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1
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Kumar S, Pedersen R, Sahajpal A. Impact of Donation After Circulatory Death Allografts on Outcomes After Liver Transplant for Hepatitis C: A Single-Center Experience and Review of the Literature. EXP CLIN TRANSPLANT 2022; 20:984-991. [PMID: 36524884 DOI: 10.6002/ect.2022.0320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVES We investigated the impact of liver transplant from donors after circulatory death on incidence and severity of recurrent hepatitis C virus infection, graft and patient survival and aimed to identify predictors of outcomes. MATERIALS AND METHODS We retrospectively reviewed all liver transplants performed at a single center (July 2007-February 2014). Patients with hepatitis C who underwent liver transplant from donors after circulatory death (group 1) were compared with hepatitis C patients who received grafts from donors after brain death (group 2) and patients without hepatitis C who received grafts from donors after circulatory death (group 3).We used the Kaplan-Meier method for survival analysis and performed a multivariable analysis for predictors of outcomes using Cox regression. Competing risk was used to analyze hepatitis C recurrence. RESULTS Of 196 patients, 107 were included: 25 in group 1, 46 in group 2, and 36 in group 3. All 3 groups were comparable, except for longer cold ischemia time (P < .01) in group 1, lower Model for End-Stage Liver Disease score at transplant in groups 1 and 3 (P < .01), and greater proportion of recipients with hepatocellular carcinoma in groups 1 and 2 (P = .02). Hepatitis C recurrence and severe recurrence at 1 and 3 years were higher in group 1 (but not statistically significant). Severe recurrence was noted in 17% versus 8% at 1 year (P = .12) and 30% versus 14% at 3 years (P = .08). Graft and patient survival rates at 1, 3, and 5 years were comparable in all 3 study groups. CONCLUSIONS Recurrent hepatitis C, including severe recurrence, was greater following donation after circulatory death compared with donation after brain death liver transplant. However, graft survival and patient survival were comparable, including in recipients of donation after circulatory death grafts without hepatitis C.
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Affiliation(s)
- Shiva Kumar
- From the Transplant Center, Advocate Aurora Health, Milwaukee, Wisconsin, USA.,From the Department of Gastroenterology and Hepatology, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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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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Smith N, Chadha R, Zerillo J, Lin HM, Ouyang Y, DeMaria S. Research Priorities in Liver Transplant Anesthesiology: Results of a Survey of Liver Transplant Anesthesiologists. Clin Transplant 2022; 36:e14607. [PMID: 35141959 DOI: 10.1111/ctr.14607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/11/2022] [Accepted: 01/31/2022] [Indexed: 11/29/2022]
Abstract
Optimal perioperative care contributes to improved patient outcomes, as demonstrated in the field of liver transplant (LT). The evolution in perioperative care over the past two decades has been driven by research in areas such as preoperative testing, coagulation management, and intraoperative monitoring. However, much of this research is driven by local institutional pressures and practices with a dearth of studies emanating from research consortia or other groups of experts within the field. To better characterize the top research questions in the field, we queried a group of 128 LT anesthesiologists representing 87 international liver transplant centers with a response from 71 practitioners (59.2%). Three experts then codified the responses into the top 20 questions, which were sent to the survey recipients as a second survey to rank order. Seventy-five respondents (61.5%) provided responses which were merged into a weighted ranked priority list and analyzed by respondent location and center size. The highest ranked question was, "What intraoperative anesthetic management/interventions affect graft outcome?" Most of the top research questions focused on preoperative risk factor management or optimization and intraoperative management techniques. In general, this priorities list may serve as a guide for transplant anesthesiology researchers to focus future research endeavors on shared interests that improve patient care. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Natalie Smith
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ryan Chadha
- Department of Anesthesiology, The Mayo Clinic Florida, Jacksonville, FL, USA
| | - Jeron Zerillo
- Department of Anesthesiology, The Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - Hung-Mo Lin
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yuxia Ouyang
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Samuel DeMaria
- Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Colucci G, Invernizzi F, Uceda Renteria S, Perbellini R, Degasperi E, D'Ambrosio R, Galmozzi E, Lunghi G, Sguazzini E, Lampertico P, Donato MF. The CCR5 and CXCR3 Pathways in Hepatitis C Virus Liver Transplanted Recipients Treated by a Direct Antiviral Agent Regimen: Informative Kinetics Profiles. Viral Immunol 2021; 34:542-551. [PMID: 34252334 DOI: 10.1089/vim.2021.0035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The CC5 and CXC3 chemokines (CK) pathways are involved in the pathogenesis and outcome of several disease states, including chronic hepatitis C (CHC). The kinetics of Regulated upon Activation Normal T cell Expressed and Secreted (RANTES) (CCL5) and IP-10 (CXCL10) during direct-acting antivirals (DAA) treatment was retrospectively analyzed in 18 liver transplant recipients (LT-R) compared with 20 patients with CHC and 49 healthy controls (HC). CK levels were determined at baseline, week 4, end of treatment, 24 weeks post-treatment (sustained virological response [SVR]), and later-on during follow-up (FU), 12 and 24 months post-DAA. At baseline, median RANTES levels were higher in HC than in both LT-R (p > 0.01) and CHC (p > 0.01), whereas IP-10 levels were higher in LT-R and CHC than in HC (p > 0.05 and p = 0.01), respectively. Mean RANTES values increased during DAA therapy to peak at SVR and FU with significantly higher levels than at baseline in LT-R (p < 0.01) and in CHC, but only at FU (p < 0.003). A subsequent return to baseline or lower levels was observed at extended FU. On the contrary, IP-10 values showed a significant decrease from baseline to SVR and FU in both LT-R (p < 0.03) and CHC (p < 0.01). RANTES profiles during the first 4 weeks of DAA treatment showed an increase or decrease from baseline according to baseline RANTES levels. CCR5 genotyping in LT-R showed the presence of 1 homozygous Δ32/Δ32 and 2 heterozygous WT/Δ32 haplotypes with a prevalence of 5.5% and 11.1%, respectively. In conclusion, although IP-10 showed the expected kinetics, the CC5 pathway appears extensively altered during CHC infection: monitoring these patients may be indicated as they may be at risk of other infections or immune-mediated disorders.
