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Lu K, Chiu KY. Lifetime Risk of Hepatorenal Events Assessed in Longitudinal Cohort of Renal Transplant Recipients with HBV Infection. Transplant Proc 2023; 55:1581-1587. [PMID: 37380588 DOI: 10.1016/j.transproceed.2023.05.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/16/2023] [Accepted: 05/16/2023] [Indexed: 06/30/2023]
Abstract
BACKGROUND Kidney transplantation is a treatment option for patients with end-stage renal disease (ESRD) who are infected with hepatitis B virus (HBV). However, the impact of nucleos(t)ide analogues usage on the clinical outcomes in HBV-infected ESRD patients undergoing kidney transplantation is not well understood. This study aimed to assess the outcomes of kidney transplant recipients with HBV infection using real-world data to provide insight into the disease course over time. METHODS A nationwide retrospective longitudinal population-level cohort study was conducted using the National Health Insurance Research Database. The study evaluated patient and allograft survival and kidney-related and liver-related events and identified factors contributing to these events. RESULTS Of the 4838 renal transplant recipients in the study, there were no significant differences in graft survival between the HBV-infected and non-infected groups (P = .244). However, the HBV-infected group had suboptimal patient survival compared to the non-infected group (hazard ratio [HR] for overall survival, 1.80; 95% CI 1.40-2.30; P < .001). Diabetes mellitus was associated with a higher re-dialysis rate (HR, 1.71; 95% CI, 1.38-2.12; P < .001) regarding kidney-associated events. For liver-associated events, HBV-infected status (HR, 9.40; 95% CI, 5.66-15.63; P < .001), and age >60 years (HR, 6.90; 95% CI, 3.14-15.19; P < .001) were associated with increased incidence of liver cancer. CONCLUSIONS Hepatitis B-infected renal transplant recipients have comparable graft survival but inferior patient survival outcomes due to pre-existing diseases and increasing liver-related complications. The findings of this study can help optimize treatment strategies and improve long-term outcomes for this patient population.
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Affiliation(s)
- Kevin Lu
- Department of Urology, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
| | - Kun-Yuan Chiu
- Department of Urology, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan
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Sharma P, Sawtell R, Wang Q, Sise ME. Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:343-355. [PMID: 37657881 PMCID: PMC10479952 DOI: 10.1053/j.akdh.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 09/03/2023]
Abstract
Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.
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Affiliation(s)
- Purva Sharma
- Department of Medicine, Division of Nephrology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Glomerular Disease Center at Northwell Health, Hempstead, NY
| | - Rani Sawtell
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Qiyu Wang
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
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3
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Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant 2019; 33:e13514. [DOI: 10.1111/ctr.13514] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/12/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Helen Te
- Center for Liver Diseases, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago Illinois
| | - Karen Doucette
- Division of Infectious Diseases University of Alberta Edmonton Alberta Canada
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Lee J, Cho JH, Lee JS, Ahn DW, Kim CD, Ahn C, Jung IM, Han DJ, Lim CS, Kim YS, Kim YH, Lee JP. Pretransplant Hepatitis B Viral Infection Increases Risk of Death After Kidney Transplantation: A Multicenter Cohort Study in Korea. Medicine (Baltimore) 2016; 95:e3671. [PMID: 27227927 PMCID: PMC4902351 DOI: 10.1097/md.0000000000003671] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Clinical outcomes in kidney transplant recipients (KTRs) with hepatitis B virus (HBV) have not been thoroughly evaluated. Here, we investigated recent posttransplant clinical outcomes of KTRs with HBV and compared them with KTRs with hepatitis C virus (HCV) and seronegative KTRs.Of 3855 KTRs from April 1999 to December 2011, we enrolled 3482 KTRs who had viral hepatitis serology data; the patients were followed up for 89.1 ± 54.1 months. The numbers of recipients with HBV and HCV were 160 (4.6%) and 55 (1.6%), respectively. We analyzed the clinical outcomes, including overall mortality and graft failure, among patients who had undergone kidney transplantation.Patients with HBV showed poorer survival (P = 0.019; adjusted hazard ratio [HR] = 2.370; 95% confidence interval [CI]: 1.155-4.865) than KTRs without HBV. However, the graft survival of patients with chronic hepatitis B did not differ from that of patients without HBV. Hepatic complications were the primary causes of mortality of KTRs with HBV. Mortality significantly correlated with a higher grade of inflammation (P = 0.002) and with the use of lamivudine or adefovir antiviral treatment (P = 0.016). HBV-positive KTRs treated with the new-generation antiviral agent entecavir showed improved patient survival compared with KTRs receiving lamivudine (log-rank P = 0.050). HCV did not affect patient survival; however, it increased the incidence of graft failure (P = 0.010; adjusted HR = 2.899; 95% CI: 1.289-6.519). KTRs with HCV had an increased incidence of acute rejection (log-rank P = 0.005, crude HR = 2.144; 95% CI: 1.341-3.426; P = 0.001).KTRs with chronic hepatitis B may exhibit poor survival due to post-transplantation hepatic complications. Pretransplant histological liver evaluations and adequate antiviral management with potent nucleoside/nucleotide analogues are needed to improve the survival of KTRs with chronic hepatitis B even when liver function is within the normal range.
