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Li Y, Li YW, Gao Y. Effect of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamideantiviral Therapy on Renal Function in Chronic Hepatitis B Patients: A Real-World Retrospective Study. Int J Gen Med 2025; 18:1143-1153. [PMID: 40034830 PMCID: PMC11874758 DOI: 10.2147/ijgm.s497550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 02/14/2025] [Indexed: 03/05/2025] Open
Abstract
Background Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide(TAF) are first-line nucleos(t)ide analogs (NUCs) with chronic hepatitis B (CHB). This study aimed to assess the renal safety profile in NUC-experienced CHB patients who received ETV, TDF or TAF therapy. Methods This retrospective observational cohort study investigated factors related to renal function in 154 patients with NUC-experienced CHB who received ETV, TDF, and TAF therapy for 48 weeks. Changes in UREA, uric acid (UA), creatinine (Cr), and estimated glomerular filtration rate (eGFR) were analyzed using a one-way analysis of variance. A linear mixed-effects model for repeated measures was used to evaluate the correlation between baseline information and eGFR changes 48 weeks following treatment initiation. The model considered sex, baseline age, viral load, aminotransferases, renal function, and treatment group as fixed effects, and incorporated random effects for individual subjects. Results There were no significant differences in UA or Cr levels during therapy over time. The eGFR level was elevated in ETV-treated patients (117.5 ± 16.65 mL/min/1.7m2 vs 109.8 ± 15.69 mL/min/1.7m2, P=0.027), whereas it did not change significantly in TDF- (123.6 ± 28.54 mL/min/1.7m2 vs 115.5 ± 20.44 mL/min/1.7m2, P=0.070) and TAF-treated (121.6 ± 23.44 mL/min/1.7m2 vs 113.4 ± 16.90 mL/min/1.7m2, P=0.053) patients. Younger patients (<30 years) and those with higher HBV DNA (> 7 log10IU/mL) and lower alanine aminotransferase levels (<5 × upper limit of normal) showed a significant improvement in eGFR elevation during NUCs therapy. The linear mixed-effects model showed that the baseline HBV DNA level was an important positive predictor of eGFR elevation at 48 weeks following treatment initiation (estimate was 1.437 and 2.449, P<0.001). Conclusion In real-life experience, ETV, TDF, and TAF therapy may not be associated with eGFR changes in NUC-experienced CHB patients without baseline renal impairment.
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Affiliation(s)
- Yu Li
- Department of Infectious Diseases, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi Province, 710068, People’s Republic of China
| | - Ya-Wei Li
- Division of Medical Affairs, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan, Hubei Province, 442099, People’s Republic of China
| | - Ying Gao
- Department of Hematology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi Province, 710068, People’s Republic of China
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Peng MJ, Guo XQ, Zhang WL, Chen J, Kang W, Yang XF, Guo Y, Zhang Y. Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience. Front Microbiol 2022; 13:980250. [PMID: 36329842 PMCID: PMC9622795 DOI: 10.3389/fmicb.2022.980250] [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: 06/28/2022] [Accepted: 10/03/2022] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND AND AIM Controversy remains as to pegylated interferon-α (PEG-IFNα) antiviral therapy to renal function in chronic hepatitis B (CHB) patients. The aim of this study was to evaluate the influence of PEG-IFNα2b (Y shape, 40 kD) add-on treatment for renal function in CHB patients who received entecavir therapy. METHODS This was a retrospective observational study to investigate factors related to renal function in 114 CHB patients who received PEG-IFNα2b add-on therapy to entecavir for 48 weeks. Changes of blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR), which was calculated with both Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (MDRD) formulas, were analyzed by one-way analysis of variance. A linear mixed effects model for repeated measures was used to assess the correlation between baseline information and eGFR changes at 24 and 48 weeks of therapy. The model considered the baseline age, gender, body weight, viral load, hepatitis B surface antigen, BUN, sCr, and treatment strategy as fixed effects and incorporated random effects for individual subjects. RESULTS BUN and sCr was decreased, while eGFR was increased at 12 weeks of therapy. Only eGFR maintained at 24 and 48 weeks of therapy. Patients with female gender, age ≥ 40 years, and baseline HBsAg level < 250 IU/mL showed significant improvement of renal function with PEG-IFNα2b add-on therapy. The linear mixed effects model revealed that female gender, baseline sCr, and PEG-IFNα2b add-on were significant positive predictors for eGFR elevation at 24 and 48 weeks of therapy. CONCLUSION In real-world experience, PEG-IFNα2b add-on therapy might be associated with increased eGFR in CHB patients.
