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Lu K, Chiu KY. Comparative Survival Analysis of Dialysis and Renal Transplantation in HBV-Infected End-Stage Renal Disease Patients. Transplant Proc 2023; 55:2429-2435. [PMID: 37903695 DOI: 10.1016/j.transproceed.2023.09.015] [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: 04/17/2023] [Revised: 08/01/2023] [Accepted: 09/22/2023] [Indexed: 11/01/2023]
Abstract
BACKGROUND The potential risks and benefits of kidney transplantation in patients with end-stage renal disease (ESRD) infected with hepatitis B virus (HBV) have been a subject of debate. This study aimed to provide real-world data on the relative risks of death and clinical outcomes associated with kidney transplantation in this context. METHODS We conducted a longitudinal cohort study using the National Health Insurance Research Database from 1997 to 2013, extracting cohorts of patients who are HBV-infected ESRD. The main outcome measure was overall survival, whereas the secondary measure was the relative risk of death and survival benefit through propensity-score matching (1:1). RESULTS Of the 4895 patients who are HBV-infected with ESRD, 172 renal transplant recipients were enrolled for analysis. There was a numeric trend towards higher overall survival rates in renal transplant recipients, although this was not statistically significant (P = .057). A significant survival benefit was observed in the renal transplant group if the follow-up was longer than one year (P = 0.007). The relative risks of death among renal transplant recipients were initially higher at 2.0 times that of patients on chronic dialysis, presenting in a hyperbolic pattern with equal risks at 462 days. The likelihood of survival became equal until 1649 days. CONCLUSIONS Our study suggests that kidney transplantation may be a viable option for patients who are HBV-infected with ESRD, given the significant improvement in quality of life and reduction of death risks observed four to five years after successful transplantation. This real-world data can help clinicians make informed decisions regarding the management of ESRD in patients who are HBV-infected.
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Affiliation(s)
- Kevin Lu
- Department of Urology, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
| | - Kun-Yuan Chiu
- Department of Urology, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan
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Cholongitas E, Goulis I, Antoniadis N, Fouzas I, Imvrios G, Giakoustidis D, Giouleme O, Papanikolaou V, Akriviadis E, Vasiliadis T. Nucleos(t)ide analog(s) prophylaxis after hepatitis B immunoglobulin withdrawal against hepatitis B and D recurrence after liver transplantation. Transpl Infect Dis 2016; 18:667-673. [PMID: 27421122 DOI: 10.1111/tid.12575] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 03/22/2016] [Accepted: 05/05/2016] [Indexed: 12/23/2022]
Abstract
BACKGROUND/AIMS Nucleos(t)ide analogs (NAs) have made a hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, this approach is considered controversial in patients transplanted for HBV and hepatitis D (HDV) co-infection. MATERIAL/METHODS All patients transplanted for HBV/HDV cirrhosis were evaluated. After LT, each patient received HBIG + NAs and then continued with NAs prophylaxis. All patients were followed up with HBV serum markers and HBV DNA, while anti-HDV/HDV RNA was performed in those with HBV recurrence. RESULTS A total of 34 recipients were included (22 men, age: 46.7 ± 16 years). After HBIG discontinuation, NAs were received as monoprophylaxis (lamivudine [LAM]: 2, adefovir [AFV]: 1, entecavir: 9, tenofovir [TDF]: 12) or dual prophylaxis (LAM + AFV [or TDF]: 10 patients). Two (5.8%) of the 34 patients had HBV/HDV recurrence after HBIG withdrawal (median follow-up: 28 [range, 12-58] months). These 2 patients had undetectable HBV DNA at LT. Statistical analysis revealed that those with recurrence had received HBIG for shorter period, compared to those without recurrence (median: 9 vs. 28 months, P = 0.008). CONCLUSIONS We showed for the first time, to our knowledge, that maintenance therapy with NAs prophylaxis after HBIG discontinuation was effective against HBV/HDV recurrence, but it seems that a longer period of HBIG administration might be needed before it is withdrawn after LT.
