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Hashem M, Medhat MA, Abdeltawab D, Makhlouf NA. Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time? World J Transplant 2024; 14:90382. [PMID: 38947961 PMCID: PMC11212581 DOI: 10.5500/wjt.v14.i2.90382] [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: 12/01/2023] [Revised: 02/29/2024] [Accepted: 04/12/2024] [Indexed: 06/13/2024] Open
Abstract
Liver transplantation (LT) provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma. Despite the increasing number of liver transplants performed each year, the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality. Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates. Nevertheless, further strategies can be implemented to increase the pool of potential donors in deceased donor LT, such as reducing the rate of organ discards. Utilizing hepatitis C virus (HCV) seropositive liver grafts is one of the expanded donor organ criteria. A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients. Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation. The American Society of Transplantation advises against performing transplants from HCV-infected liver donors (D+) into HCV-negative recipient (R-) unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants. Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is important. National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.
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Affiliation(s)
- Mai Hashem
- Fellow of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut 71515, Egypt
| | - Mohammed A Medhat
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Doaa Abdeltawab
- Department of Tropical Medicine and Gastroenterology, Al-Rajhi Liver Hospital, Assiut University, Assiut 71515, Egypt
| | - Nahed A Makhlouf
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
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Coilly A, Sebagh M, Fougerou-Leurent C, Pageaux GP, Leroy V, Radenne S, Silvain C, Lebray P, Houssel-Debry P, Cagnot C, Rossignol E, Danjou H, Veislinger A, Samuel D, Duclos-Vallée JC, Dumortier J. HCV eradication does not protect from fibrosis progression in patients with fibrosing cholestatic hepatitis after liver transplantation. Clin Res Hepatol Gastroenterol 2022; 46:102024. [PMID: 36122871 DOI: 10.1016/j.clinre.2022.102024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 09/05/2022] [Accepted: 09/11/2022] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Hepatitis C virus (HCV) may recur after liver transplantation (LT) in the severe form of fibrosing cholestatic hepatitis (FCH). The prognosis dramatically improved by the use of direct acting antivirals (DAAs). The aim of the present study was to describe the change in histological features of FCH after virological eradication. METHODS From the ANRS CUPILT cohort we included 17 patients who presented FCH and at least two graft biopsies, one before DAA-treatment and one after. A single expert pathologist, blinded for clinical outcome, retrospectively confirmed the diagnosis of FCH and progression of fibrosis. RESULTS Diagnosis of FCH was made after a median [IQR] 6.0 [3.1-11.8] months after LT, and the median interval between diagnosis and onset of treatment was 1.2 [0.7-6.1] months. The rate of viral eradication was 94.1%. The median delay between the pre-treatment and the treatment biopsies was 12.5 [11.1-20.0] months. Between the end of treatment and the second biopsy, the delay was 5.3 [0.6-7.4] months. Fibrosis stage worsened in 10 patients (58.8%); 6 patients had cirrhosis (35.3%). Chronic rejection appeared in 4 (23.5%) patients. CONCLUSION Our results suggest that, despite viral eradication in patients presenting FCH after LT, fibrosis progression was observed in half of patients. This should encourage monitoring fibrosis progression despite HCV cure.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire; Université Paris-Saclay, UMR-S 1193; Inserm Unité 1193; FHU Hepatinov, Villejuif 94800, France.
| | - Mylène Sebagh
- AP-HP Hôpital Bicêtre, Service d'Anatomie Pathologique, Kremlin-Bicêtre, France
| | - Claire Fougerou-Leurent
- Rennes University Hospital, Unit of Clinical Pharmacology; INSERM Clinical Investigation Centre 1414, Rennes, France
| | - Georges-Philippe Pageaux
- CHU Saint-Eloi, Département D'hépato-Gastroentérologie et de Transplantation Hépatique, Université Montpellier 1, Montpellier, France
| | - Vincent Leroy
- CHU de Grenoble, Pôle Digidune, Clinique Universitaire d'Hépato-Gastroentérologie; Unité INSERM /Université Grenoble Alpes U823, IAPC Institut Albert Bonniot, Grenoble, France
| | - Sylvie Radenne
- Hospices Civils de Lyon, Hôpital de la Croix Rousse, Service d'Hépato-gastroentérologie, Lyon, France
| | - Christine Silvain
- Département d'Hépato-gastroentérologie, CHU de Poitiers, Pôle Biologie Santé, Poitiers EA 4331, France
| | - Pascal Lebray
- AP-HP, Departement d'hépatologie et de Gastroenterologie, Groupe Hospitalier Pitié-Salpétrière, Université Pierre et Marie Curie Paris 6, Paris, France
| | | | - Carole Cagnot
- Unit for Basic and Clinical Research on Viral Hepatitis, ANRS (France Recherche Nord&sud Sida-hiv Hépatites), Paris, France
| | - Emilie Rossignol
- Rennes University Hospital, Unit of Clinical Pharmacology; INSERM Clinical Investigation Centre 1414, Rennes, France
| | - Hélène Danjou
- Rennes University Hospital, Unit of Clinical Pharmacology; INSERM Clinical Investigation Centre 1414, Rennes, France
| | - Aurélie Veislinger
- Rennes University Hospital, Unit of Clinical Pharmacology; INSERM Clinical Investigation Centre 1414, Rennes, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire; Université Paris-Saclay, UMR-S 1193; Inserm Unité 1193; FHU Hepatinov, Villejuif 94800, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire; Université Paris-Saclay, UMR-S 1193; Inserm Unité 1193; FHU Hepatinov, Villejuif 94800, France
| | - Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Hépato-gastroentérologie, Université Claude Bernard Lyon 1, Pavillons D et L, 69437, Lyon Cedex 03, France.
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Kuntzen C, Bagha Z. The Use of Hepatitis C Virus-Positive Organs in Hepatitis C Virus-Negative Recipients. Clin Liver Dis 2022; 26:291-312. [PMID: 35487612 DOI: 10.1016/j.cld.2022.01.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The use of hepatitis C virus (HCV) -positive organs in HCV-negative recipients with posttransplant antiviral treatment has increasingly been studied since the introduction of new direct-acting antivirals. This article reviews existing experience in liver and kidney transplant. Fifteen studies with 218 HCV D+/R- liver transplants, with 182 from viremic donors, show a sustained viral response for 12 weeks (SVR12) rate of 99.5%. Nine studies involving 204 HCV donor-positive recipient-negative kidney transplant recipients had an SVR12 rate of 99.5%. Complications are infrequent. Preemptive treatment in kidney transplant of for only 4 weeks or even 4 days showed surprising success rates.
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Affiliation(s)
- Christian Kuntzen
- Hofstra University at Northwell Health, 300 Community Drive, Manhasset, NY 11030, USA.
| | - Zohaib Bagha
- Hofstra University at Northwell Health, 300 Community Drive, Manhasset, NY 11030, USA
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4
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Hanif FM, Majid Z, Luck NH, Tasneem AA, Laeeq SM, Mubarak M. Revolution in the diagnosis and management of hepatitis C virus infection in current era. World J Hepatol 2022; 14:647-669. [PMID: 35646260 PMCID: PMC9099099 DOI: 10.4254/wjh.v14.i4.647] [Citation(s) in RCA: 1] [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: 08/15/2021] [Revised: 02/05/2022] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is a major global public health problem, particularly in developing part of the world. Significant advances have been made in the early diagnosis and treatment of the disease. Its management has been particularly revolutionized during the past two decades. In this review, we summarize the major advances in the diagnostic and management armamentarium for chronic HCV infection. The focus of the present review is on the newer directly acting anti-viral agents, which have revolutionized the management of chronic HCV infection. Management of uncomplicated chronic HCV infection and of specific complications and special at-risk populations of patients will be covered in detail. Despite the advent and approval of highly effective and well tolerable oral agents, still many challenges remain, particularly the affordability, the equitable distribution and access to later drugs. The World Health Organization aims to eliminate viral hepatitis including HCV by 2030 since its poses a major public health threat. There is an urgent need to ensure uniform and early access to diagnostic and therapeutic facilities throughout the world if the later goal has to be realized.
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Affiliation(s)
- Farina M Hanif
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Zain Majid
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Nasir Hassan Luck
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Abbas Ali Tasneem
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Syed Muddasir Laeeq
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation , Karachi 74200, Sindh, Pakistan
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5
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Elzorkany K, Kora MAE, Wahed ASA, Zaghla HES, Zahran AM, Yassein YS, El Naggar AZ, Essa A, Gadallah AA. Assessment of Renal Function in Post-Liver Transplant HCV-Positive Patients Treated with Direct Acting Antivirals. Int J Nephrol Renovasc Dis 2020; 13:351-358. [PMID: 33273842 PMCID: PMC7705253 DOI: 10.2147/ijnrd.s275721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/21/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose Direct acting antiviral agents (DAAs) have greatly improved the clearance of hepatitis C virus (HCV) infection. The effect of DAAs on renal function in post-liver transplant HCV-positive patients remains questionable, especially considering the possibility of drug interactions between immunosuppressants and DAAs. Patients and methods A retrospective observational study included 84 post-liver transplant patients with HCV infection. Patients were divided into two groups: group I received sofosbuvir plus ribavirin for 24 weeks, group II received sofosbuvir plus daclatasvir for 12 weeks. Laboratory data and eGFR were determined before, at the end, and 6 months after completion of treatment. Results The treatment was well tolerated with 100% sustained virologic response (SVR 12). There was no statistically significant difference between the two groups regarding clinical and laboratory data before treatment. Mean eGFR significantly reduced from 87.36 mL/min to 76.16 mL/min in group I (P=0.001). However, within 6 months after treatment, mean eGFR recovered to 81.51 mL/min, which was not significant when compared to baseline eGFR (P=0.09). Mean eGFR in group II showed non-significant change. There were no significant changes in immunosuppressive drug levels and eGFR in either group of patients, who received either ciclosporin or tacrolimus before and at the end of treatment. Conclusion DDAs in post-liver transplant patients with HCV infection were well tolerated and associated with stable renal function. Moreover, sofosbuvir plus daclatasvir regimen showed relatively better renal safety compared to sofosbuvir plus ribavirin.
