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Yap DYH, Wu CK, Tang C, Chang KC, Lee WC, Lui DTW, Ma MKM, Hu TH, Chan TM. A long term bone and renal safety of TAF treatment on renal transplant recipients. Biomed J 2025:100833. [PMID: 39956376 DOI: 10.1016/j.bj.2025.100833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 01/15/2025] [Accepted: 02/13/2025] [Indexed: 02/18/2025] Open
Abstract
RATIONALE & OBJECTIVE The data on tenofovir alafenamide (TAF) in kidney transplant recipients (KTRs) with chronic hepatitis B virus (HBV) infection is limited. STUDY DESIGN Retrospective cohort study SETTING & STUDY POPULATIONS: HBsAg-positive KTRs who received TAF between 2019 and 2022 were included in the analysis, categorized into treatment-naïve and treatment-experienced groups. Additionally, a subgroup of patients receiving ETV was analyzed for comparison. RESULTS Four treatment-naïve (Group I) and 35 treatment-experienced (Group II) patients received TAF for 26.4±11.3 and 43.7±19.0 months, respectively. Both groups showed significant HBV DNA reduction, but Group I achieved higher rates of undetectable HBV DNA (50%, 75%, 75%, 100% at 6, 12, 24, 30 months, compared with 16.7%, 25.3%, 31.4%, 34.7% in Group II, p=0.018). Renal allograft function remained stable during follow-up, and bone toxicity was minimal. For ETV, 10 patients demonstrated excellent viral suppression (HBV DNA undetectable in 70% at 48 weeks and 100% at 96 weeks) with stable renal function over a median of 5.2 years. LIMITATIONS Retrospective study with a lack of prospective comparison of TAF and ETV. CONCLUSIONS Our results suggest that TAF provides favorable efficacy, renal safety, and tolerability in KTRs. ETV also provided effective and sustainable viral suppression. TAF may offer additional advantages such as no concern of viral resistance and dose adjustment by eGFR levels for long-term management of HBsAg-positive KTRs.
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Affiliation(s)
- Desmond Y H Yap
- Division of Nephrology, Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
| | - Cheng-Kun Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung College of Medicine, Taiwan
| | - Colin Tang
- Division of Nephrology, Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung College of Medicine, Taiwan
| | - Wen-Chin Lee
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung College of Medicine, Taiwan
| | - David T W Lui
- Division of Endocrinology and Metabolism, Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong
| | - Maggie K M Ma
- Division of Nephrology, Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung College of Medicine, Taiwan.
| | - Tak Mao Chan
- Division of Nephrology, Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
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Cerrillos-Gutiérrez JI, Parra-Guerra R, Gutiérrez-Govea A, Andrade-Sierra J, González-Espinoza E, Nuño-Díaz D, Herrera-Rodríguez MJ, Ávila-Morán M, Corona-Nakamura AL, Hinogiante-Segura LY, Mendoza-Cerpa CA. Kidney transplant recipient with history of HIV, HBV, and past HCV infection. AIDS Res Ther 2024; 21:57. [PMID: 39187870 PMCID: PMC11348749 DOI: 10.1186/s12981-024-00647-y] [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: 01/13/2024] [Accepted: 08/15/2024] [Indexed: 08/28/2024] Open
Abstract
Chronic viral infections caused by the human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common among patients with end-stage renal disease (ESKD). These infections were once considered contraindications to kidney transplantation due to potential risks associated with long-term immunosuppression. Improved management and antiviral therapies have changed the prognosis and survival of this group of patients, along with an increased experience in transplanting people with these viral infections. We report the first successful kidney transplant in an ESKD patient on hemodialysis with a history of concomitant HIV, HCV and HBV infection in Mexico.
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Affiliation(s)
- José Ignacio Cerrillos-Gutiérrez
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Ricardo Parra-Guerra
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
- University Center of Health Sciences, University of Guadalajara, Guadalajara, Mexico
| | - Alfredo Gutiérrez-Govea
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico.
- University Center of Health Sciences, University of Guadalajara, Guadalajara, Mexico.
| | - Jorge Andrade-Sierra
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
- University Center of Health Sciences, University of Guadalajara, Guadalajara, Mexico
| | - Eduardo González-Espinoza
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Daniel Nuño-Díaz
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Martha Jessica Herrera-Rodríguez
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Maribel Ávila-Morán
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Ana Luisa Corona-Nakamura
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Luz Yasmin Hinogiante-Segura
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
| | - Claudia Alejandra Mendoza-Cerpa
- Nephrology and Transplantation Division, UMAE, National Medical Center of the West, Mexican Institute of Social Security, Guadalajara, Mexico
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Bellamy CO, Burt AD. Liver in Systemic Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1039-1095. [DOI: 10.1016/b978-0-7020-8228-3.00015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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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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The Impact of Antiviral Treatment of Hepatitis B Virus after Kidney Transplant and the Latest Insights. Pathogens 2023; 12:pathogens12020340. [PMID: 36839612 PMCID: PMC9962423 DOI: 10.3390/pathogens12020340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 02/19/2023] Open
Abstract
BACKGROUND The current frequency of hepatitis B virus infection in patients with advanced chronic kidney disease (CKD) (including patients on maintenance dialysis and kidney transplant recipients) is low but not negligible worldwide. HBV has a deleterious effect on survival after a kidney transplant; antiviral treatments improved the short-term outcomes of kidney transplant recipients, but their long-term impact remains uncertain. AIM The aim of this review is to assess the role of antiviral therapy for HBV in improving survival after a kidney transplant. The recent publication of large surveys has prompted us to update the available evidence on the impact of HBV on patient and graft survival after a kidney transplant. METHODS We have conducted an extensive review of the medical literature, and various research engines have been used. RESULTS We retrieved several studies (n = 11; n = 121,436 unique patients) and found an association between positive serologic HBsAg status and diminished patient and graft survival after a kidney transplant; the adjusted relative risk (aRR) of all-cause mortality and graft loss was 2.85 (95% CI, 2.36; 3.33, p < 0.0001) and 1.26 (95% CI, 1.02; 1.51, p < 0.0001), respectively. To our knowledge, at least six studies reported improved patient and graft survival after the adoption of antiviral therapies for HBV (this result was reported with both survival curves and multivariable regression). According to novel clinical guidelines, entecavir has been suggested as a 'first line' antiviral agent for the treatment of HBV after a kidney transplant. CONCLUSIONS The recent availability of safe and effective antiviral drugs for the treatment of HBV has meant that the survival curves of HBsAg-positive patients on antiviral therapy and HBsAg-negative patients after a kidney transplant can be comparable. Antiviral therapy should be systematically proposed to HBV-positive kidney transplant recipients and candidates to avoid the deleterious hepatic and extra-hepatic effects of chronic HBV replication.
