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1
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Sohal A, Singh C, Bhalla A, Kalsi H, Roytman M. Renal Manifestations of Chronic Hepatitis C: A Review. J Clin Med 2024; 13:5536. [PMID: 39337023 PMCID: PMC11433393 DOI: 10.3390/jcm13185536] [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: 08/31/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
Hepatitis C virus (HCV) has emerged as a major global health concern and, if left untreated, can lead to significant liver damage, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC). Approximately 40% of patients with HCV infection experience extrahepatic manifestations, including renal involvement. HCV-related renal disease is of significant importance among patients with chronic kidney disease (CKD), leading to higher morbidity and mortality. The renal damage due to HCV infection primarily results from cryoglobulinemia and glomerulonephritis, with conditions such as membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) being most prevalent. Despite advancements in treatment, including the use of directly acting antiviral agents (DAAs), renal complications remain a significant burden in untreated patients. HCV-positive patients on hemodialysis (HD) or those who have undergone kidney transplantation face increased mortality rates compared to their HCV-negative counterparts. Managing HCV infection before kidney transplantation is crucial to mitigate the risk of HCV-related renal complications. Conversely, kidney transplantation from HCV-infected donors is well established, as post-transplant treatment for HCV is safe and effective, potentially reducing mortality and morbidity for patients on transplant waiting lists. This review aims to provide a comprehensive analysis of the renal manifestations of HCV, emphasizing the importance of early diagnosis and treatment to improve patient outcomes.
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Affiliation(s)
- Aalam Sohal
- Division of Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 2500, USA
| | - Carol Singh
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Akshita Bhalla
- Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar 144006, Punjab, India
| | - Harsimran Kalsi
- Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA
| | - Marina Roytman
- Division of Gastroenterology and Hepatology, University of California San Francisco, Fresno, CA 93701, USA
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2
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Jadoul M, Awan A, Berenguer M, Bruchfeld A, Fabrizi F, Goldberg D, Jia J, Kamar N, Mohamed R, Pessôa M, Pol S, Sise M, Martin P. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:S129-S205. [PMID: 36410841 DOI: 10.1016/j.kint.2022.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/19/2022]
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Abstract
Hepatitis C virus (HCV) is associated with increased mortality and morbidity in patients with chronic kidney disease (CKD). The early detection and treatment of Hepatitis C associated with kidney disease is paramount to preventing the progressive loss of kidney function. HCV treatment until the advent of direct acting anti-viral agents (DAAs) was limited to interferon and ribavirin. Interferon and ribavirin treatment resulted in only modest success but with frequent adverse events and poor tolerability. Furthermore, interferon and ribavirin could not be used in certain patient populations including those with advanced CKD, were on dialysis, or those who have received a kidney transplant. DAAs have now made treatment possible in these sub-groups with a sustained viral response (SVR) of 90-100% and minimal side effects. DAAs have helped increase transplant rates by allowing for the use of HCV positive kidneys in recipients who are HCV negative. Although the choice of DAAs should be carefully considered and based on patient characteristics, concomitant medications, and HCV genotype.
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4
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Radhakrishnan RC, Gopal B, Zachariah UG, Abraham P, Mohapatra A, Valson AT, Alexander S, Jacob S, Tulsidas KS, David VG, Varughese S. The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2019; 29:1092-1099. [PMID: 30381505 DOI: 10.4103/1319-2442.243964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.
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Affiliation(s)
| | - Basu Gopal
- Central Northern Adelaide Renal and Transplant Service, Royal Adelaide Hospital, Adelaide, Australia
| | - Uday G Zachariah
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Priya Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Anjali Mohapatra
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Anna T Valson
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Shibu Jacob
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Vinoi G David
- Department of Nephrology, Christian Medical College, Vellore, India
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5
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Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int 2019; 22 Suppl 1:S61-S70. [PMID: 29694723 DOI: 10.1111/hdi.12643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus (HCV) infection is prevalent in patients with kidney disease including transplant candidates and recipients. It is associated with increased morbidity and mortality in end-stage renal disease patients and also increases the risk of allograft rejection and decreases allograft and patient survival post-transplant. Newly developed direct acting antivirals have revolutionized the way HCV is treated. Whether patients are treated before or after kidney transplantation, the cure rates with direct acting antivirals are >90%. Great debate has formed revolving the optimal timing to treat kidney transplant candidates. On the one hand, treatment before transplantation decreases early post-transplant complications related to HCV. On the other, postponing treatment until after transplantation opens the possibility of transplanting a kidney from a HCV positive donor, which is associated with shorter waiting time and improved organ utilization by expanding the organ donor pool. Most patients living in an area where waiting time is reduced by accepting an HCV positive kidney would benefit by the strategy of treatment post-transplantation, but this decision needs to be individualized in a patient-by-patient basis given that there are special circumstances (i.e., severe HCV-related extrahepatic manifestations, availability of live donors, etc.) in which treatment before transplant might be preferred.
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Affiliation(s)
- Abraham Cohen-Bucay
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA.,Division of Nephrology and Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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6
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Del Bello A, Abravanel F, Alric L, Lavayssiere L, Lhomme S, Bellière J, Izopet J, Kamar N. No evidence of occult hepatitis C or E virus infections in liver-transplant patients with sustained virological response after therapy with direct acting agents. Transpl Infect Dis 2019; 21:e13093. [PMID: 30972874 DOI: 10.1111/tid.13093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 02/21/2019] [Accepted: 04/07/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS It has been recently suggested that occult hepatitis C virus (HCV) infection and hepatitis E virus (HEV) reactivation might occur after direct acting antiviral agent-induced (DAA-induced) sustained virological response (SVR). The aim of our study was to identify occult HCV and HEV infection in a cohort of organ transplant patients who had achieved SVR and had persistent elevation in liver-enzyme levels. PATIENTS AND METHOD Sixty-six liver and/or kidney transplant patients were treated with DAAs. All but one achieved SVR12. Twenty-nine (8-39) months post-SVR12, 8 of the 65 patients (12.3%) who achieved SVR12 had persistently elevated liver enzyme levels. In 1 patient, this was related to hepatitis B virus reactivation. In the 7 remaining patients, blood samples (n = 7), liver biopsies (n = 4), and peripheral blood mononuclear cells (PBMCs) (n = 7) were collected simultaneously in order to identify occult HCV or HEV infection. RESULTS Hepatitis C virus RNA and HEV RNA were not detected in serum, liver tissues, or PBMCs. No HEV reactivation was observed after HCV clearance in patients who had anti-HEV IgG. CONCLUSION Our study suggests that there is no occult HCV or HEV infection in transplant patients after successful treatment of HCV infection with DAAs, even in patients with a persistent elevation of liver enzyme levels. However, due to the small number of patients included in our study, this finding should be confirmed in a larger cohort.
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Affiliation(s)
- Arnaud Del Bello
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Florence Abravanel
- Department of Virology, Institut Fédératif de Biologie de Purpan, CHU Toulouse, France.,Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152 Pharma Dev, IRD Toulouse 3 University, Toulouse, France
| | - Laurence Lavayssiere
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Sébastien Lhomme
- Department of Virology, Institut Fédératif de Biologie de Purpan, CHU Toulouse, France.,Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
| | - Julie Bellière
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- Department of Virology, Institut Fédératif de Biologie de Purpan, CHU Toulouse, France.,Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
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7
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Abstract
Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.
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Affiliation(s)
- Abraham Cohen-Bucay
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.,Nephrology Department, American British Cowdray Medical Center, Mexico City, 05300, Mexico
| | - Craig E Gordon
- Division of Nephrology, Tufts Medical Center, Boston, MA, 02111, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, MA, 02118, USA
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8
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Wong T, Bloom RD. Management and treatment of the HCV-infected kidney transplant patient. Semin Dial 2018; 32:169-178. [PMID: 30536995 DOI: 10.1111/sdi.12766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The prevalence of hepatitis C virus infection is increased in patients with end stage kidney disease compared to the general population and is an adverse outcome determinant. Direct-acting antiviral therapy for hepatitis C virus is changing the management paradigm of infected kidney transplant candidates and recipients, with potential to reduce patient morbidity and mortality. This review describes the hepatic and nonhepatic manifestations of hepatitis C virus in kidney transplant patients as well as management and treatment strategies to optimize transplant outcomes, highlighting the importance of direct-acting antivirals in this population.
