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Kumar N, Choudhary NS. Managing HBV and HCV Infection Pre- and Post-liver Transplant. J Clin Exp Hepatol 2024; 14:101287. [PMID: 38076445 PMCID: PMC10709521 DOI: 10.1016/j.jceh.2023.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 09/19/2023] [Indexed: 03/03/2025] Open
Abstract
Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation.
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Affiliation(s)
- Naveen Kumar
- Hepatology and Gastroenterology, Narayana Hospital Delhi, India
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Gorris M, van der Lecq BM, van Erpecum KJ, de Bruijne J. Treatment for chronic hepatitis E virus infection: A systematic review and meta-analysis. J Viral Hepat 2021; 28:454-463. [PMID: 33301609 PMCID: PMC7898834 DOI: 10.1111/jvh.13456] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/09/2020] [Accepted: 11/23/2020] [Indexed: 12/19/2022]
Abstract
Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty-four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta-analysis of 395 patients showed a pooled SVR rate of 78% (95-CI 72%-84%) after ribavirin treatment. Twenty-five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon-alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon-alpha increases the risk of transplant rejection and should therefore be administered with great caution.
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Affiliation(s)
- Myrte Gorris
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Bernice M. van der Lecq
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Karel J. van Erpecum
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Joep de Bruijne
- Department of Gastroenterology & HepatologyUniversity Medical Center UtrechtUtrechtThe Netherlands
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Coilly A, Roche B, Samuel D. Management of HCVInfection After Liver Transplantation. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:753-764. [DOI: 10.1002/9781119211419.ch50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Kwong A, Kim WR, Mannalithara A, Heo NY, Udompap P, Kim D. Decreasing mortality and disease severity in hepatitis C patients awaiting liver transplantation in the United States. Liver Transpl 2018; 24:735-743. [PMID: 29125676 PMCID: PMC5945341 DOI: 10.1002/lt.24973] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 08/16/2017] [Accepted: 10/13/2017] [Indexed: 12/13/2022]
Abstract
Hepatitis C virus (HCV) infection has been the leading indication for liver transplantation (LT) in the United States. Since 2013, interferon-free antiviral therapy has led to sustained virological response in many LT candidates. We compared the wait-list mortality of HCV patients with that of patients with other chronic liver diseases. Data for primary LT candidates were obtained from the Organ Procurement and Transplantation Network database. Adult wait-list registrants were divided into 3 cohorts: cohort 1 included patients on the waiting list as of January 1, 2004; cohort 2 as of January 1, 2009; and cohort 3 as of January 1, 2014. The primary outcome was wait-list mortality, and the secondary outcome was the rate of change in Model for End-Stage Liver Disease (MELD). Multivariate Cox proportional hazards analysis was performed to evaluate 12-month wait-list mortality. The cohorts included 7627 LT candidates with HCV and 13,748 patients without HCV. Compared with cohort 2, HCV patients in cohort 3 had a 21% lower risk of death (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67-0.93). Among patients with non-HCV liver disease, no difference in mortality was seen between cohorts 2 and 3 (HR, 0.97; 95% CI, 0.86-1.09). Among HCV patients, the mean rate of change in MELD decreased from 2.35 per year for cohort 2 to 1.90 per year for cohort 3, compared with 1.90 and 1.66 in cohorts 2 and 3, respectively, among non-HCV patients. In this population-based study, wait-list mortality and progression of disease severity decreased in recent HCV patients for whom direct-acting antiviral agents were available. Liver Transplantation 24 735-743 2018 AASLD.
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Affiliation(s)
- Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States
| | - W. Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States
| | - Ajitha Mannalithara
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States
| | - Nae-Yun Heo
- Department of Medicine, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Prowpanga Udompap
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States
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Liao HT, Tan P, Huang JW, Yuan KF. Ledipasvir + Sofosbuvir for Liver Transplant Recipients With Recurrent Hepatitis C: A Systematic Review and Meta-analysis. Transplant Proc 2018; 49:1855-1863. [PMID: 28923637 DOI: 10.1016/j.transproceed.2017.04.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/15/2017] [Accepted: 04/27/2017] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Studies focusing on the efficacy and safety of ledipasvir (LDV) + sofosbuvir (SOF) therapy in liver transplant (LT) recipients with hepatitis C virus (HCV) recurrence are still limited. Therefore, the aim of our work was to perform a systematic review and meta-analysis to evaluate outcome data of LDV + SOF therapy in LT recipients. METHODS Multiple databases were systematically searched for eligible studies. We included studies reporting sustained virological response 12 weeks after treatment (SVR12) and treatment-related adverse events (AEs) in LT recipients treated with LDV + SOF ± ribavirin (RBV) for HCV recurrence. All statistical analyses were conducted by using R version 3.3.1 (The R Foundation for Statistical Computing, Vienna, Austria). RESULTS Twelve studies with a total of 994 LT recipients were included, most of which were diagnosed with HCV genotype 1 infection. The overall SVR12 reached 96.3% (95% confidence interval [CI]: 94.9%-97.5%) and no significant heterogeneity was observed (Q statistic = 10.63, P = .47; I2 = 0%). No difference was found in SVR12 between treatments for 12 weeks and 24 weeks (P = .18). Patients treated with LDV + SOF + RBV (n = 525) exhibited an SVR12 rate of 95.1% (95% CI 92.8%-96.6%), which showed no difference from the findings in the LDV + SOF treatment group (n = 314) with an SVR12 reaching 94.9% (95% CI 91.5%-97.0%; P = .92). There was a tendency for a higher SVR12 in patients without cirrhosis than those with cirrhosis (P < .05). The most common AEs were listed as following: anemia 41.9% (n = 203 of 484), fatigue 39.1% (n = 207 of 530), headache 24.2% (n = 128 of 530), nausea 21.9% (n = 106 of 484), and diarrhea 19.0% (n = 92 of 484). CONCLUSION LDV + SOF-based treatment is highly effective and well tolerated in LT recipients with HCV reinfection.
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Affiliation(s)
- H-T Liao
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
| | - P Tan
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - J-W Huang
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China.
| | - K-F Yuan
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China.
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Tronina O, Ślubowska K, Mikołajczyk-Korniak N, Komuda-Leszek E, Wieczorek-Godlewska R, Łągiewska B, Pacholczyk M, Lisik W, Kosieradzki M, Durlik M. Fibrosing Cholestatic Hepatitis C After Liver Transplantation: Therapeutic Options Before and After Introduction of Direct-Acting Antivirals: Our Experience and Literature Review. Transplant Proc 2018; 49:1409-1418. [PMID: 28736015 DOI: 10.1016/j.transproceed.2017.01.077] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 01/24/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND Cirrhosis caused by hepatitis C is the most common indication for liver transplantation. The most aggressive form of hepatitis C virus (HCV) relapse after liver transplantation is fibrosing cholestatic hepatitis C, which can be observed in 2% to 15% of recipients. METHODS Double therapy with peg-interferon and ribavirin was characterized by low antiviral response, rapid fibrosis, and frequent graft failure within 1 year after surgery. RESULTS Introduction of direct-acting antivirals for HCV treatment allows for more efficient therapy with less adverse reactions, including patients with fibrosing cholestatic hepatitis C. CONCLUSIONS We present 4 (2.5%) cases of cholestatic viral hepatitis C recurrence in patients undergoing transplantation between 2006 and 2015 at the Transplantation Institute of Warsaw; during this period, 158 liver transplants were performed in patients with cirrhosis caused by HCV infection.