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Abraham G, Anupama S, Parthasarathy R, Mathew M, Anupama P. Rectal carcinoma 27 years' postkidney transplant in a chronic hepatitis B patient - A case report. INDIAN JOURNAL OF TRANSPLANTATION 2022. [DOI: 10.4103/ijot.ijot_128_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Yuan Q, Haque O, Hong S, Ortiz A, Bethea ED, Sise ME, Markmann JF, Elias N. Influence of donor and recipient hepatitis B virus infection on long-term outcomes after kidney transplantation. Clin Transplant 2021; 35:e14466. [PMID: 34545965 DOI: 10.1111/ctr.14466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/23/2021] [Accepted: 08/16/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The demand for transplantable kidneys continues to outstrip supply, and the risk of donor-derived infection limits utilization. The effect of donor or recipient HBV status, defined by surface antigen (HBsAg) positivity, on long-term survival outcomes of kidney transplant (KT) is unknown. METHODS We conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D-R, D-R+, and D+R-. Pairwise comparisons of patient survival (PS) and all-cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients. RESULTS Our findings showed that there were no statistically significant differences in PS and GS among D-R, D-R+, and D+R-groups, nor was the patient or GS different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg- donors. CONCLUSIONS HBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary.
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Affiliation(s)
- Qing Yuan
- Department of Urology, Chinese PLA General Hospital, Beijing, China.,Center for Transplantation Sciences, and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Omar Haque
- Center for Transplantation Sciences, and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA.,Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.,Shriners Hospitals for Children, Boston, Massachusetts, USA
| | - Shanjuan Hong
- Center for Transplantation Sciences, and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Andric Ortiz
- Center for Transplantation Sciences, and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Emily D Bethea
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Meghan E Sise
- Harvard Medical School, Boston, Massachusetts, USA.,Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - James F Markmann
- Center for Transplantation Sciences, and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Nahel Elias
- Center for Transplantation Sciences, and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
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8
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Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies. J Pediatr Gastroenterol Nutr 2020; 70:527-538. [PMID: 31977956 DOI: 10.1097/mpg.0000000000002628] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.
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Yap DYH, Tang C, Fung JYY, Seto WK, Ma MKM, Choy BY, Chan TM. Long-term data on entecavir treatment for treatment-naive or lamivudine-resistant chronic hepatitis B infection in kidney transplant recipients. Transpl Infect Dis 2019; 21:e13143. [PMID: 31282041 DOI: 10.1111/tid.13143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 04/17/2019] [Accepted: 06/23/2019] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Entecavir (ETV) showed short-term efficacy and safety in HBsAg-positive kidney transplant recipients (KTRs), but long-term data are lacking. METHODOLOGY We retrospectively reviewed 30 HBsAg-positive KTRs who received ETV during 2007-2017. RESULTS Eighteen treatment-naïve (Group I) and 12 lamivudine-resistant (Group II) patients received ETV for 48.4 ± 35.2 and 66.0 ± 26.0 months, respectively. Both groups show significant HBV DNA decline, but Group I achieved earlier undetectability after 11.9 ± 9.6 months (compared with 28.8 ± 24.2 months in Group II, P = .033). Group I showed higher rates of undetectable HBV DNA (89%, 94%, 94%, 100%, and 100% at 12, 24, 36, 48, and 60 months, respectively, compared with 25%, 50%, 50%, 91%, and 91% in Group II, P = .003). ALT normalized after 6.0 ± 1.9 and 6.8 ± 2.1 months in Group I and Group II, respectively. Four patients (33.3%) in Group II developed drug resistance (2 had persistent viraemia and 2 had virological breakthrough, at 40.3 ± 15.0 months). Group II showed higher liver stiffness after 5 years (7.7 ± 4.1 kPa, compared with 5.0 ± 1.6 kPa in Group I, P = .046) and incidence of cirrhosis (4 patients [33.3%], compared with 1 [5.6%] patient in Group I, P = .049). Two patients (one in each group) developed hepatocellular carcinoma. Renal allograft function remained stable during follow-up of 63.2 ± 33.4 months for both groups. There was no difference in patient and graft survival between two groups at 5 years (P = .62 and .36, respectively). CONCLUSION ETV showed favorable long-term efficacy and tolerability in treatment-naïve KTRs. One-third of lamivudine-resistant subjects showed non-response or viral breakthrough after ETV treatment.
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Affiliation(s)
- Desmond Y H Yap
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Colin Tang
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - James Y Y Fung
- Division of Gastroenterology and Hepatology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Division of Gastroenterology and Hepatology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Maggie K M Ma
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Bo Ying Choy
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
| | - Tak Mao Chan
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, Hong Kong
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
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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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Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560-1599. [PMID: 29405329 PMCID: PMC5975958 DOI: 10.1002/hep.29800] [Citation(s) in RCA: 2769] [Impact Index Per Article: 395.6] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Norah A Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska NativeTribal Health Consortium, Anchorage, AK
| | - Kyong-Mi Chang
- Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | | | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Tufts University School of Medicine, Boston, MA
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Thongprayoon C, Kaewput W, Sharma K, Wijarnpreecha K, Leeaphorn N, Ungprasert P, Sakhuja A, Cabeza Rivera FH, Cheungpasitporn W. Outcomes of kidney transplantation in patients with hepatitis B virus infection: A systematic review and meta-analysis. World J Hepatol 2018; 10:337-346. [PMID: 29527269 PMCID: PMC5838452 DOI: 10.4254/wjh.v10.i2.337] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 01/10/2018] [Accepted: 02/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus (HBV) infection, and the trends of patient's outcomes overtime. METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios (OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen (HBsAg) positive] were included. The comparison group consisted of HBsAg-negative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017080657). RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBsAg-negative recipients, HBsAg-positive status was significantly associated with increased risk of mortality after kidney transplantation (pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBsAg-positive recipients and year of study (slopes = -0.062, P = 0.001). HBsAg-positive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46 (95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure (slopes = -0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBsAg-positive recipients, respectively. CONCLUSION Among kidney transplant patients, there are significant associations between HBsAg-positive status and poor outcomes including mortality and allograft failure. However, there are potential improvements in patient and graft survivals in HBsAg-positive recipients overtime.