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Affiliation(s)
- Khaled Elzorkany
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt.,Internal Medicine Department, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mahmoud Abd-Elaziz Kora
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | - Aliaa Sabry Abdel Wahed
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt
| | - Hassan El-Sayed Zaghla
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt
| | - Ahmed Mohamed Zahran
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | - Yassein Salah Yassein
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | | | - Abdallah Essa
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
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Kapila N, Menon KVN, Al-Khalloufi K, Vanatta JM, Murgas C, Reino D, Ebaid S, Shaw JJ, Agrawal N, Rhazouani S, Navas V, Sheffield C, Rahman AU, Castillo M, Lindenmeyer CC, Miller C, Quintini C, Zervos XB. Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience. Hepatology 2020; 72:32-41. [PMID: 31659775 DOI: 10.1002/hep.31011] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 10/22/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.
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Affiliation(s)
- Nikhil Kapila
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL.,Department of Gastroenterology and Hepatology, Duke University, Durham, NC
| | | | | | - Jason M Vanatta
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Carla Murgas
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Diego Reino
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Samer Ebaid
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Joshua J Shaw
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Neerja Agrawal
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Salwa Rhazouani
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Viviana Navas
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | | | - Asad Ur Rahman
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL
| | | | | | - Charles Miller
- Department of Transplant, Cleveland Clinic, Cleveland, OH
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7
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Kapila N, Al-Khalloufi K, Bejarano PA, Vanatta JM, Zervos XB. Fibrosing cholestatic hepatitis after kidney transplantation from HCV-viremic donors to HCV-negative recipients: A unique complication in the DAA era. Am J Transplant 2020; 20:600-605. [PMID: 31448549 DOI: 10.1111/ajt.15583] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 08/09/2019] [Accepted: 08/11/2019] [Indexed: 01/25/2023]
Abstract
Fibrosing cholestatic hepatitis (FCH) posttransplantation can lead to graft failure and death. In the era of direct acting antiviral therapy (DAA), several studies have demonstrated the efficacy and safety of transplanting hepatitis C virus (HCV)-positive allografts into HCV-negative recipients. In this case series, we present two cases of HCV-negative recipients who underwent kidney transplantation from viremic donors and developed FCH. Both patients presented after transplant with abnormal liver function tests and HCV viral loads of greater than 100 000 000 IU/mL. FCH was diagnosed by histology and/or clinical data. Both patients were started on DAA therapy within 24 hours of admission with improvement in LFTs. One patient has undetectable HCV 12 weeks after completing treatment and the other patient has undetectable HCV after completing DAA treatment. The introduction of DAAs has changed the landscape of solid organ transplantation with the potential to expand the donor pool and increase access to organs. While HCV viremic organs have tremendous potential to increase access to a scarce resource, FCH is a potentially fatal complication and therefore clinicians must maintain a high index of suspicion for this unique complication.
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Affiliation(s)
- Nikhil Kapila
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, Florida.,Division of Transplant Hepatology, Duke University, Durham, North Carolina
| | | | - Pablo A Bejarano
- Department of Pathology, Cleveland Clinic Florida, Weston, Florida
| | - Jason M Vanatta
- Department of Transplant, Cleveland Clinic Florida, Weston, Florida
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Wu SH, Loong CC, Chu CJ, Su CW, Lin CC, Hsia CY, Liu C, Lee SD, Wang YJ, Lee FY, Linb NC, Chen CY, Huang YH, Hou MC. Highly effective treatment response and well tolerability by all oral direct acting antivirals for chronic hepatitis C patients post organ transplantation. J Chin Med Assoc 2020; 83:18-24. [PMID: 31714442 DOI: 10.1097/jcma.0000000000000222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.
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Affiliation(s)
- Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yuan Hsia
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chinsu Liu
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Niang-Cheng Linb
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Cheng-Yen Chen
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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9
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Ekpanyapong S, Reddy KR. Hepatitis C virus therapy in advanced liver disease: Outcomes and challenges. United European Gastroenterol J 2019; 7:642-650. [PMID: 31210942 PMCID: PMC6545711 DOI: 10.1177/2050640619840149] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/26/2019] [Indexed: 01/06/2023] Open
Abstract
While for many years investigators had worked on highly effective direct-acting antiviral agent (DAA) therapy, we are now encountering challenges on the appropriate timing of DAA therapy in patients with decompensated cirrhosis. Improvement in hepatic function and quality of life can be achieved following successful therapy but not in all patients. Predictors of improvement or failure to improve have been noted but these are currently not robust enough to ubiquitously apply them to clinical practice. The lowest probability of improvement in hepatic function and avoidance of Model for End-stage Liver Disease (MELD) "purgatory" appears to be in those with MELD >20 while the more likely scenario of improvements is in those with MELD <15. Ideally, patients with a MELD score >20 should be transplanted first and treated for hepatitis C virus (HCV) infection after liver transplantation (LT). Those with MELD score <15 should be considered readily for treatment while in those with MELD of 15-20, treatment has to be individualized with full discussion of the pros and cons of treating them pre- or post-LT. However, it is to be appreciated that the majority of patients with decompensated cirrhosis across the world may not be eligible for liver transplant or may not have access to LT; thus, these patients should be considered for HCV therapy with the hope and expectation that they still gain variable degrees of benefit from successful DAA therapy.
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Affiliation(s)
- Sirina Ekpanyapong
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA
| | - K Rajender Reddy
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, USA
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10
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Al-Judaibi B, Thomas B, Wong P, Benmassaoud A, Chen JH, Dokus MK, Hussaini T, Bilodeau M, Burak KW, Marotta P, Yoshida EM. Sofosbuvir-Based Therapy in the Pre-Liver Transplant Setting: The Canadian National Experience. Ann Hepatol 2019; 17:437-443. [PMID: 29735784 DOI: 10.5604/01.3001.0011.7388] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transplant eligible patient populations is unknown. The aim of this study was to assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate short term changes in liver function and the effect on their liver transplant status. MATERIAL AND METHODS A retrospective multicenter Canadian study of liver transplant candidates with advanced HCV cirrhosis treated with SOF-based therapy. Outcomes included sustained virologic response (SVR), and liver transplant status. RESULTS 105 liver transplant candidates with advanced liver disease due to HCV were evaluated. The overall SVR was 83.8%. Hepatocellular carcinoma was diagnosed in 39 (37.1%) prior to transplant evaluation. In short term follow-up, 14 (13.3%) remained active on the list at the time of SVR12, 22 (20.9%) patients underwent liver transplantation, 7 (6.6%) patients were deactivated due to clinical improvement, 3 patients were delisted, and 10 deaths were reported. CONCLUSIONS SOF-based therapy for patients progressing to liver transplantation leads to high SVR rates, short term stability in liver function, and deactivation from the transplant list .
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Affiliation(s)
- Bandar Al-Judaibi
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine and Dentistry at the University of Western Ontario, London, Canada
| | - Benson Thomas
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine and Dentistry at the University of Western Ontario, London, Canada
| | - Philip Wong
- Department of Medicine, Division of Gastroenterology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada
| | - Amine Benmassaoud
- Department of Medicine, Division of Gastroenterology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Canada
| | - Jo-Hua Chen
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada
| | - M Katherine Dokus
- Department of Medicine, Division of Gastroenterology, University of Rochester, Rochester, New York, United States of America
| | - Trana Hussaini
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada
| | - Marc Bilodeau
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, Canada
| | - Kelly W Burak
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, Alberta, Canada
| | - Paul Marotta
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine and Dentistry at the University of Western Ontario, London, Canada
| | - Eric M Yoshida
- Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, Canada
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11
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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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12
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Xue W, Liu K, Qiu K, Shen Y, Pan Z, Hu P, Peng M, Chen M, Ren H. A systematic review with meta-analysis: Is ribavirin necessary in sofosbuvir-based direct-acting antiviral therapies for patients with HCV recurrence after liver transplantation? Int J Infect Dis 2019; 83:56-63. [PMID: 30959250 DOI: 10.1016/j.ijid.2019.03.038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 03/29/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after liver transplantation (LT). Whether ribavirin (RBV) is needed by patients after LT in combination with SOF-based DAAs remains to be determined. This meta-analysis was conducted to evaluate the necessity of RBV with SOF-based DAAs for post-LT patients. METHODS PubMed, Web of Science, Cochrane Library and EMBASE databases were systematically searched for eligible studies from the databases' inceptions until November 2018. We accepted the studies that included HCV recurrence in post-LT patients who were treated with SOF-based DAAs ± RBV, and evaluated the rate of sustained virological response 12 weeks (SVR12) after the end of treatment. RESULTS Twelve studies, comprising a total of 1466 LT recipients, were included in this study. The pooled SVR12 of these patients was 91% (95% CI: 84% to 95%). There was no statistical difference of SVR12 in the patients treated with SOF-based DAAs + RBV versus -RBV group (risk ratio [RR] = 0.97; 95% CI: 0.92 to 1.03; P = 0.35) by different therapy duration (P = 0.26), with different targets of DAAs (P = 0.13) and in different regions (P = 0.34) but a tendency for a higher incidence of anemia in the +RBV group than in the -RBV group (RR = 5.18; 95% CI: 3.41 to 7.86; p < 0.00001). CONCLUSION The addition of RBV may not contribute to a higher SVR rate and could increase the incidence of anemia, so RBV is not necessary in SOF-based DAAs for patients with HCV recurrence after LT.
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Affiliation(s)
- Wei Xue
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kai Liu
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Medical Laboratory, The People's Hospital of Leshan, Leshan, China
| | - Ke Qiu
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; West China Hospital, Sichuan University, Chengdu, China
| | - Yanxi Shen
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhaojun Pan
- Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Hong Ren
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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13
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Shoreibah M, Romano J, Sims OT, Guo Y, Jones D, Venkata K, Kommineni V, Orr J, Fitzmorris P, Massoud OI. Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients. J Clin Transl Hepatol 2018; 6:391-395. [PMID: 30637216 PMCID: PMC6328736 DOI: 10.14218/jcth.2018.00026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 06/17/2018] [Accepted: 06/23/2018] [Indexed: 12/13/2022] Open
Abstract
Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment. Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin. Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18). Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.