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Affiliation(s)
- Tiffany Wong
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Roy D Bloom
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011) 2018; 8:91-165. [PMID: 30675443 PMCID: PMC6336217 DOI: 10.1016/j.kisu.2018.06.001] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Salvadori M, Tsalouchos A. Hepatitis C and renal transplantation in era of new antiviral agents. World J Transplant 2018; 8:84-96. [PMID: 30148074 PMCID: PMC6107518 DOI: 10.5500/wjt.v8.i4.84] [Citation(s) in RCA: 3] [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: 02/28/2018] [Revised: 04/17/2018] [Accepted: 05/30/2018] [Indexed: 02/05/2023] Open
Abstract
Data from World Health Organization estimates that the hepatitis C virus (HCV) prevalence is 3% and approximately 71 million persons are infected worldwide. HCV infection is particularly frequent among patients affected by renal diseases and among those in dialysis treatment. In addition to produce a higher rate of any cause of death, HCV in renal patients and in renal transplanted patients produce a deterioration of liver disease and is a recognized cause of transplant glomerulopathy, new onset diabetes mellitus and lymphoproliferative disorders. Treatment of HCV infection with interferon alpha and/or ribavirin had a poor efficacy. The treatment was toxic, expensive and with limited efficacy. In the post-transplant period was also cause of severe humoral rejection. In this review we have highlighted the new direct antiviral agents that have revolutionized the treatment of HCV both in the general population and in the renal patients. Patients on dialysis or with low glomerular filtration rate were particularly resistant to the old therapies, while the direct antiviral agents allowed achieving a sustained viral response in 90%-100% of patients with a short period of treatment. This fact to date allows HCV patients to enter the waiting list for transplantation easier than before. These new agents may be also used in renal transplant patients HCV-positive without relevant clinical risks and achieving a sustained viral response in almost all patients. New drug appears in the pipeline with increased profile of efficacy and safety. These drugs are now the object of several phases II, III clinical trials.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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11
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Dumortier J, Bailly F, Pageaux GP, Vallet-Pichard A, Radenne S, Habersetzer F, Gagnieu MC, Grangé JD, Minello A, Guillaud O, Kamar N, Alric L, Leroy V. Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure. Nephrol Dial Transplant 2018; 32:2065-2071. [PMID: 27760839 DOI: 10.1093/ndt/gfw348] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 08/10/2016] [Indexed: 12/23/2022] Open
Abstract
Background Chronic hepatitis C virus (HCV) infection is the most common chronic liver disease in patients with end-stage renal disease (ESRD). Over the last few years, second-generation direct-acting antivirals have been revolutionary in the treatment of hepatitis C, and sofosbuvir (SOF) is the backbone of most modern treatment strategies. Since SOF is eliminated through the kidney, the aim of this multicentre retrospective study was to assess its antiviral efficacy and safety in HCV-infected patients with severe renal failure [including haemodialysis (HD) patients]. Methods Fifty patients (36 males, mean age ± standard deviation 60.5 ± 7.5 years) with chronic HCV infection (G1: 28/56%, cirrhosis: 27/54%) and severe renal failure [i.e. MDRD estimated glomerular filtration rate (eGFR) <35 mL/min], including 35 on HD, were enrolled. Antiviral treatment consisted of SOF/ribavirin (RBV) (n = 7), SOF/RBV/pegylated interferon (n = 2), SOF/daclatasvir ± RBV (n = 30) or SOF/simeprevir ± RBV (n = 11) for 12 or 24 weeks. A reduced dose of SOF (400 mg three times a week or 400 mg every other day) was given to all HD patients. Initial dose of RBV (n = 12) ranged from 400 to 4200 mg/week. Results On an intent-to-treat-based analysis, sustained virological response rate was 86% at 12 weeks. During therapy, haemoglobin levels were not significantly modified, but recombinant erythropoietin (rEPO) dose significantly increased in patients treated with RBV. Two patients (4%) required blood transfusion. No patient had treatment discontinuation due to side effects. Dose of RBV was reduced in two patients (16.7%) during antiviral therapy. Dose of SOF was reduced in two non-HD patients because of side effects. In non-HD patients, median eGFR was not significantly modified during treatment. Conclusions Our results strongly suggest that SOF-based antiviral therapy, with a reduced dose of SOF, is safe and effective for the treatment of HCV patients with ESRD, including HD patients.
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Affiliation(s)
- Jérôme Dumortier
- Department of Digestive Diseases, Edouard Herriot Hospital and University of Lyon 1, Hospices Civils de Lyon, Lyon, France
| | - François Bailly
- Department of Hepatogastroenterology, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - Georges-Philippe Pageaux
- Department of Hepatogastroenterology and Liver Transplantation, Saint Eloi University Hospital, University of Montpellier, Montpellier, France
| | - Anaïs Vallet-Pichard
- Department of Hepatology, Cochin Hospital, APHP, INSERM UMS-20 Institut Pasteur, Paris, France
| | - Sylvie Radenne
- Department of Hepatogastroenterology, Croix-Rousse Hospital, Hospices Civils de Lyon, Lyon, France
| | - François Habersetzer
- Hepatology Unit, Pôle Hépato-digestif, IHU Strasbourg, INSERM U1110, University of Strasbourg, Strasbourg, France
| | - Marie-Claude Gagnieu
- Department of Pharmacology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | | | - Anne Minello
- Department of Hepatogastroenterology, Dijon University Hospital, Dijon, France
| | - Olivier Guillaud
- Department of Digestive Diseases, Edouard Herriot Hospital and University of Lyon 1, Hospices Civils de Lyon, Lyon, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, Toulouse University Hospital, Université Paul Sabatier, INSERM U1043, IFR-BMT, Toulouse, France
| | - Laurent Alric
- Internal Medicine-Digestive Department, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France
| | - Vincent Leroy
- Department of Hepatology and Gastroenterology and INSERM U823, CHU A Michallon, Université Grenoble Alpes, Grenoble, France
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12
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Reddy S, Sharma RK, Mehrotra S, Prasad N, Gupta A, Kaul A, Singh Bhadauria D. Efficacy and safety of sofosbuvir-based antiviral therapy to treat hepatitis C virus infection after kidney transplantation. Clin Kidney J 2018; 11:429-433. [PMID: 29942507 PMCID: PMC6007709 DOI: 10.1093/ckj/sfx112] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Accepted: 08/10/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The objectives of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir and ribavirin combination regimen to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients and to study the impact of sofosbuvir on calcineurin inhibitor (CNI) drug levels. METHODS A total of 10 kidney transplant recipients with chronic HCV infection were included in the study. All received sofosbuvir and ribavirin combination therapy. The virological response to therapy and the adverse effects of the drugs were studied. The area under the curve (AUC) and pharmacokinetic data of levels of CNI were compared while the patients were receiving sofosbuvir and ribavirin drugs and when they were no longer on these drugs. RESULTS In all, 9 of 10 patients (90%) achieved rapid virological response (RVR) with undetectable HCV RNA at 4 weeks and the remaining patient achieved undetectable HCV RNA at 8 weeks. A sustained virological response was seen at 3, 6 and 12 months and was maintained in all 10 patients (100%). The important aspect of the study is the effect of treatment with the sofosbuvir-ribavirin combination regimen on the CNI AUC levels, which resulted in a reduction in the CNI AUC. While used as part of triple-drug immunosuppression, no change in the dose of CNI (tacrolimus and cyclosporine) was required based on measurement of C0 levels. CONCLUSIONS The sofosbuvir and ribavirin combination therapy is effective and safe to treat HCV infection in the post-renal transplant setting. There is a need for close CNI level monitoring while these patients are on sofosbuvir therapy. With therapy and viral clearance, there could be reduction in CNI levels due to increased clearance of CNI drugs, which is shown by the AUC measurements. This could be important for patients at high risk for rejection.