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Affiliation(s)
- Charat Thongprayoon
- Karn wijarnpreecha, Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand
| | - Konika Sharma
- Karn wijarnpreecha, Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | | | - Napat Leeaphorn
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Ankit Sakhuja
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Franco H Cabeza Rivera
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, United States
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, United States
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Abstract
Renal involvement in hepatitis B occurs in various spectrums and its knowledge is important for clinicians in management of patients. The renal diseases most commonly associated with hepatitis B virus (HBV) infection include membranous nephropathy, membranoproliferative glomerulonephritis and Polyarteritis nodosa. The widespread use of hepatitis B vaccination has decreased the incidence of HBV-related renal diseases. The incidence of HBV infection in dialysis patients has significantly decreased over the past few decades because of screening of blood products for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, implementation of infection control measures and hepatitis B vaccination. The definition of acute kidney injury has been recently modified in cirrhotic population, helping in prognosis and prediction of mortality. The most common etiologies of acute kidney injury in this cirrhotic population, which account for 80% to 90% of all cases, include volume depletion, acute tubular necrosis and hepatorenal syndrome. Treatment with oral nucleoside/tide analogues (NA) brought a new paradigm in the management of HBsAg positive glomerulonephritis, kidney transplant recipients and dialysis patients, resulting in effective viral suppression, reduced hepatic complications and improved patient survival, without compromising renal allograft outcome. NAs are cleared by the kidneys and therefore their dosage has to be adjusted in all patients with impaired renal function. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related glomerulonephritis and discusses the management of hepatitis B in patients on dialysis, kidney transplant recipients and cirrhotics, which is continuously evolving.
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Affiliation(s)
- Apurva S Shah
- Department of Gastroenterology, Bombay Hospital and Medical Research Institute, Mumbai, Maharashtra, India
| | - Deepak N Amarapurkar
- Department of Gastroenterology, Bombay Hospital and Medical Research Institute, Mumbai, Maharashtra, India
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Marinaki S, Kolovou K, Sakellariou S, Boletis JN, Delladetsima IK. Hepatitis B in renal transplant patients. World J Hepatol 2017; 9:1054-1063. [PMID: 28951777 PMCID: PMC5596312 DOI: 10.4254/wjh.v9.i25.1054] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 07/18/2017] [Accepted: 08/16/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates, especially in developed countries. The best preventive method is vaccination. Patients with chronic renal disease should ideally be vaccinated prior to dialysis, otherwise, reinforced vaccination practices and close antibody titer monitoring should be applied while on dialysis. HBV infected dialysis patients who are renal transplant candidates must be thoroughly examined by HBV-DNA, and liver enzyme testing and by liver biopsy. When needed, one must consider treating patients with tenofovir or entecavir rather than lamivudine. Depending on the cirrhosis stage, dialysis patients are eligible transplant recipients for either a combined kidney-liver procedure in the case of decompensated cirrhosis or a lone kidney transplantation since even compensated cirrhosis after sustained viral responders is no longer considered an absolute contraindication. Nucleoside analogues have led to improved transplantation outcomes with both long-term patient and graft survival rates nearing those of HBsAg(-) recipients. Moreover, in the cases of immunized HBsAg(-) potential recipients with concurrent prophylaxis, we are enabled today to safely use renal grafts from both HBsAg(+) and HBsAg(-)/anti-HBc(+) donors. In so doing, we avoid unnecessary organ discarding. Universal prophylaxis with entecavir is recommended in HBV kidney recipients and should start perioperatively. One of the most important issues in HBV(+) kidney transplantation is the duration of antiviral prophylaxis. In the absence of robust data, it seems that prophylactic treatment may be discontinued in selected stable, low-risk recipients during maintenance immunosuppression and should be reintroduced when the immune status is altered. All immunosuppressive agents in kidney transplantation can be used in HBV(+) recipients. Immunosuppression is intimately associated with increased viral replication; thus it is important to minimize the total immunosuppression burden long term.
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Affiliation(s)
- Smaragdi Marinaki
- Department of Nephrology and Renal Transplantation Unit, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece
| | - Kyriaki Kolovou
- Department of Nephrology and Renal Transplantation Unit, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece
| | | | - John N Boletis
- Department of Nephrology and Renal Transplantation Unit, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece
| | - Ioanna K Delladetsima
- First Department of Pathology, Medical School, University of Athens, 11527 Athens, Greece
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Yap DYH, Chan TM. Use of telbivudine in kidney transplant recipients with chronic hepatitis B virus infection: A preliminary experience. Nephrology (Carlton) 2017; 21:438-41. [PMID: 26484932 DOI: 10.1111/nep.12651] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 09/16/2015] [Accepted: 10/10/2015] [Indexed: 12/01/2022]
Abstract
Telbivudine is a relatively novel oral nucleoside analogue with favourable efficacy and tolerability in treatment-naïve chronic hepatitis B virus (HBV) infection, but its data in kidney transplant recipients (KTRs) was lacking. The efficacy and tolerability of telbivudine in four treatment-naïve HBsAg-positive KTRs were reviewed (treatment duration 54 (36-72) months) HBV DNA declined from 2.6 × 10(5) (7.8 × 10(3) -1.5 × 10(7) ) copies/mL at baseline to 170 (0.0-3.2 × 10(4) ) copies/mL at 12 months, and became undetectable at 24 and 36 months (P = 0.060, 0.118 and 0.005 compared with baseline). Alanine aminotransferase levels dropped from 46.5 (30-48) IU/mL at baseline to 28 (13-45) IU/mL, 34.5 (15-71) IU/mL and 26 (12-41) IU/mL at 12, 24 and 36 months, respectively (P = 0.109, 0.715 and 0.068 compared with baseline). Serum creatinine level and estimated glomerular filtration rate (eGFR) remained stable after 36 months of treatment (P all > 0.05 compared with baseline). No virological breakthrough, cirrhosis or hepatocellular carcinoma occurred. Our pilot data suggests that telbivudine has favourable efficacy and renal safety profiles in HBsAg-positive KTRs.
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Affiliation(s)
- Desmond Y H Yap
- Nephrology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
| | - Tak Mao Chan
- Nephrology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
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Comparison of Clinical Outcomes in Hepatitis B Virus–Positive and –Negative Renal Transplant Recipients. Int Surg 2016. [DOI: 10.9738/intsurg-d-15-00144.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Our aim was to compare the short- and long-term clinical outcomes of hepatitis B surface antigen–positive (HbsAg+) renal transplant recipients with HbsAg− recipients. A total of 204 patients who underwent renal transplantation in our center between 2001 and 2014 were included in the study. The patients were divided into 2 groups. Group 1 was the HbsAg− group (n = 136), and group 2 was the HbsAg+ group (n = 68). There was no significant difference between the groups in terms of lymphocyte crossmatches, numbers of mismatches, immunosuppressive treatment protocols, and induction treatments. In the HbsAg+ group, 51 patients were hepatitis B virus DNA+, 64 patients were HbeAg−, and 4 patients were HbeAg+. A total of 57 patients (83.8%) were treated with lamivudine, 4 patients (5.9%) with entecavir, and 7 patients (10.3%) with tenofovir for hepatitis B infection. Graft and patient survival rates, graft functions, acute hepatitis rates, acute rejection rates, and other clinical outcomes of the groups were compared. Demographic data and immunologic risk profiles of the groups were similar. Acute rejection rates, graft survival rates, and patient survival rates were similar. Acute hepatitis rates, glomerular filtration rates on the last controls, and delayed graft function rates were higher in group 2, whereas chronic allograft dysfunction and new-onset diabetes mellitus after transplantation rates were similar between the groups. Our study revealed that graft and patient survival, and acute rejection rates were similar between HbsAg+ and HbsAg− recipients, whereas acute hepatitis rate was higher in HbsAg+ recipients.
