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Roche B, Coilly A, Samuel D. Management of Transplant Patients Infected with HCV. HEPATITIS C: CARE AND TREATMENT 2021:153-173. [DOI: 10.1007/978-3-030-67762-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Impact of Donor Age on Recipient Survival in Adult-to-Adult Living-donor Liver Transplantation. Ann Surg 2019; 267:1126-1133. [PMID: 28288061 DOI: 10.1097/sla.0000000000002194] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To investigate the influence of donor age on recipient outcome after living-donor partial liver transplantation (LDLT). BACKGROUND Donor age is a well-known prognostic factor in deceased donor liver transplantation; however, its role in LDLT remains unclear. METHODS We retrospectively analyzed 315 consecutive cases of primary adult-to-adult LDLT in our center between April 2006 and March 2014. Recipients were divided into 5 groups according to the donor age: D-20s (n = 60); D-30s (n = 72); D-40s (n = 57); D-50s (n = 94); and D-60s (n = 32). The recipient survival and the association with various clinical factors were investigated. RESULTS Recipient survival proportions were significantly higher in D-20s compared with all the other groups (P = 0.008, < 0.001, < 0.001, and = 0.006, vs D-30s, -40s, -50s, and -60s, respectively), whereas there was no association between recipient survival and their own age. There are 3 typical relationships between donors and recipients in adult-to-adult LDLT: from child-to-parent, between spouses/siblings, and from parent-to-child. The overall survival in child-to-parent was significantly higher than in spouses/siblings (P = 0.002) and in parent-to-child (P = 0.005), despite significantly higher recipient age in child-to-parent [59 (42-69) years, P < 0.001]. Contrastingly, parent-to-child exhibited the lowest survival, despite the youngest recipient age [26 (20-43) years, P < 0.001]. In addition, younger donor age exhibited significantly better recipient survival both in hepatitis C virus-related and in non-hepatitis C virus diseases. Univariate and multivariate analyses both demonstrated that donor age and graft-type (right-sided livers) are independent prognostic factors for recipient survival. CONCLUSIONS Donor age is an independent, strong prognostic factor in adult-to-adult LDLT.
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Coilly A, Roche B, Samuel D. Management of HCVInfection After Liver Transplantation. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:753-764. [DOI: 10.1002/9781119211419.ch50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Chen K, Lu P, Song R, Zhang J, Tao R, Wang Z, Zhang W, Gu M. Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection: A PRISMA-compliant study. Medicine (Baltimore) 2017; 96:e7568. [PMID: 28746204 PMCID: PMC5627830 DOI: 10.1097/md.0000000000007568] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Revised: 06/13/2017] [Accepted: 06/25/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). RESULTS Six studies (360 RTRs) were included. Two hundred thirty six RTRs (98.3%) achieved sustained virological response within 12 weeks; HCV infection was cleared in 239 RTRs after 24-week treatment. Liver function differed significantly pre- and posttreatment (alanine aminotransferase, SMD: 0.96, 95%CIs: 0.65, 1.26; aspartate aminotransferase, SMD: 0.89, 95%CIs: 0.60, 1.18); allograft function pre- and posttreatment was not statistically different (serum creatinine, SMD: -0.13, 95%CIs: -0.38, 0.12; estimated glomerular filtration rate, SMD: 0.20, 95%CIs: -0.11, 0.51). General symptoms (fatigue nausea dizziness or headache) were the most common adverse events (AEs) (39.3%). Severe AEs, that is, anemia, portal vein thrombosis, and streptococcus bacteraemia and pneumonia, were present in 1.1%, 0.6%, and 1.1% of RTRs, respectively. CONCLUSION Our findings suggest that DAAs are highly efficacious and safe for treating HCV-infected RTRs and without significant AE.
