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Fuochi E, Anastasio L, Lynch EN, Campani C, Dragoni G, Milani S, Galli A, Innocenti T. Main factors influencing long-term outcomes of liver transplantation in 2022. World J Hepatol 2023; 15:321-352. [PMID: 37034235 PMCID: PMC10075010 DOI: 10.4254/wjh.v15.i3.321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/24/2022] [Accepted: 02/22/2023] [Indexed: 04/11/2023] Open
Abstract
Liver transplant (LT) outcomes have markedly improved in the recent decades, even if long-term morbidity and mortality are still considerable. Most of late deaths are independent from graft function and different comorbidities, including complications of metabolic syndrome and de novo neoplasms, seem to play a key role in determining long-term outcomes in LT recipients. This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation. In particular, the reduction of drug toxicity, the use of tools to identify high-risk patients, and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
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Affiliation(s)
- Elisa Fuochi
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Lorenzo Anastasio
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Stefano Milani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
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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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The use of organs from hepatitis C virus-viremic donors into uninfected recipients. Curr Opin Organ Transplant 2021; 25:620-625. [PMID: 33105203 DOI: 10.1097/mot.0000000000000826] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW There has been an ongoing disparity between the number of organs available for solid organ transplantation (SOT) relative to the need. This has resulted in significant waitlist mortality, may affect transplant outcomes due to transplants being performed on sicker patients and may even increase healthcare costs due to extended hospital stays. Transplanting organs from hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R-) is now a reality, due to the advent of highly affective direct-acting antivirals (DAAs) which not only have very high efficacy, but also a favorable side effect and drug-drug interaction profile. RECENT FINDINGS Data from multiple centers reporting outcomes of kidney, liver, heart, lung and liver-kidney transplant during the past few years reveal that SOT from HCV-infected donors into noninfected recipients is safe, efficacious and can result in excellent recipient outcomes, with an opportunity to decrease the time on the waitlist, waitlist mortality and to improve outcomes after transplant due to less morbidity at the time of surgery. When livers are the transplanted organ, 8-12 weeks of DAA treatment will be required. For other organs, 2-4 weeks is likely sufficient. The available DAAs have profiles such that patients with all genotypes, with or without renal insufficiency an on renal replacement therapy and those who fail treatment may be successfully treated, with a sustained virologic response rate of more than 95%. Based upon the available data, starting DAAs shortly after transplant will likely limit posttransplant complications. that This will require cooperation between the transplant team, transplant hospital and insurer providing medication coverage. SUMMARY SOT from HCV infected recipients is safe, is associated with excellent outcomes and should be considered for recipients who would benefit from receiving an organ earlier than they would if they waited for an organ from an uninfected donor.
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Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol 2021; 27:1691-1715. [PMID: 33967551 PMCID: PMC8072198 DOI: 10.3748/wjg.v27.i16.1691] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.
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Affiliation(s)
- Daniel Castaneda
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | | - Mohammad Alomari
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Kanwarpreet Tandon
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
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Choudhary NS, Saraf N, Saigal S, Rastogi A, Bhangui P, Thiagrajan S, Soin AS. Outcome of hepatitis C-related liver transplantation in direct-acting antiviral era. Indian J Gastroenterol 2020; 39:539-543. [PMID: 33230754 DOI: 10.1007/s12664-020-01105-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 09/28/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hepatitis C virus (HCV) has become an easily treatable disease after the introduction of sofosbuvir-based direct-acting antiviral (DAA) regimens. This is a large single center experience of changing severity and outcome profile of HCV-related liver disease after availability of DAAs. METHODS A retrospective analysis of prospectively collected liver transplantation (LT) database of adults (age > 18 years at the time of LT) was performed from June 2010 to July 2018. A total of 410 patients (including 26 co-infection with hepatitis B) underwent LT for hepatitis C-related decompensated cirrhosis and/or hepatocellular carcinoma (HCC) out of 1754 adult transplantation in the defined period. RESULTS The study group comprised of 296 males and 114 females aged 52.1 ± 7.9 years. HCV-related decompensated cirrhosis and/or HCC as indication of LT was present in 289/1016 (28.4%) during 2010-2014, which was reduced to 121/738 (16.3%) during 2015-2018 (p = 0.000). The LT recipients for HCV-related cirrhosis had significantly lower Child's and model for end-stage liver disease (MELD) score during 2015-2018 as compared to that during 2010-2014; Child's score was 7.9 ± 2.2 vs. 8.6 ± 2.1, p = 0.003; MELD score was 13.9 ± 5.3 vs. 17.1 ± 5.8, p = 0.000, respectively. There was a trend towards better survival in HCV patients during 2015-2018 as compared to that during 2010-2014. Significantly more patients had HCV RNA negative status before LT during 2015-2018 (38.8% vs. 13%, p = 0.000); moreover, the proportion of LT for decompensated cirrhosis (without HCC) decreased significantly in the latter period, 64.0% vs. 42.1% (p = 0.000). CONCLUSION In the DAA era, HCV as an indication for LT has decreased and patients have less severe disease at transplantation. There is a trend towards better patient survival.
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Affiliation(s)
- Narendra S Choudhary
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India
| | - Neeraj Saraf
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India.
| | - Sanjiv Saigal
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India
| | - Amit Rastogi
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India
| | - Srinivas Thiagrajan
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India
| | - Arvinder S Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity Hospital, Sector 38, Gurugram, Delhi (NCR), 122 413, India
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Mikulic D, Mrzljak A. Liver transplantation and aging. World J Transplant 2020; 10:256-266. [PMID: 32995320 PMCID: PMC7504190 DOI: 10.5500/wjt.v10.i9.256] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 05/03/2020] [Accepted: 07/19/2020] [Indexed: 02/05/2023] Open
Abstract
An increase in the average life expectancy, paralleled by a demographic shift in the population with end-stage liver disease lies behind the rising demand for liver transplantation (LT) among the elderly. Some of the most common indications for LT including hepatocellular carcinoma, alcohol-related liver disease, chronic hepatitis C and non-alcoholic fatty liver disease tend to affect older patients. Transplant professionals are faced with an increasing demand for LT among elderly patients in an age of organ shortage and it is important that risk and benefits are carefully weighed in order to achieve the optimum use of precious liver grafts.
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Affiliation(s)
- Danko Mikulic
- Department of Abdominal and Transplant Surgery, Merkur University Hospital, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Medicine, Merkur University Hospital; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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Ghazal K, Morales O, Barjon C, Dahlqvist G, Aoudjehane L, Ouaguia L, Delhem N, Conti F. Early high levels of regulatory T cells and T helper 1 may predict the progression of recurrent hepatitis C after liver transplantation. Clin Res Hepatol Gastroenterol 2019; 43:273-281. [PMID: 30713032 DOI: 10.1016/j.clinre.2018.10.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 09/25/2018] [Accepted: 10/02/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. METHODS Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence. RESULTS mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed. CONCLUSION These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.
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Affiliation(s)
- K Ghazal
- Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; AP-HP, Bicêtre Hospital, Biochemistry Laboratory, 94275 Le Kremlin-Bicêtre cedex, France.