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Moosa MR, Maree JD, Chirehwa MT, Benatar SR. Use of the 'Accountability for Reasonableness' Approach to Improve Fairness in Accessing Dialysis in a Middle-Income Country. PLoS One 2016; 11:e0164201. [PMID: 27701466 PMCID: PMC5049822 DOI: 10.1371/journal.pone.0164201] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 09/21/2016] [Indexed: 01/02/2023] Open
Abstract
Universal access to renal replacement therapy is beyond the economic capability of most low and middle-income countries due to large patient numbers and the high recurrent cost of treating end stage kidney disease. In countries where limited access is available, no systems exist that allow for optimal use of the scarce dialysis facilities. We previously reported that using national guidelines to select patients for renal replacement therapy resulted in biased allocation. We reengineered selection guidelines using the ‘Accountability for Reasonableness’ (procedural fairness) framework in collaboration with relevant stakeholders, applying these in a novel way to categorize and prioritize patients in a unique hierarchical fashion. The guidelines were primarily premised on patients being transplantable. We examined whether the revised guidelines enhanced fairness of dialysis resource allocation. This is a descriptive study of 1101 end stage kidney failure patients presenting to a tertiary renal unit in a middle-income country, evaluated for dialysis treatment over a seven-year period. The Assessment Committee used the accountability for reasonableness-based guidelines to allocate patients to one of three assessment groups. Category 1 patients were guaranteed renal replacement therapy, Category 3 patients were palliated, and Category 2 were offered treatment if resources allowed. Only 25.2% of all end stage kidney disease patients assessed were accepted for renal replacement treatment. The majority of patients (48%) were allocated to Category 2. Of 134 Category 1 patients, 98% were accepted for treatment while 438 (99.5%) Category 3 patients were excluded. Compared with those palliated, patients accepted for dialysis treatment were almost 10 years younger, employed, married with children and not diabetic. Compared with our previous selection process our current method of priority setting based on procedural fairness arguably resulted in more equitable allocation of treatment but, more importantly, it is a model that is morally, legally and ethically more defensible.
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Affiliation(s)
- Mohammed Rafique Moosa
- Division of Nephrology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Renal Unit, Tygerberg Academic Hospital, Cape Town, South Africa
- * E-mail:
| | | | - Maxwell T. Chirehwa
- Biostatistics Unit, Centre for Evidence-based Health Care, Department of Interdisciplinary Health Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Harmancı Ö, İlin S, Öcal S, Korkmaz M, Moray G, Çolak T, Selçuk H, Özdemir BH, Haberal M. The Effect of Hepatitis B Virus on Graft and Overall Survival in Kidney Transplant Patients. EXP CLIN TRANSPLANT 2016; 13 Suppl 3:36-40. [PMID: 26640908 DOI: 10.6002/ect.tdtd2015.o24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES We investigated the effect of hepatitis B virus in kidney transplant patients in terms of patient care and survival. MATERIALS AND METHODS We retrospectively analyzed kidney transplant patients from 1993 to 2013. A control group with negative serology was selected. The hepatitis B virus-positive group was divided into 2 subgroups based on serologic status, treatments, and treatment responses. Group A had viral suppression, and group B had hepatitis B virus DNA persistence. Overall and allograft survival rates were compared. RESULTS We identified 32 hepatitis B virus-positive and 74 hepatitis B virus-negative patients. Positive group was treated with lamivudine (n = 23), lamivudine plus entecavir (n = 4), lamivudine plus tenofovir (n = 4), or lamivudine plus entecavir and tenofovir (n = 1). In group A (n = 15), antiviral treatment was given based on the presence of either hepatitis B surface antigen with negative hepatitis B virus DNA (n = 11) or hepatitis B virus DNA positivity (n = 4). Group B patients (n = 17) received antiviral treatment for persistence of hepatitis B virus DNA (n = 7) or for viral reactivation (ie, recurrence of hepatitis B virus DNA) (n = 10). Groups A and B did not differ significantly in terms of graft or overall survival. Liver biopsy was performed in 17 patients; 3 patients had high-grade fibrosis or cirrhosis, and 14 patients had normal histology or mild hepatitis. Median graft survival time was longer in positive group (69.5 mo vs 54 mo; P = .007). Five- and 10-year overall survival rates were comparable (89%-84% vs 96%-96%; P = .107). CONCLUSIONS Hepatitis B virus-positive kidney transplant patients have increased liver transaminase levels, longer graft survival times, and similar median overall survival rates compared with hepatitis B virus-negative patients.
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Affiliation(s)
- Özgür Harmancı
- From the Department of Gastroenterology, Başkent University Faculty of Medicine, Ankara, Turkey
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Tenofovir and kidney transplantation: case report. Clin Nephrol Case Stud 2016; 4:18-23. [PMID: 29043137 PMCID: PMC5438008 DOI: 10.5414/cncs108929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Accepted: 06/29/2016] [Indexed: 12/15/2022] Open
Abstract
Background: Hepatitis B viral infection (HBV) has been regarded as a contraindication for kidney transplantation because of the high risk of viral activation induced by immunosuppressive therapy. Anti-retroviral drugs have changed the prognosis of patients with hepatitis B viral infection (HBV+) who are candidates for renal transplant; indeed, therapy with antiretroviral drugs may ensure lower rates of morbidity and mortality compared to traditional therapies. Entecavir is the first-line antiviral therapy recommended for the treatment of HBV+ kidney-transplanted patients. In case of resistance to entecavir, tenofovir may be an alternative drug, either alone or in combination with entecavir. However, the best strategy of treatment is still unknown. In this case-report, a HBV+ kidney-transplanted patient who presented resistance to entecavir was initially treated by associating tenofovir to entecavir and with tenofovir alone afterward. This strategy induced complete remission of viral replication. Case presentation: In a HBV+ kidney-transplanted patient under monotherapy with entecavir, HBV flare (HBV DNA > 170.000 × 103 UI/mL, HBeAg+, HbeAb–) occurred 9 months after transplantation; at that time, blood chemistry highlighted: creatinine 1.46 mg/dL, blood urea 65 mg/dL, e-GFR 50 mL/min, proteinuria 300 mg/24 h, calciuria 2,12 mmol/24 h, phosphaturia 0.56 g/24 h, vitamin D 11.5 ng/mL, PTH 130 pg/mL, calcemia 2.3 mmol/L, and phosphoremia 2 mg/dL. Liver elastometry (FibroScan) showed moderate fibrosis. Tenofovir was associated to entecavir. Three months after the combination therapy, reduction in HBV DNA replication (351 × 103 UI/mL) was obtained. Creatinine and e-GFR were 1.48 mg/dL and 52 mL/min, respectively. At this point, entecavir was discontinued. After 13 months of tenofovir monotherapy, complete remission of viral replication was achieved but renal function deteriorated and proteinuria increased. Conclusion: This case-report indicates that tenofovir is effective in reducing viral replication of hepatitis B virus in a kidney-transplanted patient who presented resistance to previous treatment with entecavir. However, it should be taken into account that tenofovir could affect renal function.