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Affiliation(s)
- O Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - K Ślubowska
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - N Mikołajczyk-Korniak
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - E Komuda-Leszek
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - R Wieczorek-Godlewska
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - B Łągiewska
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Pacholczyk
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - W Lisik
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Kosieradzki
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Durlik
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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Idossa DW, Simonetto DA. Infectious Complications and Malignancies Arising After Liver Transplantation. Anesthesiol Clin 2017; 35:381-393. [DOI: 10.1016/j.anclin.2017.04.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2023]
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Yu ML, Chen YL, Huang CF, Lin KH, Yeh ML, Huang CI, Hsieh MH, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL. Paritaprevir/ritonavir/ombitasvir plus dasabuvir with ribavirin for treatment of recurrent chronic hepatitis C genotype 1 infection after liver transplantation: Real-world experience. J Formos Med Assoc 2017; 117:518-526. [PMID: 28662883 DOI: 10.1016/j.jfma.2017.06.006] [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: 04/16/2017] [Revised: 05/17/2017] [Accepted: 06/12/2017] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/AIMS The registered trial has demonstrated that paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD) with ribavirin was effective for recurrent hepatitis C virus genotype 1 (HCV-1) infection after liver transplantation in patients with mild fibrosis; however, the real-world efficacy and safety of this regimen have not been determined. METHODS The efficacy (sustained virological response, SVR12, undetectable HCV RNA 12 weeks post-treatment) and safety were evaluated in 12 patients with recurrent HCV-1 infection after liver transplantation. RESULTS Nine patients were treated for 24 weeks, and three patients (two treatment-naïve patients and one interferon-intolerant patient) were treated for 12 weeks. HCV RNA was undetectable at treatment day 1, week 1, week 4, week 12, and at the end of treatment in 8.3% (n = 1), 25% (n = 3), 83.3% (n = 10), 100% (n = 12), and 100% (n = 12) of patients, respectively. All twelve patients achieved SVR12. Treatment was temporarily stopped in one patient because of leucopenia. The other patient with minimal fibrosis experienced an elevation in alanine aminotransferase concentration, which returned to normal levels after dose reduction. Seven (58.3%) patients required RBV dose reduction and two (16.7%) required transient RBV discontinuation during treatment. There were no serious adverse events, and most adverse events were related to ribavirin. No patient developed graft rejection or deterioration in hepatic or renal function during treatment. Treatment efficacy and safety were comparable between patients with and without advanced liver fibrosis. CONCLUSION PrOD plus ribavirin had a highly satisfactory real-world efficacy and safety profile in the treatment of recurrent HCV-1 infection after liver transplantation in Asian patients.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Taiwan; Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Yao-Li Chen
- Transplantation Center, Third Xiangya Hospital of Central South University, Changsha, China; Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Hua Lin
- Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Liao H, Tan P, Zhu Z, Yan X, Huang J. Sofosbuvir in combination with daclatasvir in liver transplant recipients with HCV infection: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2017; 41:262-271. [PMID: 28082137 DOI: 10.1016/j.clinre.2016.12.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Revised: 11/23/2016] [Accepted: 12/06/2016] [Indexed: 02/05/2023]
Abstract
BACKGROUND Studies focusing on the efficacy of SOF+DCV regimen on liver transplantation recipients with HCV infection are still limited. In the current study, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and tolerability of SOF+DCV regimen, with or without ribavirin, on post-LT setting. METHODS A systematic literature search of various databases as well as abstracts of major liver diseases conferences was performed. Studies with SVR data in HCV infected liver transplantation recipients treated with daclatasvir/sofosbuvir regimen were included. All statistical analyses were conducted by R version 3.3.1 (The R Foundation for Statistical Computing, Vienna, Austria). RESULTS Seven studies with a total of 379 LT recipients were included in this study. Most of these LT recipients had genotype 1 HCV infection. The overall rate of SVR12 reached 93.3% (95% CI: 83.3% to 99.4%). After excluding the study of Fontana et al., the SVR12 reached 96.8% and heterogeneity was lowered down (P=0.17). In three studies, patients treated with SOF+DCV (n=146) had a higher SVR12 rate than that of patients treated with SOF+DCV+RBV (n=83) (OR 0.33, 95% CI: 0.12 to 0.87; P=0.02). There was no difference in SVR12 between patients infected with HCV genotype 1 and genotype 3 (P=0.57) and no difference was found in SVR12 rate between 12-week therapy and 24-week therapy (P=0.82). The most common adverse effects (AEs) were: anemia 32% (n=64/202), infections 26% (n=38/149), neutropenia 23% (n=35/149), thrombocytopenia 21% (n=32/149) and renal failure 8% (n=12/149). CONCLUSION SOF+DCV±RBV regimen is of high efficacy and tolerability in LT recipients with HCV infection.
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Affiliation(s)
- Haotian Liao
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ping Tan
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zexin Zhu
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiaokai Yan
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jiwei Huang
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu 610041, China.
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Little EC, Berenguer M. The New Era of Hepatitis C: Therapy in Liver Transplant Recipients. Clin Liver Dis 2017; 21:421-434. [PMID: 28364822 DOI: 10.1016/j.cld.2016.12.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) is the leading cause of end-stage liver disease in both Europe and the United States and is the most common reason for liver transplant. In the absence of antiviral therapy, recurrent infection is the norm with subsequent graft hepatitis and impaired survival. Whether it may be better to postpone therapy in patients in whom higher risk of failure and toxicity is coupled with lower chance of liver function improvement likely depends on several factors, including waiting time, center allocation policy, presence of hepatocellular carcinoma and local prevalence of anti-HCV-positive donors.
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Affiliation(s)
- Ester Coelho Little
- Banner Transplant Institute, 1441 North 12th Street, Second floor, Phoenix, AZ 85006, USA; Banner University Medical Center Phoenix, Phoenix, AZ, USA
| | - Marina Berenguer
- Servicio de Medicina Digestivo (Torre F-5), La Fe University Hospital, Ciberehd*, University of Valencia, Avda Fernando Abril Martorell n 106, Valencia 46026, Spain.
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Lin TY, Yeh ML, Huang CI, Chen YL, Dai CY, Huang JF, Lin ZY, Chen SC, Huang CF, Yu ML, Chuang WL. Pegylated interferon plus ribavirin combination therapy in postliver transplant recipients with recurrent hepatitis C virus infection. Kaohsiung J Med Sci 2017; 33:284-289. [PMID: 28601232 DOI: 10.1016/j.kjms.2017.03.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Revised: 02/01/2017] [Accepted: 03/06/2017] [Indexed: 11/19/2022] Open
Abstract
Posttransplant hepatitis C virus (HCV) recurrence is universal in chronic hepatitis C recipients. Antiviral therapy is suggested after liver transplant to halt disease progression. Pegylated interferon plus ribavirin therapy remains the standard of care in many areas where direct antiviral agents are poorly accessible. This study aimed to assess the treatment efficacy and safety of the regimen for Taiwanese patients with post-transplant HCV recurrence. Nine patients with HCV recurrence postliver transplantation were allocated. Patients received either pegylated interferon α-2a 180 μg/wk or pegylated interferon α-2b 1.5 mg/kg/wk plus ribavirin for 24-48 weeks. The primary endpoint was the achievement of sustained virological response (SVR), defined as undetectable HCV RNA throughout 6 months of follow-up after the end of treatment. The safety profiles were also documented. The rates of rapid virological response, early virological response, end-of-treatment virological response, and SVR were 33%, 63%, 75%, and 56% respectively. Of the four patients who failed antiviral treatment, the treatment responses were nonresponse (n = 1), loss of follow-up (n = 1), and relapse (n = 2). Three patients terminated therapy early due to severe adverse events, including severe anemia, intra-abdomen infection, and hepatocellular carcinoma recurrence. One of the three patients who terminated treatment early at Week 6 experienced rapid virological response followed by SVR. Pegylated interferon/ribavirin combination allowed a chance for cure with a fair SVR rate in Taiwanese chronic hepatitis C patients postliver transplantation. Early identification of side effects and careful monitoring during therapy might enhance the treatment efficacy.