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Affiliation(s)
- Giuseppe Colucci
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Federica Invernizzi
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Sara Uceda Renteria
- Virology Unit, Division of Clinical Laboratory, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Riccardo Perbellini
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Elisabetta Degasperi
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Roberta D'Ambrosio
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Enrico Galmozzi
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Giovanna Lunghi
- Virology Unit, Division of Clinical Laboratory, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Enrico Sguazzini
- Department of Medical Biotechnology, Università Degli Studi di Milano, Milan, Italy
| | - Pietro Lampertico
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy.,Department of Medical Surgical Physiopatology and Transplantation, University of Milan, Milan, Italy
| | - Maria Francesca Donato
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
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Current management & future directions in post-liver transplant recurrence of viral hepatitis. JOURNAL OF LIVER TRANSPLANTATION 2021. [DOI: 10.1016/j.liver.2021.100027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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6
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Brown KA. From Heresy to Standard of Care: A Virologic Journey. Liver Transpl 2021; 27:486-488. [PMID: 37160033 DOI: 10.1002/lt.25983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 01/04/2021] [Indexed: 12/14/2022]
Affiliation(s)
- Kimberly A Brown
- Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
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7
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Liu D, Ndongwe TP, Puray-Chavez M, Casey MC, Izumi T, Pathak VK, Tedbury PR, Sarafianos SG. Effect of P-body component Mov10 on HCV virus production and infectivity. FASEB J 2020; 34:9433-9449. [PMID: 32496609 DOI: 10.1096/fj.201800641r] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 03/28/2020] [Accepted: 05/04/2020] [Indexed: 12/11/2022]
Abstract
Mov10 is a processing body (P-body) protein and an interferon-stimulated gene that can affect replication of retroviruses, hepatitis B virus, and hepatitis C virus (HCV). The mechanism of HCV inhibition by Mov10 is unknown. Here, we investigate the effect of Mov10 on HCV infection and determine the virus life cycle steps affected by changes in Mov10 overexpression. Mov10 overexpression suppresses HCV RNA in both infectious virus and subgenomic replicon systems. Additionally, Mov10 overexpression decreases the infectivity of released virus, unlike control P-body protein DCP1a that has no effect on HCV RNA production or infectivity of progeny virus. Confocal imaging of uninfected cells shows endogenous Mov10 localized at P-bodies. However, in HCV-infected cells, Mov10 localizes in circular structures surrounding cytoplasmic lipid droplets with NS5A and core protein. Mutagenesis experiments show that the RNA binding activity of Mov10 is required for HCV inhibition, while its P-body localization, helicase, and ATP-binding functions are not required. Unexpectedly, endogenous Mov10 promotes HCV replication, as CRISPR-Cas9-based Mov10 depletion decreases HCV replication and infection levels. Our data reveal an important and complex role for Mov10 in HCV replication, which can be perturbed by excess or insufficient Mov10.
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Affiliation(s)
- Dandan Liu
- Christopher Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA
| | - Tanyaradzwa P Ndongwe
- Christopher Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA
| | - Maritza Puray-Chavez
- Christopher Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA
| | - Mary C Casey
- Christopher Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO, USA
| | - Taisuke Izumi
- Viral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute-Frederick, Frederick, MD, USA
| | - Vinay K Pathak
- Viral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute-Frederick, Frederick, MD, USA
| | - Philip R Tedbury
- Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Stefan G Sarafianos
- Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
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8
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Fu H, Dong J, Sun Z, Zhang X, Yu A, Chen G, Li W. Efficacy and safety of sofosbuvir-containing regimens in patients with chronic hepatitis C virus infection after liver transplantation: a meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:648. [PMID: 32566585 PMCID: PMC7290620 DOI: 10.21037/atm-20-3074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). Methods We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. Results A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. Conclusions The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.
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Affiliation(s)
- Hua Fu
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Jiahong Dong
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Center of Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Zhide Sun
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Xuejun Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Aijun Yu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Guoli Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Wei Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
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Morgan TR. Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases-Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Hepatology 2020; 71:686-721. [PMID: 31816111 PMCID: PMC9710295 DOI: 10.1002/hep.31060] [Citation(s) in RCA: 510] [Impact Index Per Article: 102.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Affiliation(s)
| | - Timothy R. Morgan
- Chief of Hepatology Veterans Affairs Long Beach Healthcare System Long Beach CA
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Llovet LP, Sciarrone S, Rodríguez-Tajes S, Montironi C, Mescoli C, Rugge M, Crespo G, Burra P, Forns X, Diaz A, Londoño MC. Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation. GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 43:14-21. [PMID: 31495536 DOI: 10.1016/j.gastrohep.2019.07.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 06/18/2019] [Accepted: 07/04/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. AIM To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). PATIENTS AND METHODS Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. RESULTS Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50-64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1-5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p=0.047) and 20.58 (p=0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k=0.033). DISCUSSION Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH.
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Affiliation(s)
| | - Salvatore Sciarrone
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | | | - Carla Montironi
- Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain
| | - Claudia Mescoli
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy
| | - Massimo Rugge
- Surgical Pathology & Cytopathology Unit, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Xavier Forns
- Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - Alba Diaz
- Pathology Department, Hospital Clínic Barcelona, Barcelona, Spain
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Serin A, Sahin T, Emek E, Arikan T, Koculu S, Yazici P, Mammadov E, Yuzer Y, Tokat Y. Role of Preoperative Viral Load and Presence of Hepatocellular Carcinoma in the Biliary Complications After Liver Transplantation Due to Hepatitis C Virus. Transplant Proc 2019; 51:2482-2485. [PMID: 31405736 DOI: 10.1016/j.transproceed.2019.02.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 02/17/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection is a global health problem, and the need for liver transplants is ever-growing. For optimal surgical success, risk factors must be identified and HCV viral load must be reduced to a minimum to avoid complications. In this study, we aimed to investigate the role of HCV viral load on the post-transplant biliary complications. METHOD Between 2004 and 2018, the cases of 114 liver transplant recipients with HCV infection were retrospectively reviewed. Data collection included demographic variables, preoperative and postoperative amount of serum HCV RNA copies, preoperative diagnosis of hepatocellular carcinoma (HCC), and postoperative biliary complications in the early and late period. After missing values were excluded, the remaining 97 patients were divided into 2 groups according to preoperative HCV RNA status (Group A: HCV RNA [+] and Group B: HCV RNA [-]). RESULTS Demographic parameters were similar among both groups. There were 67 patients in Group A and 30 patients in Group B. The overall rate of biliary complications was higher in Group A without statistical significance (20% [n = 14] vs 13% [n = 4], respectively, P = .573). Biliary stricture occurrence in the late period was also higher in Group A. In HCC (+) patients (n = 26), biliary complications were significantly higher compared to HCC (-) patients (34% vs 12%, P = .018). However, in patients with biliary complications, the rate of multiple duct anastomoses was higher with no statistical significance (45% vs 26%, respectively, P = .14). CONCLUSION The biliary complications on patient survival has been previously established, and this is mostly evident in those patients with viral etiology and hepatocellular carcinoma. As was also suggested in our study, hepatocellular carcinoma and positive viral status should be considered as predisposing factors for postoperative biliary complications after liver transplantation. However, the rate of multiple duct anastomoses should also be taken into consideration. New standards of antiviral medications and bridge therapy for HCC may improve transplant outcomes.