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Affiliation(s)
- Suresh Reddy
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Raj Kumar Sharma
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Sonia Mehrotra
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Amit Gupta
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Anupma Kaul
- Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
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Oruc A, Ersoy A. Transplantation Opportunities of Hepatitis C Virus-Seropositive Patients on the Kidney Waiting List. Transplant Proc 2018; 50:3181-3184. [PMID: 29803528 DOI: 10.1016/j.transproceed.2018.04.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 04/12/2018] [Indexed: 11/27/2022]
Abstract
OBJECTIVE Besides severe organ shortage, hepatitis C virus (HCV) infection is an important obstacle for kidney transplantation because of long waiting times on deceased kidney donor waiting lists. We aimed to evaluate calling number of candidates according to HCV serology. METHOD A total of 404 adults on the deceased donor waiting list invited for cadaveric transplantation was evaluated. Demographic data, waiting time, calling number for transplantation, and viral serology were obtained during the 6-year period. RESULTS Mean waiting duration and calling number of all patients were 42.7 ± 34 months and 1.56 ± 4.37 times, respectively. Twenty-six candidates had chronic HCV infection and 12 of 26 were HCV RNA-positive. Mean waiting duration and calling number in anti-HCV-positive candidates were significantly higher compared with anti-HCV-negative candidates (85.3 ± 38.8 vs 39.8 ± 31.6 months, and 10.8 ± 10.3 vs 0.92 ± 2.6 times, respectively; P < .001). Mean waiting duration and total calling number in HCV-RNA-positive candidates were significantly higher than in HCV-RNA-negative ones (107.5 ± 7.5 vs 66.2 ± 44.8 months; P = .018; 15 ± 9.7 vs 7.3 ± 9.8 times, respectively; P = .026). CONCLUSIONS Chronic HCV infection is an important issue leading to longer waiting time on the list. Our observation showed that waiting durations of anti-HCV-positive candidates were longer than that of negative patients, although they had more frequent opportunity for transplantation.
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Affiliation(s)
- A Oruc
- Department of Internal Medicine, Division of Nephrology, Uludağ University Medical School, Bursa, Turkey.
| | - A Ersoy
- Department of Internal Medicine, Division of Nephrology, Uludağ University Medical School, Bursa, Turkey
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14
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Li Vecchi M, La Spada E, Li Vecchi V, Montalto G. Hepatitis C Virus Infection in Hemodialyzed Patients. Int J Artif Organs 2018; 30:100-7. [PMID: 17377904 DOI: 10.1177/039139880703000204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in non-infected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders. Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.
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Affiliation(s)
- M Li Vecchi
- Department of Nephrology, University of Palermo, Palermo, Italy
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15
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Chute DF, Chung RT, Sise ME. Direct-acting antiviral therapy for hepatitis C virus infection in the kidney transplant recipient. Kidney Int 2018; 93:560-567. [PMID: 29325996 DOI: 10.1016/j.kint.2017.10.024] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/12/2017] [Accepted: 10/05/2017] [Indexed: 12/26/2022]
Abstract
Hepatitis C virus infection (HCV) is a common comorbidity in patients who have undergone kidney transplantation and is associated with increased morbidity and mortality compared with recipients who do not have chronic HCV infection. Because interferon-α-based therapies can precipitate acute rejection, they are relatively contraindicated after kidney transplantation. Thus, the majority of kidney transplant recipients with HCV remain untreated. There are now all-oral, interferon-free direct-acting antiviral therapies for HCV infection that are extremely effective and well tolerated in the general population. Recent reports in the literature demonstrate that direct-acting antiviral therapies effectively cured HCV in 406 of 418 kidney transplant recipients (97%); the majority were treated with sofosbuvir-based regimens. Smaller numbers of kidney transplant recipients have been treated with paritaprevir-ritonavir, ombitasvir and dasabuvir, elbasvir-grazoprevir, or glecaprevir-pibrentasvir with excellent success. Direct-acting antiviral therapies were well tolerated and did not increase the rate of acute rejection. The latest advances include approval of regimens that can treat patients with advanced allograft dysfunction (eGFR < 30 ml/min per 1.73 m2) and "pan-genotypic" regimens that have activity against all 6 major genotypes of HCV. This review summarizes what is known about the epidemiology of HCV infection in kidney transplant recipients, and presents the landscape of direct-acting antiviral therapies and areas in need of further investigation.
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Affiliation(s)
- Donald F Chute
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
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16
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Kesiraju S, Srikanti P, Sahariah S. Hepatitis C infection in renal transplantation: pathogenesis, current impact and emerging trends. Virusdisease 2017; 28:233-241. [PMID: 29291208 DOI: 10.1007/s13337-017-0393-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 08/17/2017] [Indexed: 02/07/2023] Open
Abstract
Prevalence of hepatitis C infection, which is associated with mortality and morbidity, is higher in chronic kidney disease patients on hemodialysis and transplant recipients when compared to non HCV infected patients. In addition to the conventional risk factors, HCV infection maybe an additional risk factor in the development of chronic kidney disease. HCV causes adverse effects leading to the poor long term outcome in renal transplant recipients; hepatitis C infection can cause both hepatic as well as extra hepatic complications. Prior evaluation and management of HCV infection is recommended for better long term outcome as there are chances of higher rejection rates with HCV treatment. However transplantation is not contraindicated in those patients who cannot be treated prior to the transplantation as patient survival is better when compared to dialysis patients. Kidney Disease Outcome Quality Initiative Clinical Practice Guidelines recommend interferon based therapy only when there is a rapid worsening of HCV related hepatic injury in transplant recipients. HCV treatment has been improved by the addition of direct acting antiviral, protease inhibitors and polymerase inhibitors. Combination therapies are showing improved sustained virological response rates. NS3-4A protease inhibitors, nucleotidic/nucleosidic NS5A and NS5B polymerase inhibitors are promising treatments which are under trials with different combinations. The focus of this review is to evaluate and optimize the treatment options of co-existing HCV infection in renal transplant recipients and discuss more promising alternative treatment regimen.
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Affiliation(s)
- Sailaja Kesiraju
- Transimmun- Transplantation Immunology and Research Centre, Somajiguda, Hyderabad, Andhra Pradesh 500082 India.,Department of Immunology, Bhagwan Mahavir Medical Research Centre, Hyderabad, India
| | | | - S Sahariah
- Transimmun- Transplantation Immunology and Research Centre, Somajiguda, Hyderabad, Andhra Pradesh 500082 India.,Department of Nephrology and Transplantation, Krishna Institute of Medical Sciences, Hyderabad, India
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17
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Rostaing L, Alric L, Kamar N. Use of direct-acting agents for hepatitis C virus-positive kidney transplant candidates and kidney transplant recipients. Transpl Int 2016; 29:1257-1265. [DOI: 10.1111/tri.12870] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 12/14/2015] [Accepted: 09/30/2016] [Indexed: 12/15/2022]
Affiliation(s)
- Lionel Rostaing
- Department of Nephrology and Organ Transplantation; CHU Rangueil; Toulouse France
- INSERM U563, IFR-BMT; CHU Purpan; Toulouse France
- Université Paul Sabatier; Toulouse France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases; CHU Purpan; Toulouse France
- UMR 152, IRD; Toulouse 3 University; Toulouse France
| | - Nassim Kamar
- Université Paul Sabatier; Toulouse France
- INSERM U858; CHU Rangueil & Purpan; Toulouse France
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18
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Han E, Kim MS, Kim YS, Kang ES. Risk assessment and management of post-transplant diabetes mellitus. Metabolism 2016; 65:1559-69. [PMID: 27621191 DOI: 10.1016/j.metabol.2016.07.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/13/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023]
Abstract
The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.
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Affiliation(s)
- Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center; Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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19
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Agarwal SK, Bhowmik D, Mahajan S, Bagchi S. Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study. Indian J Nephrol 2016; 26:244-51. [PMID: 27512295 PMCID: PMC4964683 DOI: 10.4103/0971-4065.172228] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 10(6) copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.