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Nguyen NH, Yee BE, Chang C, Jin M, Lutchman G, Lim JK, Nguyen MH. Tolerability and effectiveness of sofosbuvir and simeprevir in the post-transplant setting: systematic review and meta-analysis. BMJ Open Gastroenterol 2016; 3:e000066. [PMID: 26966549 PMCID: PMC4782279 DOI: 10.1136/bmjgast-2015-000066] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 11/18/2015] [Accepted: 11/20/2015] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Outcome data on simeprevir and sofosbuvir (SMV+SOF) in patients with liver transplantation (LT) with hepatitis C virus genotype 1 (HCV-1) are limited with individual studies having a small sample size and limited SVR12 (sustained virological response) data. Our goal was to perform a meta-analysis to study the outcome of SMV+SOF±ribavirin (RBV) in recipients with LT. METHODS In April 2015, we conducted a literature search for 'simeprevir' in MEDLINE/EMBASE and five major liver meetings. We included studies with SVR12 data in ≥5 post-LT mono-infected HCV-1 patients treated with SMV+SOF±RBV. We used random-effects models to estimate effect sizes, and the Cochrane Q-test (p value <0.10) with I(2) (>50%) to assess study heterogeneity. RESULTS We included nine studies with a total of 325 patients with post-LT. Studies included mostly men (59-81%). Pooled SVR12 was 88.0% (95% CI 83.4% to 91.5%). In two studies, HCV-1a patients with mild fibrosis (n=108) had an SVR12 rate of 95.0% (95% CI 82.4% to 98.7%), which was significantly higher than that of HCV-1a patients with advanced fibrosis (n=49) with an SVR12 rate of 81.7% (95% CI 69.8% to 89.5%), OR 4.2 (95% CI 1.1 to 16.1, p=0.03). The most common pooled side effects were: fatigue 21% (n=48/237), headache 9% (n=23/254), dermatological symptoms 15% (n=38/254), and gastrointestinal symptoms 6% (12/193). CONCLUSIONS SMV+SOF±RBV is safe and effective in recipients with LT with HCV-1 infection.
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Affiliation(s)
- Nghia H Nguyen
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Brittany E Yee
- School of Medicine, University of California, San Diego, La Jolla, California, USA
| | - Christine Chang
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Minjuan Jin
- Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hang Zhou, China
| | - Glen Lutchman
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Joseph K Lim
- Yale Liver Center, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Mindie H Nguyen
- Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
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Kim H, Lee KW, Yi NJ, Lee HW, Choi Y, Suh SW, Jeong J, Suh KS. Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation. J Korean Med Sci 2015; 30:1577-83. [PMID: 26539000 PMCID: PMC4630472 DOI: 10.3346/jkms.2015.30.11.1577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 07/29/2015] [Indexed: 11/20/2022] Open
Abstract
Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, ≥ moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.
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Affiliation(s)
- Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Suk-Won Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jaehong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Coilly A, Dumortier J, Botta-Fridlund D, Latournerie M, Leroy V, Pageaux GP, Agostini H, Giostra E, Moreno C, Roche B, Antonini TM, Guillaud O, Lebray P, Radenne S, Saouli AC, Calmus Y, Alric L, Debette-Gratien M, De Ledinghen V, Durand F, Duvoux C, Samuel D, Duclos-Vallée JC. Multicenter Experience with Boceprevir or Telaprevir to Treat Hepatitis C Recurrence after Liver Transplantation: When Present Becomes Past, What Lessons for Future? PLoS One 2015; 10:e0138091. [PMID: 26394142 PMCID: PMC4578772 DOI: 10.1371/journal.pone.0138091] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 08/25/2015] [Indexed: 12/20/2022] Open
Abstract
Background and aims First generation protease inhibitors (PI) with peg-interferon (PEG-IFN) and ribavirin (RBV) have been the only therapy available for hepatitis C virus (HCV) genotype 1 infection in most countries for 3 years. We have investigated the efficacy and tolerance of this triple therapy in transplanted patients experiencing a recurrence of HCV infection on the liver graft. Patients This cohort study enrolled 81 liver transplant patients (Male: 76%, mean age: 55.8±9.7 years) with severe HCV recurrence (F3 or F4: n = 34 (42%), treatment experienced: n = 44 (54%)), treated with boceprevir (n = 36; 44%) or telaprevir (n = 45; 56%). We assessed the percentages of patients with sustained virological responses 24 weeks after therapy (SVR24), and safety. Results The SVR24 rate was 47% (telaprevir: 42%; boceprevir: 53%, P = ns). At baseline, a normal bilirubin level (p = 0.0145) and albumin level >35g/L (p = 0.0372) and an initial RBV dosage of ≥800 mg/day (p = 0.0033) predicted SVR24. During treatment, achieving an early virological response after 12 weeks was the strongest independent factor to predict SVR24 (p<0.0001). A premature discontinuation of anti-HCV therapy due to a serious adverse event (SAE) was observed in 22 patients (27%). Hematological toxicity, infections and deaths were observed in 95%, 28% and 7% of patients, respectively. A history of post-LT antiviral therapy and thrombocytopenia (<50G/L) during treatment were both independent predictors of the occurrence of infections or SAE (p = 0.0169 and p = 0.011). Conclusions The use of first generation PI after liver transplantation enabled an SVR24 rate of 47% in genotype 1 patients, but induced a high rate of SAE. The identification of predictive factors for a response to treatment, and the occurrence of SAE, have enabled us to establish limits for the use of this anti-HCV therapy in the transplant setting.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France
| | - Jérôme Dumortier
- Department of Digestive Diseases, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France
| | - Danielle Botta-Fridlund
- Assistance Publique—Hôpitaux de Marseille, Centre Hospitalo-Universitaire Conception, Service d'Hépato-Gastro-Entérologie, Marseille, France
| | | | - Vincent Leroy