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Affiliation(s)
- Mei-Juan Peng
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiao-Qing Guo
- Department of Hepatology, The Third People’s Hospital of Taiyuan, Taiyuan, China
| | - Wei-Lu Zhang
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Jing Chen
- Xiamen Amoytop Biotech Co., Ltd., Xiamen, China
| | - Wen Kang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiao-Fei Yang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Ying Guo
- Department of Hepatology, The Third People’s Hospital of Taiyuan, Taiyuan, China
| | - Ye Zhang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
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Cornberg M, Sandmann L, Protzer U, Niederau C, Tacke F, Berg T, Glebe D, Jilg W, Wedemeyer H, Wirth S, Höner Zu Siederdissen C, Lynen-Jansen P, van Leeuwen P, Petersen J. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:691-776. [PMID: 34255317 DOI: 10.1055/a-1498-2512] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Markus Cornberg
- Deutsches Zentrum für Infektionsforschung (DZIF), Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover; Centre for individualised infection Medicine (CiiM), Hannover.,Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Ulrike Protzer
- Institut für Virologie, Technische Universität München/Helmholtz Zentrum München, München
| | | | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig
| | - Dieter Glebe
- Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Gießen
| | - Wolfgang Jilg
- Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensberg, Regensburg
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Stefan Wirth
- Zentrum für Kinder- und Jugendmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal
| | | | - Petra Lynen-Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Pia van Leeuwen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg
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Telbivudine for renal transplant recipients with chronic hepatitis B infection: a randomized controlled trial with early termination. Clin Exp Nephrol 2020; 24:474-482. [PMID: 32219622 DOI: 10.1007/s10157-020-01850-7] [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: 04/06/2019] [Accepted: 01/05/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND The aim of this study was to analyze changes in renal function in HBsAg-positive renal transplant recipients receiving lamivudine who did or did not switch to telbivudine. METHODS In this prospective randomized clinical trial (RCT), HBsAg-positive renal transplant recipients who had received lamivudine prophylaxis for at least 6 months were 1:2 randomized to receive either lamivudine or telbivudine for another 24 months. Renal function was evaluated by creatinine level and estimated glomerular filtration rate (eGFR) at the time of randomization (baseline), 6, 12, 18, and 24 months respectively. RESULTS This RCT was prematurely terminated after recruiting only 17 patients due to a high incidence (61.5%; 8/13) of clinical myalgia in the telbivudine group. Cox's proportional hazards model revealed that there was no independent predictor of myalgia. Based on intention-to-treat and per protocol analyses using generalized estimating equations, the patients in the randomized telbivudine group had a significantly increased eGFR and the patients in the lamivudine group had a significantly decreased eGFR at the end of follow-up compared to the values at study enrollment. However, there was no significant difference between the lamivudine and telbivudine groups. CONCLUSIONS The renal protective effect of telbivudine for HBsAg positive renal transplant recipients was uncertain for high incidence of myalgia and only patients who were on telbivudine for 24 months had renal function maintenance.
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Jindal A, Vyas A, Sharma M, Kumar G, Sarin SK. A randomized open label trial of tenofovir monotherapy versus tenofovir plus telbivudine in spontaneous reactivation of hepatitis B. Saudi J Gastroenterol 2019; 25:319-326. [PMID: 31044748 PMCID: PMC6784432 DOI: 10.4103/sjg.sjg_537_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIM Acute-on-chronic liver failure (ACLF-B) in spontaneous reactivation of chronic hepatitis B (SR-CHB) has high mortality. Tenofovir disoproxil fumarate (TDF) improves survival by ~40% in ACLF-B but is potentially nephrotoxic. Combining telbivudine (LDT) with TDF may negate this risk and could boost rapid viral clearance and improve clinical outcomes. PATIENTS AND METHODS Seventy consecutive patients with SR-CHB were randomized to TDF (300 mg/day, n = 35) or TDF plus LDT (600 mg/day; n = 35). In all, 25 had ACLF-B and none had option for liver transplantation. Primary endpoint was survival at 3 months. Secondary endpoints were survival at 3 months in ACLF-B, serial reduction in hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg) loss and liver-related complications. RESULTS Overall baseline clinical and laboratory parameters in the two groups were comparable. Reduction in HBV DNA at weeks 2, 4 and 12 was independent of treatment groups and presence of ACLF-B (P < 0.01). All six patients with HBsAg loss at 12 weeks had lower HBV DNA at baseline and none had ACLF-B. Patients with no ACLF-B had more rapid decline in bilirubin and alanine aminotraminase at week 2 compared with ACLF-B. Patients on TDF plus LDT showed significant improvement in AKI on follow-up (five of six patients) compared with TDF monotherapy (none of six patients) and had less reduction in estimated glomerular filtration rate at week 12. Eight of 10 patients with liver-related deaths received TDF monotherapy (P = 0.02). New-onset septic shock, TDF monotherapy, e-antibody positivity, and higher baseline model for end-stage liver disease score were predictors of mortality in ACLF-B. None had treatment-related severe adverse effects. CONCLUSION Addition of LDT to tenofovir is safe and may be renoprotective in spontaneous reactivation of hepatitis B. Combination therapy improves survival in ACLF-B despite comparable HBV DNA suppression to tenofovir monotherapy.