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Affiliation(s)
- Jeonghwan Lee
- From the Internal Medicine (JL), Hallym University Hangang Sacred Heart Hospital, Seoul; Internal Medicine (JHC, CDK), Kyungpook National University Hospital, Daegu; Department of Internal Medicine (JSL), Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan; Internal Medicine (DWA, CSL, JPY), Seoul National University Boramae Medical Center; Internal Medicine (CA, YSK), Seoul National University Hospital; Surgery (IMJ), Seoul National University Boramae Medical Center; Surgery (DJH, YHK), Ulsan University Seoul Asan Medical Center, Seoul, Korea
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Jung CW, Park KT, Jun H, Kim SY, Kim SJ, Kim MG, Jo SK, Cho W, Kim HK. A Single-Center Experience of Overseas Kidney Transplant for Immunologically High-Risk Patients. EXP CLIN TRANSPLANT 2015; 13 Suppl 1:251-5. [DOI: 10.6002/ect.mesot2014.p59] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Yap DY, Chan TM. Antiviral treatment for chronic hepatitis B infection in renal transplant recipients. Int J Organ Transplant Med 2015. [DOI: 10.1016/j.hkjn.2015.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Ridruejo E. Antiviral treatment for chronic hepatitis B in renal transplant patients. World J Hepatol 2015; 7:189-203. [PMID: 25729474 PMCID: PMC4342601 DOI: 10.4254/wjh.v7.i2.189] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 11/07/2014] [Accepted: 11/17/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some data showing a favorable safety and efficacy profile of nucleos(t)ide analogue (NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC naïve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under antiHBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population.
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Affiliation(s)
- Ezequiel Ridruejo
- Ezequiel Ridruejo, Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Ciudad Autónoma de Buenos Aires, C1425ASG Buenos Aires, Argentina
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Chembo CL, Manley P, Dittmer I. Outcomes in hepatitis B surface antigen-positive renal transplant recipients. Nephrology (Carlton) 2014; 20:40-3. [PMID: 25535866 DOI: 10.1111/nep.12344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/24/2014] [Indexed: 11/29/2022]
Affiliation(s)
- Caroline L Chembo
- Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand
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Tsai SF, Shu KH, Ho HC, Cheng CY, Lin CH, Chang SN, Wu MJ. Trend of outcomes in renal transplant recipients with hepatitis B virus: a longitudinal analysis using a national database. Transplant Proc 2014; 46:578-82. [PMID: 24656017 DOI: 10.1016/j.transproceed.2013.11.053] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 11/07/2013] [Accepted: 11/27/2013] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Manifestations of hepatitis B virus (HBV) infection in renal transplant (RTx) recipients tend to be worse because of the higher viral load. RTx recipients with Asian heritage have a higher HBV infection rate and have unique characteristics. To date, no large-scale study on the outcomes of Asian RTx recipients has been conducted. Furthermore, there are few longitudinal studies comparing outcomes before and after availability of anti-HBV drugs. MATERIAL AND METHODS We conducted a nationwide, population-based study to elucidate patient survival, graft survival, and hepatic outcome (incidence of hepatoma) in Asian RTx recipients. The study includes all RTx recipients in Taiwan from 1997 to 2006. Patients were divided into 2 groups according to HBV infection status to examine the effect of antiviral drug therapy. RESULTS In all, 3826 RTx recipients were followed for a mean of 7.4 years, with a mean age of 43.7 years. There were no differences between the HBV and non-HBV groups in patient or graft survival rates. At 5 years after RTx, 89.2% of the patients were still alive and 84.5% RTx recipients were still dialysis free. In the era before anti-HBV drugs were available (1997-2001), patient survival in the HBV and non-HBV groups were similar (P = .614). This result can also be seen in the anti-HBV drug era, from 2002 to 2006 (P = .148). The unusual lack of a significant effect of drug anti-HBV administration on HBV-related mortality in RTx patients may be explained by the short duration of follow-up in the 2 eras. Another explanation may be the confounding effect of the different health status of RTx patients in the pre-anti-HBV drug era, when cardiovascular and infection-related mortality rates were considerably greater than HBV-related mortality rates. CONCLUSION These results demonstrate that HBV is not a contraindication for RTx. Asian recipients with HBV can still achieve a similar graft outcome and survival rate compared with those of patients without HBV.
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Affiliation(s)
- S-F Tsai
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taiwan; Department of Life Science, Tunghai University (S.-F.T), Taiwan
| | - K-H Shu
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taiwan
| | - H-C Ho
- Division of Urology, Taichung Veterans General Hospital, Taiwan
| | - C-Y Cheng
- Department of Pharmacy, Taichung Veterans General Hospital, Taiwan
| | - C-H Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taiwan
| | - S-N Chang
- Department of Medical Research, Taichung Veterans General Hospital, Taiwan
| | - M-J Wu
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taiwan; School of Medicine, Chung Shan Medical University, Taiwan; Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taiwan; Institute of Biomedical Science, National Chung Hsing University, Taiwan.