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Affiliation(s)
- Ta-Ya Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan
| | - Yao-Li Chen
- Division of General Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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Saleem A, Akhtar MF, Mushtaq MF, Saleem M, Muhammad ST, Akhtar B, Sharif A, Peerzada S. Current trends in the treatment of hepatitis C: interventions to avoid adverse effects and increase effectiveness of anti-HCV drugs. EXCLI JOURNAL 2016; 15:578-588. [PMID: 28096788 PMCID: PMC5225681 DOI: 10.17179/excli2016-582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 09/26/2016] [Indexed: 12/14/2022]
Abstract
Viral hepatitis, an inflammatory liver disease, is caused by various genotypes of hepatitis C viruses (HCV). Hepatitis C slowly sprouts into fibrosis, which progresses to cirrhosis. Over a prolonged period of time compensated cirrhosis can advance to decompensated cirrhosis culminating in hepatic failure and death. Conventional treatment of HCV involves the administration of interferons. However, association of interferon with the adverse drug reactions led to the development of novel anti-HCV drugs given as monotherapy or in combination with the other drugs. Advances in drug delivery systems (DDS) improved the pharmacokinetic profile and stability of drugs, ameliorated tissue damages on extravasation and increased the targeting of affected sites. Liposomes and lipid based vehicles have been employed with polyethylene glycol (PEG) so as to stabilize the formulations as PEG drug complex. Sofosbuvir, a novel anti-HCV drug, is administered as monotherapy or in combination with daclatasvir, ledipasivir, protease inhibitors, ribavirin and interferon for the treatment of HCV genotypes 1, 2 and 3. These drug combinations are highly effective in eradicating the interferon resistance, recurrent HCV infection in liver transplant, concurrent HIV infection and preventing interferon related adverse effects. Further investigations to improve drug targeting and identification of new drug targets are highly warranted due to the rapid emergence of drug resistance in HCV.
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Affiliation(s)
- Ammara Saleem
- Faculty of Pharmaceutical Sciences, GC University, Faisalabad, Pakistan
| | | | | | - Muhammad Saleem
- Faculty of Pharmaceutical Sciences, GC University, Faisalabad, Pakistan
| | | | - Bushra Akhtar
- Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan
| | - Ali Sharif
- Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
| | - Sohaib Peerzada
- Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
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13
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Felmlee DJ, Coilly A, Chung RT, Samuel D, Baumert TF. New perspectives for preventing hepatitis C virus liver graft infection. THE LANCET. INFECTIOUS DISEASES 2016; 16:735-745. [PMID: 27301929 PMCID: PMC4911897 DOI: 10.1016/s1473-3099(16)00120-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 01/29/2016] [Accepted: 02/15/2016] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20-30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be used synergistically with DAAs to prevent or treat graft infection.
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Affiliation(s)
- Daniel J Felmlee
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Hepatology Research Group, Peninsula School of Medicine and Dentistry, University of Plymouth, Plymouth, UK
| | - Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France
| | - Raymond T Chung
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France.
| | - Thomas F Baumert
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
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14
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Two-Year Follow-Up Analysis of Telaprevir-Based Antiviral Triple Therapy for HCV Recurrence in Genotype 1 Infected Liver Graft Recipients as a First Step towards Modern HCV Therapy. HEPATITIS RESEARCH AND TREATMENT 2016; 2016:8325467. [PMID: 27195149 PMCID: PMC4852367 DOI: 10.1155/2016/8325467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 03/08/2016] [Indexed: 12/15/2022]
Abstract
Objective. The introduction of protease inhibitors telaprevir and boceprevir in 2011 had extended the antiviral treatment options especially in genotype 1 infected hepatitis C relapsers and nonresponders to interferon/ribavirin therapy. The aim of this study was to analyze the long-term treatment efficiency of telaprevir-based triple therapy for patients with hepatitis C reinfection after orthotopic liver transplantation. Patients and Methods. We included 12 patients with histologically confirmed graft fibrosis due to hepatitis C reinfection. The treatment duration was scheduled as 12 weeks of telaprevir-based antiviral triple therapy followed by 36 weeks of dual therapy with pegylated interferon/ribavirin. The patients were followed up for two years after the end of triple therapy. Results. Of the 12 patients, 6 (50%) completed the full 48 weeks of antiviral treatment. An end of treatment response and a sustained virological response 52 weeks after the end of the antiviral treatment course were achieved in 8/12 (67%) and 7/12 (58%) patients, respectively. Conclusion. Telaprevir-based triple therapy was shown to be a long-term effective but complex treatment option for individual patients with hepatitis C graft. With the recent improvements in hepatitis C therapy options telaprevir may not be recommended as a standard therapy for this indication anymore.
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15
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Ajlan A, Al-Jedai A, Elsiesy H, Alkortas D, Al-Hamoudi W, Alarieh R, Al-Sebayel M, Broering D, Aba Alkhail F. Sofosbuvir-Based Therapy for Genotype 4 HCV Recurrence Post-Liver Transplant Treatment-Experienced Patients. Can J Gastroenterol Hepatol 2016; 2016:2872371. [PMID: 27446833 PMCID: PMC4904700 DOI: 10.1155/2016/2872371] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 11/10/2015] [Indexed: 12/20/2022] Open
Abstract
Background and Aim. This is an open label prospective cohort study conducted at a tertiary care hospital. The primary endpoint is SVR12 in patients treated with sofosbuvir-based therapy in post-liver transplant patients with genotype 4 HCV recurrence. Methodology. Thirty-six treatment-experienced liver transplant patients with HCV recurrence received sofosbuvir and ribavirin ± peginterferon. Results. We report here safety and efficacy data on 36 patients who completed the follow-up period. Mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. Mean baseline HCV RNA was 6.2 log10 IU/mL. The majority of patients had ≥ stage 2 fibrosis. Twenty-eight patients were treated with pegylated interferon plus ribavirin in addition to sofosbuvir for 12 weeks and the remaining were treated with sofosbuvir plus ribavirin only for 24 weeks. By week 4, only four (11.1%) patients had detectable HCV RNA. Of the 36 patients, 2 (5.5%) relapsed and one died (2.75%). Conclusion. Our results suggest that sofosbuvir + ribavirin ± pegylated interferon can be utilized successfully to treat liver transplant patients with HCV recurrence.