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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: 16] [Impact Index Per Article: 1.8] [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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Veroux M, Ardita V, Corona D, Giaquinta A, Ekser B, Sinagra N, Zerbo D, Patanè M, Gozzo C, Veroux P. Kidney Transplantation From Donors with Hepatitis B. Med Sci Monit 2016; 22:1427-34. [PMID: 27123988 PMCID: PMC4915324 DOI: 10.12659/msm.896048] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The growing demand for organ donors to supply the increasing number of patients on kidney waiting lists has led most transplant centers to develop protocols that allow safe use of organs from donors with special clinical situations previously regarded as contraindications. Deceased donors with previous hepatitis B may be a safe resource to increase the donor pool even if there is still controversy among transplantation centers regarding the use of hepatitis B surface antigen-positive donors for renal transplantation. However, when allocated to serology-matched recipients, kidney transplantation from donors with hepatitis B may result in excellent short-term outcome. Many concerns may arise in the long-term outcome, and studies must address the evaluation of the progression of liver disease and the rate of reactivation of liver disease in the recipients. Accurate selection and matching of both donor and recipient and correct post-transplant management are needed to achieve satisfactory long-term outcomes.
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Affiliation(s)
- Massimiliano Veroux
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Vincenzo Ardita
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Daniela Corona
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Alessia Giaquinta
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Burcin Ekser
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Nunziata Sinagra
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, university Hospital of Catania, Catania, Italy
| | - Domenico Zerbo
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, university Hospital of Catania, Catania, Italy
| | - Marco Patanè
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Cecilia Gozzo
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
| | - Pierfrancesco Veroux
- Vascular Surgery and Organ Transplant Unit, Department of Medical and Surgical Sciences and Advanced Technologies, University Hospital of Catania, Catania, Italy
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García Agudo R, Aoufi Rabih S, Barril Cuadrado G, Proy Vega B, Arias Arias Á, Herruzo Gallego JA. Spanish multicentre PIBHE study: Prevalence and immunization of chronic hepatitis B in haemodialysis patients in Spain. Nefrologia 2016; 36:126-32. [PMID: 26875043 DOI: 10.1016/j.nefro.2015.10.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 10/06/2015] [Accepted: 10/19/2015] [Indexed: 10/22/2022] Open
Abstract
INTRODUCTION The PIBHE study, promoted by the Spanish Liver and Kidney Association and the Dialysis Virus Group of the Spanish Society of Nephrology, is the first study to determine the status of haemodialysis patients with chronic HBV infection and the immunisation against the vaccine. METHOD The study has a national multicentre, observational, cross-sectional design and was carried out between January 2013 and 2014. A data collection folder was sent to all the nephrology departments and outpatient haemodialysis units in Spain, to be completed based on patient medical files after informed consent. The data were recorded in a central database. RESULTS A total of 215 centres participated (15,645 patients), with an HBV prevalence of 1.03%. HCV or HIV was present in 7.2% of the HBV(+) patients. Viral load was below 2,000 IU/ml in 80%. GOT and GPT levels were 19.1±10.1 and 15.9±9.6 IU/ml, respectively. Liver biopsy was performed in 7.1%. Antiviral treatment was prescribed in 30% and suspended in 12.5%: entecavir (13.3%), lamivudine (10%), adefovir and tenofovir (6.7%), and interferon (3.3%). A total of 34.5% were candidates for renal transplantation and 6.9% had not been evaluated; 64.3% were followed up by a gastroenterologist; 27.2% of HBV(-) patients without immunisation had not been vaccinated. Fourteen different immunisation schedules had been used, with an immunisation rate of 58.8%. Mean anti-HBs stood at 165.7±297.8mIU/ml. A total of 72.7% of patients had received a vaccination course; 26.4%, 2 cycles; 1.0%, 3 cycles; and 11.6%, a booster dose. A total of 28.3% had a poor response (anti-HBs 10-99mIU/ml); 22.4%, an optimal response (anti-HBs 100-999mIU/ml); and 7.9%, an excellent response (anti-HBs ≥ 1,000mIU/ml). Age was significantly associated with response to vaccination; the mean age of nonresponders was significantly higher than patients who had a response of any kind (P<.05). The highest probability of an immune response was achieved with 4 doses of 40 mcg of adjuvanted vaccine (OR: 7.3; 95% CI 3.4 to 15.7), for the same age and number of cycles and boosters. Age, adjuvanted vaccine, dose and vaccination schedule influenced the immune response and the anti-HBs titres reached (P<.05). CONCLUSION The prevalence of chronic HBV infection in haemodialysis in Spain is low and so are the rates of immunisation against the virus. The vaccination schedules used are very diverse and have been observed to correlate with the immune response. It would therefore be necessary to establish a protocol for the most effective vaccination schedule to increase immunisation in these patients.
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Affiliation(s)
- Rebeca García Agudo
- Unidad Hepatorrenal, Servicio de Nefrología, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), España.