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11
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Fabrizi F, Dixit V, Martin P, Messa P. Hepatitis B and survival after renal transplant: meta-analysis of observational studies. J Viral Hepat 2013. [DOI: 10.1111/jvh.12184] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
Affiliation(s)
- F. Fabrizi
- Division of Nephrology and Dialysis; Maggiore Hospital; IRCCS Foundation; Milano Italy
- Division of Hepatology; School of Medicine; University of Miami; Miami FL USA
| | - V. Dixit
- Division of Hepatology; School of Medicine; University of Miami; Miami FL USA
| | - P. Martin
- Division of Hepatology; School of Medicine; University of Miami; Miami FL USA
| | - P. Messa
- Division of Nephrology and Dialysis; Maggiore Hospital; IRCCS Foundation; Milano Italy
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Magiorkinis E, Paraskevis D, Pavlopoulou I, Kantzanou M, Haida C, Hatzakis A, Boletis I. Renal transplantation from hepatitis B surface antigen ( HBsAg)‐positive donors to HBsAg‐negative recipients: a case of post‐transplant fulminant hepatitis associated with an extensively mutated hepatitis B virus strain and review of the current literature. Transpl Infect Dis 2013; 15:393-399. [DOI: 10.1111/tid.12094] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Revised: 11/25/2012] [Accepted: 12/08/2012] [Indexed: 02/06/2023]
Abstract
AbstractPurposeThe purpose of this study was to present a fatal case of fulminant hepatitis B (FHB) that developed in a renal transplant recipient, immunized against hepatitis B, 1 year post transplantation.MethodsPolymerase chain reaction amplification and full genome sequencing were performed to investigate whether specific mutations were associated with hepatitis B virus (HBV) transmission and FHB.ResultsMolecular analysis revealed multiple mutations in various open reading frames of HBV, the most important being the G145R escape mutation and a frameshift mutation–insertion (1838insA) within the pre‐C/C reading frame.ConclusionsOur results highlight the possibility of developing FHB, despite previous immunization against HBV or administration of hyperimmune gammaglobulin, because of the selection of escape virus mutants. The current literature and guidelines regarding renal transplantation from hepatitis B surface antigen (HBsAg)‐positive to HBsAg‐negative patients were also reviewed.
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Affiliation(s)
- E. Magiorkinis
- Department of Hygiene, Epidemiology and Medical Statistics Athens University Medical School Athens Greece
| | - D. Paraskevis
- Department of Hygiene, Epidemiology and Medical Statistics Athens University Medical School Athens Greece
| | - I.D. Pavlopoulou
- Pediatric Research Laboratory Faculty of Nursing University of Athens Athens Greece
| | - M. Kantzanou
- Department of Hygiene, Epidemiology and Medical Statistics Athens University Medical School Athens Greece
| | - C. Haida
- Department of Hygiene, Epidemiology and Medical Statistics Athens University Medical School Athens Greece
| | - A. Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics Athens University Medical School Athens Greece
| | - I.N. Boletis
- Department of Nephrology and Renal Transplantation Unit “Laikon” Hospital Athens University Medical School Athens Greece
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Treatment of hepatitis B in patients with chronic kidney disease. Kidney Int 2013; 84:880-5. [PMID: 23783238 DOI: 10.1038/ki.2013.249] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Revised: 04/17/2013] [Accepted: 04/25/2013] [Indexed: 02/07/2023]
Abstract
Although the prevalence of chronic hepatitis B virus (HBV) infection in patients with chronic kidney disease remains low in developed countries, clinicians should be aware of the rationale for treatment in this setting. This patient population presents particular features and various complicating conditions requiring special treatment strategies. Interferon, the standard treatment for HBV infection, has been poorly tolerated by patients with chronic kidney disease, has presented relatively low efficacy, and has posed renal transplant recipients under the risk of acute rejection. The advent of effective nucleos(t)ide analogs (NAs) has offered the opportunity to minimize the consequences of HBV infection in HBV-positive patients with chronic kidney disease. Combination with immunosuppressive agents might be considered in cases of rapid renal function deterioration and/or severe proteinuria. Among the newer NAs, entecavir may be preferred, because of its high potency, high genetic barrier to resistance, and favorable renal safety profile. However, entecavir presented low efficacy in case of lamivudine or telbivudine resistance, and thus tenofovir may be a better option in that setting. All HBsAg-positive candidates should be treated with NAs before renal transplantation in order to maintain undetectable HBV DNA, reduce liver fibrosis, and prevent hepatic decompensation after renal transplantation. This review summarizes updated issues related to treatment of chronic HBV infection in all categories of population with chronic kidney disease (those exhibiting HBV-associated glomerular disease, those treated with hemodialysis, as well as renal transplant candidates, donors, and recipients).
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