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Affiliation(s)
- A. Ajlan
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
| | - A. Al-Jedai
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
| | - H. Elsiesy
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - D. Alkortas
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
| | - W. Al-Hamoudi
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
- King Saud University, College of Medicine, Riyadh, Saudi Arabia
| | - R. Alarieh
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - M. Al-Sebayel
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - D. Broering
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - F. Aba Alkhail
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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16
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Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
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17
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Brown RS, O’Leary JG, Reddy KR, Kuo A, Morelli GJ, Burton JR, Stravitz RT, Durand C, Di Bisceglie AM, Kwo P, Frenette CT, Stewart TG, Nelson DR, Fried MW, Terrault NA. Interferon-free therapy for genotype 1 hepatitis C in liver transplant recipients: Real-world experience from the hepatitis C therapeutic registry and research network. Liver Transpl 2016; 22:24-33. [PMID: 26519873 PMCID: PMC5208040 DOI: 10.1002/lt.24366] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 09/29/2015] [Accepted: 10/21/2015] [Indexed: 12/13/2022]
Abstract
Recurrent infection with the hepatitis C virus (HCV) after liver transplantation (LT) is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon (IFN)-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition to IFN-free direct-acting antiviral (DAA) regimens. This article describes the experience with DAAs in the treatment of posttransplant genotype (GT) 1 HCV from a consortium of community and academic centers (Hepatitis C Therapeutic Registry and Research Network [HCV-TARGET]). Twenty-one of the 54 centers contributing to the HCV-TARGET consortium participated in this study. Enrollment criteria included positive posttransplant HCV RNA before treatment, HCV GT 1, and documentation of use of a simeprevir (SMV)/sofosbuvir (SOF) containing DAA regimen. Safety and efficacy were assessed. SVR was defined as undetectable HCV RNA 64 days or later after cessation of treatment. A total of 162 patients enrolled in HCV-TARGET started treatment with SMV+SOF with or without ribavirin (RBV) following LT. The study population included 151 patients treated with these regimens for whom outcomes and safety data were available. The majority of the 151 patients were treated with SOF and SMV alone (n = 119; 79%) or with RBV (n = 32; 21%), The duration of therapy was 12 weeks for most patients, although 15 patients received 24 weeks of treatment. Of all patients receiving SOF/SMV with or without RBV, 133/151 (88%) achieved sustained virological response at 12 weeks after therapy and 11 relapsed (7%). One patient had virological breakthrough (n = 1), and 6 patients were lost to posttreatment follow-up. Serious adverse events occurred in 11.9%; 3 patients (all cirrhotic) died due to aspiration pneumonia, suicide, and multiorgan failure. One experienced LT rejection. IFN-free DAA treatment represents a major improvement over prior IFN-based therapy. Broader application of these and other emerging DAA regimens in the treatment of posttransplant hepatitis C is warranted.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Paul Kwo
- Indiana University, Indianapolis, IN
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18
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Kim H, Lee KW, Yi NJ, Lee HW, Choi Y, Suh SW, Jeong J, Suh KS. Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation. J Korean Med Sci 2015; 30:1577-83. [PMID: 26539000 PMCID: PMC4630472 DOI: 10.3346/jkms.2015.30.11.1577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 07/29/2015] [Indexed: 11/20/2022] Open
Abstract
Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, ≥ moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.
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Affiliation(s)
- Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Suk-Won Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jaehong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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19
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Roche B, Coilly A, Roque-Afonso AM, Samuel D. Interferon-Free Hepatitis C Treatment before and after Liver Transplantation: The Role of HCV Drug Resistance. Viruses 2015; 7:5155-68. [PMID: 26404355 PMCID: PMC4584308 DOI: 10.3390/v7092864] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 09/09/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection progressing to cirrhosis within five years in 20% to 30% of them. Obtaining a sustained virological response (SVR) greatly improves overall and graft survival. Until 2011, standard antiviral therapy using PEGylated interferon (PEG-IFN) and ribavirin (RBV) was the only effective therapy, with an SVR rate around 30% in this setting. For patients infected with genotype 1, first generation NS3/4A protease inhibitors (PIs), boceprevir (BOC) or telaprevir (TVR), associated with PEG-IFN and RBV for 48 weeks have increased the SVR rates to 60% in non-transplant patients. However, tolerability and drug-drug interactions with calcineurin inhibitors (CNI) are both limiting factors of their use in the liver transplant setting. Over recent years, the efficacy of antiviral C therapy has improved dramatically using new direct-acting antiviral (DAA) agents without PEG-IFN and/or RBV, leading to SVR rates over 90% in non-transplant patients. Results available for transplant patients showed a better efficacy and tolerability and less drug-drug interactions than with first wave PIs. However, some infrequent cases of viral resistance have been reported using PIs or NS5A inhibitors pre- or post-LT that can lead to difficulties in the management of these patients.
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Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.
- Hepatinov, Villejuif, F-94800, France.
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.
- Hepatinov, Villejuif, F-94800, France.
| | - Anne-Marie Roque-Afonso
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France
- Hepatinov, Villejuif, F-94800, France
- AP-HP Hôpital Paul-Brousse, Laboratoire de Virologie, Villejuif F-94800, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.
- Hepatinov, Villejuif, F-94800, France.
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20
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Hüsing A, Kabar I, Schmidt HH, Heinzow HS. Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine. Int J Mol Sci 2015; 16:18033-53. [PMID: 26251895 PMCID: PMC4581234 DOI: 10.3390/ijms160818033] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 07/16/2015] [Accepted: 07/27/2015] [Indexed: 12/16/2022] Open
Abstract
Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.
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Affiliation(s)
- Anna Hüsing
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
| | - Iyad Kabar
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
| | - Hartmut H Schmidt
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
| | - Hauke S Heinzow
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
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21
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Verna EC, Saxena V, Burton JR, O'Leary JG, Dodge JL, Stravitz RT, Levitsky J, Trotter JF, Everson GT, Brown RS, Terrault NA. Telaprevir- and Boceprevir-based Triple Therapy for Hepatitis C in Liver Transplant Recipients With Advanced Recurrent Disease: A Multicenter Study. Transplantation 2015; 99:1644-51. [PMID: 25715116 PMCID: PMC4818984 DOI: 10.1097/tp.0000000000000629] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. METHODS The LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety. RESULTS Forty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation. CONCLUSIONS For LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.
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Affiliation(s)
- Elizabeth C Verna
- 1 Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University, New York, NY. 2 Division of Gastroenterology and Hepatology, University of California, San Francisco, CA. 3 Division of Gastroenterology and Hepatology, University of Colorado, Denver, Aurora, CO. 4 Division of Hepatology and Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 5 Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA. 6 Department of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
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22
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23
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Price JC, Terrault NA. Treatment of hepatitis C in liver transplant patients: interferon out, direct antiviral combos in. Liver Transpl 2015; 21:423-34. [PMID: 25604355 DOI: 10.1002/lt.24080] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Revised: 11/20/2014] [Accepted: 01/11/2015] [Indexed: 12/14/2022]
Abstract
Although chronic infection with hepatitis C virus (HCV) is the leading indication for liver transplantation in the United States, graft and patient survival rates are reduced because of HCV recurrence after transplant. Interferon-based antiviral treatment administered either before or after transplant to prevent or treat HCV recurrence, respectively, is limited because of poor tolerability and low efficacy. However, the treatment of HCV in the transplant setting is changing considerably with the availability of newer direct-acting antivirals and interferon-free regimens. This article will review the experience to date with treating HCV in the setting of cirrhosis and liver transplantation and will discuss the unique challenges encountered when this population is being treated.