| | - Sami Aoufi Rabih
- Unidad Hepatorrenal, Servicio de Aparato Digestivo, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), España
| | | | - Beatriz Proy Vega
- Grupo de Investigación de la Asociación Española de Hígado y Riñón, Alcázar de San Juan (Ciudad Real), España
| | - Ángel Arias Arias
- Unidad de Apoyo a la Investigación, Hospital La Mancha-Centro, Alcázar de San Juan (Ciudad Real), España
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Yilmaz V, Aliosmanoglu İ, Erbis H, Ulger B, Cetinkaya R, Suleymanlar G, Kocak H. Effects of hepatitis B surface antigen (HBsAg) positivity of donors in HBsAg(+) renal transplant recipients: comparison of outcomes with HBsAg(+) and HBsAg(−) donors. Transpl Infect Dis 2016; 18:55-62. [DOI: 10.1111/tid.12482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 08/20/2015] [Accepted: 09/25/2015] [Indexed: 12/14/2022]
Affiliation(s)
- V.T. Yilmaz
- Department of Internal Medicine; Division of Nephrology; Akdeniz University Medical School; Antalya Turkey
| | - İ. Aliosmanoglu
- Department of General Surgery; Akdeniz University Medical School; Antalya Turkey
| | - H. Erbis
- Department of General Surgery; Akdeniz University Medical School; Antalya Turkey
| | - B.V. Ulger
- Department of General Surgery; Dicle University Medical School; Diyarbakir Turkey
| | - R. Cetinkaya
- Department of Internal Medicine; Division of Nephrology; Akdeniz University Medical School; Antalya Turkey
| | - G. Suleymanlar
- Department of Internal Medicine; Division of Nephrology; Akdeniz University Medical School; Antalya Turkey
| | - H. Kocak
- Department of Internal Medicine; Division of Nephrology; Akdeniz University Medical School; Antalya Turkey
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Pipili C, Cholongitas E. Pharmaceutical management of hepatitis B and C in liver and kidney transplant recipients. World J Gastrointest Pharmacol Ther 2015; 6:105-10. [PMID: 26558143 PMCID: PMC4635149 DOI: 10.4292/wjgpt.v6.i4.105] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Revised: 07/05/2015] [Accepted: 07/29/2015] [Indexed: 02/06/2023] Open
Abstract
The combination of hepatitis B immune globulin with entecavir or tenofovir (at least for a certain period of time) seems to be the most reasonable prophylaxis against recurrent hepatitis B after liver transplantation. Entecavir represents an attractive option for treatment of naïve kidney transplant recipients, because of its high efficacy and the low rates of resistance. However antiviral treatment should be individualized in the view of kidney function and the previous resistance. To date, new captivating therapeutic strategies could make interferon-free regimens viable for treatment of hepatitis C virus positive liver transplant recipients. The recent combinations of sofosbuvir with simeprevir or daclatasvir or ledipasvir plus/minus ribavirin have boosted the on treatment and sustained virological response to rates approaching 100% within liver transplant recipients with recurrent chronic hepatitis C (CHC). Preliminary data showed that the second generation direct oral antivirals could result to high treatment rates of recurrent CHC in kidney transplant recipients as well. Ongoing studies will clarify the optimal treatment of recurrent CHC in kidney transplant recipients.
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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: 14] [Impact Index Per Article: 1.4] [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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Cholongitas E, Tziomalos K, Pipili C. Management of patients with hepatitis B in special populations. World J Gastroenterol 2015; 21:1738-1748. [PMID: 25684938 PMCID: PMC4323449 DOI: 10.3748/wjg.v21.i6.1738] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 10/27/2014] [Accepted: 11/18/2014] [Indexed: 02/06/2023] Open
Abstract
The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.
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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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Yap DYH, Yung S, Tang CSO, Seto WK, Ma MKM, Mok MMY, Kwan LPY, Chan GCW, Choy BY, Yuen MF, Chan TM. Entecavir treatment in kidney transplant recipients infected with hepatitis B. Clin Transplant 2014; 28:1010-5. [PMID: 24974788 DOI: 10.1111/ctr.12410] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2014] [Indexed: 01/13/2023]
Abstract
Although nucleotide/side analogs improve the clinical outcome of hepatitis B surface antigen-positive (HBsAg+) kidney transplant recipients (KTR), a significant proportion of subjects have developed resistance to lamivudine (LAM). We retrospectively analyzed the efficacy and tolerability of entecavir (ETV) in HBsAg+ KTR at Queen Mary Hospital during 2005-2013. Twenty-one patients (10 treatment-naïve, 11 with LAM resistance) were included (duration of ETV treatment 34.7 ± 22.9 months, range 6-75 months). ETV treatment led to a decline of hepatitis B virus (HBV) DNA titer compared to baseline and is more significant in the treatment-naïve group (treatment-naïve: p = 0.028, <0.001 and <0.001; LAM-resistant p = 0.273, 0.180, and 0.109 after 12, 24, and 36 months). The cumulative rate of HBV DNA undetectability at 12, 24, and 36 months was 60%, 100%, and 100% for treatment-naïve group, and 27%, 45%, and 45% for LAM-resistant group, respectively. Time-to-HBV DNA undetectability and time-to-alanine transaminase (ALT) normalization were 15.7 ± 4.6 and 12.6 ± 3.7 months for treatment-naïve patients, and 24.5 ± 4.2 and 28.2 ± 3.5 months for those with LAM resistance. Genotypic resistance to ETV emerged after 20.0 ± 3.5 months with increase in ALT and HBV DNA in two patients with LAM resistance, but was not observed in the treatment-naïve group. Allograft dysfunction, de novo cirrhosis, or hepatocellular carcinoma did not occur during follow-up.
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Affiliation(s)
- Desmond Y H Yap
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
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Ruhi Ç, Süleymanlar İ, Koçak H, Dinçkan A, Ersoy F, Süleymanlar G. Effect of prophylactic versus preemptive lamivudine treatment and tenofovir on HBsAg+ kidney transplant recipients. EXP CLIN TRANSPLANT 2014; 13:35-40. [PMID: 25019317 DOI: 10.6002/ect.2013.0280] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVES Chronic hepatitis B virus infection remains a clinical problem for HBsAg (+) kidney transplant recipients. Lamivudine is the approved treatment; however, there are contrary views about optimal initiation. In case of resistance, novel nucleoside analogs should be considered but experience is limited. MATERIALS AND METHODS The study was a retrospective cohort study that included 58 HBsAg (+) kidney transplant recipients. Medical records were reviewed for nucleoside analogs, viral replication, and graft/hepatic functions. Prophylactic and preemptive lamivudine modalities were compared to reveal optimal initiation. Additionally, novel nucleoside analogs were evaluated for safety and efficacy. RESULTS The graft/patient survival rates for HBsAg (+) recipients were the same as those of hepatitis-free recipients (P = .18). Prophylactic group had 24 and the preemptive had 34 patients. In the prophylactic group, there were fewer hepatic dysfunctions (12.5% vs. 30%, P = .12), viral breakthroughs (16% vs. 32%, P = .17) and elevated alanine aminotransferase concentrations (37% vs. 52%, P = .24), however these did not reach statistical significance. Progressive hepatic dysfunction was observed in 5 patients. Treatment was altered to tenofovir (n = 4) and adefovir (n = 1), and adequate virologic/biochemical response was achieved. These nucleoside analogs were almost as safe as lamivudine, as there were no significant differences among proteinuria (4740 ± 9480 vs 1250 ± 430 mg/L; P = .60) and estimated glomerular filtration rate (1.23 ± 0.37 vs 1.10 ± 0.35 mL/s; P = .33) CONCLUSIONS: Lamivudine is an efficient means of providing comparable graft/patient survival with hepatitis-free kidney transplant recipients. The prophylactic initiation of lamivudine may be better in preventing hepatic dysfunction. Tenofovir can be an effective and safe treatment for lamivudine-resistant kidney transplant recipients.