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Affiliation(s)
- Ayfer Serin
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey.
| | - Tolga Sahin
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Ertan Emek
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Turkmen Arikan
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Safiye Koculu
- Sisli Florence Nightingale Hospital, Infectious Diseases Department, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Pinar Yazici
- Sisli Hamidiye Etfal Training And Research Hospital, Department of General Surgery, Istanbul, Turkey
| | - Elmar Mammadov
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Yildiray Yuzer
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
| | - Yaman Tokat
- Sisli Florence Nightingale Hospital, Liver Transplantation Institute, Hospital of Istanbul Bilim University, Istanbul, Turkey
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Simoncini GM, Oyola-Jimenez J, Singleton D, Volgraf J, Ramsey FV, Goldberg A. HIV and HCV screening among trauma patients. Int J STD AIDS 2019; 30:663-670. [PMID: 30961465 DOI: 10.1177/0956462419829590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The purpose of this study was to develop a hepatitis C virus (HCV) and HIV screening program for patients evaluated by the trauma service and link to care. Patients were offered screening for HCV antibody and HIV. Demographics were collected on gender, race, age, and history of intravenous drug use. A navigator connected patients to treatment. In total, 1160 trauma patients were screened for HCV and/or HIV. There were 162 (14%) patients with HCV antibodies. Patients who inject drugs comprised 39.5% (64) of the HCV antibody positive group. Forty-six (68.7%) patients received linkage to care services and 55 (34%) patients were actively engaged in treatment. There were 155 (10.5%) of all eligible patients screened for HIV. Twenty-one (13.5%) patients were living with HIV (PLWH) and there were two (1.3%) new HIV infections. All new PLWH were linked to care and a total of 14 (73.7%) PLWH were on antiretroviral therapy. This is the first HCV and HIV screening and linkage to care program of trauma surgery patients. In this interim program evaluation, we found high prevalence of HCV antibody and HIV prevalence and high linkage to care rates. Trauma service HCV and HIV screening is an opportunity to diagnose, link, and re-engage a vulnerable population.
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Affiliation(s)
- Gina M Simoncini
- 1 Department of Medicine, Section of General Internal Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Josue Oyola-Jimenez
- 1 Department of Medicine, Section of General Internal Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Davone Singleton
- 1 Department of Medicine, Section of General Internal Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Jill Volgraf
- 2 Department of Nursing, Temple University Hospital, Philadelphia, PA, USA
| | - Frederick V Ramsey
- 3 Department of Clinical Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Amy Goldberg
- 4 Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
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13
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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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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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Shahriari-Fard F, Alavian SM, Farajzadegan Z, Rabiei A, Ataei B, Ataie M. Assessment of hepatitis C risk factors in center of Iran: A case-control study. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2018; 23:87. [PMID: 30505325 PMCID: PMC6225444 DOI: 10.4103/jrms.jrms_1211_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 06/17/2018] [Accepted: 06/28/2018] [Indexed: 12/15/2022]
Abstract
Background: Hepatitis C virus (HCV) infections remain as one of the major public health problems worldwide. The current study aimed at investigating the potential risk factors of HCV+ in a sample of Iranian patients. Materials and Methods: In a case–control study, 436 HCV-infected patients and 531 age-matched HCV antibody negative controls were recruited in a central region of Iran. Sociodemographic characteristics, blood and therapeutic factors, underlying diseases, and behavioral risk factors were evaluated through a standard checklist and compared between two study groups. Results: Although among studied potential risk factors, many of them were significantly associated with infected with HCV; however, in multivariable logistic regression model in the presence of other variables being male gender (odds ratio [OR]: 4.1; 95% confidence interval [CI]: 2.2–7.8), illiterate or less educated (OR: 62.64; 95% CI: 5.94–660.35), having history of intravenous (IV) drug addiction (OR: 33.0; 95% CI: 5.43–250.0), and tattooing (OR: 14.29; 95% CI: 1.82–90.91) increased risk of infection with HCV. Conclusion: In total, the current case–control study documented that socioecomical factors including economical state, marital status, education, and ethnicity and also other expected factors such as hospitalization, imprisonment, dialysis, tattooing, needle sharing, IV drug abuse, and extramarital sexual relationship represent an important source of HCV infection among adults in a central region of Iran. Thus, we suggest further considerations for prevention of HCV infection as most of related factors are preventable by close considerations.
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Affiliation(s)
- Faramarz Shahriari-Fard
- Baghiatallah Research Center of Gastroentrology and Liver Diseases, Baghiatallah University of Medical Scienes, Tehran, Iran
| | - Sayed Moayed Alavian
- Baghiatallah Research Center of Gastroentrology and Liver Diseases, Baghiatallah University of Medical Scienes, Tehran, Iran
| | - Ziba Farajzadegan
- Department of Community Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Rabiei
- Baghiatallah Research Center of Gastroentrology and Liver Diseases, Baghiatallah University of Medical Scienes, Tehran, Iran
| | - Behrooz Ataei
- Department of Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehdi Ataie
- Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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16
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Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients After Liver Transplantation: Results From the ANRS CO23 CUPILT Study. Transplantation 2018; 102:119-126. [PMID: 28846559 DOI: 10.1097/tp.0000000000001928] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation. METHODS Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort. Their antiviral treatment combined SOF, daclatasvir with or without ribavirin (n = 10/n = 6), or SOF, ledipasvir with or without ribavirin (n = 2/n = 11). RESULTS The median delay between liver transplantation and treatment initiation was 37.5 months (interquartile range [IQR], 14.4-99.2). The breakdown of HCV genotypes was G1, 22 patients (75.9%); G3, 3 patients (10.3%); and G4, 4 patients (13.8%). The treatment indications were HCV recurrence (≥ F1 n = 23) or fibrosing cholestatic hepatitis (n = 6). Before starting SOF, the HCV viral load and CD4 count were 6.7 log10 IU/mL (IQR, 5.9-7.2) and 342 cells/mm (IQR, 172-483), respectively. At week 4, the HCV viral load was less than 15 IU/mL in 12 (42.9%) patients. The overall sustained virological response 12 was 96.6%. No significant drug-drug interactions were observed. CONCLUSIONS SOF-based treatment regimens produced excellent results in HIV/HCV coinfected patients after liver transplantation, suggesting an important change in their prognosis.
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17
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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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18
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Rizk MA, Agha SAE, Zaki MES, El-mashad NBE, El-saadany MMF. Early detection of active Human Cytomegalovirus infection after living-donor liver transplantation.. [DOI: 10.1101/304360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
AbstractHuman cytomegalovirus (HCMV) is a member of the beta herpes virinae. It is one of the most important virus in transplantation. It has direct and indirect impact on liver transplant recipient outcome. We aimed to diagnose early active HCMV infection in living donor liver transplant (LDLT) recipients. Also, to correlate the associated clinical and laboratory findings with HCMV infection. Here, we investigate 76 LDLT recipients for early detection of active HCMV infection in a period of 1-6 months after liver transplantation upon their suggested clinical data. These samples were collected in the period from 4/2013 to 12/ 2015 at Gastroenterology center, Mansoura University. They were 68 males and 8 females. HCMV infection diagnosed by ELISA (Ig M, Ig G) and real time PCR. Seventy-four patients were IgG seropositive recipient. Three patients (3.9%) were positive IgM. Ten samples from 76 patients (13.2%) were positive by real-time polymerase chain reaction (PCR). In this study, we concluded that, LDLT recipients are at high risk of HCMV infection (13.2%) and the most suitable method for HCMV detection was PCR.
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19
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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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20
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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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21
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International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 2018; 101:956-967. [PMID: 28437388 DOI: 10.1097/tp.0000000000001704] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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22
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Short-term Results of Liver Transplantation With Octogenarian Donors. Transplant Proc 2018; 50:184-191. [DOI: 10.1016/j.transproceed.2017.12.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Accepted: 12/04/2017] [Indexed: 02/06/2023]
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23
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting. Transplantation 2017; 101:2739-2745. [PMID: 28795982 DOI: 10.1097/tp.0000000000001907] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. METHODS This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. RESULTS A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. CONCLUSIONS LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.