| | - O Morales
- CNRS, UMR8161, Institut de Biologie de Lille, Université de Lille, Institut Pasteur de Lille, IFR 142, 59021 Lille cedex, France
| | - C Barjon
- Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; De Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium
| | - G Dahlqvist
- Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; Cliniques Universitaires Saint-Luc, 1200 Woluwe-Saint-Lambert, Belgium
| | - L Aoudjehane
- Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; Institute of Cardiometabolism and Nutrition (ICAN), 75013 Paris, France
| | - L Ouaguia
- CNRS, UMR8161, Institut de Biologie de Lille, Université de Lille, Institut Pasteur de Lille, IFR 142, 59021 Lille cedex, France
| | - N Delhem
- CNRS, UMR8161, Institut de Biologie de Lille, Université de Lille, Institut Pasteur de Lille, IFR 142, 59021 Lille cedex, France
| | - F Conti
- Sorbonne Universités, UPMC Université Paris 06, INSERM, UMR_S 938, Saint-Antoine Research Center, 75012 Paris, France; AP-HP, Pitié-Salpêtrière hospital, Unité Médicale de Transplantation Hépatique, 75013 Paris, France
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8
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Abstract
Liver transplantation has become an important treatment modality for patients with end-stage liver disease/cirrhosis, acute liver failure, and hepatocellular carcinoma. Although surgical techniques and immunosuppressive regimens for liver transplantation have improved significantly over the past 20 years, infectious complications continue to contribute to the morbidity and mortality in this patient population. The use of standardized screening protocols for both donors and recipients, coupled with targeted prophylaxis against specific pathogens, has helped to mitigate the risk of infection in liver transplant recipients. Patients with chronic liver disease and cirrhosis have immunological deficits that place them at increased risk for infection while awaiting liver transplantation. The patient undergoing liver transplantation is prone to develop healthcare-acquired infections due to multidrug-resistant organisms that could potentially affect patient outcomes after transplantation. The complex nature of liver transplant surgery that involves multiple vascular and hepatobiliary anastomoses further increases the risk of infection after liver transplantation. During the early post-transplantation period, healthcare-acquired bacterial and fungal infections are the most common types of infection encountered in liver transplant recipients. The period of maximal immunosuppression that occurs at 1–6 months after transplantation can be complicated by opportunistic infections due to both primary infection and reactivation of latent infection. Severe community-acquired infections can complicate the course of liver transplantation beyond 12 months after transplant surgery. This chapter provides an overview of liver transplantation including indications, donor-recipient selection criteria, surgical procedures, and immunosuppressive therapies. A focus on infections in patients with chronic liver disease/cirrhosis and an overview of the specific infectious complications in liver transplant recipients are presented.
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Shoreibah M, Romano J, Sims OT, Guo Y, Jones D, Venkata K, Kommineni V, Orr J, Fitzmorris P, Massoud OI. Effect of Hepatitis C Treatment on Renal Function in Liver Transplant Patients. J Clin Transl Hepatol 2018; 6:391-395. [PMID: 30637216 PMCID: PMC6328736 DOI: 10.14218/jcth.2018.00026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 06/17/2018] [Accepted: 06/23/2018] [Indexed: 12/13/2022] Open
Abstract
Background and Aims: Hepatitis C Virus (HCV) is uniformly recurrent after liver transplant (LT) and recurrence is associated with an increased risk of mortality. Immunosuppressive medications increase the risk of chronic kidney disease, and the presence of chronic kidney disease presents a challenge for HCV treatment in LT recipients. The aim of this study was to assess changes in glomerular filtration rates (GFRs) of LT recipients receiving HCV treatment. Methods: This is a retrospective study of LT patients who received HCV treatment between 2015 and 2016 (n = 60). The outcomes of interest were differences in serum creatinine levels and in GFR, measured at treatment initiation and at 24 weeks after treatment. The average age of the patients was 59 years-old, and 17% were cirrhotic and 67% were treatment-experienced. All patients received sofosbuvir/ledipasvir without ribavirin. Results: All patients achieved sustained virologic response at 12 weeks after treatment (SVR12). At baseline, 55% of patients had GFR <60 mL/min per 1.73 m2. Among those patients, GFR did not change in 18%, 33% had improved GFR, and 48% had worsened GFR. Up to 45% of the patients had a GFR >60 mL/min per 1.73 m2. Among those patients, GFR did not change in 81%, and 19% had worsened GFR. In the entire cohort, 65% of patients had improved or stable GFR and 35% had worsened GFR. The average change in serum creatinine between baseline and 24 weeks was 0.10 (p = 0.18). Conclusions: This study showed improved or unchanged GFR in 65% and worsened GFR in 35% of LT recipients who achieved SVR12. Worsening of GFR was more frequently encountered in those with impaired renal function at baseline. Caution should be used when treating HCV in LT recipients, especially those with baseline status of renal impairment.
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Affiliation(s)
- Mohamed Shoreibah
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John Romano
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
- *Correspondence to: John Romano, Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, BDB 327, 1808 7 Ave South, Birmingham, AL 35233, USA. Tel: +1-3156574626, E-mail:
| | - Omar T. Sims
- Department of Social Work, College of Arts and Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
- Center for AIDS Research, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Yuqi Guo
- School of Social Work, University of Alabama, Tuscaloosa, AL, USA
| | - DeAnn Jones
- Department of Pharmacology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Krishna Venkata
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Vishnu Kommineni
- Department of Internal Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jordan Orr
- Division of Gastroenterology and Hepatology, Department of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Paul Fitzmorris
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Omar I. Massoud
- Division of Gastroenterology & Hepatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Trapero-Marugán M, Little EC, Berenguer M. Stretching the boundaries for liver transplant in the 21st century. Lancet Gastroenterol Hepatol 2018; 3:803-811. [DOI: 10.1016/s2468-1253(18)30213-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 06/20/2018] [Accepted: 06/22/2018] [Indexed: 12/12/2022]
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Goldaracena N, Barbas AS, Galante A, Sapisochin G, Al-Adra D, Selzner N, Galvin Z, Cattral MS, Greig PD, Lilly L, Bhat M, McGilvray ID, Ghanekar A, Levy G, Grant DR, Selzner M. Live donor liver transplantation with older donors: Increased long-term graft loss due to HCV recurrence. Clin Transplant 2018; 32:e13304. [PMID: 29947154 DOI: 10.1111/ctr.13304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 05/20/2018] [Indexed: 12/20/2022]
Abstract
Using our prospectively collected database all adult hepatitis C virus (HCV)-positive patients receiving an adult-to-adult LDLT between October 2000 and May 2014 were identified. Outcome of LDLT with grafts from younger (<50 years=128) vs older donors (≥50 years=31) was compared. Post-transplant graft function, postoperative complications and incidence of HCV recurrence were evaluated. Long-term graft and patient survival was calculated. No difference in graft function was observed between younger and older grafts. Overall complications were similar between both groups. The severity of complications determined by the Dindo-Clavien score was similar. Graft loss from HCV recurrence was significantly less frequent in younger grafts (18% vs 62%, P = 0.001). Young vs older livers had a trend toward improved 1-, 5-, and 10-year graft survival (89% vs 87%, 77% vs 69%, 70% vs 55%, P = 0.096), while patient survival was comparable between both groups (91% vs 90%, 78% vs 69%, 71% vs 60%, P = 0.25). In conclusion, LDLT with older vs younger grafts are more frequently associated with long-term graft loss due to HCV recurrence. Differences in graft survival might be more prominent with prolonged (≥5-year) follow-up. Living donor-recipient matching is particularly important for younger HCV-positive recipients.
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Affiliation(s)
- Nicolas Goldaracena
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Andrew S Barbas
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Antonio Galante
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - David Al-Adra
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Nazia Selzner
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Zita Galvin
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Mark S Cattral
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Paul D Greig
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Les Lilly
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Ian D McGilvray
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Anand Ghanekar
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Gary Levy
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - David R Grant
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Markus Selzner
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
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Efficacy And Safety of Sofosbuvir Based Regimens For Treatment of Hepatitis C Recurrence After Living Donor Liver Transplantation: An Experience From India. J Clin Exp Hepatol 2018; 8:121-124. [PMID: 29892173 PMCID: PMC5992320 DOI: 10.1016/j.jceh.2017.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 08/24/2017] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on "real world" experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. MATERIAL AND METHODS Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin (n = 58), Sofosbuvir + Ledipasvir ± Ribavirin (n = 5), Sofosbuvir + Daclatasvir ± Ribavirin (n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). RESULTS A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin < 8 g/dl; two patients complained fatigue in absence of anemia. CONCLUSION Sofosbuvir based regimens are safe and highly effective in treatment of HCV recurrence after LDLT.