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Affiliation(s)
- Mohamed Shoreibah
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John Romano
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
- *Correspondence to: John Romano, Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, BDB 327, 1808 7 Ave South, Birmingham, AL 35233, USA. Tel: +1-3156574626, E-mail:
| | - Omar T. Sims
- Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
- Center for AIDS Research, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Yuqi Guo
- School of Social Work, University of Alabama, Tuscaloosa, AL, USA
| | - DeAnn Jones
- Department of Pharmacology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Krishna Venkata
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Vishnu Kommineni
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jordan Orr
- Division of Gastroenterology and Hepatology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Paul Fitzmorris
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Omar I. Massoud
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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14
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Gambato M, Gregori J, Quer J, Koutsoudakis G, González P, Caro-Pérez N, García-Cehic D, García-González N, González-Candelas F, Esteban JI, Crespo G, Navasa M, Forns X, Pérez-Del-Pulgar S. Hepatitis C virus intrinsic molecular determinants may contribute to the development of cholestatic hepatitis after liver transplantation. J Gen Virol 2018; 100:63-68. [PMID: 30451649 DOI: 10.1099/jgv.0.001175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild hepatitis C recurrence) by deep pyrosequencing. At the time of LT, NS5B quasispecies complexity was similar between the two groups but, after LT, it decreased more sharply in CHC patients than in the control group. Interestingly, the major variant before LT propagated efficiently and remained as the dominant sequence after LT in 62 % of CHC patients versus 11 % of controls (P=0.031). Sequence analysis of the complete non-structural region in a limited number of patients revealed a potential 12 aa signature specific to the CHC group. These data suggest that intrinsic molecular determinants in the circulating HCV quasispecies may provide a fitness advantage, contributing to the development of CHC.
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Affiliation(s)
- Martina Gambato
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.,2Multivisceral Transplant Unit and Gastroenterology, Padova University Hospital, Padova, Italy.,†Present address: Multivisceral Transplant Unit and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Josep Gregori
- 3Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain.,4Roche Diagnostics SL. Sant Cugat del Vallès, Barcelona, Spain
| | - Josep Quer
- 3Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
| | - George Koutsoudakis
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Patricia González
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Noelia Caro-Pérez
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain.,‡Present address: Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden
| | - Damir García-Cehic
- 3Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
| | - Neris García-González
- 5Joint Research Unit Infección y Salud Pública, FISABIO-Universitat de València, I2SysBio, CIBERESP, Valencia, Spain
| | - Fernando González-Candelas
- 5Joint Research Unit Infección y Salud Pública, FISABIO-Universitat de València, I2SysBio, CIBERESP, Valencia, Spain
| | - Juan Ignacio Esteban
- 3Liver Unit, Vall d'Hebron Institut de Recerca-Hospital Universitari Vall d'Hebron, CIBERehd, Barcelona, Spain
| | - Gonzalo Crespo
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Miquel Navasa
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Sofía Pérez-Del-Pulgar
- 1Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
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15
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Saab S, Kardashian A, Saggi S, Choi G, Agopian V, Tong MJ. Use of hepatitis C-positive grafts in hepatitis C-negative liver transplant recipients is cost effective. Clin Transplant 2018; 32:e13383. [PMID: 30129981 DOI: 10.1111/ctr.13383] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 07/02/2018] [Accepted: 08/16/2018] [Indexed: 01/18/2023]
Abstract
BACKGROUND The number of patients needing liver transplantation (LT) exceeds the number of available allografts. The current opioid epidemic in this country has increased the number of potential donors infected with hepatitis C (HCV). METHODS We assessed the incremental cost-effectiveness ratio (ICER) by comparing the costs and number of liver transplants performed using HCV-positive and HCV-negative grafts into patients without HCV infection in a decision analysis model with a 1-year time horizon. RESULTS The use of HCV-positive grafts was found to have an ICER below $50 000 across all MELD scores. Using our baseline cohort with a model for end-stage liver disease (MELD) score of 15-22, the ICER was $21 233/additional LT performed. As the MELD scores increased, the ICER decreased. Above a MELD score of 23, the use of HCV-positive grafts became cost saving (-$115 419). Our model was robust to all variables tested in the sensitivity analyses, except drug costs. CONCLUSION The results of our decision analysis model highlight the potential pharmacoeconomic benefit of utilizing HCV-positive grafts in LT candidates who are not infected with HCV. The use of HCV-positive grafts is at least cost effective and even cost saving in patients with MELD scores above 23.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, University of California, Los Angeles, California.,Department of Surgery, University of California, Los Angeles, California
| | - Ani Kardashian
- Department of Medicine, University of California, Los Angeles, California
| | - Satvir Saggi
- Department of Surgery, University of California, Los Angeles, California
| | - Gina Choi
- Department of Medicine, University of California, Los Angeles, California.,Department of Surgery, University of California, Los Angeles, California
| | - Vatche Agopian
- Department of Surgery, University of California, Los Angeles, California
| | - Myron J Tong
- Department of Surgery, University of California, Los Angeles, California
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16
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Liver Transplantation in Hepatitis C-Infected Patients: Experience From a South American Transplant Center. Transplant Proc 2018; 50:493-498. [PMID: 29579834 DOI: 10.1016/j.transproceed.2017.11.046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Accepted: 11/11/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Around 2.4% of the world's population is infected with hepatitis C virus (HCV), and it is the most common cause of liver transplantation (LT) in the world. Latin America (LA), with nearly 9% of the world population, has had a continuous increase in the number of LTs per year. Yet, due to the lack of mandatory data collection and a well-developed health-care system, access to transplantation is limited in most LA countries. We report the first LA experience of HCV-infected LT patients. METHODS We performed a retrospective cohort study by reviewing the medical histories of all HCV-infected LT patients between 1996 and 2016 who acquired HCV before their LT, at the Fundación Valle del Lilí, Cali, Colombia. RESULTS Between January 1996 and December 2015, a total of 770 LTs were performed, of which 75 had a cirrhotic liver due to HCV infection. With a median follow-up time of 24.4 months (interquartile range [IQR] 4.7-61.2 months), patient survival was 44.9% and 66.9% for the time periods 1996-2006 and 2007-2015, respectively. Hepatocellular carcinoma (HCC) was present in 30.6% of the patients, and overall postoperative complications had an incidence of 80%. CONCLUSIONS This is the first report of LT in HCV-infected patients in Colombia and in LA. Our results are comparable to those of other transplant centers worldwide with regard to postoperative complications and patient survival. Patients with LT in the 1996-2006 time frame had higher morbidity and mortality. Studies including larger numbers of patients are needed to determine the reason for this finding.
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17
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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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18
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Successful Treatment of Fibrosing Cholestatic Hepatitis With Daclatasvir and Asunaprevir After Liver Transplantation: A Case Report. Transplant Proc 2018; 50:2877-2881. [PMID: 30401415 DOI: 10.1016/j.transproceed.2018.03.057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 03/02/2018] [Indexed: 11/22/2022]
Abstract
BACKGROUND Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after liver transplantation (LT). Most FCH cases are fatal, occurring as a secondary disease following rapidly progressive liver dysfunction and graft failure. We report a case of early-onset FCH after LT that was successfully treated using daclatasvir and asunaprevir. CASE REPORT A 59-year-old woman underwent living donor LT for HCV-related liver cirrhosis. However, liver function was not improved after LT and gradually worsened. A liver biopsy was performed at 30 and 47 days after the living donor LT to identify the cause of the liver dysfunction. The first biopsy result showed no specific finding. However, combined treatment with pegylated interferon and ribavirin was started because of a high HCV viral load (> 8.0 log IU/mL). Nevertheless, liver function and HCV viral load deteriorated, and the second biopsy performed on postoperative day 47 revealed FCH. We converted the antiviral agents into daclatasvir and asunaprevir and performed plasmapheresis twice. Since then, the liver dysfunction and HCV viral load gradually improved, and HCV RNA clearance occurred at week 11 after treatment. The patient achieved a sustained virologic response at week 24 after completion of the treatment. CONCLUSION Daclatasvir combined with asunaprevir can be a useful treatment option in potentially fatal FCH after LT.
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19
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Bodro M, Sanclemente G, Crespo G, Linares L, Marcos MA, Marco F, Miquel R, Forns X, Navasa M, Moreno A. Severe Hepatitis C Recurrence as a Risk Factor for Opportunistic Infections in Liver Transplant Recipients. Transplant Proc 2018; 50:1437-1443. [PMID: 29880367 DOI: 10.1016/j.transproceed.2018.02.081] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 12/13/2017] [Accepted: 02/17/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The aim of the study was to determine the clinical characteristics, frequency of opportunistic infections (OI), and the outcomes for liver transplant recipients with severe hepatitis C virus (HCV) recurrence. In addition, the objective was to evaluate HCV recurrence as a risk factor for developing an OI. METHODS We conducted a retrospective observational study recording all liver transplant recipients from July 1, 2003, to December 31, 2012. Patients with liver disease due to HCV were selected. Active surveillance of infections was conducted periodically, and patients were classified according to presence of severe HCV recurrence. RESULTS Three hundred seventy patients underwent liver transplantation because of chronic HCV. One hundred forty-seven patients presented severe recurrence (SR) (49%) and 50 (17%) of them had post-liver transplant cholestatic hepatitis C. Patients with SR presented OI, especially cytomegalovirus (CMV) infections and invasive fungal infections, more frequently than patients without SR (33% vs 13%; P < .001). From the diagnosis of SR to the presentation of OI, the median number of days was 169 (6-2083). Acute allograft rejection (OR 1.8 95% confidence interval [CI] 1.1-3.3) donor age ≥60 years (OR 2.9 95% CI 1.3-6.8), and SR (OR 2.8, 95% CI 1.6-5.1) were independently associated with the development of OI in liver transplant recipients. CONCLUSION A high index of suspicion of opportunistic infections must be maintained when faced with severe HCV recurrence in liver transplant recipients. Moreover, active surveillance against CMV infection and other prophylactic strategies against opportunistic infections should be considered.
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Affiliation(s)
- M Bodro
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain.
| | - G Sanclemente
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - G Crespo
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - L Linares
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - M A Marcos
- Microbiology Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - F Marco
- Microbiology Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - R Miquel
- Pathology Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - X Forns
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - M Navasa
- Liver Transplant Unit, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
| | - A Moreno
- Infectious Diseases Department, Hospital Clínic-IDIBAPS-CIBERHED, University of Barcelona, Barcelona, Spain
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20
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Hepatic Failure Due to Cholestatic Hepatitis C in an Immunosuppressed Patient Treated With Elbasvir and Grazeprevir. ACG Case Rep J 2018; 5:e6. [PMID: 29392153 PMCID: PMC5772065 DOI: 10.14309/crj.2018.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/15/2017] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C-induced cholestatic hepatitis is a well-known fatal complication of postorthotropic liver transplantation and prolonged immunosuppression. Recent studies on direct-acting antiviral agents have shown promising results in terms of morbidity and mortality of this condition in postorthotropic liver, heart, and renal transplant patients. However, hepatitis C-induced cholestatic hepatitis remains a highly fatal condition in non-transplant patients. We report the first-ever use of the oral direct-acting antiviral combination, elbasvir and grazeprevir, in the treatment of a non-liver transplant patient with cholestatic hepatitis.