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Gambato M, Crespo G, Torres F, LLovet L, Carrión J, Londoño M, Lens S, Mariño Z, Bartres C, Miquel R, Navasa M, Forns X. Simple prediction of long-term clinical outcomes in patients with mild hepatitis C recurrence after liver transplantation. Transpl Int 2017; 29:698-706. [PMID: 26661662 DOI: 10.1111/tri.12730] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 08/20/2015] [Accepted: 12/01/2015] [Indexed: 01/11/2023]
Abstract
Little is known about the long-term outcomes of mild hepatitis C recurrence after liver transplantation (LT). In an era where most patients request treatment with direct acting antivirals (DAAs), data on the natural history in these patients are relevant. We have prospectively assessed the clinical outcomes of 173 patients with mild hepatitis C recurrence 1 year after LT. The endpoints were cirrhosis development (F = 4, HVPG ≥10 mmHg, liver stiffness measurement ≥14 kPa) and HCV-related graft loss. After a median follow-up of 80 months, the cumulative probability (CP) of HCV-related graft loss 5 and 10 years after LT were only 3% and 10%, respectively. Graft cirrhosis developed in 26 (15%) patients over time, with a CP of 13% and 30% at 5 and 10 years after LT, respectively. The CP of cirrhosis 5 years after LT was only 8% in patients with a donor <50 years and AST <60 IU/l 1 year after LT (n = 67), compared with 46% in those 24 individuals with both risk factors. Our data support an excellent long-term outcome of patients with mild hepatitis C recurrence 1 year after LT. There are, however, some patients progressing to cirrhosis who can be easily identified and who should receive prompt antiviral therapy.
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Affiliation(s)
- Martina Gambato
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Ferran Torres
- Medical Statistics Core Facility, Hospital Clinic, IDIBAPS, Barcelona, Spain.,Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Laura LLovet
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - José Carrión
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - María Londoño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Concepció Bartres
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Rosa Miquel
- Pathology Department, Hospital Clínic, Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
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26
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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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27
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Bernuth S, Grimm D, Vollmar J, Darstein F, Mittler J, Heise M, Hoppe-Lotichius M, Galle PR, Lang H, Zimmermann T. Efficacy and safety of direct-acting antiviral therapy in previous hard-to-treat patients with recurrent hepatitis C virus infection after liver transplantation: a real-world cohort. Drug Des Devel Ther 2017; 11:2131-2138. [PMID: 28744104 PMCID: PMC5513830 DOI: 10.2147/dddt.s139837] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has been a frequent and relevant problem in the past two decades. This analysis evaluated the efficacy and safety of new interferon (IFN)-free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV patients after LT. METHODS We retrospectively analyzed a cohort of 157 patients infected with HCV who underwent deceased donor LT between 1997 and 2014. Patient survival, outcome, and side effects of antiviral therapy were assessed. RESULTS Survival with recurrent HCV genotype 1 (GT1) infection was inferior to other HCV GTs (P=0.01). The overall sustained virological response (SVR) rate with new DAA therapy was 94.6% (n=37). Patients with both GT1 and other GTs reached SVR rates >90%. We noticed a few side effects, mainly caused by ribavirin, and only one discontinuation in DAA-treated patients. CONCLUSION DAA therapy was effective and safe in previous hard-to-treat patients after LT in this real-world cohort.
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Affiliation(s)
| | - Daniel Grimm
- First Department of Internal Medicine, Transplant Hepatology
| | - Johanna Vollmar
- First Department of Internal Medicine, Transplant Hepatology
| | - Felix Darstein
- First Department of Internal Medicine, Transplant Hepatology
| | - Jens Mittler
- General-, Abdominal- and Transplant-Surgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Michael Heise
- General-, Abdominal- and Transplant-Surgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Maria Hoppe-Lotichius
- General-, Abdominal- and Transplant-Surgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Peter R Galle
- First Department of Internal Medicine, Transplant Hepatology
| | - Hauke Lang
- General-, Abdominal- and Transplant-Surgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Tim Zimmermann
- First Department of Internal Medicine, Transplant Hepatology
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28
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Lee DD, Li J, Wang G, Croome KP, Burns JM, Perry DK, Nguyen JH, Hopp WJ, Taner CB. Looking inward: The impact of operative time on graft survival after liver transplantation. Surgery 2017; 162:937-949. [PMID: 28684160 DOI: 10.1016/j.surg.2017.05.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 04/27/2017] [Accepted: 05/12/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Operative time often has been cited as an important factor for postoperative outcomes. Despite this belief, most efforts to improve liver transplant outcomes have largely focused on only patient and donor factors, and little attention has been paid on operative time. The primary objective of this project was to determine the impact of operative time on graft survival after liver transplant. METHODS A retrospective review of 2,877 consecutive liver transplants performed at a single institution was studied. Data regarding recipient, donor, and operative characteristics, including detailed granular operative times were collected prospectively and retrospectively reviewed. Using an instrument variable approach, Cox multivariate modeling was performed to assess the impact of operative time without the confounding of known and unknown variables. RESULTS Of the 2,396 patients who met the criteria for review, the most important factors determining liver transplant graft survival included recipient history of Hepatitis C (hazard ratio 1.45, P = .02), donor age (hazard ratio 1.23, P = .03), use of liver graft from donation after cardiac death donor (hazard ratio 1.50, P < .01), and operative time (hazard ratio 1.26, P = .01). In detailed analysis of stages of the liver transplant operation, the time interval from incision to anhepatic phase was associated with graft survival (hazard ratio 1.33; P = .02). CONCLUSION Using a novel instrument variable approach, we demonstrate that operative time (in particular, the time interval from incision to anhepatic time) has a significant impact on graft survival. It also seems that some of this efficiency is under the influence of the transplant surgeon.
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Affiliation(s)
- David D Lee
- Mayo Clinic Collaborative in Transplant Research and Outcomes, Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Jun Li
- Department of Technology and Operations, Ross School of Business, University of Michigan, Ann Arbor, MI
| | - Guihua Wang
- Department of Technology and Operations, Ross School of Business, University of Michigan, Ann Arbor, MI
| | - Kristopher P Croome
- Mayo Clinic Collaborative in Transplant Research and Outcomes, Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Justin M Burns
- Mayo Clinic Collaborative in Transplant Research and Outcomes, Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Dana K Perry
- Mayo Clinic Collaborative in Transplant Research and Outcomes, Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Justin H Nguyen
- Mayo Clinic Collaborative in Transplant Research and Outcomes, Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Wallace J Hopp
- Department of Technology and Operations, Ross School of Business, University of Michigan, Ann Arbor, MI
| | - C Burcin Taner
- Mayo Clinic Collaborative in Transplant Research and Outcomes, Department of Transplant, Mayo Clinic Florida, Jacksonville, FL.
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29
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Abstract
Mortality rates on the liver transplant waiting list are increasing. The shortage of organs has resulted in higher utilization of extended criteria donors (ECDs), with centers pushing the limits of what is acceptable for transplantation. Donor quality is more appropriately represented as a continuum of risk, and careful selection and matching of ECD grafts with recipients may lead to excellent outcomes. Although there is no precise definition for what constitutes an ECD liver, this review focuses on frequently cited characteristics, including donor age, steatosis, donation after cardiac death, and donors with increased risk of disease transmission.