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Affiliation(s)
- S K Agarwal
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - D Bhowmik
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - S Mahajan
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
| | - S Bagchi
- Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India
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20
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Kamar N, Marion O, Rostaing L, Cointault O, Ribes D, Lavayssière L, Esposito L, Del Bello A, Métivier S, Barange K, Izopet J, Alric L. Efficacy and Safety of Sofosbuvir-Based Antiviral Therapy to Treat Hepatitis C Virus Infection After Kidney Transplantation. Am J Transplant 2016; 16:1474-9. [PMID: 26587971 DOI: 10.1111/ajt.13518] [Citation(s) in RCA: 165] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 08/11/2015] [Accepted: 08/30/2015] [Indexed: 01/25/2023]
Abstract
There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new-generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir-based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty-five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated-interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti-HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New-generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation.
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Affiliation(s)
- N Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - O Marion
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - L Rostaing
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - O Cointault
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - D Ribes
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - L Lavayssière
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - L Esposito
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - A Del Bello
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - S Métivier
- Department of Hepatology and Gastroenterology, Toulouse, France
| | - K Barange
- Department of Hepatology and Gastroenterology, Toulouse, France
| | - J Izopet
- INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,Laboratory of Virology, CHU Purpan, Toulouse, France
| | - L Alric
- Université Paul Sabatier, Toulouse, France.,MR 152 IRD-Toulouse 3 University, Toulouse, France.,Internal Medicine-Digestive Department, CHU Purpan, Toulouse, France
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21
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Sawinski D, Kaur N, Ajeti A, Trofe-Clark J, Lim M, Bleicher M, Goral S, Forde KA, Bloom RD. Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct-Acting Antiviral Agents. Am J Transplant 2016; 16:1588-95. [PMID: 26604182 DOI: 10.1111/ajt.13620] [Citation(s) in RCA: 170] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 10/04/2015] [Accepted: 10/31/2015] [Indexed: 01/25/2023]
Abstract
The direct-acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end-stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon-free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy-proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon-based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment-related side effects.
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Affiliation(s)
- D Sawinski
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - N Kaur
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - A Ajeti
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - J Trofe-Clark
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.,Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - M Lim
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - M Bleicher
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - S Goral
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - K A Forde
- Department of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - R D Bloom
- Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Abstract
With a worldwide prevalence of 6% to 40% among patients with end-stage renal disease, hepatitis C virus (HCV) infection is a significant cause of comorbidity in kidney transplant candidates and recipients alike. Hepatitis C infection negatively impacts patient and allograft outcomes, predisposes to progressive liver disease and increases the risks of glomerular disease as well as new onset diabetes after transplantation. Treatment options until now have revolved around interferon, limited in efficacy, restricted to pretransplant administration because of concerns related to allograft dysfunction and immune stimulation, and fraught with high rates of intolerance. Direct-acting antivirals therapies are now emerging, providing the opportunity to effectively cure chronic HCV infection and to reduce the burden of hepatic and extrahepatic complications of HCV that are observed in kidney recipients, thereby offering hope of improved patient outcomes. Against a description of the major outcomes and risks that HCV+ kidney candidates and recipients encounter, and a summary of the pertinent studies of interferon-based therapies in this population, this review discusses the potential role for emerging direct-acting antivirals, proposing treatment algorithms that should be considered in the management of these complex patients. Conundrums relating to the new treatment, including the potential impact on the utilization of kidneys from HCV-infected donors, are presented.
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23
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Vallet-Pichard A, Pol S. [Management of hepatitis B virus and hepatitis C virus infection in chronic kidney failure]. Nephrol Ther 2015; 11:507-20. [PMID: 26423779 DOI: 10.1016/j.nephro.2015.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic infections by hepatitis B (HBV) and C virus (HCV) result in diagnosis and therapeutic issues in dialysis and kidney recipients patients. The exposure to nosocomial, including blood transfusion, risk explains the high prevalence of HBV and HCV infection in this setting. Chronic infection reduces the survival of both patients and allografts, including a specific risk of de novo glomerulonephritis. Cirrhosis was considered as a contra-indication to renal transplantation given the high risk of decompensation and death, questionning the indication of a combined liver and kidney transplantation. Thus, it is mandatory to screen HBV and HCV markers in all dialysis patients, whether or not they are candidates to transplantation. Liver biopsy allows evaluating the severity of the liver disease since the noninvasive markers of fibrosis appear to be less accurate in "renal" patients than in the general population and to better define antiviral therapeutic indications. HCV treatment was mainly based on pegylated interferon α (and low doses of ribavirin), which is contra-indicated in kidney recipients given the risk of graft rejection; HCV treatment is now based on the use of oral direct acting antivirals, which are very potent and well tolerated. HBV replication is now easily suppressed by second-generation nucleos(t)tidic analogues (entecavir and tenofovir), which will be indicated in all the dialysis patients with significant fibrosis (F2,3 or 4 according to the Metavir scoring system) and in any candidate to renal transplantation and to any HBsAg-positive kidney recipients. The best treatment remains preventive by anti-HBV vaccination for HBV and by the respect of universal hygiene rules for HCV.
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Affiliation(s)
- Anaïs Vallet-Pichard
- Unité d'hépatologie, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Inserm U 1016, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Université Paris-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France
| | - Stanislas Pol
- Unité d'hépatologie, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Inserm U 1016, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Université Paris-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
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New-onset diabetes after kidney transplant in children. Pediatr Nephrol 2015; 30:405-16. [PMID: 24894384 DOI: 10.1007/s00467-014-2830-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 04/01/2014] [Accepted: 04/11/2014] [Indexed: 02/08/2023]
Abstract
The development of new-onset diabetes after kidney transplantation (NODAT) is associated with reduced graft function, increased cardiovascular morbidity and lower patient survival among adult recipients. In the pediatric population, however, the few studies examining NODAT have yielded inconsistent results. Therefore, the true incidence of NODAT in the pediatric population has been difficult to establish. The identification of children and adolescents at risk for NODAT requires appropriate screening questions and tests pre- and post-kidney transplant. Several risk factors have been implicated in the pathogenesis of NODAT and post-transplant glucose intolerance, including African American race, obesity, family history of diabetes and the type of immunosuppressant regimen. Moreover, uremia per se results in a state of insulin resistance that increases the risk of developing diabetes post-transplant. When an individual becomes glucose intolerant, early lifestyle modification and antihyperglycemic measures with tailoring of the immunosuppressant regimen should be implemented to prevent the development of NODAT. For the child or adolescent with NODAT, antihyperglycemic therapy should be prescribed in order to achieve optimal glycemic control, ultimately reducing complications and improving overall allograft and patient survival. In this article, we review the risk factors, screening methods, diagnosis, management and outcome of children and adolescents with NODAT and post-kidney transplant glucose intolerance.
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Aguirre Valadez J, García Juárez I, Rincón Pedrero R, Torre A. Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review. Ther Clin Risk Manag 2015; 11:329-38. [PMID: 25767389 PMCID: PMC4354469 DOI: 10.2147/tcrm.s74282] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation.
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Affiliation(s)
- Jonathan Aguirre Valadez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Ignacio García Juárez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Rodolfo Rincón Pedrero
- Department of Nephrology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Aldo Torre
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
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26
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Sezer S, Erkmen Uyar M, Tutal E, Bal Z, Guliyev O, Colak T, Hasdemir E, Haberal M. New-onset diabetes and glucose regulation are significant determinants of left ventricular hypertrophy in renal transplant recipients. J Diabetes Res 2015; 2015:293896. [PMID: 25945353 PMCID: PMC4405014 DOI: 10.1155/2015/293896] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Revised: 02/17/2015] [Accepted: 02/24/2015] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is associated with decreased graft survival and an increased risk for cardiovascular disease. The objective of this study was to evaluate the risk factors for development of NODAT and its' relationship with arterial stiffness and left ventricular mass index (LVMI) in kidney transplant recipients. METHODS 159 kidney transplant recipients were selected from our transplantation center who underwent renal transplantation between years 2007 and 2010. RESULTS Among 159 patients, 57 (32.2%) patients were with NODAT who were significantly older than patients without diabetes (P: 0.0001). Patients with NODAT had significantly higher pulse wave velocity (PWv) (P: 0.033) and left ventricular mass index LVMI (P: 0.001) compared to patients without NODAT. Further analysis was done according to LVMI as follows: LVMI > 130 g/m(2) (n: 57) and LVMI ≤ 130 g/m(2) (n: 102). We observed higher office systolic and diastolic BP, serum trygliceride, glucose, creatinine, age, and HbA1c (P: 0.0001) levels in patients with LVMI > 130 g/m(2). Linear regression analysis revealed that HbA1c was the major determinant of LVMI (P: 0.026, β: 0.361). CONCLUSIONS HbA1c is the major determinant of LVMI, so strict control of serum glucose levels is essential for preventing cardiovascular disease in patients with NODAT.