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21
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Schlabe S, Rockstroh JK. Advances in the treatment of HIV/HCV coinfection in adults. Expert Opin Pharmacother 2017; 19:49-64. [DOI: 10.1080/14656566.2017.1419185] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Stefan Schlabe
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany
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22
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Sugawara Y, Hibi T. Direct-acting agents for hepatitis C virus before and after liver transplantation. Biosci Trends 2017; 11:606-611. [PMID: 29238003 DOI: 10.5582/bst.2017.01293] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains a widespread public health concern and many people are infected with HCV. HCV is one of the leading indications for liver transplantation. Direct-acting antiviral agents (DAAs) against HCV have changed the course of chronic HCV infection, however, making it a curable disease. DAA treatment may be initiated before or after liver transplantation. In the present review, we present the available data on DAA treatment of HCV in liver transplant recipients.
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Affiliation(s)
- Yasuhiko Sugawara
- Departments of Transplantation/Pediatric Surgery and Gastroenterology and Hepatology, Postgraduate School of Life Science, Kumamoto University
| | - Taizo Hibi
- Departments of Transplantation/Pediatric Surgery and Gastroenterology and Hepatology, Postgraduate School of Life Science, Kumamoto University
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23
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Predictors of hepatitis C virus recurrence after living donor liver transplantation: Mansoura experience. Arab J Gastroenterol 2017; 18:151-155. [PMID: 28958486 DOI: 10.1016/j.ajg.2017.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 06/22/2017] [Accepted: 09/05/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV)-related cirrhosis is the leading cause of liver transplantation (LT). All patients who undergo LT with detectable serum HCV-RNA experience graft reinfection, which is the most frequent cause of graft loss and death in these patients. We estimated the rate of HCV recurrence and evaluated the current therapeutic regimens. PATIENTS AND METHODS The records of consecutive 325 living donor LT (LDLT) surgeries performed between May 2004 and August 2014 were retrospectively analysed; 207 of them were followed-up throughout the study. Clinical, laboratory, radiological and histopathological examinations were performed thoroughly. Patients received treatment in the form of either pegylated interferon (PEG-IFN) or sofosbuvir, both in combination with ribavirin. RESULTS In total, 90.3% of recipients who were transplanted because of HCV-related end-stage liver disease experienced recurrence due to the virus. The donor age was older in the HCV recurrent group versus the non-recurrence group (28.7±7.1 versus 22.6±2.6years: p≤0.001), warm ischaemia time was prolonged (46.1±18.1 versus 28.6±4.1min: p≤0.001), median cold ischaemia time was 40.0 (10-175) versus 22.5 (15-38) min (p≤0.001) and basal PCR was 414000 (546-116000000) versus 10766 (1230-40000) (p≤0.001). Sustained virological response was achieved in 95.4% of patients treated with a combination of a fixed daily dose of 400mg sofosbuvir with ribavirin and in 65.1% of those who were treated with PEG-IFN with ribavirin. CONCLUSIONS Older donor age and prolonged warm ischaemia time are independent predictors of HCV recurrence after LDLT, and early treatment with the direct-acting sofosbuvir is helpful in resolving the problem of post-LT HCV recurrence.
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Abstract
Since 1988 nearly 150,000 liver transplants have been performed in the United States. Over the past 3 decades the indications for liver transplant have changed from end-stage liver disease from alcohol and cholestatic liver diseases to hepatitis C and most recently nonalcoholic fatty liver disease. Liver transplant recipients are living longer with 10-year survival rates exceeding 60%. Gastroenterologists are likely to encounter or consult on postliver transplant recipients as they live longer and seek care closer to home. Complications after liver transplant are related to immunosuppression, malignancy, recurrent disease, and conditions associated with metabolic syndrome. This review will discuss postliver transplant care and complications in liver transplant recipients.
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Affiliation(s)
- Mark W Russo
- Division of Hepatology, Carolinas HealthCare System, Charlotte, NC
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25
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Disease Reversibility in Patients With Post-Hepatitis C Cirrhosis: Is the Point of No Return the Same Before and After Liver Transplantation? A Review. Transplantation 2017; 101:916-923. [PMID: 28060241 DOI: 10.1097/tp.0000000000001633] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver fibrosis can regress in patients with chronic hepatitis in whom the underlying cause of liver damage is adequately treated. Studies documenting this benefit have been mostly performed in the setting of viral hepatitis, particularly hepatitis C virus, where sustained viral response has been unequivocally shown to result in histological and clinical improvement. With the advent of the new IFN-free regimens, highly effective and safe even in those historically considered "difficult to treat and cure patients," additional benefits have been documented in patients treated at advanced stages of disease, including improvement in liver function with hepatic "recompensation," reduction of portal hypertension, and eventually avoidance of liver transplantation. Disease reversibility has been also demonstrated in the posttransplant setting and appears to be similar to what is observed in the nontransplant patient.
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26
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Herzer K, Welzel TM, Spengler U, Hinrichsen H, Klinker H, Berg T, Ferenci P, Peck-Radosavljevic M, Inderson A, Zhao Y, Jimenez-Exposito MJ, Zeuzem S. Real-world experience with daclatasvir plus sofosbuvir ± ribavirin for post-liver transplant HCV recurrence and severe liver disease. Transpl Int 2017; 30:243-255. [PMID: 28012215 DOI: 10.1111/tri.12910] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Revised: 11/18/2016] [Accepted: 12/13/2016] [Indexed: 02/06/2023]
Abstract
Optimizing therapy of post-transplant HCV recurrence remains important, especially in advanced liver disease. We evaluated daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in patients with post-liver transplant recurrence in a real-world European cohort at high risk of decompensation or death within 12 months. Recommended treatment was DCV 60 mg plus SOF 400 mg once daily for 24 weeks; RBV use/shorter treatment duration was at physicians' discretion. Patients (N = 87) were 70% male, 93% white, and mostly infected with HCV genotypes 1b (48%), 1a (32%), or 3 (9%); 37 (43%) had cirrhosis (16 decompensated), five had fibrosing cholestatic hepatitis. Sustained virologic response at post-treatment week 12 (SVR12) was 94% (80/85) in a modified intention-to-treat analysis: 95% (58/61) without RBV and 92% (22/24) with RBV, with no virologic failures. SVR12 was 100% (80/80) in an as-observed analysis excluding five nonvirologic failures. Four patients (5%) discontinued therapy for adverse events (AEs); 16 (18%) experienced serious AEs. One patient died on treatment and five during follow-up. Most AEs were associated with advanced liver disease and unrelated to therapy. No clinically significant drug-drug interactions were observed. DCV + SOF ± RBV was well tolerated and achieved high SVR12 (94%) in patients with post-transplant HCV recurrence, including patients with severe liver disease.
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Affiliation(s)
| | - Tania M Welzel
- Universitätsklinikum der Johann Wolfgang Goethe Universität, Frankfurt, Germany
| | | | | | | | - Thomas Berg
- Universitätsklinikum Leipzig, Leipzig, Germany
| | | | - Markus Peck-Radosavljevic
- Medical University of Vienna, Vienna, Austria.,Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Akin Inderson
- Leiden University Medical Center, Leiden, The Netherlands
| | - Yue Zhao
- Bristol-Myers Squibb, Princeton, NJ, USA
| | | | - Stefan Zeuzem
- Universitätsklinikum der Johann Wolfgang Goethe Universität, Frankfurt, Germany
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27
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Rezaee-Zavareh MS, Hesamizadeh K, Sharafi H, Alavian SM. Treatment of Hepatitis C Infection with Direct-Acting Antiviral Agents in Liver-Transplant Patients: A Systematic Review and Meta-Analysis. HEPATITIS MONTHLY 2017; 17. [DOI: 10.5812/hepatmon.12324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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28
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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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29
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Salazar J, Saxena V, Kahn JG, Roberts JP, Mehta N, Volk M, Lai JC. Cost-Effectiveness of Direct-Acting Antiviral Treatment in Hepatitis C-Infected Liver Transplant Candidates With Compensated Cirrhosis and Hepatocellular Carcinoma. Transplantation 2017; 101:1001-1008. [PMID: 27926593 PMCID: PMC5403544 DOI: 10.1097/tp.0000000000001605] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV)(+) donors represent an effective strategy to increase liver donor availability to HCV-infected recipients. However, many HCV(+) transplant candidates are now receiving treatment with direct-acting anti-viral (DAA) agents that lower the risk of posttransplant HCV recurrence but could make the patient ineligible for HCV(+) livers. METHODS We compared pretransplant DAA treatment versus deferred DAA treatment using a cost-effectiveness decision analysis model to estimate incremental cost-effectiveness ratios (cost per quality-adjusted life year gained) from the societal perspective across a range of HCV(+) liver availability rates. For practical considerations, the population modeled was restricted to well-compensated HCV(+) cirrhotics listed for liver transplantation with hepatocellular carcinoma MELD exception points. RESULTS Under base case conditions, the deferred DAA treatment strategy was found to be the "dominant" strategy. That is, it provided superior health outcomes at cost savings compared to the pretransplant DAA treatment strategy. The pretransplant DAA treatment strategy trended towards cost-effectiveness as HCV(+) donor liver availability declined. However, only in 1 scenario that was highly optimized for favorable outcomes in the pretransplant DAA treatment arm (low availability of HCV(+) organs, low cost of DAA treatment, high cost of HCV recurrence) was the incremental cost-effectiveness ratio associated with HCV DAA treatment before transplant less than US $150 000/quality-adjusted life-year gained. CONCLUSIONS Deferring HCV treatment until after liver transplant and maintaining access to the expanded pool of HCV(+) donors appears to be the most cost-effective strategy for well-compensated HCV-infected cirrhotics listed for liver transplantation with hepatocellular carcinoma, even in geographic areas of relatively low HCV(+) donor availability.