- Service d’hépato-gastro-entérologie, hôpital A.-Michallon, 38700, La Tronche, France
| | - Georges-Philippe Pageaux
- Fédération médico-chirurgicale des maladies de l’appareil digestif, hôpital Saint-Eloi, 34295, Montpellier, France
| | - Hélène Agostini
- AP-HP, Hôpital Bicêtre, Unité de recherche clinique Paris-Sud, Kremlin-Bicêtre, France
| | - Emiliano Giostra
- Department of Gastroenterology and Hepatology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, 14, Switzerland
| | - Christophe Moreno
- Liver unit, Department of Gastroenterology, Hepatopancreatology and Digestive oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Bruno Roche
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France
| | - Teresa Maria Antonini
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France
| | - Olivier Guillaud
- Department of Digestive Diseases, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France
| | - Pascal Lebray
- Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Sylvie Radenne
- Service d’hépatologie, HCL, hôpital de la Croix-Rousse, 69205, Lyon, France
| | - Anne-Catherine Saouli
- Hepato-Bilio-Pancreatic Surgery and Liver Transplantation Center, Université de Strasbourg, Strasbourg, France
| | - Yvon Calmus
- Department of Hepatobiliary and Liver Transplantation Surgery, Hopital Saint Antoine, Assistance publique-Hopitaux de Paris, 184 rue du Faubourg Saint-Antoine, 75012, Paris Cedex, France
| | - Laurent Alric
- Internal medecine-Digestive department UMR 152 IRD Toulouse 3 University, Toulouse, France
| | - Maryline Debette-Gratien
- Service d'Hépato-gastroentérologie, CHU de Limoges, 2 avenue Martin-Luther-King, 87042, Limoges, France, Inserm UMR 1092, Faculté de médecine de Limoges, Université de Limoges, Limoges, France
| | | | - François Durand
- Service d’hépatologie, hôpital Beaujon, AP–HP, 92118, Clichy, France
| | - Christophe Duvoux
- Service d’hépatologie, hôpital Henri-Mondor, AP–HP, 94000, Créteil, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France, Université Paris-Sud, UMR-S 785, Villejuif, F-94800, France, Inserm, Unité 785, Villejuif, F-94800, France, Hepatinov, Villejuif, F-94800, France
- * E-mail:
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Pipili C, Cholongitas E. Treatment of chronic hepatitis C in liver transplant candidates and recipients: Where do we stand? World J Hepatol 2015; 7:1606-16. [PMID: 26140081 PMCID: PMC4483543 DOI: 10.4254/wjh.v7.i12.1606] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2014] [Revised: 05/18/2015] [Accepted: 06/01/2015] [Indexed: 02/06/2023] Open
Abstract
The first generation direct antiviral agents (DAAs) highlighted substantial prognosis improvement among liver transplant (LT) candidates and recipients with recurrent hepatitis C virus (HCV) infection. During 2014, second generation DAAs are associated with high sustained virological response rates (> 95%), shortened duration courses and relatively few toxicities. In keeping with the currently available data, patients with decompensated cirrhosis awaiting LT is preferable to be treated with interferon-free, new generation DAAs, with or without ribavirin combinations. Although data about the safety of new DAAs combinations in this patient population are limited, sofosbuvir and daclatasvir pharmacokinetics do not appear to change significantly in moderate or severe liver impairment, while other new DAAs (simeprevir, asunaprevir) seem to be contraindicated in patients with severe liver impairment (Child-Pugh class C). On the other hand, sofosbuvir should not be given in patients with glomerular filtration rate ≤ 30 mL/min, but ongoing trials will clarify better this issue. With the objective that newer antiviral combinations will yield safer and more efficient manipulation of HCV recurrence post-transplant, the European Association for the Study of the Liver has recently updated its recommendations towards this direction. Nevertheless the new antivirals' high cost may be the biggest challenge to their implementation worldwide.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
| | - Evangelos Cholongitas
- Chrysoula Pipili, Division of Nephrology, Royal Infirmary of Edinburgh, Scotland EH16 4SA, United Kingdom
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Cavalcante LN, Lyra AC. Predictive factors associated with hepatitis C antiviral therapy response. World J Hepatol 2015; 7:1617-31. [PMID: 26140082 PMCID: PMC4483544 DOI: 10.4254/wjh.v7.i12.1617] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/16/2014] [Accepted: 05/05/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection may lead to significant liver injury, and viral, environmental, host, immunologic and genetic factors may contribute to the differences in the disease expression and treatment response. In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) became the standard of care for HCV treatment. In this PR era, predictive factors of therapy response related to virus and host have been identified. In 2010/2011, therapeutic regimens for HCV genotype 1 patients were modified, and the addition of NS3/4a protease inhibitors (boceprevir or telaprevir) to dual therapy increased the effectiveness and chances of sustained virologic response (SVR). Nevertheless, the first-generation triple therapy is associated with many adverse events, some of which are serious and associated with death, particularly in cirrhotic patients. This led to the need to identify viral and host predictive factors that might influence the SVR rate to triple therapy and avoid unnecessary exposure to these drugs. Over the past four years, hepatitis C treatment has been rapidly changing with the development of new therapies and other developments. Currently, with the more recent generations of pangenotipic antiviral therapies, there have been higher sustained virologic rates, and prognostic factors may not have the same importance and strength as before. Nonetheless, some variables may still be consistent with the low rates of non-response with regimens that include sofosbuvir, daclatasvir and ledipasvir. In this manuscript, we review the predictive factors of therapy response across the different treatment regimens over the last decade including the new antiviral drugs.