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Effects of the Mammalian Target of Rapamycin Inhibitor Everolimus on Hepatitis C Virus Replication In Vitro and In Vivo. Transplant Proc 2018; 49:1947-1955. [PMID: 28923653 DOI: 10.1016/j.transproceed.2017.04.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 03/28/2017] [Accepted: 04/27/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND The influence of immunosuppressants on hepatitis C virus (HCV) re-infection after liver transplantation, particularly mammalian target of rapamycin inhibitors, remains unclear. The aim of our study was to analyze the influence of everolimus (EVR) on HCV replication activity in the context of underlying molecular mechanisms, with focus on the pro-myelocytic leukemia protein (PML). METHODS HCV viral load was recorded in 40 patients with post-transplant HCV re-infection before and 8 weeks after introduction of EVR. An HCV cell culture replicon system for genotype (GT) 1b, GT2b, and GT3a was used to compare the influence of EVR on HCV replication for the respective genotypes in vitro. Fluorescence-activated cell-sorting analysis was used to test for effects on cell proliferation. PML expression was silenced with the use of small hairpin RNA constructs, and PML expression was quantified by means of quantitative real-time polymerase chain reaction. RESULTS In patients with HCV, the viral load of GT1a and GT1b was hardly affected by EVR, whereas the viral load was reduced in patients with GT2a (P ≤ .0001) or GT3 infection (P ≤ .05). In vitro EVR impairs HCV replication activity of GT2a and GT3a up to 60% (P ≤ .0005), whereas in GT1b cells, HCV replication activity is increased by 50% (P ≤ .005). Replicon cell viability was not impaired. HCV replication activity is impaired in the absence of PML, which can be reversed by overexpression of PML isoforms. Furthermore, in the absence of PML, the effect of EVR on HCV replication activity is nearly abrogated. CONCLUSIONS The mammalian target of rapamycin inhibitor EVR influences HCV replication via PML. The herein presented results suggest a genotype-dependent benefit for an EVR-based immunosuppressive regimen in patients with GT2a or GT3 re-infection after liver transplantation.
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14
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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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15
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Feng H, Caro L, Fandozzi CM, Guo Z, Talaty J, Wolford D, Panebianco D, Iwamoto M, Butterton JR, Yeh WW. Pharmacokinetic Interactions Between Elbasvir/Grazoprevir and Immunosuppressant Drugs in Healthy Volunteers. J Clin Pharmacol 2018; 58:666-673. [DOI: 10.1002/jcph.1052] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 11/07/2017] [Indexed: 11/10/2022]
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16
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Ikegami T, Ueda Y, Akamatsu N, Ishiyama K, Goto R, Soyama A, Kuramitsu K, Honda M, Shinoda M, Yoshizumi T, Okajima H, Kitagawa Y, Inomata Y, Ku Y, Eguchi S, Taketomi A, Ohdan H, Kokudo N, Shimada M, Yanaga K, Furukawa H, Uemoto S, Maehara Y. Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience. Clin Transplant 2017; 31. [PMID: 28881052 DOI: 10.1111/ctr.13109] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2017] [Indexed: 02/06/2023]
Abstract
The safety and efficacy of an IFN-free regimen using asunaprevir (ASV) and daclatasvir (DCV) for recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) have not been evaluated in Japan. A multicenter study of LT recipients (n = 74) with recurrent HCV genotype 1b infection treated with ASV-DCV for 24 weeks was performed. Medical history was positive for pegylated interferon and ribavirin (Peg-IFN/RBV) in 40 (54.1%) patients, and for simeprevir (SMV) with Peg-IFN/RBV in 12 (16.2%) patients. Resistance-associated variants (RAVs) were positive at D168 (n = 1) in the NS3, and at L31 (n = 4), Y93 (n = 4), and L31/Y93 (n = 1) in the NS5A region of the HCV genome. Sixty-one (82.4%) patients completed the 24-week treatment protocol. Although sustained viral response (SVR) was achieved in 49 (80.3%) patients, it was achieved in only two (16.7%) patients among those with histories of receiving SMV (n = 12). Univariate analysis showed that a history of SMV (P < .01) and the presence of mutations in NS5A (P = .02) were the significant factors for no-SVR. By excluding the patients with either a history of SMV-based treatment or RAVs in NS3/NS5A, the SVR rate was 96.4%. By excluding the patients with a history of SMV and those with RAVs in NS3/NS5A, viral clearance of ASV-DCV was favorable, with a high SVR rate.
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Affiliation(s)
- Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihide Ueda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Nobuhisa Akamatsu
- Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
| | - Kohei Ishiyama
- Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryoichi Goto
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kaori Kuramitsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masaki Honda
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Masahiro Shinoda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hideaki Okajima
- Department of Surgery, University of Tokushima, Tokushima, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Yonson Ku
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Hideki Ohdan
- Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Norihiro Kokudo
- Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
| | - Mitsuo Shimada
- Department of Surgery, University of Tokushima, Tokushima, Japan
| | - Katsuhiko Yanaga
- Department of Surgery, School of Medicine, The Jikei University, Tokyo, Japan
| | - Hiroyuki Furukawa
- Department of Surgery, Asahikawa Medical University, Asahikawa, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Predictors of hepatitis C virus recurrence after living donor liver transplantation: Mansoura experience. Arab J Gastroenterol 2017; 18:151-155. [PMID: 28958486 DOI: 10.1016/j.ajg.2017.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 06/22/2017] [Accepted: 09/05/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND STUDY AIMS Hepatitis C virus (HCV)-related cirrhosis is the leading cause of liver transplantation (LT). All patients who undergo LT with detectable serum HCV-RNA experience graft reinfection, which is the most frequent cause of graft loss and death in these patients. We estimated the rate of HCV recurrence and evaluated the current therapeutic regimens. PATIENTS AND METHODS The records of consecutive 325 living donor LT (LDLT) surgeries performed between May 2004 and August 2014 were retrospectively analysed; 207 of them were followed-up throughout the study. Clinical, laboratory, radiological and histopathological examinations were performed thoroughly. Patients received treatment in the form of either pegylated interferon (PEG-IFN) or sofosbuvir, both in combination with ribavirin. RESULTS In total, 90.3% of recipients who were transplanted because of HCV-related end-stage liver disease experienced recurrence due to the virus. The donor age was older in the HCV recurrent group versus the non-recurrence group (28.7±7.1 versus 22.6±2.6years: p≤0.001), warm ischaemia time was prolonged (46.1±18.1 versus 28.6±4.1min: p≤0.001), median cold ischaemia time was 40.0 (10-175) versus 22.5 (15-38) min (p≤0.001) and basal PCR was 414000 (546-116000000) versus 10766 (1230-40000) (p≤0.001). Sustained virological response was achieved in 95.4% of patients treated with a combination of a fixed daily dose of 400mg sofosbuvir with ribavirin and in 65.1% of those who were treated with PEG-IFN with ribavirin. CONCLUSIONS Older donor age and prolonged warm ischaemia time are independent predictors of HCV recurrence after LDLT, and early treatment with the direct-acting sofosbuvir is helpful in resolving the problem of post-LT HCV recurrence.
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HCV Antiviral Therapy in Liver Transplant Candidates and Recipients With Renal Insufficiency. Transplantation 2017; 101:924-932. [PMID: 28212220 DOI: 10.1097/tp.0000000000001688] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective direct-acting antiviral therapy, such that most patients can be cured in the pretransplant or posttransplant setting. In addition, there are now direct-acting antiviral regimens specifically approved for use in patients with severe renal insufficiency. However, patients with pre or posttransplant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism in hepatic and renal failure, as well as posttransplant drug-drug interactions. Treatment options are even more restricted in non-1 HCV genotypes. Because renal insufficiency is common among patients with HCV, with decompensated cirrhosis, and in the posttransplant setting, this difficult scenario is relatively common. However, ongoing development of pangenotypic regimens with improved safety profiles, as well as additional data on dosing and safety among patients with severe renal insufficiency, will continue to expand options for cure even in these most difficult to treat patients.
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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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Yoshida EM, Kwo P, Agarwal K, Duvoux C, Durand F, Peck-Radosavljevic M, Lilly L, Willems B, Vargas H, Kumar P, Brown Jr. RS, Horsmans Y, De-Oertel S, Arterburn S, Dvory-Sobol H, Brainard DM, McHutchison JG, Terrault N, Rizzetto M, Müllhaupt B. Persistence of Virologic Response after Liver Transplant in Hepatitis C Patients Treated with Ledipasvir / Sofosbuvir Plus Ribavirin Pretransplant. Ann Hepatol 2017; 16:375-381. [DOI: 10.5604/01.3001.0009.8592] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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21
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Antonucci F, Cento V, Sorbo MC, Manuelli MC, Lenci I, Sforza D, Di Carlo D, Milana M, Manzia TM, Angelico M, Tisone G, Perno CF, Ceccherini-Silberstein F. HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay. J Virol Methods 2017; 246:1-7. [PMID: 28408312 DOI: 10.1016/j.jviromet.2017.04.001] [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: 01/13/2017] [Revised: 04/03/2017] [Accepted: 04/06/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. METHODS Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/106 liver-cells, respectively. RESULTS HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. CONCLUSIONS HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available.