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Affiliation(s)
- James Salazar
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - Varun Saxena
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - James G. Kahn
- Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, San Francisco, California, United States of America
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, California, United States of America
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Transplantation Institute, Loma Linda University Health, Loma Linda, California, United States of America
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America
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30
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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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31
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van Tilborg M, Maan R, van der Meer AJ, de Knegt RJ. Interferon-free antiviral therapy for chronic hepatitis C among patients in the liver transplant setting. Best Pract Res Clin Gastroenterol 2017. [PMID: 28624110 DOI: 10.1016/j.bpg.2017.04.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis C (HCV) infection remains a major public health problem with many infected individuals worldwide. The revolutionary discovery of highly effective direct-acting antivirals (DAAs) makes chronic HCV infection a curable disease, even in patients with advanced liver disease. Liver function may improve shortly after initiation of antiviral therapy in patients on the waiting list and could even obviate the need for transplantation. However, whether these short term benefits also result in a favorable prognosis on the long-term remains to be seen and this fuels the discussion whether DAAs should be used prior to liver transplantation in all patients. Following liver transplantation, DAA treatment is also highly effective so that postponing antiviral treatment to the post-transplant setting may be better for certain patients. Furthermore, the discussion whether HCV positive organ donors should be used now viral eradication is achieved in almost all patients has regained interest.
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Affiliation(s)
| | - Raoel Maan
- Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | | | - Robert J de Knegt
- Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
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32
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Abstract
Cirrhosis due to chronic hepatitis C (HCV) is the leading indication for liver transplantation in North America and Europe. HCV re-infection post-transplant is nearly universal and if left untreated negatively affects patient and graft survival. Until recently, treatment options for HCV were limited to interferon (IFN)-based therapies which had low sustained viral response (SVR) rates and were poorly tolerated in the post-transplant setting. In the last 3 years, the promise of the directly acting antivirals (DAAs) for the treatment of HCV has been fulfilled with high sustained viral response (SVR) rates and a low side effect profile demonstrated in both registration trials and real-world studies. This innovation has allowed post-liver transplant patients with HCV recurrence access to interferon-free therapies with extraordinary efficacy, safety, tolerability, and fewer drug-drug interactions.
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33
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Smith HL, Chung RT, Mantry P, Chapman W, Curry MP, Schiano TD, Boucher E, Cheslock P, Wang Y, Molrine DC. Prevention of allograft HCV recurrence with peri-transplant human monoclonal antibody MBL-HCV1 combined with a single oral direct-acting antiviral: A proof-of-concept study. J Viral Hepat 2017; 24:197-206. [PMID: 28127942 DOI: 10.1111/jvh.12632] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 09/17/2016] [Indexed: 12/25/2022]
Abstract
Patients with active hepatitis C virus (HCV) infection at transplantation experience rapid allograft infection, increased risk of graft failure and accelerated fibrosis. MBL-HCV1, a neutralizing human monoclonal antibody (mAb) targeting the HCV envelope, was combined with a licensed oral direct-acting antiviral (DAA) to prevent HCV recurrence post-transplant in an open-label exploratory efficacy trial. Eight subjects received MBL-HCV1 beginning on the day of transplant with telaprevir initiated between days 3 and 7 post-transplantation. Following FDA approval of sofosbuvir, two subjects received MBL-HCV1 starting on the day of transplant with sofosbuvir initiated on day 3. Combination treatment was administered for 8-12 weeks or until the stopping rule for viral rebound was met. The primary endpoint was undetectable HCV RNA at day 56 with exploratory endpoints of sustained virologic response (SVR) at 12 and 24 weeks post-treatment. Both subjects receiving mAb and sofosbuvir achieved SVR24. Four of eight subjects in the mAb and telaprevir group met the primary endpoint; one subject achieved SVR24 and three subjects relapsed 2-12 weeks post-treatment. The other four subjects experienced viral breakthrough. There were no serious adverse events related to study treatment. This proof-of-concept study demonstrates that peri-transplant immunoprophylaxis combined with a single oral direct-acting antiviral in the immediate post-transplant period can prevent HCV recurrence.
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Affiliation(s)
- H L Smith
- MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA
| | - R T Chung
- Department of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - P Mantry
- Liver Institute, Methodist Dallas Medical Center, Dallas, TX, USA
| | - W Chapman
- Division of General Surgery, Washington University, St Louis, MO, USA
| | - M P Curry
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - T D Schiano
- Recanati-Miller Transplantation Institute and The Division of Liver Diseases, The Mount Sinai Medical Center, New York, NY, USA
| | - E Boucher
- MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA
| | - P Cheslock
- MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA
| | - Y Wang
- MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA
| | - D C Molrine
- MassBiologics of the University of Massachusetts Medical School, Boston, MA, USA
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34
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Wadhawan M, Vij V, Makki K, Bansal N, Kumar A. Early Acute Severe HCV Recurrence After Transplantation: From Universal Mortality to Cure. J Clin Exp Hepatol 2017; 7:28-32. [PMID: 28348468 PMCID: PMC5357714 DOI: 10.1016/j.jceh.2016.10.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Accepted: 10/21/2016] [Indexed: 12/12/2022] Open
Abstract
Acute severe recurrence of hepatitis C virus (HCV) after solid organ transplant is associated with high mortality. Pegylated interferon and ribavirin are suboptimal in treatment of this severe form of recurrence. We report 4 cases of acute severe HCV recurrence (within 6 months after transplant), including 3 cases with fibrosing cholestatic hepatitis treated with sofosbuvir and ribavirin. All four patients achieved a rapid suppression of HCV RNA with a normalization of liver function tests within 4 weeks of starting therapy. All patients were HCV RNA negative at 12 weeks after stopping therapy. The combination was found to be safe as anemia was the only adverse effect, which developed in 2 patients (1 patient required blood transfusion, while another managed with erythropoietin). Sofosbuvir and ribavirin appear to be safe and efficacious in treatment of acute severe HCV recurrence after organ transplant.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- DAA's, sofosbuvir
- FCH, fibrosing cholestatic hepatitis
- Fibrosing cholestatic hepatitis
- GGTP, gamma glutamyl transpeptidase
- HCV, hepatitis C virus
- IHBR, intrahepatic biliary radicals
- Kidney transplant
- LFT, liver function tests
- LRLT, living-related liver transplant
- Liver transplant
- MMF, mycophenolate mofetil
- MRCP, magnetic resonance cholangiopancreatography
- POD, postoperative day
- TND, target not detected
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Affiliation(s)
- Manav Wadhawan
- Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases Institute, Delhi/NCR, India,Address for correspondence: Manav Wadhawan, Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases Institute, Delhi/NCR, India.Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases InstituteDelhi/NCRIndia
| | - Vivek Vij
- Department of Surgical Gastroenterology & Liver Transplant, Fortis Hospitals (Escorts & Noida), Delhi/NCR, India
| | - Kausar Makki
- Department of Surgical Gastroenterology & Liver Transplant, Fortis Hospitals (Escorts & Noida), Delhi/NCR, India
| | - Nalini Bansal
- Department of Pathology, Fortis Escorts Hospital, Delhi, India
| | - Ajay Kumar
- Department of Gastroenterology & Hepatology, Fortis Escorts Liver & Digestive Diseases Institute, Delhi/NCR, India
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35
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Kawaoka T, Imamura M, Morio K, Nakamura Y, Tsuge M, Nelson Hayes C, Kawakami Y, Aikata H, Ochi H, Ishiyama K, Ohdan H, Chayama K. Three patients treated with sofosbuvir plus ledipasvir for recurrent hepatitis C after liver transplantation. Clin J Gastroenterol 2017; 10:179-184. [PMID: 28224470 DOI: 10.1007/s12328-017-0722-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 02/08/2017] [Indexed: 01/12/2023]
Abstract
We previously reported results of interferon (IFN)-free daclatasvir and asunaprevir for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). Here we report three patients who achieved viral response with no effect on the blood concentrations of immunosuppressive agents following sofosbuvir plus ledipasvir treatment. The first patient was a 68-year-old female with HCV-related liver cirrhosis who failed to respond to pegylated-IFN and ribavirin (PEG-IFN/RBV) after living donor LT. She had been treated with 50 mg/day of cyclosporine. The second was a 63-year-old male with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. He had been treated with 50 mg/day of cyclosporine. The third was a 63-year-old female with HCV-related liver cirrhosis. She had been treated with tacrolimus. High alanine aminotransferase levels persisted after LT. Liver biopsy examination revealed active hepatitis or chronic rejection. Therefore, sofosbuvir plus ledipasvir therapy was started. However, the combination treatment was stopped at 4 weeks due to development of interstitial pneumonia. Serum HCV RNA became negative at the time treatment was discontinued and remained negative 12 weeks after cessation of therapy in all three cases. Sofosbuvir plus ledipasvir treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yuki Nakamura
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Clair Nelson Hayes
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Hidenori Ochi
- Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan
| | - Kouhei Ishiyama
- Programs for Biomedical Research, Division of Frontier Medical Science, Department of Surgery, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Programs for Biomedical Research, Division of Frontier Medical Science, Department of Surgery, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
- Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan
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Shah NJ, Russo MW. Is it time to rethink combined liver-kidney transplant in hepatitis C patients with advanced fibrosis? World J Hepatol 2017; 9:288-292. [PMID: 28261386 PMCID: PMC5316849 DOI: 10.4254/wjh.v9.i5.288] [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: 09/27/2016] [Revised: 12/04/2016] [Accepted: 12/19/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To reduce hepatic and extrahepatic complications of chronic hepatitis C in kidney transplant recipients.
METHODS We conducted a systematic review of kidney only transplant in patients with hepatitis C and advanced fibrosis.
RESULTS The 5 year patient survival of kidney transplant recipients with and without hepatitis C cirrhosis ranged from 31% to 90% and 85% to 92%, respectively. Hepatitis C kidney transplant recipients had lower 10-year survival when compared to hepatitis B patients, 40% and 90% respectively. There were no studies that included patients with virologic cure prior to kidney transplant that reported post-kidney transplant outcomes. There were no studies of direct acting antiviral therapy and effect on patient or graft survival after kidney transplantation.
CONCLUSION Data on kidney transplant only in hepatitis C patients that reported inferior outcomes were prior to the development of potent direct acting antiviral. With the development of potent directing acting antiviral therapy for hepatitis C with high cure rates studies are needed to determine if patients with hepatitis C, including those with advanced fibrosis, can undergo kidney transplant alone with acceptable long term outcomes.