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Affiliation(s)
- Siren Sezer
- Department of Nephrology, Baskent University Medical School, 06490 Ankara, Turkey
| | - Mehtap Erkmen Uyar
- Department of Nephrology, Baskent University Medical School, 06490 Ankara, Turkey
- *Mehtap Erkmen Uyar:
| | - Emre Tutal
- Department of Nephrology, Baskent University Medical School, 06490 Ankara, Turkey
| | - Zeynep Bal
- Department of Nephrology, Baskent University Medical School, 06490 Ankara, Turkey
| | - Orhan Guliyev
- Department of Nephrology, Baskent University Medical School, 06490 Ankara, Turkey
| | - Turan Colak
- Department of Nephrology, Baskent University Medical School, 06490 Ankara, Turkey
| | - Efe Hasdemir
- Department of Internal Medicine, Baskent University Medical School, 06490 Ankara, Turkey
| | - Mehmet Haberal
- Department of Transplantation Surgery, Baskent University Medical School, 06490 Ankara, Turkey
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Tufton N, Ahmad S, Rolfe C, Rajkariar R, Byrne C, Chowdhury TA. New-onset diabetes after renal transplantation. Diabet Med 2014; 31:1284-92. [PMID: 24975051 DOI: 10.1111/dme.12534] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 05/08/2014] [Accepted: 06/24/2014] [Indexed: 12/12/2022]
Abstract
Renal transplantation has important benefits in people with end-stage renal disease, with improvements in mortality, morbidity and quality of life. Whilst significant advances in transplantation techniques and immunosuppressive regimens have led to improvements in short-term outcomes, longer-term outcomes have not improved dramatically. New-onset diabetes after transplantation appears to be a major factor in morbidity and cardiovascular mortality in renal transplant recipients. The diagnosis of new-onset diabetes after renal transplantation has been hampered by a lack of clarity over diagnostic tests in early studies, although the use of the WHO criteria is now generally accepted. HbA1c may be useful diagnostically, but should probably be avoided in the first 3 months after transplantation. The pathogenesis of new-onset diabetes after renal transplantation is likely to be related to standard pathogenic factors in Type 2 diabetes (e.g. insulin resistance, β-cell failure, inflammation and genetic factors) as well as other factors, such as hepatitis C infection, and could be exacerbated by the use of immunosuppression (glucocorticoids and calcineurin inhibitors). Pre-transplant risk scores may help identify those people at risk of new-onset diabetes after renal transplantation. There are no randomized trials of treatment of new-onset diabetes after renal transplantation to determine whether intensive glucose control has an impact on cardiovascular or renal morbidity, therefore, treatment is guided by guidelines used in non-transplant diabetes. Many areas of uncertainty in the pathogenesis, diagnosis and management of new-onset diabetes after renal transplantation require further research.
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Affiliation(s)
- N Tufton
- Department of Diabetes and Metabolism, Barts and the London School of Medicine and Dentistry, London, UK
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Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C virus infection and kidney transplantation in 2014: what's new? Am J Transplant 2014; 14:2206-20. [PMID: 25091274 DOI: 10.1111/ajt.12835] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 05/15/2014] [Accepted: 05/16/2014] [Indexed: 01/25/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.
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Affiliation(s)
- S Baid-Agrawal
- Department of Nephrology and Medical Intensive Care, Campus Virchow-Klinikum, Charité Universitaetsmedizin Berlin, Berlin, Germany
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Vidimliski PD, Nikolov I, Geshkovska NM, Dimovski A, Rostaing L, Sikole A. Review: Occult hepatitis C virus infection: still remains a controversy. J Med Virol 2014; 86:1491-8. [PMID: 24895180 DOI: 10.1002/jmv.23979] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2014] [Indexed: 02/06/2023]
Abstract
Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system.
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Wei F, Liu J, Liu F, Hu H, Ren H, Hu P. Interferon-based anti-viral therapy for hepatitis C virus infection after renal transplantation: an updated meta-analysis. PLoS One 2014; 9:e90611. [PMID: 24699257 PMCID: PMC3974660 DOI: 10.1371/journal.pone.0090611] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 01/31/2014] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is highly prevalent in renal transplant (RT) recipients. Currently, interferon-based (IFN-based) antiviral therapies are the standard approach to control HCV infection. In a post-transplantation setting, however, IFN-based therapies appear to have limited efficacy and their use remains controversial. The present study aimed to evaluate the efficacy and safety of IFN-based therapies for HCV infection post RT. METHODS We searched Pubmed, Embase, Web of Knowledge, and The Cochrane Library (1997-2013) for clinical trials in which transplant patients were given Interferon (IFN), pegylated interferon (PEG), interferon plus ribavirin (IFN-RIB), or pegylated interferon plus ribavirin (PEG-RIB). The Sustained Virological Response (SVR) and/or drop-out rates were the primary outcomes. Summary estimates were calculated using the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis. RESULTS We identified 12 clinical trials (140 patients in total). The summary estimate for SVR rate, drop-out rate and graft rejection rate was 26.6% (95%CI, 15.0-38.1%), 21.1% (95% CI, 10.9-31.2%) and 4% (95%CI: 0.8%-7.1%), respectively. The overall SVR rate in PEG-based and standard IFN-based therapy was 40.6% (24/59) and 20.9% (17/81), respectively. The most frequent side-effect requiring discontinuation of treatment was graft dysfunction (14 cases, 45.1%). Meta-regression analysis showed the covariates included contribute to the heterogeneity in the SVR logit rate, but not in the drop-out logit rate. The sensitivity analyses by the random model yielded very similar results to the fixed-effects model. CONCLUSIONS IFN-based therapy for HCV infection post RT has poor efficacy and limited safety. PEG-based therapy is a more effective approach for treating HCV infection post-RT than standard IFN-based therapy. Future research is required to develop novel strategies to improve therapeutic efficacy and tolerability, and reduce the liver-related morbidity and mortality in this important patient population.
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Affiliation(s)
- Fang Wei
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Junying Liu
- Department of Gastroenterology, The Central hospital of Zhoukou, Henan Province, China
| | - Fen Liu
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Huaidong Hu
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Hong Ren
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
| | - Peng Hu
- Department of infectious Disease, Institute for Viral hepatitis, Key Laboratory of Molecular Biology for infectious disease, The second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
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Affiliation(s)
- Yujung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Severance Hospital Diabetes Center, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Severance Hospital Diabetes Center, Seoul, Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
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Uchida J, Iwai T, Machida Y, Kuwabara N, Kabei K, Kumada N, Nakatani T. Insulin resistance and insulin secretion in renal transplant recipients with hepatitis C. Transplant Proc 2013; 45:1540-3. [PMID: 23726615 DOI: 10.1016/j.transproceed.2013.01.053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Accepted: 01/03/2013] [Indexed: 01/07/2023]
Abstract
BACKGROUND Several reports have suggested an association between hepatitis C virus (HCV) infection and new-onset diabetes after transplantation (NODAT). NODAT is a common complication after renal transplantation, and it has been associated with increased long-term morbidity and mortality. HCV-positive recipients may have abnormal glucose metabolism, even though NODAT has never been previously diagnosed. The aim of this study was to analyze the pathogenic factors responsible for glucose metabolism in a series of HCV-positive renal transplant recipients. METHODS The study population comprised 16 renal transplant patients who received their grafts from deceased or living donors with anti-HCV antibodies. HCV-negative transplant recipients were individually matched with these HCV-positive recipients by year of transplantation, sex, age, serum creatinine levels, and type of calcineurin inhibitors. None of the patients had been diagnosed with diabetes. Insulin secretion and insulin resistance were determined by a 75-g oral glucose tolerance test (OGTT) and compared between the 2 groups. Categories of glucose tolerance were defined according to World Health Organization criteria. RESULTS Glucose intolerance (impaired fasting glucose, impaired glucose tolerance, diabetes mellitus) as assessed by OGTT was detected in 7 of the HCV-positive recipients (43.8%) and 3 of the HCV-negative recipients. The homeostasis model assessment of insulin resistance was greater in the HCV-positive recipients than in the HCV-negative recipients. The homeostasis model assessment of β-cell function was higher in the HCV-positive recipients than in the HCV-negative recipients. CONCLUSIONS The frequency of glucose intolerance tended to be higher in HCV-positive recipients. Furthermore, insulin resistance was greater and insulin secretion higher in HCV-positive recipients, which indicated that the increase in insulin secretion compensated for insulin resistance observed in these patients. However, HCV-positive renal transplant recipients may ultimately develop NODAT as this compensation diminishes with time.