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Affiliation(s)
- Irine Vodkin
- Division of Gastroenterology and Hepatology, University of California, San Diego, 200 West Arbor Drive M/C 8413, San Diego, CA, USA.
| | - Alexander Kuo
- Division of Gastroenterology and Hepatology, University of California, San Diego, 200 West Arbor Drive M/C 8413, San Diego, CA, USA
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30
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Abstract
Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes progressive liver damage, which might result in liver cirrhosis and hepatocellular carcinoma. Globally, between 64 and 103 million people are chronically infected. Major risk factors for this blood-borne virus infection are unsafe injection drug use and unsterile medical procedures (iatrogenic infections) in countries with high HCV prevalence. Diagnostic procedures include serum HCV antibody testing, HCV RNA measurement, viral genotype and subtype determination and, lately, assessment of resistance-associated substitutions. Various direct-acting antiviral agents (DAAs) have become available, which target three proteins involved in crucial steps of the HCV life cycle: the NS3/4A protease, the NS5A protein and the RNA-dependent RNA polymerase NS5B protein. Combination of two or three of these DAAs can cure (defined as a sustained virological response 12 weeks after treatment) HCV infection in >90% of patients, including populations that have been difficult to treat in the past. As long as a prophylactic vaccine is not available, the HCV pandemic has to be controlled by treatment-as-prevention strategies, effective screening programmes and global access to treatment.
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31
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Tong A, Sautenet B, Chapman JR, Harper C, MacDonald P, Shackel N, Crowe S, Hanson C, Hill S, Synnot A, Craig JC. Research priority setting in organ transplantation: a systematic review. Transpl Int 2017; 30:327-343. [PMID: 28120462 DOI: 10.1111/tri.12924] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 01/16/2017] [Accepted: 01/19/2017] [Indexed: 02/06/2023]
Abstract
Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. Databases were searched to October 2016. We synthesized the findings descriptively. The 28 studies (n = 2071 participants) addressed kidney [9 (32%)], heart [7 (25%)], liver [3 (11%)], lung [1 (4%)], pancreas [1 (4%)], and nonspecified organ transplantation [7 (25%)] using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique. Nine (32%) reported patient involvement. The 336 research priorities addressed the following: organ donation [43 priorities (14 studies)]; waitlisting and allocation [43 (10 studies)]; histocompatibility and immunology [31 (8 studies)]; immunosuppression [21 (10 studies)]; graft-related complications [38 (13 studies)]; recipient (non-graft-related) complications [86 (14 studies)]; reproduction [14 (1 study)], psychosocial and lifestyle [49 (7 studies)]; and disparities in access and outcomes [10 (4 studies)]. The priorities identified were broad but only one-third of initiatives engaged patients/caregivers, and details of the process were lacking. Setting research priorities in an explicit manner with patient involvement can guide investment toward the shared priorities of patients and health professionals.
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Affiliation(s)
- Allison Tong
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Benedicte Sautenet
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Jeremy R Chapman
- Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
| | - Claudia Harper
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Peter MacDonald
- Heart Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia.,Transplantation Research Laboratory, Victor Chang, Cardiac Research Institute, Sydney, NSW, Australia
| | - Nicholas Shackel
- Department of Medicine, University of New South Wales, Sydney, NSW, Australia
| | | | - Camilla Hanson
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Sophie Hill
- Centre for Health Communication and Participation, La Trobe University, Melbourne, Vic., Australia
| | - Anneliese Synnot
- Centre for Health Communication and Participation, La Trobe University, Melbourne, Vic., Australia.,School of Preventive Medicine and Public Health, Monash University, Melbourne, Vic., Australia
| | - Jonathan C Craig
- Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
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32
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Determinant Factors of the Direct Medical Costs Associated with Genotype 1 Hepatitis C Infection in Treatment-Experienced Patients. Drugs R D 2016; 15:335-49. [PMID: 26416653 PMCID: PMC4662942 DOI: 10.1007/s40268-015-0109-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective Limited evidence is available on predictors of medical resource utilization (MRU) and related direct costs, especially in treatment-experienced patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at investigating patient and treatment characteristics that predict MRU and related non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC) treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated interferon and ribavirin (PegIFN/R). Patients and Methods A total of 709 patients who completed the 72-week ATTAIN trial were included in the study. Cost data were analysed from the UK NHS perspective. Descriptive statistics and regression analyses were used to determine patterns and predictors of total MRU-related costs associated with SMV/PegIFN/R and TVR/PegIFN/R. Results Independent predictors for total MRU-related costs were age, region and the following interaction terms: (1) gender × F3–F4 METAVIR score × baseline viral load (BLVL), (2) body mass index (BMI) × F3–F4 METAVIR score × prior response to PegIFN/R and (3) gender × achievement of SVR at 12 weeks (SVR12) × BLVL. A F3–F4 METAVIR score was a stronger predictor of total MRU-related costs than SVR12. Predictors of adverse events included older age, female gender, low BMI, TVR/PegIFN/R and SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between SMV/PegIFN/R and TVR/PegIFN/R. Conclusion To the best of our knowledge, this study is the first to describe the relationship between commonly admitted predictors of MRU-related costs and their joint effect on total MRU-related costs in treatment-experienced patients with CHC. The identified predictors of MRU-related costs suggest that significant treatment costs can be avoided by starting treatment early before the disease progresses. Furthermore, adverse events seem to be the most important factor to take into consideration for the choice of treatment, especially when therapeutic options are associated with similar levels of medical resource utilization and associated costs. Electronic supplementary material The online version of this article (doi:10.1007/s40268-015-0109-5) contains supplementary material, which is available to authorized users.
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33
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Perspectives on treating hepatitis C infection in the liver transplantation setting. Curr Opin Organ Transplant 2016; 21:111-9. [PMID: 26927201 DOI: 10.1097/mot.0000000000000288] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW This article reviews treatment options of the approved and soon-to-be approved direct-acting antiviral (DAA)-based therapies in the transplant setting. RECENT FINDINGS DAA-based therapies have been shown to be effective and safe in achieving viral eradication in the majority of pre- and postliver transplant (LT) populations. Treatment decisions are guided by hepatitis C virus (HCV) genotype, the degree of renal dysfunction, and severity of cirrhosis. The addition of ribavirin is frequently needed to achieve highest viral eradication rates. Viral eradication pre-LT has been associated with fewer portal hypertensive complications and improved survival and effectively prevents recurrent HCV post-LT. For those with shorter time to LT, an alternative strategy is treatment with DAAs up to the time of LT to reduce the risk of post-LT recurrence. Therapies should be considered for all post-LT patients with recurrent HCV given the risk of accelerated disease progression. The sustained virological response rates among LT recipients parallel those of nontransplant patients. SUMMARY With broader application of DAA therapy in the transplant setting, improved graft and patient survival and simplified post-LT management are likely. The availability of high potency DAA therapy with excellent safety profiles has transformed the HCV-infected LT population into a group that is no longer 'difficult-to-treat.'
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34
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Seifert LL, Heinzow H, Kabar I, Christensen S, Hüsing A, Schmidt HHJ. Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:605-10. [PMID: 27554644 PMCID: PMC4999016 DOI: 10.12659/ajcr.895839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 04/22/2016] [Indexed: 02/02/2023]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. CASE REPORT The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated. CONCLUSIONS Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant interactions with the patient's immunosuppressive regimens. Still, the peritransplant setting is a very demanding environment for anti-HCV therapy, and further studies are needed.