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Use of Sofosbuvir-Based Treatment of Chronic Hepatitis C in Liver Transplant Recipients on Hemodialysis. J Clin Gastroenterol 2017; 51:167-173. [PMID: 27548734 DOI: 10.1097/mcg.0000000000000640] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The use of direct acting agents has changed the management paradigm of hepatitis C (HCV) in liver transplant (LT) recipients. However, the appropriate antiviral regimen in LT recipients on hemodialysis (HD) remains unclear. METHODS We retrospectively evaluated the safety and efficacy of sofosbuvir-based LT recipients on HD followed at the University of California Los Angeles. RESULTS Twelve LT recipients on HD were treated for recurrent HCV with sofosbuvir-based therapy. Indications for antiviral therapy included fibrosing cholestatic hepatitis, symptomatic cryoglobulinemia, and recurrent HCV. The causes of renal failure included hepatorenal syndrome, acute tubular necrosis and cryoglobulinemia. Of those who were not on dialysis at the time of transplantation, the mean creatinine (±SD) was 1.7 (±0.8) mg/dL. The mean age (±SD) of the cohort was 62.2 (±6.0) years. Most recipients were male (67%) and infected with genotype 1 (83%). Baseline alanine aminotransferase, total bilirubin, hemoglobin and HCV RNA values (±SD) were 53.2 (±59.4) IU/L, 3.2 (±5.5) mg/dL, 10.5 (±1.8) g/dL, and 30,499,500 (±29,655,754) IU/mL. HCV RNA levels were undetectable in all recipients at the end of therapy. The trough mean (±SD) hemoglobin of patients on treatment and on HD was 8.4 (±2.3). The sustained viral response was 58% (7/12), and the overall patient survival was 42%. All the deaths occurred a mean (±SD) after 5.4 (±3.6) months after treatment was completed. CONCLUSIONS All patients achieved viral suppression from therapy, and over half the recipients achieved a sustained virological response. A high mortality underscores the necessity of starting antiviral treatment sooner in LT recipients and the need for larger cohort studies.
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Shoreibah M, Orr J, Jones D, Zhang J, Venkata K, Massoud O. Ledipasvir/sofosbuvir without ribavirin is effective in the treatment of recurrent hepatitis C virus infection post-liver transplant. Hepatol Int 2017; 11:434-439. [PMID: 28083718 DOI: 10.1007/s12072-016-9778-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 12/09/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIM Recurrent hepatitis C virus infection is a challenging complication post-liver transplant. Current guidelines recommend the combination of ribavirin and ledipasvir/sofosbuvir for 12 weeks for the treatment of recurrent HCV genotype 1 post-liver transplant. Data are limited on the use of ledipasvir/sofosbuvir without ribavirin. The aim of this study was to evaluate the use of ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus post-liver transplant. METHODS This is a retrospective study of liver transplant patients who received ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus in our liver center from 2014 to 2016. RESULTS A total of 60 patients were enrolled of which 70% were male, 88% Caucasian, age 60 ± 7 years, 15% cirrhotic, and 45% treatment-experienced with recurrent hepatitis C virus infection genotype 1 post-liver transplant. Treatment duration varied from 8 to 24 weeks. There were no serious adverse events and no discontinuation of treatment. A total of 71% of patients had undetectable serum hepatitis C virus at 4 weeks. However, irrespective of treatment duration, 100% of patients had undetectable serum hepatitis C virus at the end of treatment and 100% of patients achieved sustained viral response at 12 weeks. CONCLUSION Ledipasvir/sofosbuvir without ribavirin is an effective treatment of recurrent hepatitis C virus infection post-liver transplant. The entire group achieved sustained viral response at 12 weeks irrespective of the length of treatment. The combination of ledipasvir/sofosbuvir was well tolerated without serious adverse effects or discontinuation.
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Affiliation(s)
- Mohamed Shoreibah
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1808 7th Ave South, BDB 391, Birmingham, AL, 5294, USA
| | - Jordan Orr
- Department of Internal Medicine, Tinsley Harrison Internal Medicine Residency Program, University of Alabama at Birmingham, 1720 2nd Ave South, BDB 327, Birmingham, AL, 35294, USA.
| | - DeAnn Jones
- The University of Alabama at Birmingham, 1802 6th Ave South, Birmingham, 35233, AL, USA
| | - Jie Zhang
- The University of Alabama at Birmingham, 1802 6th Ave South, Birmingham, 35233, AL, USA
| | - Krishna Venkata
- Department of Medicine, Montgomery Internal Medicine Residency Program, University of Alabama at Birmingham, 2055 E. South Blvd., Suite 200, Montgomery, 36116, AL, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, 1808 7th Ave South, BDB 391, Birmingham, AL, 5294, USA
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Dumortier J, Leroy V, Duvoux C, de Ledinghen V, Francoz C, Houssel-Debry P, Radenne S, d'Alteroche L, Fougerou-Leurent C, Canva V, di Martino V, Conti F, Kamar N, Moreno C, Lebray P, Tran A, Besch C, Diallo A, Rohel A, Rossignol E, Abergel A, Botta-Fridlund D, Coilly A, Samuel D, Duclos-Vallée JC, Pageaux GP. Sofosbuvir-based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation. Liver Transpl 2016; 22:1367-78. [PMID: 27348086 DOI: 10.1002/lt.24505] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 05/24/2016] [Accepted: 05/31/2016] [Indexed: 12/12/2022]
Abstract
Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)-based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367-1378 2016 AASLD.
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Affiliation(s)
- Jérôme Dumortier
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Université Claude Bernard Lyon 1, Lyon, France.
| | - Vincent Leroy
- Pôle Digidune, Clinique Universitaire d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Grenoble, INSERM/Université Grenoble Alpes U823, Institut Albert Bonniot, Grenoble, France
| | | | - Victor de Ledinghen
- Service d'Hépatologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, INSERM U1053, Université Bordeaux, Bordeaux, France
| | - Claire Francoz
- Service d'Hépatologie, Hôpital Beaujon, AP-HP, Université Paris Diderot et INSERM U1149, Centre de Recherche sur l'Inflammation, Clichy, France
| | - Pauline Houssel-Debry
- Service des Maladies du Foie, Centre Hospitalier Universitaire de Rennes, Rennes, France
| | - Sylvie Radenne
- Service d'Hépatologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France
| | - Louis d'Alteroche
- Service d'hépato-gastroentérologie, Centre Hospitalier Universitaire Trousseau, Tours, France
| | - Claire Fougerou-Leurent
- Unité de Pharmacologie Clinique, Centre Hospitalier Universitaire de Rennes, Centre d'Investigation Clinique INSERM 1414, Rennes, France
| | - Valérie Canva
- Services Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France
| | - Vincent di Martino
- Service d'Hépatologie, Hôpital Jean Minjoz, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Besançon, France
| | - Filomena Conti
- Service d'hépato-gastroentérologie, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM Unités Mixtes de Recherche S938, Paris, France
| | - Nassim Kamar
- Département de Néphrologie et de Transplantation d'Organes, Centre Hospitalier Universitaire Rangueil, Université de Toulouse, Toulouse, France
| | - Christophe Moreno
- Cliniques Universitaires de Bruxelles, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Pascal Lebray
- Service d'hépato-gastroentérologie, Groupe Hospitalier Pitié-Salpétrière, AP-HP, Université Pierre et Marie Curie Paris 6, INSERM Unités Mixtes de Recherche S938, Paris, France
| | - Albert Tran
- Service d'Hépatologie, Hôpital de l'Archet 2, Centre Hospitalier Universitaire de Nice, INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, France
| | - Camille Besch
- Service de Transplantation, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France
| | - Alpha Diallo
- Unit for Basic and Clinical Research on Viral Hepatitis, France Recherche Nord&Sud Sida-HIV Hépatites, Agence Nationale de Recherche sur le Sida, Paris, France
| | - Alexandra Rohel
- Unit for Basic and Clinical Research on Viral Hepatitis, France Recherche Nord&Sud Sida-HIV Hépatites, Agence Nationale de Recherche sur le Sida, Paris, France
| | - Emilie Rossignol
- Unité de Pharmacologie Clinique, Centre Hospitalier Universitaire de Rennes, Centre d'Investigation Clinique INSERM 1414, Rennes, France
| | - Armand Abergel
- Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire Estaing, Université d'Auvergne, Unités Mixtes de Recherche CNRS 6284, Clermont-Ferrand, France
| | | | - Audrey Coilly
- Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Université Paris-Sud, Université Paris-Saclay, UMR-S 1193, INSERM Unité 1193, Département Hospitalo-Universitaire Hepatinov, Villejuif, France
| | - Didier Samuel
- Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Université Paris-Sud, Université Paris-Saclay, UMR-S 1193, INSERM Unité 1193, Département Hospitalo-Universitaire Hepatinov, Villejuif, France
| | - Jean-Charles Duclos-Vallée
- Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, Université Paris-Sud, Université Paris-Saclay, UMR-S 1193, INSERM Unité 1193, Département Hospitalo-Universitaire Hepatinov, Villejuif, France
| | - Georges-Philippe Pageaux
- Département d'Hépato-Gastroentérologie et de Transplantation Hépatique, Centre Hospitalier Universitaire Saint-Eloi, Université de Montpellier, Montpellier, France
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Optimum timing of treatment for hepatitis C infection relative to liver transplantation. Lancet Gastroenterol Hepatol 2016; 1:165-172. [PMID: 28404073 DOI: 10.1016/s2468-1253(16)30008-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/03/2016] [Accepted: 06/03/2016] [Indexed: 12/19/2022]
Abstract
The approval of direct-acting antiviral agents that may be given orally in an interferon-free regimen has greatly changed the landscape of treatment for hepatitis C virus (HCV) infection, especially for patients with the most severe disease, who have decompensated cirrhosis, or who are waiting for or have undergone liver transplantation. Treatment with interferon proved to be ineffective and poorly tolerated because of high risks of infection and transplant rejection. The availability of new drugs poses new questions about the optimum time to give treatment to prevent HCV recurrence, taking into account efficacy, tolerance, and drug-drug interactions. Treatment is acceptable before and after transplantation, but the two strategies have subtle differences. In this Review, we present the available data on the treatment of HCV infection before and after transplantation, and discuss new challenges for practice.