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Affiliation(s)
- Çağlar Ruhi
- From the Haydarpaşa Numune Training and Research Hospital, Istanbul, Turkey
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35
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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36
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Cho JH, Lim JH, Park GY, Kim JS, Kang YJ, Kwon O, Choi JY, Park SH, Kim YL, Kim HK, Huh S, Kim CD. Successful withdrawal of antiviral treatment in kidney transplant recipients with chronic hepatitis B viral infection. Transpl Infect Dis 2014; 16:295-303. [PMID: 24628837 DOI: 10.1111/tid.12202] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Revised: 10/18/2013] [Accepted: 10/20/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long-term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection. METHODS We retrospectively investigated the hepatitis B surface antigen (HBsAg)-positive KTR with antiviral agents between January 2002 and January 2012. Antiviral treatments were withdrawn in patients who met all of the following 7 criteria: (i) no clinical and histologic evidence of cirrhosis, (ii) normal liver biochemistry, (iii) negative for both HBV DNA and hepatitis B envelope antigen (HBeAg), (iv) no resistance to antiviral agent, (v) antiviral therapy > 9 months, (vi) maintenance dosage of immunosuppressant for > 3 months, and (vii) no history of acute rejection during recent 6 months. All patients were followed regularly at approximately 3-6 months for liver enzyme, viral markers, and HBV DNA level after antiviral withdrawal. RESULTS Among a total of 445 KTR, 14 HBsAg-positive patients were included in this study. Antiviral agents were used, with lamivudine in 11 patients, and with adefovir, entecavir, and telbivudine in 3 patients, respectively. Discontinuation of antiviral agent was attempted in 6 (42.9%) of 14 patients who satisfied the criteria. The median duration of antiviral therapy before withdrawal was 14.3 months (range, 9-24 months). Four (66.7%) of 6 patients were successfully withdrawn and remained negative for HBV DNA for a median 60.5 months (range, 47-82 months). The baseline HBV DNA level was not related to maintenance of remission after withdrawal. Two reactivated patients resumed antiviral treatment immediately, with subsequent normalization of HBV DNA. During the follow-up, 1 patient developed hepatocellular carcinoma; however, no patient death or graft failure was reported for all HBsAg-positive KTR. CONCLUSIONS Antiviral therapy can be discontinued successfully and safely in selected KTR with chronic HBV infection, after complete suppression of HBV and sufficient duration of antiviral therapy.
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Affiliation(s)
- J-H Cho
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea; Clinical Research Center for End Stage Renal Disease in Korea, Daegu, Korea
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Yap DYH, Chan TM. Evolution of hepatitis B management in kidney transplantation. World J Gastroenterol 2014; 20:468-474. [PMID: 24574715 PMCID: PMC3923021 DOI: 10.3748/wjg.v20.i2.468] [Citation(s) in RCA: 15] [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: 09/07/2013] [Revised: 10/26/2013] [Accepted: 11/19/2013] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection adversely influences the clinical outcomes of renal transplant recipients owing to increased hepatic complications. Management of HBV infection in kidney transplant recipients presents a challenge to clinicians, especially in endemic regions. Interferon precipitates renal allograft dysfunction. Treatment with lamivudine, the first oral nucleoside analogue available, resulted in effective viral suppression, reduced liver-related complications, and improved patient survival so that medium-term data showed comparable patient survival rates between hepatitis B surface antigen-positive and HBsAg-negative kidney transplant recipients in the era of effective antiviral therapies. Entecavir has replaced lamivudine as first-line therapy for treatment-naïve subjects in view of the propensity for drug resistance with the latter. Management of HBV infection in kidney transplant patients needs to take into consideration the nephrotoxicity of nucleoside/tide analogues such as adefovir and tenofovir. Prevention of HBV-related complications in kidney transplant recipients starts much earlier prior to transplantation, with vaccination of patients with chronic kidney disease and donor-recipient matching with regard to HBV status. In addition to anti-viral treatment, patients with chronic HBV infection must have regular surveillance for liver cancer and assessment for the development of cirrhosis.
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38
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Pipili C, Cholongitas E, Papatheodoridis G. Review article: nucleos(t)ide analogues in patients with chronic hepatitis B virus infection and chronic kidney disease. Aliment Pharmacol Ther 2014; 39:35-46. [PMID: 24299322 DOI: 10.1111/apt.12538] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Revised: 05/28/2013] [Accepted: 10/02/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND The treatment of chronic hepatitis B (CHB) in patients with chronic kidney disease (CKD) is based on nucleoside (lamivudine, telbivudine, entecavir) or nucleotide (adefovir, tenofovir) analogues (NAs), but it may be complex and the information is scarce. Entecavir and tenofovir represent the currently recommended first-line NAs for NA-naive CHB patients, while tenofovir is the NA of choice for CHB patients with resistance to nucleosides. AIM To review the efficacy and safety of NAs in adult CHB patients with CKD and to provide reasonable recommendations for their optimal management. METHODS Literature search in PubMed/Medline and manual search of relevant articles, reviews and book chapters. RESULTS NAs are cleared by kidneys and their dosage should be adjusted in patients with creatinine clearance <50 mL/min. There are concerns about nephrotoxic potential of the nucleotides, particularly adefovir, while improvements of creatinine clearance have been reported under telbivudine. Most existing data in CHB patients with CKD are for lamivudine and, less frequently, for other NAs, mostly entecavir. Besides CHB, NA should be used in case of immunosuppressive therapy in any HBsAg-positive patient with CKD including renal transplant (RT) recipients and in anti-HBs-positive recipients of kidney grafts from HBsAg-positive donors. CONCLUSIONS Chronic hepatitis B patients with chronic kidney disease receiving nucleoside analogues should be followed carefully for treatment efficacy and renal safety. Despite the absence of strong data, entecavir and telbivudine seem to be the preferred options for nucleoside analogue-naive CHB patients with chronic kidney disease, depending on viraemia and severity of renal dysfunction. More studies are certainly needed in this setting.