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Affiliation(s)
- Leon Louis Seifert
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Hauke Heinzow
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Iyad Kabar
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Stefan Christensen
- Center for Interdisciplinary Medicine (CIM) Infectious Diseases, Münster, Germany
| | - Anna Hüsing
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
| | - Hartmut H.-J. Schmidt
- Department of Transplantation Medicine, University Hospital Münster, Münster, Germany
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35
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Hori T, Onishi Y, Kamei H, Kurata N, Ishigami M, Ishizu Y, Ogura Y. Fibrosing Cholestatic Hepatitis in a Complicated Case of an Adult Recipient After Liver Transplantation: Diagnostic Findings and Therapeutic Dilemma. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:597-604. [PMID: 27545580 PMCID: PMC4994933 DOI: 10.12659/ajcr.898427] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Patient: Male, 66 Final Diagnosis: Fibrosing cholestatic hepatitis Symptoms: Prolonged jaundice and intractable ascites Medication: Steroid pulse therapy and direct-acting antivirals Clinical Procedure: Liver transplantation Specialty: Transplantology
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Affiliation(s)
- Tomohide Hori
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Yasuharu Onishi
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Hideya Kamei
- Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Nobuhiko Kurata
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Yoji Ishizu
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
| | - Yasuhiro Ogura
- Department of Transplant Surgery, Nagoya University Hospital, Nagoya, Japan
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36
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Hori T, Onishi Y, Kamei H, Kurata N, Ishigami M, Ishizu Y, Ogura Y. Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver transplantation. Ann Gastroenterol 2016; 29:454-459. [PMID: 27708510 PMCID: PMC5049551 DOI: 10.20524/aog.2016.0069] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 06/06/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review.
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Affiliation(s)
- Tomohide Hori
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Yasuharu Onishi
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Hideya Kamei
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Nobuhiko Kurata
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology (Masatoshi Ishigami), Nagoya University Hospital, Nagoya, Japan
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology (Masatoshi Ishigami), Nagoya University Hospital, Nagoya, Japan
| | - Yasuhiro Ogura
- Department of Transplant Surgery (Tohomide Hori, Yasuharu Onishi, Hideya Kamei, Nobuhiko Kurata, Yasuhiro Ogura), Nagoya University Hospital, Nagoya, Japan
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37
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Kuo HT, Lum E, Martin P, Bunnapradist S. Effect of diabetes and acute rejection on liver transplant outcomes: An analysis of the organ procurement and transplantation network/united network for organ sharing database. Liver Transpl 2016; 22:796-804. [PMID: 26850091 DOI: 10.1002/lt.24414] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 01/19/2016] [Accepted: 01/29/2016] [Indexed: 12/18/2022]
Abstract
The effects of diabetic status and acute rejection (AR) on liver transplant outcomes are largely unknown. We studied 13,736 liver recipients from the United Network for Organ Sharing/Organ Procurement Transplant Network database who underwent transplantation between 2004 and 2007 with a functioning graft for greater than 1 year. The association of pretransplant diabetes mellitus (PDM), new-onset diabetes after transplant (NODAT), and AR rates on allograft failure, all-cause mortality, and cardiovascular mortality were determined. To determine the differential and joint effects of diabetic status and AR on transplant outcomes, recipients were further stratified into 6 groups: neither (reference, n = 6600); NODAT alone (n = 2054); PDM alone (n = 2414); AR alone (n = 1448); NODAT and AR (n = 707); and PDM and AR (n = 513). An analysis with hepatitis C virus (HCV) serostatus was also performed (HCV recipients, n = 6384; and non-HCV recipient, n = 5934). The median follow-up was 2537 days. The prevalence of PDM was 21.3%. At 1 year after transplant, the rates of NODAT and AR were 25.5% and 19.4%, respectively. Overall, PDM, NODAT, and AR were associated with increased risks for graft failure (PDM, hazard ratio [HR] = 1.31, P < 0.01; NODAT, HR = 1.11, P = 0.02; AR, HR = 1.28, P < 0.01). A multivariate Cox regression analysis of the 6 recipient groups demonstrated that NODAT alone was not significantly associated with any study outcomes. The presence of PDM, AR, NODAT and AR, and PDM and AR were associated with higher overall graft failure risk and mortality risk. The presence of PDM was associated with higher cardiovascular mortality risk. The analyses in both HCV-positive and HCV-negative cohorts showed a similar trend as in the overall cohort. In conclusion, PDM and AR, but not NODAT, is associated with increased mortality and liver allograft failure. Liver Transplantation 22 796-804 2016 AASLD.
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Affiliation(s)
- Hung-Tien Kuo
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.,Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Erik Lum
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Paul Martin
- Division of Hepatology, Center for Liver Diseases, University of Miami School of Medicine, Miami, FL
| | - Suphamai Bunnapradist
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA
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38
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Campos-Varela I, Moreno A, Morbey A, Guaraldi G, Hasson H, Bhamidimarri KR, Castells L, Grewal P, Baños I, Bellot P, Brainard DM, McHutchison JG, Terrault NA. Treatment of severe recurrent hepatitis C after liver transplantation in HIV infected patients using sofosbuvir-based therapy. Aliment Pharmacol Ther 2016; 43:1319-29. [PMID: 27098374 DOI: 10.1111/apt.13629] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 03/14/2016] [Accepted: 03/26/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND For liver transplant recipients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, recurrence after LT is associated with a higher risk of graft loss than for HCV mono-infected patients. Prior HCV treatment options were limited by side effects and drug-drug interactions. AIM To evaluate treatment outcomes with sofosbuvir (SOF)-based therapy among HIV/HCV coinfected liver transplant recipients. METHODS Access to SOF and ribavirin (RBV) prior to regulatory approval was attained via an international compassionate access program for transplant recipients with a life expectancy of 1 year or less in the absence of HCV treatment. This report focuses on the short and longer term outcomes in HCV-HIV co-infected liver transplant recipients. RESULTS Twenty patients were treated, nine with early severe recurrence and 11 with cirrhosis. Eleven patients received SOF and RBV, one SOF, RBV and Peg-interferon, three SOF, RBV and simeprevir and five SOF, RBV and daclatasvir. Of the 18 patients who completed treatment, 16 (89%) achieved sustained virological response 12 weeks after the end of treatment (SVR12). Liver function tests (including bilirubin and albumin) improved significantly over time. Nineteen serious adverse events occurred in eight (40%) patients, none of them related to SOF. Two patients died during treatment and another, 1 year after the end of therapy, due to progressive end-stage liver disease. Importantly, HIV suppression was not compromised. No significant drug-drug interactions were reported. CONCLUSIONS Sofosbuvir-based regimens are safe, well-tolerated and provide high rates of SVR in HCV-HIV co-infected patients with severe recurrence after-liver transplant.