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Affiliation(s)
- Jennifer C Price
- Department of Medicine, University of California San Francisco, San Francisco, CA
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Coilly A, Roche B, Duclos-Vallée JC, Samuel D. Management of post transplant hepatitis C in the direct antiviral agents era. Hepatol Int 2015; 9:192-201. [PMID: 25820797 DOI: 10.1007/s12072-015-9621-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 02/23/2015] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation. Viral recurrence occurs in all patients with detectable serum HCV RNA at the time of transplantation leading to cirrhosis in 20-30% of patients within 5 years. Viral eradication using antiviral therapy has been shown to improve patient and graft survival. Pegylated interferon (PEG-IFN) and ribavirin (RBV) antiviral therapy achieved SVR in around 30% of transplant recipients. In the non-transplant setting, first generation NS3/4 protease inhibitors, boceprevir or telaprevir associated with PEG-IFN and RBV, has improved the SVR rates to 75% in genotype 1 infected patients. However, tolerability and drug-drug interactions with calcineurin inhibitors are both limiting factors of their use in transplant recipients. In the non-transplant patients, using new direct-acting antiviral therapy has dramatically improved the efficacy of antiviral C therapy over recent years leading to SVR rates over 90% in phase II and III clinical trials, without PEG-IFN and/or RBV. Preliminary results in transplant patients showed better efficacy, better tolerability and less drug-drug interactions.
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Affiliation(s)
- Audrey Coilly
- Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, 12, Avenue Paul Vaillant-Couturier, 94800, Villejuif, France,
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Herzer K, Gerken G. Hepatitis C virus reinfection after liver transplant: New chances and new challenges in the era of direct-acting antiviral agents. World J Hepatol 2015; 7:532-538. [PMID: 25848476 PMCID: PMC4381175 DOI: 10.4254/wjh.v7.i3.532] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 10/21/2014] [Accepted: 12/17/2014] [Indexed: 02/06/2023] Open
Abstract
The first interferon-free regimens have been approved for the treatment of patients with chronic hepatitis C virus (HCV). In the liver transplant (LT) setting, these regimens are expected to have an important effect, because graft loss due to HCV recurrence is a serious problem after LT. The response to the hitherto conventional treatment with pegylated interferon and ribavirin is poor. The significantly better response rates achieved with boceprevir-based and telaprevir-based triple therapy have led to better graft and patient survival rates, but severe drug interactions with immunosuppressants limit the feasibility of this therapy for LT patients. With the approval of sofosbuvir in January 2014, of simeprevir in May 2014, and of daclatasvir in August 2014, three antiviral agents are now available and promise to be applicable without relevant adverse effects or negative interactions with immunosuppressants. Thus, 2014 marks the beginning of a new era of treatment options for HCV recurrence after LT. Although safety and efficacy studies of several interferon-free regimens for patients with HCV recurrence after LT have achieved good preliminary results, reports of clinical experiences with LT patients are scarce. The lack of randomized studies, the small number of enrolled and carefully selected patients, and the heterogeneity of these studies make the results questionable. Real-life experiences are eagerly awaited so that clinicians can estimate the usefulness and the pitfalls of these new regimens. Additionally, the high costs of these agents may limit their accessibility for many patients. The aim of this review is to summarize the current experience with and the expectations of the new direct-acting antiviral agents for LT patients.
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Saab S, Manne V, Bau S, Reynolds JA, Allen R, Goldstein L, Durazo F, El-Kabany M, Han S, Busuttil RW. Boceprevir in liver transplant recipients. Liver Int 2015; 35:192-7. [PMID: 24673728 DOI: 10.1111/liv.12548] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2014] [Accepted: 03/18/2014] [Indexed: 02/13/2023]
Abstract
BACKGROUND There has been increasing interest in using protease inhibitors with pegylated interferon and ribavirin to treat recurrent hepatitis C (HCV) disease in liver transplant recipients. METHODS We retrospectively evaluated the safety and efficacy in liver transplant recipients treated for recurrent hepatitis C genotype 1 with the combination of peginterferon, ribavirin and boceprevir. RESULTS Twenty liver transplant recipients were treated for recurrent hepatitis C. Baseline alanine aminotransferase, total bilirubin and HCV RNA values (± SD) were 67.5 (±50.9) mg/dl, 1.78 (±1.99) U/L, and 16 955 510 (±21 620 675) IU/ml. Anaemia was a common adverse event requiring epoetin in 16 of 20 recipients and ribavirin dose reductions in 17 of 20 recipients. One-third of recipients required a blood transfusion. Filgrastim was used in 11 of 20 patients (55%) and eltrombopag in two of 20 recipients (10%) over the course of treatment. Serum creatinine level increased significantly from a baseline value of 1.33 mg/dl to 1.59 mg/dl at week 20 of boceprevir (P < 0.005). The overall sustained viral response (SVR) was 50%. Of the 14 patients who had a viral load less than 1000 IU/ml at week 4 of boceprevir, the SVR was 71%. The SVR was 83% of the 11 patients who had undetectable viral levels at week 4 of boceprevir. CONCLUSIONS Antiviral therapy utilizing boceprevir in liver transplant recipients requires close monitoring. Anaemia and neutropenia were common requiring growth factors in most recipients. On-treatment viral responses appear promising but long-term data are needed.
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Affiliation(s)
- Sammy Saab
- Departments of Medicine, The University of California, Los Angeles, CA, USA; Departments of Surgery, The University of California, Los Angeles, CA, USA
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Coilly A, Roche B, Duclos-Vallée JC, Samuel D. Optimal therapy in hepatitis C virus liver transplant patients with direct acting antivirals. Liver Int 2015; 35 Suppl 1:44-50. [PMID: 25377540 DOI: 10.1111/liv.12728] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hepatitis C virus (HCV) end stage liver disease is a main indication for liver transplantation (LT). Recurrent HCV always occurs when patients are transplanted with a detectable viral load, leading to cirrhosis in 20-30% of patients within 5 years. Achieving a sustained virological response (SVR) with antiviral treatment is the only way to improve patient and graft survival. Dual therapy based on pegylated interferon and ribavirin (PEG-IFN/RBV) was the standard of care for many years with limited efficacy and a poor safety profile. The addition of first generation NS3/4 protease inhibitors (PI) improved SVR rates from 30 to 50-60%. But the occurrence of serious adverse events and drug-drug interactions with calcineurin inhibitors have both been limiting factors for their use during LT. The preliminary results of the use of second generation direct acting antivirals (DAA) in transplant patients showed better efficacy with an SVR rate >70%. The pre- and post-transplantation safety profile is good. Although fewer drug-drug interactions are expected, some new DAA still interact with immunosuppressive drugs. Certain questions such as the use of RBV or the optimal duration of therapy have still not been resolved but should be answered by the many ongoing studies in the coming year.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Univ. Paris-Sud, UMR-S 785, Villejuif, France; Inserm, Unité 785, Villejuif, France; Hepatinov, Villejuif, France
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Lens S, Mariño Z, Forns X. Efficacy of new direct acting antivirals in transplant recipients and patients with advanced disease. Dig Liver Dis 2014; 46 Suppl 5:S197-205. [PMID: 25458782 DOI: 10.1016/j.dld.2014.10.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 10/06/2014] [Indexed: 12/11/2022]
Abstract
The development of new direct acting antivirals constitutes a clinical revolution in the field of hepatitis C therapy and, most probably, in the history of Hepatology. Difficult-to-treat patients, such as cirrhotics or patients in the peri-transplant setting, will clearly benefit from these therapies, particularly from interferon-free all-oral combinations. However, despite the substantial improvement of the hepatitis C drug market, access to these therapies will likely be different around the world due to economic restrictions. This review aims to clarify the current stage of different antiviral strategies (with or without interferon) in these difficult populations by analysing specific efficacy and safety results in patients with cirrhosis, patients on the waiting list for liver transplantation and recipients with hepatitis C recurrence after liver transplantation. Hitherto, some important challenges still remain unanswered in these patients and will need to be assessed in clinical practice, such as the evaluation of safety and efficacy in advanced cirrhotic patients with portal hypertension, the impact (if any) of viral clearance on clinical outcomes in patients with decompensated liver disease, the role of ribavirin in all-oral combinations, the relevance of the development of multi-drug viral resistant strains and the drug-drug interaction profiles of these drugs, especially after liver transplantation.