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Affiliation(s)
- C Pipili
- Department of Nephrology, Laiki Merimna, Athens, Greece
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39
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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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40
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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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Long-term effects of prophylactic and therapeutic lamivudine treatments in hepatitis B surface antigen-positive renal allograft recipients. Clin Exp Nephrol 2013; 18:144-50. [PMID: 23605388 DOI: 10.1007/s10157-013-0807-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 04/07/2013] [Indexed: 01/07/2023]
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Levitsky J, Doucette K. Viral hepatitis in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:147-68. [PMID: 23465008 DOI: 10.1111/ajt.12108] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- J Levitsky
- Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Hepatitis B-positive donors in renal transplantation: increasing the deceased donor pool. Transplantation 2012; 94:205-10. [PMID: 22430067 DOI: 10.1097/tp.0b013e31824e3db4] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is reasonable to transplant HbsAg-positive kidneys into recipients who are themselves hepatitis B surface antigen (HbsAg) positive with appropriate antiviral treatment after transplantation. Although there are limited data regarding the hepatitis B virus (HBV) transmission risk following transplantation of kidneys from HbsAg-positive donors into HBV-immune recipients, current literature suggests that the risk of chronic infection in the recipient can be prevented by using antiviral agents or by boosting protective anti-HBs titers. The risk of chronic HBV infection following transplantation of kidneys from HbsAg-positive donors for HBV-naive recipients is high but can be minimized by administering lifelong antiviral therapy. Such a policy could be considered in an urgent situation. The most cost-effective antiviral prophylaxis strategy is lifelong lamivudine. Kidneys from HBsAg neg/anti-HBcore pos recipients are associated with a low rate of chronic HBV infection in the recipient and therefore can no longer be regarded as marginal donors. Booster vaccination to achieve protective HBV immunity or lifelong lamivudine therapy should prevent posttransplant HBV infection. Hence, we believe that strategies allowing transplantation of kidneys from donors with HBV can be undertaken safely with careful selection and matching of donors and recipients increasing access to kidney transplantation.
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Blackadar CB. Systematic review of hepatocellular carcinoma mortality rates among hepatitis B virus-infected renal transplant recipients, with supplemental analyses of liver failure and all-cause mortality. Int J Infect Dis 2012; 17:e24-36. [PMID: 23036372 DOI: 10.1016/j.ijid.2012.08.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Revised: 08/15/2012] [Accepted: 08/19/2012] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES The purpose of this review was to compare the mortality rates for hepatocellular carcinoma (HCC) among hepatitis B surface antigen (HBsAg)-seropositive renal transplant (RT) patients versus HBsAg-seropositive persons of the general population. METHODS A comprehensive search was performed to identify cohort studies of HBsAg-seropositive RT patients with at least 4 years of follow-up. Data were analyzed as outlined below. HCC was a rare event in regions of low and intermediate seroprevalence of HBsAg. Subsequently, studies from low and intermediate seroprevalence areas were analyzed separately from those of high seroprevalence areas. RESULTS Thirty-one retrospective studies that followed 1277 seropositive RT patients were identified for inclusion. The studies were pooled and compared to four different general population studies that included 12558 seropositive persons using Poisson methods. The mortality rate of HCC was increased in low and intermediate seroprevalence areas (RR 7.67, 95% confidence interval (CI) 3.93-15.0; RR 9.92, 95% CI 5.38-18.3). In high seroprevalence areas, the mortality rate of HCC was increased compared to one population study, but not another (RR 2.76, 95% CI 1.64-4.63; RR 1.02, 95% CI 0.61-1.69). CONCLUSIONS Mortality due to HCC was increased in low and intermediate seroprevalence areas, but the evidence was inconclusive for high seroprevalence areas.
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Abstract
UNLABELLED The guideline on the management of chronic hepatitis B (CHB) was first developed in 2004 and revised in 2007 by the Korean Association for the Study of the Liver (KASL). Since then there have been many developments, including the introduction of new antiviral agents and the publications of many novel research results from both Korea and other countries. In particular, a large amount of knowledge on antiviral resistance--which is a serious issue in Korea--has accumulated, which has led to new strategies being suggested. This prompted the new guideline discussed herein to be developed based on recent evidence and expert opinion. TARGET POPULATION The main targets of this guideline comprise patients who are newly diagnosed with CHB and those who are followed or treated for known CHB. This guideline is also intended to provide guidance for the management of patients under the following special circumstances: malignancy, transplantation, dialysis, coinfection with other viruses, pregnancy, and children.
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MESH Headings
- Acute Disease
- Adolescent
- Adult
- Aged
- Alanine Transaminase/blood
- Antiviral Agents/therapeutic use
- Asian People
- Aspartate Aminotransferases/blood
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/etiology
- Child
- Child, Preschool
- Coinfection/drug therapy
- DNA, Viral/blood
- Drug Resistance, Viral
- Drug Therapy, Combination
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B virus/genetics
- Hepatitis B, Chronic/complications
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Immunosuppression Therapy
- Infectious Disease Transmission, Vertical/prevention & control
- Liver/pathology
- Liver/physiology
- Liver Cirrhosis/physiopathology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/etiology
- Liver Transplantation
- Male
- Middle Aged
- Pregnancy
- Renal Dialysis
- Republic of Korea
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Grossi PA, Costa AN, Fehily D, Blumberg EA, Kuehnert MJ, Fishman JA, Ison MG, Lattes R, Kotton CN, Lilleri D, Kabanova A, Lanzavecchia A, Gerna G, Razonable RR, Comoli P, Zecca M, Basso S, Ginevri F, Grossi A, Schena FP, Rimola A, Burra P, De Martin E, Rodriguez-Castro KI, Fagiuoli S, Pasulo L, Bruno R, Andreone P, Loggi E, Arena F, Rossolini GM, Sganga G, Cozza V. Infections and organ transplantation: new challenges for prevention and treatment--a colloquium. Transplantation 2012; 93:S4-S39. [PMID: 22374265 DOI: 10.1097/tp.0b013e3182481347] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Paolo A Grossi
- Infectious Diseases Department, University of Insubria, Varese, ISMETT-UPMC Palermo, National Center for Transplantation, Rome, Italy.
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Current world literature. Curr Opin Organ Transplant 2011; 16:650-60. [PMID: 22068023 DOI: 10.1097/mot.0b013e32834dd969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in potential kidney transplant candidates-once considered absolute contraindications to kidney transplantation-no longer creates overt barriers to transplantation. Advances in the medical management of HBV and HCV infection have created opportunities for a substantial number of patients to be effectively treated with antiviral therapy before transplantation. For HBV infection, a number of new drugs enable clearance of the virus with minimal adverse effects and drug resistance. Pretransplantation antiviral therapy is advisable for patients with HCV infection, but adverse effects are common and viral eradication remains challenging. Regardless of viral clearance, pretransplant patients without bridging fibrosis (as confirmed by liver biopsy) or clinical stigmata of cirrhosis should be considered for kidney transplantation as survival is superior when compared to treatment with dialysis, and progression of liver disease is unlikely. For patients with advanced liver disease, simultaneous liver-kidney transplantation is an important consideration. These treatment advances further increase the burden of organ donor shortage; however, organs from deceased donors with chronic HBV or HCV infection could be efficiently allocated to certain individuals with a viral infection of the same type to increase the pool of available transplant organs.
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Affiliation(s)
- Janna Huskey
- Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA
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