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Affiliation(s)
| | - Valeria Cento
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Maria Chiara Sorbo
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
| | | | - Ilaria Lenci
- Hepatology Unit, Polyclinic Tor Vergata Foundation, University of Rome Tor Vergata, Rome, Italy
| | - Daniele Sforza
- Liver Unit, Polyclinic Tor Vergata Foundation, University of Rome Tor Vergata, Rome, Italy
| | - Domenico Di Carlo
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Martina Milana
- Hepatology Unit, Polyclinic Tor Vergata Foundation, University of Rome Tor Vergata, Rome, Italy
| | - Tommaso Maria Manzia
- Liver Unit, Polyclinic Tor Vergata Foundation, University of Rome Tor Vergata, Rome, Italy
| | - Mario Angelico
- Hepatology Unit, Polyclinic Tor Vergata Foundation, University of Rome Tor Vergata, Rome, Italy
| | - Giuseppe Tisone
- Liver Unit, Polyclinic Tor Vergata Foundation, University of Rome Tor Vergata, Rome, Italy
| | - Carlo Federico Perno
- Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
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Ponziani FR, Mangiola F, Binda C, Zocco MA, Siciliano M, Grieco A, Rapaccini GL, Pompili M, Gasbarrini A. Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C. World J Hepatol 2017; 9:352-367. [PMID: 28321272 PMCID: PMC5340991 DOI: 10.4254/wjh.v9.i7.352] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 10/26/2016] [Accepted: 12/01/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylated-interferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.
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Affiliation(s)
- Francesca Romana Ponziani
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Francesca Mangiola
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Cecilia Binda
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Maria Assunta Zocco
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Massimo Siciliano
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Antonio Grieco
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Gian Lodovico Rapaccini
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Maurizio Pompili
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
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Graziadei I, Zoller H, Fickert P, Schneeberger S, Finkenstedt A, Peck-Radosavljevic M, Müller H, Kohl C, Sperner-Unterweger B, Eschertzhuber S, Hofer H, Öfner D, Tilg H, Vogel W, Trauner M, Berlakovich G. Indications for liver transplantation in adults : Recommendations of the Austrian Society for Gastroenterology and Hepatology (ÖGGH) in cooperation with the Austrian Society for Transplantation, Transfusion and Genetics (ATX). Wien Klin Wochenschr 2016; 128:679-690. [PMID: 27590261 PMCID: PMC5052293 DOI: 10.1007/s00508-016-1046-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 05/30/2016] [Indexed: 02/06/2023]
Abstract
Liver transplantation has emerged as an established and well-accepted therapeutic option for patients with acute and chronic liver failure and hepatocellular carcinoma. The disproportion between recipients and donors is still an ongoing problem that has only been solved partially over the last centuries. For several patients no life-saving organs can be distributed. Therefore, objective and internationally established recommendations regarding indication and organ allocation are imperative. The aim of this article is to establish evidence-based recommendations regarding the evaluation and assessment of adult candidates for liver transplantation. This publication is the first Austrian consensus paper issued and approved by the Austrian Society of Gastroenterology and Hepatology in cooperation with the Austrian Society of Transplantation, Infusion and Genetics.
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Affiliation(s)
- Ivo Graziadei
- Department of Internal Medicine, Academic Teaching Hospital Hall i.T., Milserstraße 10, 6060, Hall i.T., Austria. .,Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
| | - Heinz Zoller
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Peter Fickert
- Department of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thorax Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Armin Finkenstedt
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Helmut Müller
- Department of Transplant Surgery, Medical University of Graz, Graz, Austria
| | - Claudia Kohl
- Department of Psychiatry, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Stephan Eschertzhuber
- Department of Anesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Harald Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thorax Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Wolfgang Vogel
- Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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24
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Alghamdi AS, Alghamdi M, Sanai FM, Alghamdi H, Aba-Alkhail F, Alswat K, Babatin M, Alqutub A, Altraif I, Alfaleh F. SASLT guidelines: Update in treatment of Hepatitis C virus infection. Saudi J Gastroenterol 2016; 22 Suppl:S25-57. [PMID: 27538727 PMCID: PMC5004485 DOI: 10.4103/1319-3767.188067] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Abdullah S. Alghamdi
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Mohammed Alghamdi
- Department of Medicine, Division of Gastroenterology, King Fahd Military Complex, Dhahran, Saudi Arabia
| | - Faisal M Sanai
- Department of Medicine, Division of Gastroenterology, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Saudi Arabia
| | - Hamdan Alghamdi
- Department of Hepatobiliary Sciences and Liver Transplantation King Abdulaziz Medical City, and King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Faisal Aba-Alkhail
- Department of Medicine, Division of Gastroenterology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Khalid Alswat
- Department of Medicine, Gastroenterology unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Babatin
- Department of Medicine, Gastroenterology Unit, King Fahad Hospital, Jeddah, Saudi Arabia
| | - Adel Alqutub
- Department of Medical Specialties, Gastroenterology and Hepatology Section, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ibrahim Altraif
- Department of Hepatobiliary Sciences and Liver Transplantation King Abdulaziz Medical City, and King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Faleh Alfaleh
- Department of Medicine, Gastroenterology unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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25
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Kitajima T, Kaido T, Hamaguchi Y, Yagi S, Taura K, Fujimoto Y, Hatano E, Okajima H, Haga H, Uemoto S. Validation of the FIB-4 index for evaluation of fibrosis in patients with recurrent hepatitis C after living donor liver transplantation: A single center experience. Hepatol Res 2016; 46:752-7. [PMID: 26583748 DOI: 10.1111/hepr.12617] [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: 09/11/2015] [Revised: 10/19/2015] [Accepted: 10/31/2015] [Indexed: 12/13/2022]
Abstract
AIM The FIB-4 index has been proposed as a simple, non-invasive surrogate marker of liver fibrosis in patients with hepatitis C virus (HCV). However, the utility of FIB-4 in HCV positive patients after living donor liver transplantation (LDLT) has not been assessed. The aim of this study was to evaluate the efficacy of FIB-4 in the detection of significant liver graft fibrosis caused by recurrent HCV infection after LDLT compared with other simple fibrosis markers. METHODS A total of 259 liver biopsies (LB) with evidence of recurrent HCV were taken from 110 HCV positive LDLT patients who had undergone concomitant splenectomy before administration of antiviral therapy. In LB performed at 3 months or later after LT (n = 202, subject group), FIB-4 was compared between fibrosis stages and the accuracy of FIB-4 in predicting significant fibrosis (METAVIR, F ≥ 2) was assessed compared with aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, age-platelet index, and AST to platelet ratio index (APRI). RESULTS FIB-4 was significantly different between all fibrosis stages (F0 and F1-F4, P = 0.022; F0/1 and F2-F4, P < 0.0005; and F0-F2 and F3F4, P = 0.034) and provided the best area under the receiver-operator curve (AUROC) compared with other markers (FIB-4, 0.711; APRI, 0.693; age-platelet index, 0.663; and AST to ALT ratio, 0.562). The optimal cut-off value to identify significant fibrosis was 2.20 with 65% sensitivity and 69% specificity. CONCLUSION FIB-4 is a more reliable marker for diagnosing significant liver fibrosis than APRI, age-platelet index, and AST to ALT ratio in LDLT patients with HCV.
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Affiliation(s)
- Toshihiro Kitajima
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuhei Hamaguchi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yasuhiro Fujimoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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26
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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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27
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Sclair SN, Fiel MI, Wu HS, Doucette J, Aloman C, Schiano TD. Increased hepatic progenitor cell response and ductular reaction in patients with severe recurrent HCV post-liver transplantation. Clin Transplant 2016; 30:722-30. [PMID: 27027987 DOI: 10.1111/ctr.12740] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/28/2016] [Indexed: 01/05/2023]
Abstract
OBJECTIVES Post-liver transplant (LT) hepatitis C virus (HCV) patients may develop allograft cirrhosis and rarely fibrosing cholestatic hepatitis (FCH), while others have a stable course. Hepatic progenitor cells (HPC) may be implicated in liver injury and fibrogenesis through ductular reaction (DR). We studied HPC response and DR in three distinct post-LT patterns of HCV: stable recurrence, allograft cirrhosis, and FCH. METHODS We identified 52 patients with untreated recurrent HCV and longitudinal liver biopsies (20 stable/23 cirrhosis/9 FCH) and eight healthy controls. Archived liver biopsy specimens for three time points (LT; initial recurrence; and clinical outcome) were stained for cytokeratin-7. Manual HPC counts and DR quantification using image analysis were performed. RESULTS HCV counts and DR at LT did not differ across groups. At initial recurrence, HPC expansion occurred only in patients who developed cirrhosis, while prominent DR was present in those who developed FCH vs. stable and controls (p < 0.05). At outcome biopsies, HPC response and DR were increased in cirrhosis and FCH vs. stable and controls (p < 0.05). HPC response and DR did not differ in stable vs. CONCLUSIONS These findings suggest that an altered HPC response assessed by cytokeratin-7 stain after LT may predict severity of HCV recurrence.
