez M, Therapondos G, Renner EL, Lilly LB. The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver transplantation. Clin Transplant 2013; 26:E561-9. [PMID: 23061767 DOI: 10.1111/ctr.12022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long-term nucleos(t)ide analog in combination with one yr of low-dose HBIG. One hundred and fifty-two adults with HBV-related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long-term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow-up post-transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long-term follow-up, demonstrates that short course of low-dose HBIG (without anti-HBs monitoring) combined with the use of long-term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.
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Affiliation(s)
- Tomohiro Tanaka
- Liver Transplant Unit, Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
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Li Y, Shi Y, Chen J, Cai B, Ying B, Wang L. Association of polymorphisms in interleukin-18 and interleukin-28B with hepatitis B recurrence after liver transplantation in Chinese Han population. Int J Immunogenet 2012; 39:346-52. [PMID: 22325058 DOI: 10.1111/j.1744-313x.2012.01097.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Interleukin-18 (IL-18) is a potent proinflammatory cytokine, which can promote hepatitis B virus clearance. The latest studies find that genetic polymorphisms near the IL-28B gene are strongly associated with sustained viral response and spontaneous viral clearance in patients with chronically infected hepatitis C and hepatitis B. We investigated the effect of rs187238 and rs1946518 in IL-18 gene and rs8099917 in IL-28B gene on HBV recurrence in liver transplant patients. A total of 200 liver transplant recipients and relevant donors were enrolled in this study. The patients' mean follow-up was 39 month (range 10-65 month). All liver transplant recipients were in a stable stage. The total recipients (n = 200) were divided into end-stage liver disease secondary to hepatitis B (n = 140) and end-stage liver disease secondary to other diseases (n = 60) before transplantation. Recipients (n = 140) with hepatitis B before transplantation were defined to nonHBV recurrence group (n = 119) or HBV recurrence group (n = 21), which was positive for HBsAg or elevatory in HBV DNA (>2.0 × 10(2) IU mL(-1)) after transplantation. For the recipients (n = 140) had hepatitis B before transplantation, we studied the single-nucleotide polymorphisms (SNPs) of IL-18 gene (rs187238 and rs1946518) and IL-28B gene (rs8099917) by high-resolution melting (HRM) curve analysis. The serum levels of IL-18 and IFN-γ were tested by ELISA. The serums levels of IFN-γ were lower in HBV recurrence group than that in nonHBV recurrence group (P < 0.01). The genotype of IL-28B gene rs8099917 was associated with alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels in HBV-related liver transplant recipients (n = 140). The recipients with allele G (GG+GT) had higher ALT and AST levels (P < 0.05). No association was found between IL-18 gene and IL-28B gene polymorphisms with HBV recurrence in the liver transplant recipients or the donors. We identified that the IFN-γ was a protective factor of HBV recurrence after liver transplantation. The allele G of rs8099917 was associated with hepatitis B-related hepatocytes injury. The rs8099917 G allele subgroup should reinforce antiviral therapy.
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Affiliation(s)
- Y Li
- Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, China
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Li C, Mi K, Wen TF, Yan LN, Li B, Yang JY, Xu MQ, Wang WT, Wei YG. Outcomes of patients with benign liver diseases undergoing living donor versus deceased donor liver transplantation. PLoS One 2011; 6:e27366. [PMID: 22087299 PMCID: PMC3210164 DOI: 10.1371/journal.pone.0027366] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2011] [Accepted: 10/15/2011] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND/AIMS The number of people undergoing living donor liver transplantation (LDLT) has increased rapidly in many transplant centres. Patients considering LDLT need to know whether LDLT is riskier than deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcomes of patients undergoing LDLT versus DDLT. METHODS A total of 349 patients with benign liver diseases were recruited from 2005 to 2011 for this study. LDLT was performed in 128 patients, and DDLT was performed in 221 patients. Pre- and intra-operative variables for the two groups were compared. Statistically analysed post-operative outcomes include the postoperative incidence of complication, biliary and vascular complication, hepatitis B virus (HBV) recurrence, long-term survival rate and outcomes of emergency transplantation. RESULTS The waiting times were 22.10±15.31 days for the patients undergoing LDLT versus 35.81±29.18 days for the patients undergoing DDLT. The cold ischemia time (CIT) was 119.34±19.75 minutes for the LDLT group and 346±154.18 for DDLT group. LDLT group had higher intraoperative blood loss, but red blood cell (RBC) transfusion was not different. Similar ≥ Clavien III complications, vascular complications, hepatitis B virus (HBV) recurrence and long-term survival rates were noted. LDLT patients suffered a higher incidence of biliary complications in the early postoperative days. However, during the long-term follow-up period, biliary complication rates were similar between the two groups. The long-term survival rate of patients undergoing emergency transplantation was lower than of patients undergoing elective transplantation. However, no significant difference was observed between emergency LDLT and emergency DDLT. CONCLUSIONS Patients undergoing LDLT achieved similar outcomes to patients undergoing DDLT. Although LDLT patients may suffer a higher incidence of early biliary complications, the total biliary complication rate was similar during the long-term follow-up period.
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Affiliation(s)
- Chuan Li
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Kai Mi
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Tian fu Wen
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- * E-mail:
| | - Lu nan Yan
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Bo Li
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jia ying Yang
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Ming qing Xu
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Wen tao Wang
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yong gang Wei
- Division of Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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