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Bunchorntavakul C, Reddy KR. Treat chronic hepatitis C virus infection in decompensated cirrhosis - pre- or post-liver transplantation? the ironic conundrum in the era of effective and well-tolerated therapy. J Viral Hepat 2016; 23:408-18. [PMID: 27018088 DOI: 10.1111/jvh.12534] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 03/01/2016] [Indexed: 12/12/2022]
Abstract
The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically over the past few years mainly due to the availability of all-oral antiviral regimens. The currently approved all-oral direct-acting antivirals (DAA) containing sofosbuvir, ledipasvir, daclatasvir and ribavirin, in various combinations, have shown to be safe and effective in patients with decompensated cirrhosis with sustained virological response (SVR) rates nearly comparable to those with well-compensated liver disease. Unique issues yet remain such as the challenges with renal insufficiency, tolerability of ribavirin and risk of further hepatic decompensation with a protease inhibitor-based regimen. While most patients who achieve SVR have demonstrated improvement in hepatic synthetic function over the short course of follow, the long-term beneficial effects are unknown. Further, the baseline predictors of improvement in hepatic function have not been well delineated and thus have left us in a quandary as to what we might expect with successful therapy and thus we are at a loss to well educate our patients. The major concern, in potential liver transplant candidates, is of unintended 'harm' by achieving SVR but without improvement in hepatic function to an extent where the patients might function well. As HCV therapies are as effective in liver transplant recipients, there is a growing sentiment in some of the transplant quarters that those with decompensated liver disease and awaiting liver transplant be treated for HCV after liver transplant. This strategy would thus eliminate any concern of leaving a patient in 'no person's' land by treating HCV successfully pretransplant but not to the point of functional normalcy, while also would maintain the risk of HCC. Yet a contrarian view would be that not all patients have access to liver transplantation (LT), cannot bear the cost, have comorbidities or contraindications to LT. While the debate continues, it is essential that we develop robust predictors of improvement in liver function so that we can carefully select our patients for therapy in the context of liver transplantation.
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Affiliation(s)
- C Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
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Poordad F, Schiff ER, Vierling JM, Landis C, Fontana RJ, Yang R, McPhee F, Hughes EA, Noviello S, Swenson ES. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence. Hepatology 2016; 63:1493-505. [PMID: 26754432 PMCID: PMC5069651 DOI: 10.1002/hep.28446] [Citation(s) in RCA: 341] [Impact Index Per Article: 37.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 01/07/2016] [Indexed: 12/16/2022]
Abstract
UNLABELLED Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open-label ALLY-1 study assessed the safety and efficacy of a 60-mg once-daily dosage of daclatasvir (pan-genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24-week follow-up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on-treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child-Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%-92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child-Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%-99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment-related serious adverse events. CONCLUSION The pan-genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post-liver transplantation recurrence or advanced cirrhosis.
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Affiliation(s)
- Fred Poordad
- The Texas Liver InstituteUniversity of Texas Health Science CenterSan AntonioTX
| | - Eugene R. Schiff
- Schiff Center for Liver DiseasesUniversity of Miami Miller School of MedicineMiamiFL
| | - John M. Vierling
- Division of Abdominal TransplantationBaylor College of MedicineHoustonTX
| | - Charles Landis
- Division of Gastroenterology and Hepatology, Department of MedicineUniversity of WashingtonSeattleWA
| | - Robert J. Fontana
- University Division of Gastroenterology, Department of Internal MedicineUniversity of Michigan Medical CenterAnn ArborMI
| | - Rong Yang
- Bristol‐Myers SquibbLawrence TownshipNJ
| | - Fiona McPhee
- Discovery VirologyBristol‐Myers Squibb Research and DevelopmentWallingfordCT
| | | | | | - Eugene S. Swenson
- Discovery VirologyBristol‐Myers Squibb Research and DevelopmentWallingfordCT
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Abstract
Recurrence of hepatitis C after liver transplantation is a major problem; it is characterized by high hepatitis C virus (HCV)-RNA, rapid progression, and cholestatic hepatitis. Treatment for HCV infection with peginterferon and ribavirin has been administered to prevent progression of hepatitis C after liver transplantation. However, it has low efficacy and causes many adverse events, including immune-mediated graft dysfunction. Interferon-containing regimens with direct-acting antivirals (DAAs) improve treatment efficacy but DAAs cause serious adverse events and drug-drug interactions. Recent studies have demonstrated the efficacy and safety of interferon-free therapy with DAAs before and after liver transplantation, which has ushered in a new era in the strategy for treating HCV in transplant recipients. Interferon-free therapies are safe and effective in patients before and after liver transplantation as well as in those with severe cholestatic hepatitis C. Several obstacles must be overcome before the widespread adoption of interferon-free therapy, including drug-drug interactions, DAA-resistant HCV, treatment for decompensated cirrhosis, and treatment for renal failure. These problems are expected to be solved in the near future, and the poor prognosis of HCV-positive recipients will improve.
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44
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Fontana RJ, Brown RS, Moreno-Zamora A, Prieto M, Joshi S, Londoño MC, Herzer K, Chacko KR, Stauber RE, Knop V, Jafri SM, Castells L, Ferenci P, Torti C, Durand CM, Loiacono L, Lionetti R, Bahirwani R, Weiland O, Mubarak A, ElSharkawy AM, Stadler B, Montalbano M, Berg C, Pellicelli AM, Stenmark S, Vekeman F, Ionescu-Ittu R, Emond B, Reddy KR. Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. Liver Transpl 2016; 22:446-58. [PMID: 26890629 DOI: 10.1002/lt.24416] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 01/12/2016] [Accepted: 01/24/2016] [Indexed: 12/11/2022]
Abstract
Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.
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Affiliation(s)
- Robert J Fontana
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI
| | - Robert S Brown
- College of Physicians and Surgeons, Columbia University, New York, NY
| | | | - Martin Prieto
- Hospital Universitario y Politécnico La Fe and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Valencia, Spain
| | - Shobha Joshi
- Department of Gastroenterology, Ochsner Health System, New Orleans, LA
| | | | - Kerstin Herzer
- Department for General, Viszeral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Kristina R Chacko
- Einstein Center for Transplantation, Montefiore Medical Center, New York, NY
| | - Rudolf E Stauber
- Department of Internal Medicine, Karl-Franzens-University, Graz, Austria
| | - Viola Knop
- Department of Internal Medicine, University Hospital-Goethe University, Frankfurt, Germany
| | - Syed-Mohammed Jafri
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
| | - Lluís Castells
- Internal Medicine Department, Hospital Universitary Vall Hebron, University of Barcelona, Barcelona, Spain
| | - Peter Ferenci
- Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Carlo Torti
- Unit of Infectious and Tropical Diseases, Magna Graecia University, Cantanzaro, Italy
| | - Christine M Durand
- Department of Medicine Infectious Diseases, Johns Hopkins Medical Institution, Baltimore, MD
| | | | - Raffaella Lionetti
- Liver Unit, IRCCS Lazzaro Spallanzani, National Institute for Infectious Diseases, Rome, Italy
| | - Ranjeeta Bahirwani
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Ola Weiland
- Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Abdullah Mubarak
- Department of Hepatology, Dallas Medical Physicians Group, Dallas, TX
| | - Ahmed M ElSharkawy
- University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Medical Centre, Birmingham, United Kingdom
| | | | - Marzia Montalbano
- Liver Unit, IRCCS Lazzaro Spallanzani, National Institute for Infectious Diseases, Rome, Italy
| | - Christoph Berg
- Department of Internal Medicine, Hepatology, Gastroenterology, Infectious Diseases, University Hospital of Tübingen, Tübingen, Germany
| | | | | | | | | | - Bruno Emond
- Analysis Group, Inc, Montreal, Quebec, Canada
| | - K Rajender Reddy
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA
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45
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Ueda Y, Kaido T, Hatano E, Ohtsuru S, Uemoto S. Safe and effective treatment with daclatasvir and asunaprevir in a liver transplant recipient with severe cholestatic hepatitis C. Hepatol Res 2015; 45:1360-2. [PMID: 25704315 DOI: 10.1111/hepr.12509] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Revised: 02/16/2015] [Accepted: 02/16/2015] [Indexed: 02/08/2023]
Abstract
Severe cholestatic hepatitis C (SCH) is a unique variant of recurrent hepatitis C that occurs after liver transplantation. Unfortunately, the prognosis of SCH is poor, and interferon (IFN) therapy has been reported to not improve the prognosis. We herein report a case of progressive SCH with acute cellular rejection (ACR) and bacterial infection, which was successfully treated using IFN-free therapy with daclatasvir and asunaprevir. A 43-year-old man was diagnosed with SCH and mild ACR at day 48 after liver transplantation, and IFN-free therapy with daclatasvir and asunaprevir was started. Although he experienced catheter-related bacteremia on the first day, the IFN-free therapy was safely continued, which immediately caused his liver function to improve. His bilirubin levels decreased from 11.1 to 2.1 mg/dL and serum hepatitis C virus RNA levels became undetectable after 4 weeks of the treatment. This case indicates that IFN-free therapy for progressive SCH with acute cellular rejection and bacterial infection is safe and effective, and may improve the outcomes of hepatitis C virus positive transplant recipients.
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Affiliation(s)
- Yoshihide Ueda
- Department of Gastroenterology and Hepatology, Kyoto, Japan
| | - Toshimi Kaido
- Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Shinji Uemoto
- Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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46
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Abstract
The management of hepatitis C virus (HCV) infection in special populations is challenging. The efficacy and safety data of the currently approved all-oral direct-acting antiviral combinations, including sofosbuvir, ledipasvir, daclatasvir, paritaprevir/ritonavir/ombitasvir plus dasabuvir (3D), and ribavirin, is compelling for use in special HCV populations, as has recently been recommended by expert guidelines. The treatment regimens and sustained virological response rates for special populations are nearly similar to those of the general HCV population. Sofosbuvir is not recommended in patients with severe renal impairment, and simeprevir and 3D regimen are not recommended for those with decompensated liver disease.