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Affiliation(s)
- Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India,Address for correspondence: Dr. Ankur Jindal, Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi - 110 070, India. E-mail:
| | - Ashish Vyas
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9324310. [PMID: 28884132 PMCID: PMC5572574 DOI: 10.1155/2017/9324310] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 06/29/2017] [Accepted: 07/09/2017] [Indexed: 12/12/2022]
Abstract
Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n = 60) and telbivudine-replacement (n = 60) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p < 0.001). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.
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Telbivudine attenuates gentamicin-induced kidney injury in rats. Int J Antimicrob Agents 2017; 49:595-602. [PMID: 28373116 DOI: 10.1016/j.ijantimicag.2017.01.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 12/26/2016] [Accepted: 01/06/2017] [Indexed: 01/10/2023]
Abstract
Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment.
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Wu X, Cai S, Li Z, Zheng C, Xue X, Zeng J, Peng J. Potential effects of telbivudine and entecavir on renal function: a systematic review and meta-analysis. Virol J 2016; 13:64. [PMID: 27062520 PMCID: PMC4826538 DOI: 10.1186/s12985-016-0522-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 04/03/2016] [Indexed: 01/10/2023] Open
Abstract
Background To assess the potential effects of telbivudine (LdT) and entecavir (ETV) on renal function in patients with chronic hepatitis B (CHB), we performed a meta-analysis of the relevant data available on these agents to evaluate their effects on the estimated glomerular filtration rate (eGFR) during treatment. Methods The PubMed, EMBASE, Scopus, CNKI (China National Knowledge Infrastructure), Cochrane Library, and WanFang databases were searched for relevant articles appearing in the literature up to July 1, 2015. A total of 6 studies (1960 CHB patients) with 1-year eGFR outcomes were retrieved and analyzed. Results Generally, the results of the 6 studies analyzed showed that eGFR was improved after LdT treatment, but was decreased after ETV treatment. Using a fixed-effects approach, the change in eGFR was found to be significantly different between LdT and ETV treatment (Z = 3.64; P = 0.0003). Whereas the eGFR was slightly decreased with ETV compared with baseline (−1.45 mL/min/1.73 m2), the eGFR was improved with LdT (2.99 mL/min/1.73 m2) after 1 year of treatment. An overall test of effect in the meta-analysis showed that the eGFR in LdT-treated patients was significantly improved after 1-year of treatment (Z = 3.71; P = 0.0002). Conclusion This meta-analysis has confirmed that LdT has a renal protective effect whereas ETV does not. However, whether the benefit on renal function outweighs the occurrence of resistance in specific clinical situations is not yet clear.
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Affiliation(s)
- Xiaolu Wu
- First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China
| | - Shaohang Cai
- First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China.,Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Zhandong Li
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Caixia Zheng
- First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China
| | - Xiulan Xue
- First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China
| | - Jianyong Zeng
- First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, China
| | - Jie Peng
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. .,State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No.1838, Guangzhou Avenue North, Guangzhou, 510515, China.