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Affiliation(s)
- Seth N Sclair
- Division of Hepatology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.,Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Maria Isabel Fiel
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Hai-Shan Wu
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - John Doucette
- Department of Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Costica Aloman
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois, Chicago, IL, USA.,Division of Transplant Surgery, Department of Surgery, University of Illinois, Chicago, IL, USA
| | - Thomas D Schiano
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Recanati-Miller Transplant Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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28
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Jackson WE, Hanouneh M, Apfel T, Alkhouri N, John BV, Zervos X, Zein NN, Hanouneh IA. Sofosbuvir and simeprevir without ribavirin effectively treat hepatitis C virus genotype 1 infection after liver transplantation in a two-center experience. Clin Transplant 2016; 30:709-13. [PMID: 27019204 DOI: 10.1111/ctr.12738] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/29/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND The interferon-free antiviral regimen, sofosbuvir (SOF) and simeprevir (SIM) without ribavirin has been reported to achieve high sustained virologic response (SVR) rates with few adverse effects when treating patients with hepatitis C genotype 1 (HCV GT1) infection. However, there is scarcity of safety and efficacy data in this regimen after liver transplantation (LT). AIM AND METHODS We aim to report the safety, tolerability and efficacy of SOF + SIM to treat LT recipients with recurrent HCV GT1 in a multicenter cohort study. RESULTS Eighty-one patients with HCV GT1 met criteria to be considered for treatment. Sixty-seven patients received SOF + SIM following LT to date: 69% male, 39% with HCV RNA >6 000 000 IU/mL, 22% advanced hepatic fibrosis (stage 3-4), 6% cholestatic recurrence. Fifty-eight percent previously failed or did not tolerate interferon-based treatments. Mean time from LT to treatment was 6.1 ± 5.2 yr. All patients had estimated GFR >30 mL/min. Tacrolimus was primary immunosuppression in 84% of patients and minimal immunosuppression dose adjustments were required during treatment. In intention-to-treat analysis, 90% achieved end-of-treatment virologic response and 88% achieved SVR. CONCLUSIONS Sofosbuvir + SIM combination therapy without ribavirin is well tolerated and results in high virologic response rates in recurrent HCV GT1 infection after liver transplantation.
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Affiliation(s)
- Whitney E Jackson
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Mohamad Hanouneh
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Tehilla Apfel
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Naim Alkhouri
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Binu V John
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Xaralambos Zervos
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
| | - Nizar N Zein
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Ibrahim A Hanouneh
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
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29
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Ajlan A, Al-Jedai A, Elsiesy H, Alkortas D, Al-Hamoudi W, Alarieh R, Al-Sebayel M, Broering D, Aba Alkhail F. Sofosbuvir-Based Therapy for Genotype 4 HCV Recurrence Post-Liver Transplant Treatment-Experienced Patients. Can J Gastroenterol Hepatol 2016; 2016:2872371. [PMID: 27446833 PMCID: PMC4904700 DOI: 10.1155/2016/2872371] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 11/10/2015] [Indexed: 12/20/2022] Open
Abstract
Background and Aim. This is an open label prospective cohort study conducted at a tertiary care hospital. The primary endpoint is SVR12 in patients treated with sofosbuvir-based therapy in post-liver transplant patients with genotype 4 HCV recurrence. Methodology. Thirty-six treatment-experienced liver transplant patients with HCV recurrence received sofosbuvir and ribavirin ± peginterferon. Results. We report here safety and efficacy data on 36 patients who completed the follow-up period. Mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. Mean baseline HCV RNA was 6.2 log10 IU/mL. The majority of patients had ≥ stage 2 fibrosis. Twenty-eight patients were treated with pegylated interferon plus ribavirin in addition to sofosbuvir for 12 weeks and the remaining were treated with sofosbuvir plus ribavirin only for 24 weeks. By week 4, only four (11.1%) patients had detectable HCV RNA. Of the 36 patients, 2 (5.5%) relapsed and one died (2.75%). Conclusion. Our results suggest that sofosbuvir + ribavirin ± pegylated interferon can be utilized successfully to treat liver transplant patients with HCV recurrence.
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Affiliation(s)
- A. Ajlan
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
| | - A. Al-Jedai
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
| | - H. Elsiesy
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - D. Alkortas
- Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, MBC-11, P.O. Box 3354, Riyadh 11211, Saudi Arabia
| | - W. Al-Hamoudi
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
- King Saud University, College of Medicine, Riyadh, Saudi Arabia
| | - R. Alarieh
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - M. Al-Sebayel
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - D. Broering
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - F. Aba Alkhail
- Alfaisal University, College of Medicine, Riyadh, Saudi Arabia
- Liver & Small Bowel Transplant and Hepatobiliary and Pancreatic Surgery-Organ Transplant Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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30
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Sheen V, Nguyen H, Jimenez M, Agopian V, Vangala S, Elashoff D, Saab S. Routine Laboratory Blood Tests May Diagnose Significant Fibrosis in Liver Transplant Recipients with Chronic Hepatitis C: A 10 Year Experience. J Clin Transl Hepatol 2016; 4:20-5. [PMID: 27047768 PMCID: PMC4807139 DOI: 10.14218/jcth.2015.00034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 11/30/2015] [Accepted: 12/01/2015] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND AND AIMS The aims of our study were to determine whether routine blood tests, the aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) and Fibrosis 4 (Fib-4) scores, were associated with advanced fibrosis and to create a novel model in liver transplant recipients with chronic hepatitis C virus (HCV). METHODS We performed a cross sectional study of patients at The University of California at Los Angeles (UCLA) Medical Center who underwent liver transplantation for HCV. We used linear mixed effects models to analyze association between fibrosis severity and individual biochemical markers and mixed effects logistic regression to construct diagnostic models for advanced fibrosis (METAVIR F3-4). Cross-validation was used to estimate a receiving operator characteristic (ROC) curve for the prediction models and to estimate the area under the curve (AUC). RESULTS The mean (± standard deviation [SD]) age of our cohort was 55 (±7.7) years, and almost three quarter were male. The mean (±SD) time from transplant to liver biopsy was 19.9 (±17.1) months. The mean (±SD) APRI and Fib-4 scores were 3 (±12) and 7 (±14), respectively. Increased fibrosis was associated with lower platelet count and alanine aminotransferase (ALT) values and higher total bilirubin and Fib-4 scores. We developed a model that takes into account age, gender, platelet count, ALT, and total bilirubin, and this model outperformed APRI and Fib-4 with an AUC of 0.68 (p < 0.001). CONCLUSIONS Our novel prediction model diagnosed the presence of advanced fibrosis more reliably than APRI and Fib-4 scores. This noninvasive calculation may be used clinically to identify liver transplant recipients with HCV with significant liver damage.