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Affiliation(s)
- I Campos-Varela
- Universidade de Santiago de Compostela (CLINURSID), Santiago de Compostela, Spain.,Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,University of California-San Francisco, San Francisco, CA, USA
| | - A Moreno
- Hospital Ramón y Cajal, Madrid, Spain
| | - A Morbey
- Hospital Curry Cabral, Lisbon, Portugal
| | - G Guaraldi
- Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy
| | - H Hasson
- Scientific Institute Ospedale San Raffaele, Milan, Italy
| | - K R Bhamidimarri
- Division of Hepatology, University of Miami-Miller School of Medicine, Miami, FL, USA
| | - L Castells
- CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain.,Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - P Grewal
- Mount Sinai School of Medicine, New York, NY, USA
| | - I Baños
- Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - P Bellot
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Hospital General Universitario, Alicante, Spain
| | | | | | - N A Terrault
- University of California-San Francisco, San Francisco, CA, USA
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39
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Song ATW, Sobesky R, Vinaixa C, Dumortier J, Radenne S, Durand F, Calmus Y, Rousseau G, Latournerie M, Feray C, Delvart V, Roche B, Haim-Boukobza S, Roque-Afonso AM, Castaing D, Abdala E, D’Albuquerque LAC, Duclos-Vallée JC, Berenguer M, Samuel D. Predictive factors for survival and score application in liver retransplantation for hepatitis C recurrence. World J Gastroenterol 2016; 22:4547-4558. [PMID: 27182164 PMCID: PMC4858636 DOI: 10.3748/wjg.v22.i18.4547] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population.
METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation.
RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4 (SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation (LT1) in the liver retransplantation (reLT) group (94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-reLT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively (P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1 (mean age 48 ± 8 years compared to 53 ± 9 years in the no reLT group, P < 0.0001), less likely to have human immunodeficiency virus (HIV) co-infection (4% vs 14% among no reLT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1 (25% in reLT vs 12% in the no reLT group, P = 0.01), and more likely to have presented with sustained virological response (SVR) after the first transplantation (20% in the reLT group vs 7% in the no reLT group, P = 0.028).
CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.
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40
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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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41
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Beckwith CG, Kurth AE, Bazerman LB, Patry EJ, Cates A, Tran L, Noska A, Kuo I. A pilot study of rapid hepatitis C virus testing in the Rhode Island Department of Corrections. J Public Health (Oxf) 2016; 38:130-7. [PMID: 25736438 PMCID: PMC4750523 DOI: 10.1093/pubmed/fdv023] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The correctional population bears a heavy burden of hepatitis C virus (HCV) infection necessitating expansion of HCV testing and treatment opportunities. Rapid HCV testing provides point-of-care antibody results and may be ideal for correctional facilities, particularly jails, where persons are often incarcerated for short periods of time, yet feasibility has not been established. METHODS We conducted a pilot study of a rapid HCV testing algorithm among short-term inmates with unknown HCV status. Participants completed a questionnaire, viewed an informational video and underwent rapid HCV testing and confirmatory testing, when indicated. Persons with chronic infection were referred to community care after release. Baseline characteristics, risk behaviors, test results and linkage were examined by descriptive analyses. RESULTS Two hundred and fifty-two inmates were enrolled and 249 completed all study activities. Twenty-five participants (10%) had reactive rapid tests and 23 (92%) completed confirmatory testing. 15/23 (65%) had detectable HCV RNA, but only 4 linked to care after release. Persons with reactive HCV tests were more likely to be White (P = 0.01) and to have ever injected (P < 0.0001) and/or recently injected (P < 0.0001) drugs. CONCLUSIONS Rapid HCV testing within jails is feasible, identifies previously unrecognized cases of HCV infection, and implementation should be considered. Low rates of linkage to care after release remain a barrier to care.
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Affiliation(s)
- Curt G. Beckwith
- The Miriam Hospital/Alpert Medical School of Brown University, Providence, Rhode Island 02906, USA
| | | | | | | | - Alice Cates
- George Washington University, Washington, DC, USA
| | - Liem Tran
- The Miriam Hospital, Providence, Rhode Island, USA
| | - Amanda Noska
- The Miriam Hospital/Alpert Medical School of Brown University, Providence, Rhode Island 02906, USA
| | - Irene Kuo
- George Washington University, Washington, DC, USA
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42
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Ibáñez-Samaniego L, Catalina MV, Rincón D, Lo Iacono O, Fernández A, Clemente G, Bañares R, Vaquero J, Salcedo M. Liver Support With Albumin Dialysis Reduces Hepatitis C Virus Viremia and Facilitates Antiviral Treatment of Severe Hepatitis C Virus Recurrence After Liver Transplantation. Ther Apher Dial 2016; 20:189-96. [PMID: 26929255 DOI: 10.1111/1744-9987.12381] [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] [Received: 07/15/2015] [Revised: 09/11/2015] [Accepted: 10/09/2015] [Indexed: 11/29/2022]
Abstract
Patients with severe hepatitis C virus (HCV) recurrence after liver transplantation (LT) present an ominous prognosis, rarely achieving sustained virological response (SVR). Dialysis procedures may transiently decrease the HCV viral load, but the effect of albumin dialysis is currently unknown. Here, we evaluated the impact of albumin dialysis using the Molecular Adsorbent Recirculating System (MARS) used as a co-adjuvant antiviral treatment for severe HCV recurrence after LT. Thirteen patients (11 males, median age 48 years) with fibrosing cholestatic hepatitis or METAVIR fibrosis score ≥ F3 with severe portal hypertension underwent three consecutive MARS sessions. Antiviral therapy was initiated in 11 patients within 24 h after the MARS sessions. A contemporary cohort of seven patients who did not follow the MARS protocol is shown for comparison. MARS treatment resulted in consistent decreases of viral load from 7.59 log10 IU/mL [6.15-8.90] to 6.79 log10 IU/mL [5.18-7.84] (P = 0.003) as well as in decreases of serum bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The overall rate of SVR was 0% in the Control group and 54.6% in patients initiating antiviral therapy within 24 h after MARS. Survival at 1 and 3 years was, respectively, 93% and 70% in patients undergoing MARS, compared with 29% and 14% in the Control group (P = 0.001). No major adverse events related to MARS treatment were observed. In conclusion, the use of MARS may facilitate the achievement of SVR and improve the prognosis of patients with severe HCV-recurrence after LT by reducing viral load and improving liver function prior to antiviral therapy.