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Affiliation(s)
- J Uchida
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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Rostaing L, Izopet J, Kamar N. Hepatitis C virus infection in nephrology patients. J Nephropathol 2013; 2:217-33. [PMID: 24475454 PMCID: PMC3891131 DOI: 10.12860/jnp.2013.36] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Accepted: 12/29/2012] [Indexed: 12/19/2022] Open
Abstract
CONTEXT Hepatitis C virus (HCV) infection leads to chronic liver disease, but also to extra-hepatic manifestations. EVIDENCE ACQUISITIONS Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. RESULTS Herein, we provide an overview of renal diseases related to HCV and their therapies, as well as the treatment options available for HCV (+)/RNA (+) dialysis patients. We will not mention, however, HCV infection-related complications in the post-kidney transplantation setting. CONCLUSIONS Extra-hepatic manifestations of HCV infection include mixed cryoglobulinemia, lymphoproliferative disorders, and renal disease. HCV infection has been reported in association with distinct histological patterns of glomerulonephritis in native kidneys.
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Affiliation(s)
- Lionel Rostaing
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
- Department of Virology, CHU Purpan, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
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Vallet-Pichard A, Pol S. Hepatitis C virus infection in hemodialysis patients. Clin Res Hepatol Gastroenterol 2013; 37:340-6. [PMID: 23933193 DOI: 10.1016/j.clinre.2013.03.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Revised: 02/27/2013] [Accepted: 03/13/2013] [Indexed: 02/04/2023]
Abstract
Hepatitis C virus (HCV) infection is observed in around 20% of dialysis patients and in allograft recipients and results in a significant morbidity and mortality, especially after transplantation. Its prevalence has markedly decreased in patients who are candidates for transplantation since the introduction of screening, hygiene and prevention measures, including systematic screening of blood and organ donations, use of erythropoietin, and compliance with universal hygiene rules. A liver biopsy is preferable to non-invasive biochemical and/or morphological tests of fibrosis to evaluate liver fibrosis before and even after transplantation. In HCV-infected dialyzed patients who are not candidates for renal transplantation, the indication for antiviral therapy is limited to significant fibrosis (fibrosis ≥ 2 on the METAVIR scale). Antiviral treatment should be proposed to any HCV-infected candidate for renal transplantation, whatever the baseline histopathology. The recommendation is to use standard interferon-α as monotherapy, but pegylated interferon can be used, resulting in sustained virological response, while low doses of combined ribavirin may enhance the antiviral efficacy. After transplantation, interferon-α is contra-indicated but may be used in patients for whom the benefits of antiviral treatment clearly outweigh the risks, especially that of allograft rejection. All cirrhotic patients should be screened for hepatocellular carcinoma, whose risk is enhanced by immunosuppressive regimens. Sustained suppression of necro-inflammation may result in the reversal of cirrhosis, which reduces liver-related morbidity and improves patient and allograft survival. Finally, due to the high mortality after renal transplantation, active cirrhosis must be considered to be a contraindication to kidney transplantation, but an indication to combined liver-kidney transplantation; on the contrary, inactive compensated cirrhosis may permit renal transplantation alone.
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Kamar N, Alric L, Izopet J, Rostaing L. Hepatitis C virus and kidney disease. Clin Res Hepatol Gastroenterol 2013; 37:328-33. [PMID: 23522570 DOI: 10.1016/j.clinre.2013.02.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Accepted: 02/13/2013] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) is the most frequently observed viral infection in patients with kidney disease. HCV can cause glomerular disease, which can lead to end-stage renal disease that requires dialysis and/or kidney transplantation. It is recommended to test HCV patients once a year for proteinuria, microscopic hematuria and estimated glomerular filtration rate. Membranoproliferative glomerulonephritis is the most common glomerular disease induced by HCV. Over the past few decades, the prevalence of HCV infection has decreased among dialysis and kidney transplant patients. However, survival is significantly lower in HCV-positive than in HCV-negative dialysis patients whereas survival is significantly better in HCV-positive kidney transplant patients compared with HCV-positive dialysis patients. Thus, dialysis patients without a sustained virological response after anti-HCV therapy should be proposed for kidney transplantation. Recurrence or de novo occurrence of glomerular disease is responsible for the lower kidney allograft survival in HCV-positive compared with HCV-negative kidney transplant patients. Dialysis and kidney transplantation do not appear to negatively affect progression of liver fibrosis in the majority of patients. The available data also suggest that occult HCV infection does not exist in dialysis and kidney transplant patients.
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Affiliation(s)
- Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France.
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36
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Hornum M, Lindahl JP, von Zur-Mühlen B, Jenssen T, Feldt-Rasmussen B. Diagnosis, management and treatment of glucometabolic disorders emerging after kidney transplantation: a position statement from the Nordic Transplantation Societies. Transpl Int 2013; 26:1049-60. [PMID: 23634804 DOI: 10.1111/tri.12112] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Revised: 02/11/2013] [Accepted: 04/06/2013] [Indexed: 12/16/2022]
Abstract
After successful solid organ transplantation, new-onset diabetes (NODAT) is reported to develop in about 15-40% of the patients. The variation in incidence may partly depend on differences in the populations that have been studied and partly depend on the different definitions of NODAT that have been used. The diagnosis was often based on 'the use of insulin postoperatively', 'oral agents used', random glucose monitoring and a fasting glucose value between 7 and 13 mmol/l (126-234 mg/dl). Only few have used a 2-h glucose tolerance test performed before transplantation. There is a huge variation in the literature regarding risk factors for developing NODAT. They can be divided into factors related to glucose metabolism or to patient demographics and the latter into modifiable and nonmodifiable. Screening for risk factors should start early and be re-evaluated while being on the waitlist. Patients on the waiting list for renal transplantation and transplanted patients share many characteristics in having hyperglycaemia, disturbed insulin secretion and increased insulin resistance. We present guidelines for early risk factor assessment and a screening/treatment strategy for disturbed glucose metabolism, both before and after transplantation. The aim was to avoid the increased cardiovascular disease and mortality rates associated with NODAT.
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Affiliation(s)
- Mads Hornum
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
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37
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Chakkera HA, Weil EJ, Pham PT, Pomeroy J, Knowler WC. Can new-onset diabetes after kidney transplant be prevented? Diabetes Care 2013; 36:1406-12. [PMID: 23613600 PMCID: PMC3631828 DOI: 10.2337/dc12-2067] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Because the negative consequences of new-onset diabetes mellitus after transplantation (NODAT) diminish the significant gains of kidney transplantation, it is imperative to develop clinical interventions to reduce the incidence of NODAT. In this review, we discuss whether intensive lifestyle interventions that delay or prevent type 2 diabetes mellitus may decrease the incidence of NODAT. We examine the literature pertaining to incidence and timing of onset of NODAT, as well as the risk factors and pathophysiology that NODAT shares with type 2 diabetes mellitus, namely pathways related to increased insulin resistance and decreased insulin secretion. Our central hypothesis is that NODAT results from the same metabolic risk factors that underlie type 2 diabetes mellitus. These risk factors are altered and enhanced by transplantation, "tipping" some transplant recipients with seemingly normal glucose homeostasis before transplant toward the development of NODAT. We describe the diabetogenic properties of transplant immunosuppressive drugs. We describe novel methods of prevention that are being explored, including resting the pancreatic β-cells by administration of basal insulin during the period immediately after transplant. On the basis of the current evidence, we propose that intensive lifestyle modification, adapted for individuals with chronic kidney disease or end-stage renal disease, as well as resting pancreatic β-cells during the immediate postoperative period, may lower the incidence of NODAT.