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Affiliation(s)
- Victoria Sheen
- Departments of Medicine, University of California at Los Angeles, Los Angeles, California, USA
| | - Heajung Nguyen
- Departments of Medicine, University of California at Los Angeles, Los Angeles, California, USA
| | - Melissa Jimenez
- Departments of Surgery, University of California at Los Angeles, Los Angeles, California, USA
| | - Vatche Agopian
- Departments of Surgery, University of California at Los Angeles, Los Angeles, California, USA
| | - Sitaram Vangala
- Departments of Medicine, University of California at Los Angeles, Los Angeles, California, USA
| | - David Elashoff
- Departments of Medicine, University of California at Los Angeles, Los Angeles, California, USA
| | - Sammy Saab
- Departments of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Departments of Surgery, University of California at Los Angeles, Los Angeles, California, USA
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31
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Ikegami T, Yoshizumi T, Yoshida Y, Kurihara T, Harimoto N, Itoh S, Shimokawa M, Fukuhara T, Shirabe K, Maehara Y. Telaprevir versus simeprevir for the treatment of recurrent hepatitis C after living donor liver transplantation. Hepatol Res 2016; 46:E136-45. [PMID: 26096514 DOI: 10.1111/hepr.12546] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Revised: 06/16/2015] [Accepted: 06/16/2015] [Indexed: 12/17/2022]
Abstract
AIM Our aim was to evaluate the clinical outcomes of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy for recurrent hepatitis C after living donor liver transplantation. METHODS Twenty-six patients received antiviral therapy, consisting of either TVR (n = 12) or SMV (n = 14) in combination with pegylated interferon and ribavirin, plus cyclosporin. RESULTS More patients had a dose reduction of the direct-acting agent (36.3% vs 0.0%, P = 0.02) or required blood transfusion for anemia (58.3% vs 7.1%, P < 0.01) in the TVR group. The cyclosporin trough/dose ratio increased significantly from week 0 to week 4 in the TVR group (1.6 ± 0.4 to 5.1 ± 2.0, P < 0.01), but not in the SMV group (1.2 ± 0.3 to 1.3 ± 0.2, P = 0.68). The 24-week cumulative viral clearance rate was 91.7% and 85.7% in the TVR and in SMV groups, respectively. The early viral response and sustained viral response rates were 91.7% and 83.3%, respectively, in the TVR group, compared with 85.7% and 64.3%, respectively, in the SMV group. Interferon-mediated graft dysfunction occurred in four and five patients in the TVR and SMV groups, respectively; two patients were treated by oral steroids, five by steroid pulse and two by thymoglobulin, resulting in viral breakthrough in one case. CONCLUSION SMV-based triple therapy was associated with fewer adverse events and drug interactions with cyclosporin, and possibly less antiviral properties to TVR. Interferon-mediated graft dysfunction is a significant clinical problem that warrants particular caution following living donor liver transplantation.
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Affiliation(s)
- Toru Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihro Yoshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Kurihara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Norifumi Harimoto
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masahiro Shimokawa
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takasuke Fukuhara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ken Shirabe
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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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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Infectious Considerations in the Pre-Transplant Evaluation of Cirrhotic Patients Awaiting Orthotopic Liver Transplantation. Curr Infect Dis Rep 2016; 18:4. [PMID: 26743200 DOI: 10.1007/s11908-015-0514-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The incidence of end-stage liver disease (ESLD) is increasing and many of these patients may be considered for orthotopic liver transplantation. As patients with ESLD are at risk of a number of infections, infectious disease physicians should be aware of the management of these infections in order to provide optimal patient care and ensure transplantation success. We present a review of the literature pertaining to infectious disease considerations in the liver transplant candidate. It highlights several topics with recent developments including the management of hepatitis C virus infection prior to transplantation, treatment of hepatitis B virus infection, colonization and infection with multidrug resistant organisms, and management of spontaneous bacterial peritonitis.
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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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Cattaneo D, Sollima S, Charbe N, Resnati C, Clementi E, Gervasoni C. Suspected pharmacokinetic interaction between raltegravir and the 3D regimen of ombitasvir, dasabuvir and paritaprevir/ritonavir in an HIV-HCV liver transplant recipient. Eur J Clin Pharmacol 2015; 72:365-7. [PMID: 26362279 DOI: 10.1007/s00228-015-1936-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 08/31/2015] [Indexed: 11/27/2022]
Affiliation(s)
- Dario Cattaneo
- Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy
| | - Salvatore Sollima
- Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157, Milan, Italy
| | - Nitin Charbe
- Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy
| | - Chiara Resnati
- Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157, Milan, Italy
| | - Emilio Clementi
- Clinical Pharmacology Unit, CNR Institute of Neuroscience, Dept Biomedical and Clinical Sciences, L. Sacco University Hospital, Università di Milano, 20157, Milan, Italy
- Scientific Institute IRCCS E. Medea, 23842, Bosisio Parini, Italy
| | - Cristina Gervasoni
- Department of Infectious Diseases, Luigi Sacco University Hospital, Via GB Grassi 74, 20157, Milan, Italy.
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Burra P, De Martin E, Zanetto A, Senzolo M, Russo FP, Zanus G, Fagiuoli S. Hepatitis C virus and liver transplantation: where do we stand? Transpl Int 2015. [DOI: 10.1111/tri.12642] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology; Department of Surgery, Oncology and Gastroenterology; Padua University Hospital; Padua Italy
| | - Eleonora De Martin
- Multivisceral Transplant Unit, Gastroenterology; Department of Surgery, Oncology and Gastroenterology; Padua University Hospital; Padua Italy
- Centre Hepato-Biliaire Paul Brousse; Villejuif France
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Gastroenterology; Department of Surgery, Oncology and Gastroenterology; Padua University Hospital; Padua Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Gastroenterology; Department of Surgery, Oncology and Gastroenterology; Padua University Hospital; Padua Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology; Department of Surgery, Oncology and Gastroenterology; Padua University Hospital; Padua Italy
| | - Giacomo Zanus
- Hepatobiliary Surgery and Liver Transplantation Unit; Department of Surgery, Oncology and Gastroenterology; Padua University Hospital; Padua Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology; Papa Giovanni XXIII Hospital; Bergamo Italy
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Increasing Volume but Decreasing Mortality of Hospitalized Hepatitis C Patients in the United States, 2005 to 2011. J Clin Gastroenterol 2015; 49:620-7. [PMID: 25203363 DOI: 10.1097/mcg.0000000000000216] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Patients with hepatitis C virus infection often require hospitalization for progressive liver disease and complications, incurring high cost and risk of death. GOALS The aim of our study was to investigate recent trends in the economic burden and outcomes of patients hospitalized for hepatitis C in the United States. STUDY Patients with hepatitis C-associated hospitalization were identified from the Nationwide Inpatient Sample 2005 to 2011. We analyzed the in-hospital mortality, hospital service utilization, demographic, and clinical features of patients. A prognostic model to predict in-hospital survival and death with independent risk factors for mortality was developed. RESULTS A total of 607,279 cases of hepatitis C-associated hospitalization were identified. Over 7 years, the annual hospitalized volume increased by 28.8%. In-hospital mortality declined from 8.2% to 6.4%. Median length of stay (4 d) was unchanged but the inflation-adjusted hospital charges increased by 33.3%. Acute respiratory failure was the greatest independent risk factor for mortality [odds ratio (OR)=7.3; 95% confidence interval (CI), 7.0-7.5], followed by septicemia (OR=4.1; 95% CI, 4.0-4.3), renal failure (OR=3.4; 95% CI, 3.3-3.5), and acute liver failure (OR=2.9; 95% CI, 2.7-3.0). On the basis of the major risk factors for mortality, a risk-adjusted model was developed that could predict the in-hospital outcome of hepatitis C patients with an accurate rate of 89.2%. CONCLUSIONS Despite decreasing in-hospital mortality, both hospital volume and charges related to hepatitis C increased from 2005 to 2011. Use of a risk-adjusted model could help predict mortality and improve outcomes of hepatitis C inpatients.
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Toussaint-Miller KA, Andres J. Treatment Considerations for Unique Patient Populations With HCV Genotype 1 Infection. Ann Pharmacother 2015; 49:1015-30. [PMID: 26139639 DOI: 10.1177/1060028015592015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE To review the literature for the treatment of hepatitis C virus (HCV) genotype 1 in certain populations of patients that require further considerations before therapy initiation. DATA SOURCES A systematic electronic literature search using the MEDLINE database was performed using the search terms hepatitis C, chronic hepatitis C, drug therapy, end stage liver disease, liver transplantation, HIV, hepatitis B, African Americans, renal insufficiency, obesity, pregnancy, and pediatrics. STUDY SELECTION AND DATA EXTRACTION English language studies from January 1985 to March 2015 were considered. Additional references were identified from ongoing trials obtained from clinicaltrials.gov, conference proceedings, online databases, and citations in relevant review articles. DATA SELECTION Direct-acting antivirals are first-line recommendations for the treatment of HCV genotype 1 infection, and these include combinations of sofosbuvir, simeprevir, ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, and ribarvirin. Historical and clinical data focusing on the treatment of HCV with these agents in the following populations were selected: decompensated cirrhosis, post-liver transplant, HIV, African Americans, obesity, hepatitis B coinfection, renal impairment, pregnancy, and pediatrics. CONCLUSION Depending on the population studied, clinicians must consider differences in efficacy outcomes, potential drug interactions, and adverse effects that patients may experience.