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47
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Saab S, Jimenez M, Fong T, Wu C, El Kabany M, Tong MJ. Timing of Antiviral Therapy in Candidates for Liver Transplant for Hepatitis C and Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2015; 14:66-71. [PMID: 26581477 DOI: 10.6002/ect.2015.0069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Hepatitis C virus infection is the most common underlying reason for hepatocellular carcinoma and indication for liver transplant. The increased availability of non-interferon-based therapy has expanded the number of treatment-eligible patients. MATERIALS AND METHODS We used a decision analysis model to compare 2 strategies of treating hepatitis C virus. Included patients were followed for 1 year after liver transplant. The probabilities and costs were obtained from a literature review, an expert panel, and our institution's experience. Sensitivity analyses were performed on all variables. RESULTS Our model demonstrated that it would be less costly to treat patients after liver transplant than to treat patients while they wait for transplant. When we compared baseline values, the cost difference between the 2 strategies was $25,011 per patient and $41,535 per sustained viral response. Overall survival was 60.1% for both strategies. Our model was robust across most of the variables tested in the sensitivity analysis. CONCLUSIONS Our results indicated that there is no substantial pharmacoeconomic or survival advantage of treating hepatitis C virus in patients with compensated cirrhosis and hepatocellular carcinoma before liver transplant versus after transplant.
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Affiliation(s)
- Sammy Saab
- From the Departments of Medicine and Surgery, University of California at Los Angeles, Los Angeles, USA
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48
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Kawaoka T, Takahashi S, Kawakami Y, Tsuge M, Hiramatsu A, Imamura M, Hyogo H, Aikata H, Ishiyama K, Tashiro H, Ohdan H, Tanaka J, Chayama K. Sustained virological response to antiviral therapy improves survival rate in patients with recurrent hepatitis C virus infection after liver transplantation. Hepatol Res 2015; 45:1047-54. [PMID: 25376902 DOI: 10.1111/hepr.12447] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 10/28/2014] [Accepted: 10/28/2014] [Indexed: 02/08/2023]
Abstract
AIM Previous European and North American studies analyzed the relationship between survival rate and sustained virological response (SVR) to interferon (IFN) therapy in patients with recurrent hepatitis C viral (HCV) infection after liver transplantation (LT). The present study was designed to define the same relationship in Japanese patients who had undergone LT. METHODS Forty-seven patients (genotype 1, 40; genotype 2, 7) with recurrent HCV after LT were treated with pegylated interferon (PEG IFN) or IFN/ribavirin (RBV). In possible, within 3 months after LT, patients started treatment with PEG IFN-α-2b or IFN-α-2b s.c. once weekly combined with RBV (200 mg/day). RESULTS The SVR rate was 51% (24/47) for all patients, 42.5% (17/40) for genotype 1 and 100% (7/7) for genotype 2. The median follow-up period was 71 months (range, 24-152). The survival rate of 24 patients who achieved SVR was 95% at 5 years and 92% at 10 years. These rates were significantly better than those of 23 patients who did not achieve SVR (82% at 5 years, 58% at 10 years) (P = 0.027). Two patients of the SVR group died during follow up (due to hepatocellular carcinoma in one and chronic rejection in one), while six non-SVR patients died during the same period (three died due to liver failure by recurrent HCV). CONCLUSION SVR following IFN therapy contributes to improvement of survival rate in patients with recurrent post-LT HCV infection.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Shoichi Takahashi
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Kohei Ishiyama
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hirotaka Tashiro
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
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49
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Saxena V, Terrault N. Current Management of Hepatitis C Virus: Regimens for Peri-Liver Transplant Patients. Clin Liver Dis 2015; 19:669-88, vi. [PMID: 26466655 PMCID: PMC8115933 DOI: 10.1016/j.cld.2015.06.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis C virus (HCV) infection currently remains the leading indication for liver transplant in the United States. However, recurrent HCV infection after transplant is universal in those who enter transplant with viremia resulting in reduced posttransplant graft and patient survival rates, caused in large part by progressive recurrent HCV disease. Therefore, successful treatment of HCV in the peri-transplant period, either before or after transplant, is paramount in ensuring improved posttransplant outcomes. This article reviews the experience to date treating HCV in wait-listed patients and liver transplant recipients and the unique challenges encountered when treating this population.
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Affiliation(s)
- Varun Saxena
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Norah Terrault
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
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50
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Leroy V, Dumortier J, Coilly A, Sebagh M, Fougerou-Leurent C, Radenne S, Botta D, Durand F, Silvain C, Lebray P, Houssel-Debry P, Kamar N, D'Alteroche L, Petrov-Sanchez V, Diallo A, Pageaux GP, Duclos-Vallee JC, Duclos-Vallée JC, Coilly A, Bellissant E, Botta-Fridlund D, Diallo A, Dumortier J, Durand F, Duvoux C, Fougerou-Leurent C, Leroy V, Petrov-Sanchez V, Renault A, Rohel A, Roque AM, Taburet AM, Veislinger A. Efficacy of Sofosbuvir and Daclatasvir in Patients With Fibrosing Cholestatic Hepatitis C After Liver Transplantation. Clin Gastroenterol Hepatol 2015; 13:1993-2001.e1-2. [PMID: 26044317 DOI: 10.1016/j.cgh.2015.05.030] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 05/20/2015] [Accepted: 05/20/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Fibrosing cholestatic hepatitis (FCH) is a life-threatening disorder that develops in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation. Until recently, therapeutic options have been limited. We evaluated the efficacy and safety of sofosbuvir- and daclatasvir-based regimens. METHODS We analyzed data from 23 patients with FCH who participated in a prospective cohort study in France and Belgium of the effects of antiviral agents in patients with recurrence of HCV infection after liver transplantation, from October 2013 through April 2014. Most of the patients had genotype 1 infections that had not responded to previous treatment; 4 patients also were infected with human immunodeficiency virus. Eight patients (37%) had ascites and 15 patients (65%) had bilirubin levels greater than 100 mmol/L; their median serum level of HCV RNA was 7 log IU/mL. The median time between transplantation and treatment initiation was 5 months. Subjects were given either sofosbuvir and daclatasvir (n = 15) or sofosbuvir and ribavirin (n = 8) for 24 weeks. The primary outcome was complete clinical response (survival without re-transplantation, bilirubin level <34 μmol/L, and no ascites or hepatic encephalopathy 36 weeks after treatment began). RESULTS All patients survived, without re-transplantation, until week 36. Rapid and dramatic improvements in clinical status were observed. The patients' median bilirubin concentration decreased from 122 μmol/L at baseline to a normal value at week 12 of treatment. Twenty-two patients (96%) had a complete clinical response at week 36. Despite the low rate of rapid virologic response, 22 patients (96%) achieved a sustained virologic response at week 12. The only relapse of HCV infection occurred in a patient with human immunodeficiency virus infection who received sofosbuvir and ribavirin. Tolerance was satisfactory, with no grade 3 or 4 adverse events related to sofosbuvir or daclatasvir and no significant interactions among drugs. CONCLUSIONS Sofosbuvir therapy with daclatasvir or ribavirin leads to major clinical improvement and high rates of sustained virologic response at week 12 in most patients with recurrence of HCV infection and FCH after liver transplantation. ClinicalTrial.gov no: NCT01944527.
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Affiliation(s)
- Vincent Leroy
- Clinique Universitaire d'Hépato-Gastroentérologie, Pôle Digidune, Centre Hospitalier Universitaire de Grenoble, Grenoble, France; Unité INSERM/Université Grenoble Alpes U823, Immunologie Analytique des Pathologies Chroniques Institut Albert Bonniot, Grenoble, France.
| | - Jérôme Dumortier
- Hôpital Edouard Herriot, Unité de Transplantation Hépatique, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France
| | - Audrey Coilly
- Assistance Publique-Hôpitaux de Paris Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France; Université Paris-Sud, UMR-S 1193, Villejuif, France; Inserm, Unité 1193, Villejuif, France; DHU Hepatinov, Villejuif, France
| | - Mylène Sebagh
- Assistance Publique-Hôpitaux de Paris Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France; Université Paris-Sud, UMR-S 1193, Villejuif, France; Inserm, Unité 1193, Villejuif, France; DHU Hepatinov, Villejuif, France
| | - Claire Fougerou-Leurent
- Unit of Clinical Pharmacology, Rennes University Hospital, Rennes, France; INSERM Clinical Investigation Centre 1414, Rennes, France
| | - Sylvie Radenne
- Hôpital de la Croix Rousse, Service de Transplantation Hépatique et INSERM 1052, Lyon, France
| | - Danielle Botta
- Centre Hospitalier Universitaire Conception, Service d'Hépato-Gastroentérologie, Marseille, France
| | - François Durand
- Département d'Hépatologie, Hôpital Beaujon-Assistance Publique-Hôpitaux de Paris, Clichy, France; Université Paris Diderot et INSERM U1149, Centre de Recherche sur l'Inflammation, Clichy, France
| | - Christine Silvain
- Département d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France; EA 4331, Pôle Biologie Santé, Poitiers, France
| | - Pascal Lebray
- Departement of d'Hépatologie et de Gastroenterologie, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, Paris, France
| | - Pauline Houssel-Debry
- Service des Maladies du Foie, Centre Hospitalier Universitaire Rennes, Rennes, France
| | - Nassim Kamar
- Département de Néphrologie et de Transplantation d'Organes, Centre Hospitalier Universitaire Rangueil, Toulouse, France; Université Paul Sabatier, Toulouse, France; INSERM U1043, IFR-BMT, Centre Hospitalier Universitaire Purpan, Toulouse, France
| | - Louis D'Alteroche
- Service d'Hépato-Gastroentérologie, Centre Hospitalier Universitaire Trousseau, Tours, France
| | - Ventzislava Petrov-Sanchez
- Unit for Basic and Clinical Research on Viral Hepatitis, ANRS (France Recherche Nord and Sud Sida-HIV Hépatites FRENSH), Paris, France
| | - Alpha Diallo
- Unit for Basic and Clinical Research on Viral Hepatitis, ANRS (France Recherche Nord and Sud Sida-HIV Hépatites FRENSH), Paris, France
| | - Georges-Philippe Pageaux
- Département d'Hépato-Gastroentérologie et de Transplantation Hépatique, Centre Hospitalier Universitaire Saint-Eloi, Montpellier, France; Université Montpellier 1, Montpellier, France
| | - Jean-Charles Duclos-Vallee
- Assistance Publique-Hôpitaux de Paris Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, France; Université Paris-Sud, UMR-S 1193, Villejuif, France; Inserm, Unité 1193, Villejuif, France; DHU Hepatinov, Villejuif, France
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