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Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
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Jiang L, Hu S, He M, Tian D. Estimated Glomerular Filtration Rate Increases in Chronic Hepatitis B Patients Treated With Telbivudine Monotherapy and Combination Treatment. HEPATITIS MONTHLY 2016; 16:e32528. [PMID: 27110258 PMCID: PMC4834183 DOI: 10.5812/hepatmon.32528] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 11/23/2015] [Accepted: 11/23/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several studies have reported a renoprotective effect of telbivudine during the treatment of patients for chronic hepatitis B (CHB). OBJECTIVES This longitudinal retrospective study aimed to examine the effects of telbivudine monotherapy and combination therapy (adefovir plus telbivudine) on renal function. PATIENTS AND METHODS This study included 336 Chinese CHB patients, who were selected from outpatients in Tongji Hospital. 44, 122, 66, 58, and 46 of these patients had been orally taking adefovir, telbivudine, entecavir, adefovir plus telbivudine, and adefovir plus lamivudine, respectively, for at least 24 months. RESULTS The estimated glomerular filtration rate (eGFR) in the telbivudine and adefovir plus telbivudine groups increased by 5.14 mL/min (P < 0.001) and 6.19 mL/min (P = 0.005), respectively. The patients taking the five drug regimens were further grouped into the following three subpopulations: those with compensated hepatic cirrhosis, those aged 50 or more years, and those with baseline eGFR values of 50 - 90 mL/min. The three subgroups that received telbivudine monotherapy exhibited eGFR increases of 6.38, 6.74, and 10.82 mL/min, respectively. The three subgroups that received combination therapy of adefovir plus telbivudine exhibited eGFR increases of 18.31, 14.73, and 16.59 mL/min, respectively (P < 0.05). The predictive factors for the change in eGFR levels over time were analyzed by means of two linear mixed effects models for the three monotherapy regimens and two combination regimens. Age, gender, and medication are predictive factors of eGFR changes. In addition, abnormal creatinine kinase (CK) levels in the telbivudine group were not correlated with eGFR changes (P = 0.992). CONCLUSIONS These findings indicate that telbivudine, used in both monotherapy and combination therapy, improves the renal function of patients with CHB. The improvements are particularly significant in patients at high renal risk.
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Affiliation(s)
- Libin Jiang
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Song Hu
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Man He
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Deying Tian
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Corresponding Author: Deying Tian, Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Tel: +86-2783663268; +86-13707184968, E-mail:
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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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Turan I, Yapali S, Bademkiran F, Kose T, Duman S, Sozbilen M, Gunsar F, Ersoz G, Akarca US, Ozutemiz O, Karasu Z. Telbivudine in liver transplant recipients: Renal protection does not overcome the risk of polyneuropathy and myopathy. Liver Transpl 2015; 21:1066-75. [PMID: 25845464 DOI: 10.1002/lt.24131] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Revised: 02/21/2015] [Accepted: 03/25/2015] [Indexed: 12/31/2022]
Abstract
The recently reported benefit of telbivudine for renal function has not been systematically studied in long-term liver transplantation (LT) recipients who are at high risk for renal impairment. We aimed to examine whether switching lamivudine therapy to telbivudine could improve renal function in LT recipients who have impaired renal function. This single-center, prospective cohort study enrolled LT recipients who were on lamivudine for hepatitis B virus (HBV) prophylaxis and who had renal impairment for at least 1 year. Lamivudine was switched to telbivudine. The primary outcome was to evaluate the change in renal function at weeks 12, 24, 36, and 48. The secondary outcomes were to assess the efficacy of telbivudine for HBV prophylaxis and the safety profile of telbivudine in the posttransplant setting. After 45 patients were enrolled, the study was terminated early because of increased rates of polyneuropathy/myopathy. During telbivudine treatment (median, 64 weeks), estimated glomerular filtration rate (eGFR) increased in 34 patients (76%). The improvement in renal function was prominent after 24 weeks of telbivudine treatment. Telbivudine was effective as prophylaxis against HBV recurrence. Twenty-six patients (58%) developed polyneuropathy and/or myopathy. The 1-year estimated incidence of polyneuropathy/myopathy was 28%. Diabetes was the strongest predictor of polyneuropathy/myopathy (hazard ratio, 4.13; 95% confidence interval, 1.49-11.50; P = 0.007). In conclusion, although it seems to have a favorable effect in the improvement of renal function and seems to be effective in the prevention of HBV recurrence, the high risk of polyneuropathy and myopathy hampers the use of telbivudine in LT recipients.
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Affiliation(s)
- Ilker Turan
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Suna Yapali
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Fikret Bademkiran
- Department of Neurology, School of Medicine, Ege University, Izmir, Turkey
| | - Timur Kose
- Department of Biostatistics, School of Medicine, Ege University, Izmir, Turkey
| | - Soner Duman
- Section of Nephrology, School of Medicine, Ege University, Izmir, Turkey
| | - Murat Sozbilen
- Department of Organ Transplantation and Research Center, School of Medicine, Ege University, Izmir, Turkey
| | - Fulya Gunsar
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Galip Ersoz
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Ulus Salih Akarca
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Omer Ozutemiz
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
| | - Zeki Karasu
- Section of Gastroenterology, School of Medicine, Ege University, Izmir, Turkey
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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: 11/19/2014] [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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