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Saigal S, Choudhary NS, Saraf N, Gautam D, Lipi L, Rastogi A, Goja S, Menon PB, Bhangui P, Ramachandra SK, Soin AS. Genotype 3 and higher low-density lipoprotein levels are predictors of good response to treatment of recurrent hepatitis C following living donor liver transplantation. Indian J Gastroenterol 2015; 34:305-9. [PMID: 26394853 DOI: 10.1007/s12664-015-0578-z] [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: 01/27/2015] [Accepted: 07/03/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Treatment of recurrent hepatitis C after liver transplantation is associated with poor sustained virological response (SVR) in genotype 1, and data on genotype 3 is limited to small numbers. We report one of the largest series of genotype 3 patients treated for recurrent hepatitis C following living donor liver transplantation (LDLT). METHODS From January 2002 to November 2013, of 1349 transplants, 359 patients had hepatitis C. Patients with histological recurrence were treated with pegylated interferon in escalating dose regimen for 48 weeks and weight-based ribavirin. Virological response was defined as rapid virological response (RVR-4 weeks), early virological response (EVR-12 weeks), end of treatment response (ETR-48 weeks), and SVR (24 weeks after end of treatment). SVR and no-SVR groups were compared for age, sex, body mass index (BMI), diabetes, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, ferritin, genotype, and hepatitis C virus (HCV) RNA levels before initiation of treatment. RESULTS The study included 67 patients who had at least 18 months of follow up after treatment initiation (45 males), aged 51 ± 6.3 years. Treatment was started after 16 months (median); baseline median RNA was 2.7 × 10(6) IU/mL. There was no significant difference between the SVR and no-SVR groups regarding age, sex ratio, follow up period, total cholesterol, triglycerides, HDL, BMI, prevalence of diabetes, HCV RNA, and ferritin levels. Genotype 3, RVR, EVR, ETR, and higher LDL levels were significantly associated with SVR. Genotype 3 had a significantly higher SVR rate of 71 % as compared to an SVR rate of only 14 % in genotype 1, p = 0.0003. Absence of RVR and EVR predicted treatment failure with a specificity of 88 % and 92 %, respectively. CONCLUSION Genotype 3 and higher LDL levels predict SVR in patients treated for hepatitis C recurrence following LDLT, whereas absence of RVR and EVR strongly predict treatment failure.
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Affiliation(s)
- Sanjiv Saigal
- Medanta Liver Institute, Gurgaon, Haryana, 122 001, India.
| | | | - Neeraj Saraf
- Medanta Liver Institute, Gurgaon, Haryana, 122 001, India
| | - Dheeraj Gautam
- Department of Histopathology, Medanta The Medicity, Gurgaon, Haryana, 122 001, India
| | - Lipika Lipi
- Department of Histopathology, Medanta The Medicity, Gurgaon, Haryana, 122 001, India
| | - Amit Rastogi
- Medanta Liver Institute, Gurgaon, Haryana, 122 001, India
| | - Sanjay Goja
- Medanta Liver Institute, Gurgaon, Haryana, 122 001, India
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Badri P, Dutta S, Coakley E, Cohen D, Ding B, Podsadecki T, Bernstein B, Awni W, Menon R. Pharmacokinetics and dose recommendations for cyclosporine and tacrolimus when coadministered with ABT-450, ombitasvir, and dasabuvir. Am J Transplant 2015; 15:1313-22. [PMID: 25708713 PMCID: PMC5024008 DOI: 10.1111/ajt.13111] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Revised: 11/16/2014] [Accepted: 11/16/2014] [Indexed: 01/25/2023]
Abstract
ABT-450, ombitasvir, and dasabuvir are direct-acting antiviral agents (DAAs) that have been developed for combination treatment of chronic hepatitis C virus (HCV) infection. Because these DAAs have metabolic and transporter profiles that overlap with cyclosporine and tacrolimus disposition, there is potential for drug interactions. Two Phase 1 studies assessed effects of ABT-450 (150 mg coadministered with ritonavir 100 mg once daily), ombitasvir (25 mg once daily), and dasabuvir (400 mg twice daily) on the pharmacokinetics, safety, and tolerability of a single dose of cyclosporine (30 mg) or tacrolimus (2 mg) in healthy volunteers (N = 12 per study). In the presence of steady-state concentrations of all 3 DAAs, dose-normalized cyclosporine concentration at 24 hours (C₂₄), and area under the concentration-time curve from time 0 to infinity (AUC(∞)) were 15.8-fold and 5.8-fold, respectively, and dose-normalized tacrolimus C₂₄ and AUC(∞) were 17-fold and 57-fold, respectively, of either agent alone. Cyclosporine and tacrolimus half-lives increased from 7 to 25 h and 32 to 232 h, respectively. There were no major safety or tolerability issues in these studies. The results suggest that cyclosporine and tacrolimus doses and dosing frequency should be reduced in HCV-infected posttransplant patients being treated with this 3-DAA regimen.
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de la Peña-Moral JM, Pons JA, Tome S, Gude F, Miras M, Bermejo J, Ramirez P, Berenguer M, Varo E, Forteza J, Parrilla P. Acute cellular rejection versus recurrent hepatitis C after liver transplantation: Clinical and pathological features driving a rational diagnostic approach. Hepatol Res 2015; 45:423-31. [PMID: 24906075 DOI: 10.1111/hepr.12369] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2013] [Revised: 05/20/2014] [Accepted: 06/02/2014] [Indexed: 02/08/2023]
Abstract
AIM The aim of our study was develop and validate an algorithm system based on morphological features for finding the differences between recurrent hepatitis C virus (HCV) and acute cellular rejection (ACR) in liver biopsies of HCV-transplanted patients. METHODS Two hundred and eighty-eight liver biopsies were analyzed from 121 patients transplanted for HCV. A diagnostic consensus was reached between clinicians and pathologists in 214 biopsies for the diagnosis of recurrent HCV or ACR. A random sample of 114 liver biopsies (derivation cohort) was taken to generate the diagnostic tree and was subsequently evaluated using the validation cohort in 100 liver biopsies by recursive partitioning analysis of morphological variables and time since transplantation. RESULTS The presence of endotheliitis together with a time of less than 6 weeks since LT definitely excluded recurrent HCV. After obtaining the regression tree, diagnostic accuracy was 96% and 93% in the derivation and validation cohort, respectively. Both cases surpassed the pathologist's original diagnosis, which had a diagnostic accuracy of 91% (P < 0.05, for both comparisons). CONCLUSION A recursive partitioning analysis of the morphological features in liver biopsies from HCV-transplanted patients may be useful for easily distinguishing between recurrent HCV and ACR.
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Feyznezhad R, Behzadi MA, Yaghobi R, Ziyaeyan M. Determining major genotypes of hepatitis C virus among transplant recipients by real-time polymerase chain reaction assay. Jundishapur J Microbiol 2015; 8:e16722. [PMID: 25793097 PMCID: PMC4353064 DOI: 10.5812/jjm.16722] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Revised: 06/08/2014] [Accepted: 06/24/2014] [Indexed: 01/06/2023] Open
Abstract
Background: Hepatitis C virus (HCV) infection still exists as a health concern among the transplant patients. Because of the severity of the disease, different responses to treatment, and side effects resulting from long therapeutic period, determination of genotypes and viral loads can help choose the best treatment protocols. Objectives: This study aimed to determine the HCV genotypes and its distribution patterns among liver, kidney, and bone marrow recipient candidates across Iran, referred to Namazi Hospital, southern Iran. Patients and Methods: A total of 101 individuals, including 44 (43.6%) liver, 55 (54.5%) kidney, and 2 (2%) bone marrow recipient candidates, with ages ranging between 5 and 74 years (Mean ±SD: 46.53 ± 13.73 y) participated in this study. From those, whole blood sample were collected and anti-HCV antibodies, RNA detection, and genotyping were performed on plasma using commercial chromatographic immunoassay, TaqMan one-step real-time polymerase chain reaction (RT-PCR), and genotyping RT-PCR kits, respectively. The frequencies of anti-HCV antibodies, RNA, various genotypes, and the viral load were compared with respect to gender, age, and transplant recipient groups. Results: Of 101 individuals, 47 (46.5%) were positive for anti-HCV antibodies and 34 (33.7%) for RNA with a significant difference (P < 0.05). RNA copy number ranged from 4.6 × 103 to 3.11 × 107 copies/mL, median: 2.92 × 106 copies/mL, with no statistical differences in all groups. Analyses revealed no significant differences between the frequencies of anti-HCV antibodies or RNA in different groups. The frequencies of the genotypes 1 (50%) and 3 (35.3%) were higher than those of the genotypes 2 (2.9%), 4 (2.9%), and undetermined one (8.8%). Genotype 1 was significantly more prevalent in liver transplant recipients, those older than 40 years, and male cases (P < 0.05). Conclusions: Considering the high frequency of genotypes 1 and 3 among the studied groups, it is suggested that before and after transplantation programs be improved to manage and treat the disease efficiently, based on the standard protocols for such genotypes in the region. Accordingly, the occurrence of post-transplant complications due to immunosuppression among all the recipients as well as reinfection in HCV infected liver transplant patients can be diminished.