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Ue M, Ikebe N, Munekage K, Ochi T, Hirose A, Kataoka H, Fujimoto S, Kikuchi K, Okuhara Y, Ono M, Saibara T. Hepatocyte destruction with enhanced collagen synthesis: characteristic feature of chronic hepatitis C patients on haemodialysis. J Viral Hepat 2013; 20:350-7. [PMID: 23565618 DOI: 10.1111/jvh.12031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Accepted: 10/01/2012] [Indexed: 12/09/2022]
Abstract
Hepatitis C virus (HCV) infection is frequent among patients with end-stage renal disease on haemodialysis and is considered to be an independent risk factor for mortality in this setting. However, only a few of these patients are treated with anti-hepatitis virus treatment before the development of end-stage renal disease. Recent guidelines recommend identification of patients with good prognoses who are in need of interferon treatment, but we know little of patients who must be treated urgently. Ninety-eight patients on haemodialysis (48 anti-HCV-positive and 50 anti-HCV-negative patients) were enrolled in this study; HCV RNA was detected in 43 anti-HCV-positive patients. Univariate analysis and multivariate regression analysis were applied to identify variables independently associated with persistent HCV infection. Seven variables were proven to be associated with persistent HCV infection. Among them, type IV collagen 7S and N-terminal propeptide of type III procollagen (P-III-P) were defined as independent variables useful in distinguishing HCV RNA-positive patients from HCV RNA-negative patients with 0.91 sensitivity, 0.91 specificity, 0.89 positive predictive value and 0.93 negative predictive value. Our observations suggest that hepatocyte destruction with enhanced liver fibrosis is a characteristic clinical feature of persistent HCV infection. Type IV collagen 7S of ≥ 5 ng/mL and/or P-III-P of ≥ 5 U/mL would be useful markers to identify patients in need of interferon treatment, which supports the idea of the Kidney Disease: Improving Global Outcomes guidelines that a good prognosis in patients with HCV infection on haemodialysis should prompt consideration for IFN treatment when applicable.
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Affiliation(s)
- M Ue
- Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan
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Abstract
: Hepatitis C virus (HCV) infection is common in solid organ allograft recipients and is a significant cause of morbidity and mortality after transplantation, so effective management will improve outcomes. In this review, we discuss the extent of the problem associated with HCV infection in donors and kidney, heart, and lung transplant candidates and recipients and recommend follow-up and treatment.Patients with end-stage kidney disease without cirrhosis and selected patients with early-stage cirrhosis can be considered for kidney transplant alone. In HCV-infected kidney allograft recipients, the progression of fibrosis should be evaluated serially by Fibroscan or serologic measures of fibrosis. Transplantation of kidneys from HCV-positive donors should be restricted to HCV-positive recipients as it is associated with a reduced time waiting for a graft and does not affect posttransplant outcomes. Hepatitis C virus antiviral therapy should be considered for all HCV-RNA-positive kidney transplant candidates, irrespective of the baseline liver histopathology. Protease inhibitors have yet to be fully evaluated in patients with renal dysfunction and in the transplant population. As these agents may cause anemia in patients with normal renal function, tolerability may be a problem in patients with end-stage kidney disease.The impact of HCV infection on survival in heart and lung transplantation is unclear. Because of the shortage of organs, few HCV-infected patients are accepted for transplantation.Universal use of nucleic acid amplification testing (NAT) for the screening of potential organ donors should be reserved to high-risk donors. Assays that quantify HCV core antigen may become more cost-effective than NAT for the screening of potential organ donors.
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Affiliation(s)
- Marco Carbone
- Liver Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.
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40
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New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation 2013; 93:1189-95. [PMID: 22475764 DOI: 10.1097/tp.0b013e31824db97d] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
New-Onset Diabetes After Transplantation (NODAT) is an increasingly recognized severe metabolic complication of kidney transplantation causing lower graft function and survival and reduced long-term patient survival mainly due to cardiovascular events. The real incidence of NODAT after kidney transplantation is difficult to establish, because different classification systems and definitions have been employed over the years. Several risk factors, already present before or arising after transplantation, in particular the employed immunosuppressive regimens, have been related to the development of NODAT. However the responsible pathogenic mechanisms are still far to be perfectly known. Awareness of NODAT and of the NODAT-related factors is of paramount importance for the clinicians in order to individuate higher risk patients and arrange screening strategies. The risk of NODAT can be reduced by planning preventive measures and by tailoring immunosuppressive regimens according to the patient characteristics. Once NODAT has been diagnosed, the administration of specific anti-hyperglycemic therapy is mandatory to reach a tight glycemic control, which contributes to significantly reduce posttransplant mortality and morbidity.
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Dumortier J, Guillaud O, Gagnieu MC, Janbon B, Juillard L, Morelon E, Leroy V. Anti-viral triple therapy with telaprevir in haemodialysed HCV patients: Is it feasible? J Clin Virol 2013; 56:146-9. [DOI: 10.1016/j.jcv.2012.10.009] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Revised: 10/09/2012] [Accepted: 10/17/2012] [Indexed: 01/09/2023]
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Hecking M, Werzowa J, Haidinger M, Hörl WH, Pascual J, Budde K, Luan FL, Ojo A, de Vries APJ, Porrini E, Pacini G, Port FK, Sharif A, Säemann MD. Novel views on new-onset diabetes after transplantation: development, prevention and treatment. Nephrol Dial Transplant 2013; 28:550-66. [PMID: 23328712 DOI: 10.1093/ndt/gfs583] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
New-onset diabetes after transplantation (NODAT) is associated with increased risk of allograft failure, cardiovascular disease and mortality, and therefore, jeopardizes the success of renal transplantation. Increased awareness of NODAT and the prediabetic states (impaired fasting glucose and impaired glucose tolerance, IGT) has fostered previous and present recommendations, based on the management of type 2 diabetes mellitus (T2DM). Unfortunately, the idea that NODAT merely resembles T2DM is potentially misleading, because the opportunity to initiate adequate anti-hyperglycaemic treatment early after transplantation might be given away for 'tailored' immunosuppression in patients who have developed NODAT or carry personal risk factors. Risk factor-independent mechanisms, however, seem to render postoperative hyperglycaemia with subsequent development of overt or 'full-blown' NODAT, the unavoidable consequence of the transplant and immunosuppressive process itself, at least in many cases. A proof of the concept that timely preventive intervention with exogenous insulin against post-transplant hyperglycaemia may decrease NODAT was recently provided by a small clinical trial, which is awaiting confirmation from a multicentre study. However, because early insulin therapy aimed at beta-cell protection seems to contrast the currently recommended, stepwise approach of 'watchful waiting' prior to pancreatic decompensation, we here aim at reviewing recent concepts regarding the development, prevention and treatment of NODAT, some of which seem to challenge the traditional view on T2DM and NODAT. In summary, we suggest a novel, risk factor-independent management approach to NODAT, which includes glycaemic monitoring and anti-hyperglycaemic treatment in virtually everybody after transplantation. This approach has widespread implications for future research and is intended to tackle NODAT and also ultimately cardiovascular disease.