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Affiliation(s)
- E Cholongitas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
| | - I Goulis
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - N Antoniadis
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - I Fouzas
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - G Imvrios
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - D Giakoustidis
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - O Giouleme
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - V Papanikolaou
- Department of Transplant Surgery, Medical School of Aristotle University, Thessaloniki, Greece
| | - E Akriviadis
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - T Vasiliadis
- 3rd Department of Internal Medicine, Medical School of Aristotle University Papageorgiou General Hospital of Thessaloniki, Thessaloniki, Greece
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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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Durante-Mangoni E, Vitrone M, Parrella A, Andini R, Iossa D, Ragone E, Falco E, Maiello C, Utili R, Zampino R. Efficacy and safety of tenofovir, entecavir, and telbivudine for chronic hepatitis B in heart transplant recipients. Transpl Infect Dis 2016; 18:319-25. [PMID: 26988401 DOI: 10.1111/tid.12525] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 11/23/2015] [Accepted: 01/10/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. METHODS In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. RESULTS Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate (GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF (n = 9) or LdT (n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed. CONCLUSIONS This study indicates that newer antivirals are effective and safe in HTR with CHB.
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Affiliation(s)
- E Durante-Mangoni
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy.,Units of Infectious & Transplant Medicine, Ospedale Monaldi, Napoli, Italy
| | - M Vitrone
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy
| | - A Parrella
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy
| | - R Andini
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy
| | - D Iossa
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy
| | - E Ragone
- Units of Infectious & Transplant Medicine, Ospedale Monaldi, Napoli, Italy
| | - E Falco
- Microbiology and Virology, Ospedale Monaldi, Napoli, Italy
| | - C Maiello
- Cardiac Surgery A.O.R.N. dei Colli, Ospedale Monaldi, Napoli, Italy
| | - R Utili
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy.,Units of Infectious & Transplant Medicine, Ospedale Monaldi, Napoli, Italy
| | - R Zampino
- Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Napoli, Italy
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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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Pipili C, Cholongitas E. Treatment of chronic hepatitis C in liver transplant candidates and recipients: Where do we stand? World J Hepatol 2015; 7:1606-16. [PMID: 26140081 PMCID: PMC4483543 DOI: 10.4254/wjh.v7.i12.1606] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 05/18/2015] [Accepted: 06/01/2015] [Indexed: 02/06/2023] Open
Abstract
The first generation direct antiviral agents (DAAs) highlighted substantial prognosis improvement among liver transplant (LT) candidates and recipients with recurrent hepatitis C virus (HCV) infection. During 2014, second generation DAAs are associated with high sustained virological response rates (> 95%), shortened duration courses and relatively few toxicities. In keeping with the currently available data, patients with decompensated cirrhosis awaiting LT is preferable to be treated with interferon-free, new generation DAAs, with or without ribavirin combinations. Although data about the safety of new DAAs combinations in this patient population are limited, sofosbuvir and daclatasvir pharmacokinetics do not appear to change significantly in moderate or severe liver impairment, while other new DAAs (simeprevir, asunaprevir) seem to be contraindicated in patients with severe liver impairment (Child-Pugh class C). On the other hand, sofosbuvir should not be given in patients with glomerular filtration rate ≤ 30 mL/min, but ongoing trials will clarify better this issue. With the objective that newer antiviral combinations will yield safer and more efficient manipulation of HCV recurrence post-transplant, the European Association for the Study of the Liver has recently updated its recommendations towards this direction. Nevertheless the new antivirals' high cost may be the biggest challenge to their implementation worldwide.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
| | - Evangelos Cholongitas
- Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
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Kornberg A. Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation. World J Hepatol 2015; 7:1494-1508. [PMID: 26085909 PMCID: PMC4462688 DOI: 10.4254/wjh.v7.i11.1494] [Citation(s) in RCA: 13] [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: 02/28/2015] [Revised: 04/19/2015] [Accepted: 05/08/2015] [Indexed: 02/06/2023] Open
Abstract
Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients’ infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.
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The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists. J Nephrol 2015; 28:393-402. [DOI: 10.1007/s40620-015-0214-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/22/2015] [Indexed: 12/29/2022]
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Ridruejo E. Antiviral treatment for chronic hepatitis B in renal transplant patients. World J Hepatol 2015; 7:189-203. [PMID: 25729474 PMCID: PMC4342601 DOI: 10.4254/wjh.v7.i2.189] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 10/17/2014] [Accepted: 11/19/2014] [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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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: 32] [Impact Index Per Article: 3.2] [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: 11/19/2014] [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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