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Affiliation(s)
- Luis Ibáñez-Samaniego
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - María-Vega Catalina
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Diego Rincón
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Oreste Lo Iacono
- Servicio de Gastroenterología, Hospital del Tajo, Aranjuez, Madrid, Spain
| | - Ainhoa Fernández
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Gerardo Clemente
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Bañares
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.,Facultad de Medicina, Universidad Complutense, Madrid, Spain
| | - Javier Vaquero
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Magdalena Salcedo
- Unidad de Hepatología, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.,CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
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43
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Tong MJ, Chang PW, Huynh TT, Rosinski AA, Tong LT. Adverse events associated with ribavirin in sofosbuvir-based therapies for patients with chronic hepatitis C: A community practice experience. J Dig Dis 2016; 17:113-21. [PMID: 26749171 DOI: 10.1111/1751-2980.12313] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 12/22/2015] [Accepted: 12/27/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Due to high sustained virological response (SVR) rates, sofosbuvir-based regimens are currently a mainstay for hepatitis C virus (HCV) therapies. The addition of pegylated interferon (PEG-IFN) and ribavirin impacts patients' quality of life during treatment. This study aimed to compare severe adverse events (SAEs) amongst therapeutic combinations for HCV in a community clinic setting. METHODS From December 2013 to July 2014, 128 chronic HCV-infected patients were treated with sofosbuvir, ribavirin and weekly PEG-IFN for 12 weeks (cohort 1), 12 or 24 weeks of sofosbuvir and ribavirin (cohorts 2 and 3) or sofosbuvir plus simeprevir for 12 weeks (cohort 4). Adverse events were recorded from baseline to 12 or 24 weeks of treatment. RESULTS SAEs appeared in 15.6-53.8% of ribavirin-inclusive treated patients compared to 4.8% of the ribavirin-free regimen. PEG-IFN, sofosbuvir plus ribavirin had the highest frequencies of fatigue, headache and rash compared to either 12 or 24 weeks of ribavirin and sofosbuvir. However, sofosbuvir and ribavirin regimens led to significant increases in dyspnea, need for ribavirin dose reductions and withdrawal from treatment due to SAEs. Anemia was also more frequent in ribavirin-inclusive combinations (P < 0.001). Conversely, sofosbuvir plus simeprevir reached similar SVR rates at week 12 post-treatment compared to all ribavirin-containing regimens, but with significantly fewer adverse events (P = 0.006). At week 12 post-treatment, cirrhotic patients experienced a higher virological relapse rate than non-cirrhotic patients (P = 0.019). CONCLUSIONS Ribavirin-inclusive HCV therapies increased the frequencies of SAEs, had higher dropout rates and increased patient morbidity.
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Affiliation(s)
- Myron John Tong
- Liver Center, Huntington Medical Research Institutes, Pasadena.,Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California, USA
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44
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Spontaneous clearance of hepatitis C genotype 4 after liver retransplantation. Transplant Proc 2016; 47:1234-7. [PMID: 26036561 DOI: 10.1016/j.transproceed.2014.10.065] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 10/28/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV)-related cirrhosis remains the most common indication for liver transplantation worldwide. Graft reinfection with HCV is nearly universal, causing significant morbidity and mortality. Spontaneous clearance of HCV after liver transplantation and retransplantation is extremely rare. We report a case of spontaneous clearance of HCV genotype 4 that occurred shortly after 2nd liver transplantation. CASE REPORT A 32-year-old female patient received a cadaveric liver transplant for HCV-related cirrhosis in 2007. She was not treated for HCV before transplantation. The patient developed biopsy-proven HCV recurrence with elevated transaminases and 65,553 IU/mL HCV RNA, genotype 4. She could not tolerate interferon-based treatment. The patient's condition progressively worsened and required a 2nd cadaveric liver transplantation in March 2013. Immunosuppression initially included steroids and Prograf, which was then switched to cyclosporine after the patient developed seizure. She developed acute cellular rejection which was readily treated with immunosuppression adjustment. HCV RNA became negative in April, which was confirmed in May 2013. CONCLUSIONS Spontaneous clearance of hepatitis C rarely occurs after liver transplantation and is extremely rare after retransplantation. This finding may be explained by alterations in the host immune responses to HCV after transplantation. To our knowledge, this is the first case of spontaneous clearance of HCV genotype 4 after liver retransplantation.
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45
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Nguyen NH, Yee BE, Chang C, Jin M, Lutchman G, Lim JK, Nguyen MH. Tolerability and effectiveness of sofosbuvir and simeprevir in the post-transplant setting: systematic review and meta-analysis. BMJ Open Gastroenterol 2016; 3:e000066. [PMID: 26966549 PMCID: PMC4782279 DOI: 10.1136/bmjgast-2015-000066] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 11/18/2015] [Accepted: 11/20/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Outcome data on simeprevir and sofosbuvir (SMV+SOF) in patients with liver transplantation (LT) with hepatitis C virus genotype 1 (HCV-1) are limited with individual studies having a small sample size and limited SVR12 (sustained virological response) data. Our goal was to perform a meta-analysis to study the outcome of SMV+SOF±ribavirin (RBV) in recipients with LT. METHODS In April 2015, we conducted a literature search for 'simeprevir' in MEDLINE/EMBASE and five major liver meetings. We included studies with SVR12 data in ≥5 post-LT mono-infected HCV-1 patients treated with SMV+SOF±RBV. We used random-effects models to estimate effect sizes, and the Cochrane Q-test (p value <0.10) with I(2) (>50%) to assess study heterogeneity. RESULTS We included nine studies with a total of 325 patients with post-LT. Studies included mostly men (59-81%). Pooled SVR12 was 88.0% (95% CI 83.4% to 91.5%). In two studies, HCV-1a patients with mild fibrosis (n=108) had an SVR12 rate of 95.0% (95% CI 82.4% to 98.7%), which was significantly higher than that of HCV-1a patients with advanced fibrosis (n=49) with an SVR12 rate of 81.7% (95% CI 69.8% to 89.5%), OR 4.2 (95% CI 1.1 to 16.1, p=0.03). The most common pooled side effects were: fatigue 21% (n=48/237), headache 9% (n=23/254), dermatological symptoms 15% (n=38/254), and gastrointestinal symptoms 6% (12/193). CONCLUSIONS SMV+SOF±RBV is safe and effective in recipients with LT with HCV-1 infection.
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Affiliation(s)
- Nghia H Nguyen
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Brittany E Yee
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Christine Chang
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Minjuan Jin
- Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hang Zhou, China
| | - Glen Lutchman
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Joseph K Lim
- Yale Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Mindie H Nguyen
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
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46
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Kerkar N, Yanni G. ‘De novo’ and ‘recurrent’ autoimmune hepatitis after liver transplantation: A comprehensive review. J Autoimmun 2016; 66:17-24. [DOI: 10.1016/j.jaut.2015.08.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 08/23/2015] [Indexed: 02/08/2023]
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47
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EXP CLIN TRANSPLANTExp Clin Transplant 2015; 13. [DOI: 10.6002/ect.2015.0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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48
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Late liver function test abnormalities post-adult liver transplantation: a review of the etiology, investigation, and management. Hepatol Int 2015; 10:106-14. [PMID: 26603541 DOI: 10.1007/s12072-015-9685-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 11/06/2015] [Indexed: 12/14/2022]
Abstract
Approximately 24,000 liver transplants are performed annually worldwide, almost 7000 of which are performed in the USA. Survival is excellent and continues to improve, with 1-year survival currently exceeding 85 %, but effective management of patients after liver transplantation is critical to achieve optimal results. A plethora of diseases can affect the transplanted allograft, ranging from recurrence of the original disease to de novo liver pathology, and diagnosis can be complicated by nonclassical presentation, de novo disease, or inconclusive histology. Patients can remain asymptomatic despite significant damage to the transplanted liver, so prompt identification and treatment of liver disease after transplantation is crucial to preserve allograft function. Liver function tests are routinely taken throughout the postoperative period to monitor the graft. Although nonspecific, they are inexpensive, noninvasive, and sensitive for allograft disease and can quickly alert physicians to the presence of asymptomatic pathology. This review will outline possible causes of liver function test abnormalities in the late posttransplant period and provide guidance for investigation, diagnosis, and management.
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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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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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