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Affiliation(s)
- Sabela Lens
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain.
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Ho CM, Hu RH, Lee PH. Perspective of antiviral therapeutics for hepatitis C after liver transplantation. World J Pharmacol 2014; 3:193-198. [DOI: 10.5497/wjp.v3.i4.193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 09/22/2014] [Accepted: 10/10/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) almost recurs after liver transplantation for HCV-related liver cirrhosis or hepatocellular carcinoma. Management of HCV recurrence after liver transplantation is challenging because the traditional interferon-based therapy is often patient-intolerable and inducing cytopenia, and dose reduction is needed. The response rate in liver recipients is inferior to those of chronic HCV infection. About 5 percent of liver recipients receiving interferon-based therapy would develop immune-mediated graft injury and may need retransplantation. Recent advances of anti-HCV therapy for chronic HCV infection has evolutionary changing the schema from interferon-based, to interferon-free, and even to ribavirin -free, all oral combinations for pan-genotypes. Management of HCV recurrence after liver transplantation is currently evolving too and promising results will soon come to the stage. This “fast-track” concise review focuses on the issues relevant to HCV recurrence after liver transplantation and provides up-to-date information of the trend of the management. A real-world case demonstration of management was presented here to illustrate the potential complications of anti-HCV therapy after liver transplantation.
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Abstract
Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.
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Gambato M, Lens S, Navasa M, Forns X. Treatment options in patients with decompensated cirrhosis, pre- and post-transplantation. J Hepatol 2014; 61:S120-31. [PMID: 25443340 DOI: 10.1016/j.jhep.2014.07.020] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2014] [Revised: 07/03/2014] [Accepted: 07/11/2014] [Indexed: 12/21/2022]
Abstract
Interferon-based treatments have a poor safety profile and limited efficacy in patients with advanced liver disease and in patients with hepatitis C (HCV) recurrence after liver transplantation (LT). Despite the recent approval of the first interferon-free regimen, which will be followed by several other interferon-free combinations in 2014 and 2015, data in patients with advanced cirrhosis and hepatitis C after LT are still limited. One study has already proven the concept that graft HCV infection can be prevented in a significant proportion of patients by treating them with sofosbuvir and ribavirin while awaiting LT. Two interferon-free regimens have also demonstrated a high efficacy in patients with hepatitis C recurrence after transplantation. Before these treatment strategies can be implemented in clinical practice, a few issues need to be addressed: (1) safety and efficacy of new antivirals in patients with decompensated cirrhosis, (2) the impact of viral clearance on liver function, (3) the potential consequences of virological failure (and the selection of multi-drug resistant HCV strains) in patients with decompensated cirrhosis or with severe hepatitis C recurrence after LT, and (4) drug-drug interactions (DDI) profiles. Finally, in the transplant setting it is also relevant to learn which strategy is most cost-effective in minimizing the negative impact of hepatitis C: preventing graft infection by treating patients before transplantation or treating hepatitis C recurrence after LT.
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Affiliation(s)
- Martina Gambato
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Spain.
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Kakati B, Seetharam A. Hepatitis C Recurrence after Orthotopic Liver Transplantation: Mechanisms and Management. J Clin Transl Hepatol 2014; 2:189-96. [PMID: 26355427 PMCID: PMC4521242 DOI: 10.14218/jcth.2014.00016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 06/06/2014] [Accepted: 07/07/2014] [Indexed: 12/04/2022] Open
Abstract
Chronic Hepatitis C (HCV) infection is the leading indication for orthotopic liver transplantation and recurrence is nearly universal. Chronic HCV infection is frequently established through evasion of the innate immune system. Priming of adaptive immune responses modulate the severity and rate of fibrosis progression. Those with demonstrable viremia entering the transplant period uniformly suffer recurrence post-transplant. Progression to cirrhosis is accelerated post-transplant secondary to systemic immunosuppression. In addition, a number of factors, including donor, host, and viral characteristics, influence severity and rate of fibrosis progression. Interferon-based therapy, the previous standard of care, in those with advanced cirrhosis or post-transplant has been limited by a number of issues. These include a relative lack of efficacy and poor tolerability with higher incidence of infection and anemia. Recently, approval of direct acting antivirals have ushered in a new era in HCV therapeutics and have applicability in these special populations. Their use immediately prior to or post-transplant is expected to improve both morbidity and mortality.
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Affiliation(s)
- Bobby Kakati
- Banner Transplant and Advanced Liver Disease Center, Phoenix, AZ, USA
| | - Anil Seetharam
- Banner Transplant and Advanced Liver Disease Center, Phoenix, AZ, USA
- University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
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Faisal N, Yoshida EM, Bilodeau M, Wong P, Ma M, Burak KW, Al-Judaibi B, Renner EL, Lilly LB. Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience. Ann Hepatol 2014. [DOI: 10.1016/s1665-2681(19)31252-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
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Burton JR, O'Leary JG, Verna EC, Saxena V, Dodge JL, Stravitz RT, Levitsky J, Trotter JF, Everson GT, Brown RS, Terrault NA. A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy. J Hepatol 2014; 61:508-14. [PMID: 24801415 PMCID: PMC4394742 DOI: 10.1016/j.jhep.2014.04.037] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 04/21/2014] [Accepted: 04/24/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited. METHODS This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12). RESULTS The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p<0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8g/dl and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related. CONCLUSIONS The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.
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Affiliation(s)
- James R Burton
- University of Colorado, Denver, Aurora, CO, United States
| | | | | | - Varun Saxena
- University of California at San Francisco, San Francisco, CA, United States
| | - Jennifer L Dodge
- University of California at San Francisco, San Francisco, CA, United States
| | | | | | | | | | | | - Norah A Terrault
- University of California at San Francisco, San Francisco, CA, United States.
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Knapstein J, Wörns MA, Galle PR, Zimmermann T. Combination therapy with silibinin, pegylated interferon and ribavirin in a patient with hepatitis C virus genotype 3 reinfection after liver transplantation: a case report. J Med Case Rep 2014; 8:257. [PMID: 25047566 PMCID: PMC4110930 DOI: 10.1186/1752-1947-8-257] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Accepted: 06/11/2014] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Hepatitis C virus reinfection occurs universally after liver transplantation with accelerated cirrhosis rates of up to 30% within 5 years after liver transplantation. Management of hepatitis C virus reinfection is complicated by drug interactions and pre-treatment. Dual antiviral therapy with pegylated interferon and ribavirin only reaches sustained virological response rates of approximately 30% after liver transplantation. With the approval of the viral NS3/4A protease and NS5B ribonucleic acid -dependent ribonucleic acid polymerase inhibitors, combination therapy offers new therapeutic options resulting in considerably higher sustained virological response rates in the non-transplant setting. However, silibinin has also shown potent antiviral activity in non-responders to dual therapy. CASE PRESENTATION We report the first case of antiviral therapy with pegylated interferon and ribavirin in combination with silibinin post-liver transplantation in a 50-year-old Caucasian man with genotype 3 reinfection with prior non-response.Silibinin was administered at a dose of 20mg/kg/day intravenously for 2 weeks and continued orally for 47 weeks in combination with a 48-week pegylated interferon and ribavirin therapy (180μg/week and 800mg/day), which was started on day 8. Pegylated interferon and ribavirin doses were adapted to 135μg/week and 600mg/day. After 4 weeks of therapy, the viral load declined 6 log10 and became undetectable in week 6, resulting in a sustained virological response 24 weeks after the end of therapy.In general, antiviral therapy was well tolerated. Side effects included pruritus and anaemia leading to erythropoietin therapy. CONCLUSIONS Combination therapy with pegylated interferon, ribavirin and silibinin resulted in sustained virological response 24 weeks after the end of therapy in a patient reinfected with hepatitis C virus genotype 3 who was a prior non-responder after liver transplantation. Silibinin therapy may offer a new therapeutic option for patients reinfected with non-genotype 1 hepatitis C virus who have had a liver transplanted and are non-responders.