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Affiliation(s)
- Manfred Hecking
- Department of Internal Medicine, Medical University of Vienna, Vienna, Austria
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Fabrizi F. Hepatitis C virus infection and dialysis: 2012 update. ISRN NEPHROLOGY 2012; 2013:159760. [PMID: 24959533 PMCID: PMC4045425 DOI: 10.5402/2013/159760] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Accepted: 11/14/2012] [Indexed: 12/18/2022]
Abstract
Hepatitis C virus infection is still common among dialysis patients, but the natural history of HCV in this group is not completely understood. Recent evidence has been accumulated showing that anti-HCV positive serologic status is significantly associated with lower survival in dialysis population; an increased risk of liver and cardiovascular disease-related mortality compared with anti-HCV negative subjects has been found. According to a novel meta-analysis (fourteen studies including 145,608 unique patients), the adjusted RR for liver disease-related death and cardiovascular mortality was 3.82 (95% CI, 1.92; 7.61) and 1.26 (95% CI, 1.10; 1.45), respectively. It has been suggested that the decision to treat HCV in patients with chronic kidney disease be based on the potential benefits and risks of therapy, including life expectancy, candidacy for kidney transplant, and co-morbidities. According to recent guidelines, the antiviral treatment of choice in HCV-infected patients on dialysis is mono-therapy but fresh data suggest the use of modern antiviral approaches (i.e., pegylated interferon plus ribavirin). The summary estimate for sustained viral response and drop-out rate was 56% (95% CI, 28-84) and 25% (95% CI, 10-40) in a pooled analysis including 151 dialysis patients on combination antiviral therapy (conventional or pegylated interferon plus ribavirin).
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital and IRCCS Foundation, Padiglione Croff, Via Commenda 15, 20122 Milan, Italy
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Attallah AM, Omran MM, Nasif WA, Ghaly MF, El-Shanshoury AERR, Abdalla MS, Sharada HM, Farid K, El-Shony W, Moussa ESM, El-Domany EB, Nour E, Eldosoky I. Diagnostic performances of hepatitis C virus-NS4 antigen in patients with different liver pathologies. Arch Med Res 2012; 43:555-562. [PMID: 23085447 DOI: 10.1016/j.arcmed.2012.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Accepted: 09/27/2012] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV) has emerged as the major pathogen of liver disease worldwide. The aim of this study was to quantitate and evaluate the performance of HCV-NS4 antigen as an alternative approach for confirmation of viremia. METHODS Detection of HCV-NS4 was assessed in 883 patients with chronic hepatitis C. Areas under the ROC curves (AUC) were used to assess and compare diagnostic accuracy of ELISA for HCV-NS4 with quantitative HCV-RNA as a gold standard. RESULTS HCV-NS4 was identified at 27 kDa using Western blot. AUC for HCV-NS4 detection was 0.95 for all patients with different liver pathologies: 0.93 for liver fibrosis (LF), 0.95 for liver cirrhosis (LC) and 0.98 for hepatocellular carcinoma (HCC). The mean ± SD (μg/mL) of HCV-NS4 in LF was 94.2 ± 55.6; in LC was 99.3 ± 64.8 and in HCC was 124.9 ± 70.3. CONCLUSIONS HCV-NS4 antigen detection using ELISA is a reliable test in the confirmation of HCV infection.
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Prakash J, Rathore SS, Brojen Singh T, Choudhury TA, Prabhakar, Usha. New onset diabetes after transplantation (NODAT): Analysis of pre-transplant risk factors in renal allograft recipients. INDIAN JOURNAL OF TRANSPLANTATION 2012. [DOI: 10.1016/j.ijt.2012.07.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Akiba T, Hora K, Imawari M, Sato C, Tanaka E, Izumi N, Harada T, Ando R, Kikuchi K, Tomo T, Hirakata H, Akizawa T. 2011 Japanese Society for Dialysis Therapy guidelines for the treatment of hepatitis C virus infection in dialysis patients. Ther Apher Dial 2012; 16:289-310. [PMID: 22817117 DOI: 10.1111/j.1744-9987.2012.01078.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Takashi Akiba
- Department of Blood Purification, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan.
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Stevens KK, Patel RK, Jardine AG. HOW TO IDENTIFY AND MANAGE DIABETES MELLITUS AFTER RENAL TRANSPLANTATION. J Ren Care 2012; 38 Suppl 1:125-37. [DOI: 10.1111/j.1755-6686.2012.00282.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Aljumah AA, Saeed MA, Al Flaiw AI, Al Traif IH, Al Alwan AM, Al Qurashi SH, Al Ghamdi GA, Al Hejaili FF, Al Balwi MA, Al Sayyari AA. Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients. World J Gastroenterol 2012; 18:55-63. [PMID: 22228971 PMCID: PMC3251806 DOI: 10.3748/wjg.v18.i1.55] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 04/20/2011] [Accepted: 04/27/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the efficacy and safety of combined pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) infection in renal transplant recipients.
METHODS: This is a retrospective chart review of post renal transplant patients who were positive for anti-HCV and HCV-RNA, and who have received treatment with combination of pegylated interferon and ribavirin between October 2003 and December 2008. Only patients with stable graft function and absence of evidence of cirrhosis and who received the therapy for continuous 48 wk were included. Nineteen patients (13 male and 6 female) were identified and included. The patient’s complete blood count, liver and kidney profile, and calculated glomerular filtration rate (GFR) were monitored every 6-8 wk while on treatment. HCV-RNA was tested at 12 wk for early virological response, at 48 wk for end of treatment response (ETR), and then retested at 24, and 48 wk after completion of therapy for sustained virological response (SVR). Liver biopsies were obtained before treatment from all patients and graft kidney biopsies were performed as required.
RESULTS: Of the entire cohort, 9 patients (47.4%) showed an ETR and 8 had SVR (42.1%). Of the 8 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 78.9% had their ALT normalized (including the virological non responders). ALT was normal in all responders at the end of therapy and at 24 wk post therapy (100%). Only one patient (5.3%) developed an increase in creatinine and decline in GFR from baseline towards the end of treatment. This patient’s kidney biopsy revealed borderline rejection. There was no impact on response by HCV-genotype, initial HCV RNA load, age or sex of the patient or duration post transplant before commencement of therapy. All patients tolerated treatment in the same way as non-transplant with no unusual or increased occurrence of side effects.
CONCLUSION: The combination of pegylated interferon and ribavirin is effective in suppressing HCV-RNA, with a low risk of graft rejection or failure in HCV infected renal transplant recipients.
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Ghisdal L, Van Laecke S, Abramowicz MJ, Vanholder R, Abramowicz D. New-onset diabetes after renal transplantation: risk assessment and management. Diabetes Care 2012; 35:181-8. [PMID: 22187441 PMCID: PMC3241330 DOI: 10.2337/dc11-1230] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Lidia Ghisdal
- Renal Transplantation Clinic, Erasme Hospital, University of Brussels (ULB), Brussels, Belgium.
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Pipili C, Ilonidis G, Cholongitas E. Hepatitis C virus and kidney: a strong association with different clinical aspects. Liver Int 2011; 31:1071-80. [PMID: 21745269 DOI: 10.1111/j.1478-3231.2011.02458.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis in patients with type II mixed cryoglobulinaemia. The principal clinical manifestations of glomerular disease in HCV-infected patients are the presence of proteinuria and haematuria with or without impaired kidney function. Pharmaceutical regimens vary because the main pathogenesis of renal dysfunction often mediated by cryoglobulins has not been fully elucidated. HCV infection remains common in patients on renal replacement therapy and has an adverse impact on their survival. Safe and effective pharmaceutical regimens have not been yet established and nosocomial spread within dialysis units continues to occur. Monotherapy with interferon for HCV infection is probably more effective in dialysis than in non-uraemic patients, while experience with ribavirin is limited because of its adverse haemolytic effect. Based on shortage of cadaver kidneys and the fact that HCV renal transplant recipients have better survival than stay on maintenance haemodialysis or at list for transplantation, health organization proposed the use of cadaver kidneys from anti-HCV-positive donors, bringing up concerns and conflicting views. This present review describes the main renal manifestations of HCV infection, the epidemiological and clinical characteristics of chronic kidney disease population and comments on the limitations and shortcomings of current therapeutical regiments.
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Affiliation(s)
- Chrisoula Pipili
- Department of Nephrology, Aretaieion University Hospital, Athens, Greece
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