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Affiliation(s)
- Roya Feyznezhad
- Department of Microbiology, Sciences and Research Branch, Islamic Azad University, Shiraz, IR Iran
| | - Mohammad Amin Behzadi
- Alborzi Clinical Microbiology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Ramin Yaghobi
- Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Mazyar Ziyaeyan
- Alborzi Clinical Microbiology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding author: Mazyar Ziyaeyan, Alborzi Clinical Microbiology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel: +98-7193711351, Fax: +98-7116474303, E-mail:
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Song ATW, Mello ESD, Alves VAF, Cavalheiro NDP, Melo CE, Bonazzi PR, Tengan FM, Freire MP, Barone AA, D'Albuquerque LAC, Abdala E. Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation. Mem Inst Oswaldo Cruz 2015; 110:56-64. [PMID: 25742264 PMCID: PMC4371218 DOI: 10.1590/0074-02760140192] [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] [Received: 06/02/2014] [Accepted: 12/01/2014] [Indexed: 01/20/2023] Open
Abstract
Histology is the gold standard for diagnosing acute rejection and hepatitis C
recurrence after liver transplantation. However, differential diagnosis between the
two can be difficult. We evaluated the role of C4d staining and quantification of
hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of
98 liver biopsy samples divided into four groups by histological diagnosis: acute
rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV
recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute
rejection in patients undergoing liver transplant for reasons other than hepatitis C
and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for
immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of
C4d was observed in the portal vessels and was highest in the HCVTx- group. There was
no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However,
tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+
group samples. Additionally, there was a significant correlation between tissue and
serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to
be an efficient diagnostic test for the recurrence of HCV infection.
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Affiliation(s)
- Alice Tung Wan Song
- Divisão de Transplante de Fígado e Órgãos do Aparelho Digestivo, Universidade de São Paulo
| | | | | | | | | | | | | | | | | | | | - Edson Abdala
- Divisão de Transplante de Fígado e Órgãos do Aparelho Digestivo, Universidade de São Paulo
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Abstract
Liver transplantation has become the treatment of choice for nearly all causes of end-stage liver disease, fulminant liver failure, and selected primary hepatic malignancies. The demand for liver transplantation has persistently outmatched the availability of donor organs leading to the development of novel strategies to expand the donor pool. The authors review the process of liver transplant evaluation, methods used to address the donor shortage, and disease-specific outcomes and challenges and discuss posttransplant care.
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Affiliation(s)
- Ming-Ming Xu
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH14, New York, NY 10032, USA
| | - Robert S Brown
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH14, New York, NY 10032, USA.
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Dienstag JL, Delemos AS. Viral Hepatitis. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015:1439-1468.e7. [DOI: 10.1016/b978-1-4557-4801-3.00119-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.
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Faisal N, Yoshida EM, Bilodeau M, Wong P, Ma M, Burak KW, Al-Judaibi B, Renner EL, Lilly LB. Protease inhibitor-based triple therapy is highly effective for hepatitis C recurrence after liver transplant: a multicenter experience. Ann Hepatol 2014. [DOI: 10.1016/s1665-2681(19)31252-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
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Grassi A, Ballardini G. Post-liver transplant hepatitis C virus recurrence: an unresolved thorny problem. World J Gastroenterol 2014; 20:11095-115. [PMID: 25170198 PMCID: PMC4145752 DOI: 10.3748/wjg.v20.i32.11095] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 02/15/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related cirrhosis represents the leading cause of liver transplantation in developed, Western and Eastern countries. Unfortunately, liver transplantation does not cure recipient HCV infection: reinfection universally occurs and disease progression is faster after liver transplant. In this review we focus on what happens throughout the peri-transplant phase and in the first 6-12 mo after transplantation: during this crucial period a completely new balance between HCV, liver graft, the recipient's immune response and anti-rejection therapy is achieved that will deeply affect subsequent outcomes. Nearly all patients show an early graft reinfection, with HCV viremia reaching and exceeding pre-transplant levels; in this setting, histological assessment is essential to differentiate recurrent hepatitis C from acute or chronic rejection; however, differentiating the two patterns remains difficult. The host immune response (mainly cellular mediated) appears to be crucial both in the control of HCV infection and in the genesis of rejection, and it is also strongly influenced by immunosuppressive treatment. At present no clear immunosuppressive strategy could be strongly recommended in HCV-positive recipients to prevent HCV recurrence, even immunotherapy appears to be ineffective. Nonetheless it seems reasonable that episodes of rejection and over-immunosuppression are more likely to enhance the risk of HCV recurrence through immunological mechanisms. Both complete prevention of rejection and optimization of immunosuppression should represent the main goals towards reducing the rate of graft HCV reinfection. In conclusion, post-transplant HCV recurrence remains an unresolved, thorny problem because many factors remain obscure and need to be better determined.
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Dumortier J, Boillot O, Scoazec JY. Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: Past, present and future. World J Gastroenterol 2014; 20:11069-11079. [PMID: 25170196 PMCID: PMC4145750 DOI: 10.3748/wjg.v20.i32.11069] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 03/07/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related liver disease, including cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) worldwide. Post-transplant HCV re-infection is almost universal and results in accelerated progression from acute hepatitis to chronic hepatitis, and liver cirrhosis. Comprehension and treatment of recurrent HCV infection after LT have been major issues for all transplant hepatologists and transplant surgeons for the last decades. The aim of this paper is to review the evolution of our knowledge on the natural history of HCV recurrence after LT, including risk factors for disease progression, and antiviral therapy. We will focus our attention on possible ways (present and future) to improve the final long-term results of LT for HCV-related liver disease.
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50
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Yoshida Y, Ikegami T, Yoshizumi T, Toshima T, Yamashita YI, Yoshiya S, Shirabe K, Maehara Y. rs8099917 and viral genotyping as indications for living donor liver transplantation for hepatitis C: a case report. Transplant Proc 2014; 46:2426-9. [PMID: 25150603 DOI: 10.1016/j.transproceed.2013.09.059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2013] [Accepted: 09/12/2013] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Appropriate antiviral treatment is essential for living donor liver transplantation (LDLT) to be effective for treating hepatitis C. However, it has never been reported that pre-LDLT genetic analyses of both host and virus, with prediction of the outcome of post-LDLT antiviral treatment, indicated LDLT for a borderline case. CASE REPORT We have reported the case of a 68-year-old woman with liver cirrhosis caused by genotype 1b hepatitis C, a history of ruptured esophageal varices, and adequately controlled minor ascites. Her liver function was classified as Child-Pugh grade B. The donor was a 42-year-old woman with an estimated left lobe graft volume (GV) of 33.8% based on the standard liver volume of the recipient. Molecular analyses used to confirm the indication of LDLT for this combination revealed the following: The rs8099917 genotype was T/T in the donor and recipient, the HCV core protein was double wild type, there were no mutations in the interferon sensitivity-determining region, and 8 mutations were found in the interferon/ribavirin resistance-determining region. LDLT was performed because very high sensitivity to interferon treatment was predicted. DISCUSSION Six months after LDLT and uneventful post-LDLT courses, pegylated interferon-α2a and ribavirin were administered under immunosuppression with cyclosporine and mycophenolate mofetil. This regimen was continued for 48 weeks, resulting in a viral response at 10 weeks and a sustained viral response, as predicted. CONCLUSIONS We have reported the usefulness of molecular analyses of host and viral factors for indicating LDLT to treat hepatitis C in a borderline case.
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Affiliation(s)
- Y Yoshida
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - T Ikegami
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
| | - T Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - T Toshima
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - Y-I Yamashita
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - S Yoshiya
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - K Shirabe
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
| | - Y Maehara
- Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan
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