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Affiliation(s)
| | | | | | - Tim Zimmermann
- I, Department of Internal Medicine, Johannes Gutenberg-University, Langenbeckstraße 1, 55131 Mainz, Germany.
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Gambato M, Lens S, Fernández-Carrillo C, Alfaro I, Forns X. Viral hepatitis and liver transplantation: pathogenesis, prevention and therapy of recurrent disease. Dig Dis 2014; 32:538-44. [PMID: 25034286 DOI: 10.1159/000360831] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Cirrhosis secondary to hepatitis C virus infection is the leading cause of liver transplantation in most countries. Hepatitis C has an accelerated course after transplantation, and for this reason graft and patient survival are decreased in comparison with other indications of liver transplantation. The development of direct-acting antivirals has been a major step in the management of hepatitis C and in a few years from now the infection will be eradicated with the combination of oral drugs with a good safety profile. This will likely allow prevention of hepatitis C recurrence in most cases. Meanwhile, management of hepatitis C virus infection still relies on the combination of interferon, ribavirin and the first-generation protease inhibitors telaprevir and boceprevir.
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Affiliation(s)
- Martina Gambato
- Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain
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Bunchorntavakul C, Reddy KR. Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances. J Clin Transl Hepatol 2014; 2:124-33. [PMID: 26357623 PMCID: PMC4521260 DOI: 10.14218/jcth.2014.00002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 02/13/2014] [Accepted: 02/20/2014] [Indexed: 12/14/2022] Open
Abstract
Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - K. Rajender Reddy
- Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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Terrault N, Reddy KR, Poordad F, Curry M, Schiano T, Johl J, Shaikh O, Dove L, Shetty K, Millis M, Schiff E, Regenstein F, Barnes D, Barin B, Peters M, Roland M, Stock P. Peginterferon and ribavirin for treatment of recurrent hepatitis C disease in HCV-HIV coinfected liver transplant recipients. Am J Transplant 2014; 14:1129-35. [PMID: 24636466 DOI: 10.1111/ajt.12668] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 11/13/2013] [Accepted: 12/11/2013] [Indexed: 01/25/2023]
Abstract
Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage ≤ 1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapy ± dose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients.
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Affiliation(s)
- N Terrault
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA
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Comparing outcomes of donation after cardiac death versus donation after brain death in liver transplant recipients with hepatitis C: a systematic review and meta-analysis. Can J Gastroenterol Hepatol 2014; 28:103-8. [PMID: 24288695 PMCID: PMC4071895 DOI: 10.1155/2014/421451] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Liver transplantation (LT) using organs donated after cardiac death (DCD) is increasing due, in large part, to a shortage of organs. The outcome of using DCD organs in recipients with hepatits C virus (HCV) infection remains unclear due to the limited experience and number of publications addressing this issue. OBJECTIVE To evaluate the clinical outcomes of DCD versus donation after brain death (DBD) in HCV-positive patients undergoing LT. METHODS Studies comparing DCD versus DBD LT in HCV-positive patients were identified based on systematic searches of seven electronic databases and multiple sources of gray literature. RESULTS The search identified 58 citations, including three studies, with 324 patients meeting eligibility criteria. The use of DCD livers was associated with a significantly higher risk of primary nonfunction (RR 5.49 [95% CI 1.53 to 19.64]; P=0.009; I2=0%), while not associated with a significantly different patient survival (RR 0.89 [95% CI 0.37 to 2.11]; P=0.79; I2=51%), graft survival (RR 0.40 [95% CI 0.14 to 1.11]; P=0.08; I2=34%), rate of recurrence of severe HCV infection (RR 2.74 [95% CI 0.36 to 20.92]; P=0.33; I2=84%), retransplantation or liver disease-related death (RR 1.79 [95% CI 0.66 to 4.84]; P=0.25; I2=44%), and biliary complications. CONCLUSIONS While the literature and quality of studies assessing DCD versus DBD grafts are limited, there was significantly more primary nonfunction and a trend toward decreased graft survival, but no significant difference in biliary complications or recipient mortality rates between DCD and DBD LT in patients with HCV infection. There is insufficient literature on the topic to draw any definitive conclusions.
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Coilly A, Roche B, Duclos-Vallée JC, Samuel D. Management of HCV transplant patients with triple therapy. Liver Int 2014; 34 Suppl 1:46-52. [PMID: 24373078 DOI: 10.1111/liv.12406] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection. Between 20 and 30% of patients have developed cirrhosis at 5 years post-LT. The outcome of transplant patients with cirrhosis on the graft is severe, with a rate of decompensation at 1 year of approximately 40%. To date, retransplantation is the only option in patients with decompensated liver disease. Until 2011, standard antiviral therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV), was the only effective therapy. Obtaining a sustained virological response (SVR) in patients with LT greatly improves overall and graft survival but this only occurs in 30% of transplanted patients. Direct acting antivirals (DAAs) such as protease inhibitors (PI), polymerase or other non-structural proteins inhibitors represent a new era in HCV associated liver disease. Although their use in the field of LT will certainly be essential there are some limitations because of safety and tolerance. One limitation is the potential interaction with calcineurin inhibitors. We describe the results of triple therapy with boceprevir (BOC) or telaprevir (TVR) for efficacy and safety and comment on future therapeutic strategies in liver transplant recipients.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Univ Paris-Sud, UMR-S 785, Villejuif, France; Inserm, Unité 785, Villejuif, France; Hepatinov, Villejuif, France
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Shetty S, Adams DH, Hubscher SG. Post-transplant liver biopsy and the immune response: lessons for the clinician. Expert Rev Clin Immunol 2014; 8:645-61. [DOI: 10.1586/eci.12.65] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience. J Hepatol 2014; 60:78-86. [PMID: 23994384 DOI: 10.1016/j.jhep.2013.08.018] [Citation(s) in RCA: 166] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2013] [Revised: 07/16/2013] [Accepted: 08/15/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge. METHODS This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%). RESULTS Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p=0.24). Treatment was discontinued in sixteen patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir. CONCLUSIONS Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.
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Abstract
There is a growing need for kidney and liver transplants in persons living with HIV. Fortunately, with the significant advances in antiretroviral therapy and management of opportunistic infections, HIV infection is no longer an absolute contraindication for solid organ transplantation. Data from several large prospective multi-center cohort studies have shown that solid organ transplantation in carefully selected HIV-infected individuals is safe. However, significant challenges have been identified including prevention of acute rejection, management of drug-drug interactions and treatment of recurrent viral hepatitis. This article reviews the selection criteria, outcomes, and special management considerations for HIV-infected patients undergoing liver or kidney transplantation.
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The prediction of immunological dysfunction during antiviral therapy for HCV after liver transplantation: can we improve outcomes? Hepatol Int 2013. [PMID: 26202024 DOI: 10.1007/s12072-013-9474-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Agarwal K, Barnabas A. Treatment of chronic hepatitis C virus infection after liver transplantation. Dig Liver Dis 2013; 45 Suppl 5:S349-54. [PMID: 24091115 DOI: 10.1016/j.dld.2013.07.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2013] [Accepted: 07/01/2013] [Indexed: 12/11/2022]
Abstract
Chronic hepatitis C virus infection is a leading cause of end stage liver disease and one of the leading indications for liver transplantation. Furthermore, hepatitis C virus recurrence is universal post-transplant leading to decreased graft and patient survival. Recurrent disease related to hepatitis C virus can lead to between 20 and 30% of patients developing recurrent cirrhosis within 5 years. Treatment options with antiviral therapy are limited and are associated with a significant side-effect profile, suboptimal tolerability and inferior response rates. Attention has therefore turned to strategies that can reduce hepatitis C virus recurrence rates post-transplant. Approximately only 30% of patients will achieve a sustained virologic response with current therapy with pegylated interferon and ribavirin. Successful hepatitis C virus eradication is the only factor associated with improved graft and patient survival post liver transplantation. Here we provide an overview of antiviral treatment in patients in the transplant arena and the potential opportunities and challenges with the introduction of new directly acting antivirals in G1 patients.
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Affiliation(s)
- Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK.
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Tamè M, Buonfiglioli F, Del Gaudio M, Lisotti A, Cecinato P, Colecchia A, Azzaroli F, D’Errico A, Arena R, Calvanese C, Quarneti C, Ballardini G, Pinna AD, Mazzella G. Long-term leukocyte natural α-interferon and ribavirin treatment in hepatitis C virus recurrence after liver transplantation. World J Gastroenterol 2013; 19:5278-5285. [PMID: 23983430 PMCID: PMC3752561 DOI: 10.3748/wjg.v19.i32.5278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2013] [Revised: 04/17/2013] [Accepted: 07/05/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effect of long-term treatment with leukocyte natural α-interferon (ln-α-IFN) plus ribavirin (RBV).
METHODS: Forty-six patients with hepatitis C virus (HCV) recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo; then, patients with good tolerability (n = 30) were switched to daily IFN administration, while the remaining were treated with the same schedule. Patients have been treated for 12 mo after viral clearance while non-responders (NR) entered in the long-term treatment group. Liver biopsies were planned at baseline, 1 year after sustained virological response (SVR) and at 36 mo after start of therapy in NR. MedCalc software package was used for statistical analysis.
RESULTS: About 16.7% of genotype 1-4 and 70% of genotype 2-3 patients achieved SVR. Nine patients withdrew therapy because of non-tolerance or non-compliance. A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated; 100% of patients with SVR achieved a histological response (fibrosis stabilization or improvement) with a significant reduction in mean staging value (from 2.1 to 1.0; P = 0.0031); histological response was observed in 84% of long-term treated patients compared to 57% of drop-out. Six patients died during the entire study period (follow-up 40.6 ± 7.7 mo); of them, 5 presented with severe HCV recurrence on enrollment. Diabetes (OR = 0.38, 95%CI: 0.08-0.59, P = 0.01), leukopenia (OR = 0.54, 95%CI: 0.03-0.57, P = 0.03) and severe HCV recurrence (OR = 0.51, 95%CI: 0.25-0.69, P = 0.0003) were variables associated to survival. Long-term treatment was well tolerated; no patients developed rejection or autoimmune disease.
CONCLUSION: Long-term treatment improves histology in SVR patients and slows disease progression also in NR, leading to a reduction in liver decompensation, graft failure and liver-related death.
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Safety and efficacy of peginterferon-α2a plus ribavirin treatment in renal transplant recipients with chronic hepatitis C. J Hepatol 2013; 58:1096-103. [PMID: 23428875 DOI: 10.1016/j.jhep.2013.02.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2012] [Revised: 01/16/2013] [Accepted: 02/04/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Interferon (IFN)-based therapy in chronic hepatitis C virus (HCV)-infected renal transplant (RT) recipients has been associated with a high risk of acute allograft rejection (AAR) and poor efficacy. We assessed the safety and efficacy of PegIFNα-2a and ribavirin (RBV) combination therapy in HCV-infected RT recipients. METHODS Thirty-two adult RT recipients of >12-month duration, infected with HCV genotypes 1 (62.5%) and 4 (37.5%), and significant fibrosis (Metavir ≥ F2) were recruited in an open-label trial with PegIFNα-2a 135-180 μg/week, plus RBV 200-1200 mg/day for 48 weeks, based on the estimated glomerular filtration rate. Safety assessments were performed weekly for 4 weeks, 2-weekly for 8 weeks, and 6-weekly for 36 weeks. Study end points were sustained virologic response (SVR) or development of AAR. Allograft biopsies were performed for 20% increase in creatinine from pretreatment levels, or optionally at week 12 on surveillance protocol. Renal safety was compared with matched untreated historical controls (n=31). RESULTS None of the treated patients showed AAR when biopsied for raised creatinine (12.5%) or during surveillance (37.5%), with incremental and sustained creatinine increases occurring in 6.3% of treated patients and 16.1% of untreated controls (p=0.148), by week 72 assessment. Mean pretreatment and end-of-assessment creatinine in treated patients remained similar (106.8 ± 32.0 vs. 113.4 ± 62.8, respectively; p=0.140), while levels increased significantly in the controls (106.6 ± 35.6 vs. 142.5 ± 93.0, respectively; p=0.013). Rapid, early virologic response (EVR) and SVR occurred in 12.5%, 56.3%, and 37.5% of cases, respectively. SVR was similar in both genotypes (p=1.000). PegIFN and RBV dose reductions were required in 34.4% and 78.1%, respectively; discontinuation was required in 12.5%. Binary logistic regression identified only EVR (OR, 20.4; 95% CI: 2.2-192.6; p=0.008) as an independent predictor of SVR. CONCLUSIONS PegIFN/RBV therapy is not associated with AAR in RT recipients at low risk for rejection but has modest efficacy in the treatment of HCV.
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Berenguer M, Schuppan D. Progression of liver fibrosis in post-transplant hepatitis C: mechanisms, assessment and treatment. J Hepatol 2013; 58:1028-41. [PMID: 23262248 DOI: 10.1016/j.jhep.2012.12.014] [Citation(s) in RCA: 118] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Revised: 12/10/2012] [Accepted: 12/10/2012] [Indexed: 12/12/2022]
Abstract
Liver fibrosis results from an excessive wound healing response in most chronic liver diseases, such as hepatitis C. Despite great advances in antiviral therapy in recent years, progressive liver fibrosis remains a major problem for patients with recurrent hepatitis C after liver transplantation. Liver biopsy remains a central tool in the management of HCV-positive liver transplant recipients, but reliable non-invasive methods for the assessment of liver fibrosis, such as ultrasound elastography, are increasingly being incorporated in the management of post-transplant patients, helping predict prognosis, guide treatment decisions, and stratify patients for emerging antifibrotic therapies. In this manuscript, we will review the natural history as well as tools to monitor fibrosis progression in the HCV-positive liver transplant recipient, the mechanisms underlying rapid fibrosis progression in up to 30% of these patients, the effect of antiviral therapies and highlight promising antifibrotic approaches.
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Affiliation(s)
- Marina Berenguer
- University Valencia, Dept. of Medicine, Hepatology & Liver Transplantation Unit, La Fe Hospital and CIBEREHD, National Network Center for Hepatology and Gastroenterology Research, Instituto de Salud Carlos III, Spain.
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