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Affiliation(s)
- Lourianne Nascimento Cavalcante
- Lourianne Nascimento Cavalcante, André Castro Lyra, Hospital Sao Rafael - Gastro-Hepatology Service, Salvador, Bahia 41253-190, Brazil
| | - André Castro Lyra
- Lourianne Nascimento Cavalcante, André Castro Lyra, Hospital Sao Rafael - Gastro-Hepatology Service, Salvador, Bahia 41253-190, Brazil
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Hunyady B, Gerlei Z, Gervain J, Horváth G, Lengyel G, Pár A, Rókusz L, Szalay F, Telegdy L, Tornai I, Werling K, Makara M. [In Process Citation]. Orv Hetil 2015; 156 Suppl 1:3-23. [PMID: 26039413 DOI: 10.1556/oh.2015.30107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. From a socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63-75% and 59-66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antiviral interferon-free combination therapies have been registered for the treatment of chronic hepatitis C, with a potential efficacy over 90% and typical short duration of 8-12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and / or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment as well as for on-treatment decisions, accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(Suppl. 1), 3-23.
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Affiliation(s)
- Béla Hunyady
- 1 Somogy Megyei Kaposi Mór Oktató Kórház Belgyógyászati Osztály Kaposvár Tallián Gy. u. 20-32. 7400
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Daily low-dose tacrolimus is a safe and effective immunosuppressive regimen during telaprevir-based triple therapy for hepatitis C virus recurrence after liver transplant. Transplantation 2015; 99:841-7. [PMID: 25208324 DOI: 10.1097/tp.0000000000000399] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Graft loss because of hepatitis C virus recurrence is a serious problem after liver transplantation (LT), and the response to pegylated interferon (PEG-IFN) and ribavirin (RBV) is poor. The significantly better response rates achieved with telaprevir (TVR)-based triple therapy have led to better graft and patient survival rates, but severe drug interactions may limit the usefulness of this therapy for LT patients. We report our single-center experience with a specially developed protocol that involved administering a low daily dose of tacrolimus (TAC) to a cohort of 17 patients with a recurrence of hepatitis C virus genotype 1 after LT. METHODS Patients were treated with TVR, PEG-IFN, and RBV for 12 weeks, followed by 12 or 36 weeks of dual therapy with PEG-IFN and RBV. After TVR administration was initiated, the TAC dosage was skipped until trough levels began to decline; it was then administered at a dose of 0.1 mg once or twice daily. Tacrolimus trough levels and laboratory values were closely monitored during the TVR phase. RESULTS Deviations in trough levels were avoided, thus preventing any clinically evident renal toxicity related to TAC. In addition, histologic studies performed at the end of therapy showed that no rejection episodes had occurred. All patients tolerated the medication. Sustained virologic response was documented for 10 of 17 patients (58%) 24 weeks after end of treatment. CONCLUSION In conclusion, substantial dose reduction and daily administration of low doses of TAC compose a safe and efficient immunosuppressive regimen during TVR-based triple therapy.
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Filipec Kanizaj T, Kunac N. Hepatitis C: New challenges in liver transplantation. World J Gastroenterol 2015; 21:5768-77. [PMID: 26019441 PMCID: PMC4438011 DOI: 10.3748/wjg.v21.i19.5768] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 02/28/2015] [Accepted: 04/17/2015] [Indexed: 02/06/2023] Open
Abstract
In an era of great achievements in liver transplantation, hepatitis C viral infection (HCV) remains an unsolved problem. As a leading indication for liver transplantation in Western countries, HCV poses a significant burden both before and after transplantation. Post-transplant disease recurrence occurs in nearly all patients with detectable pretransplant viremia, compromising the lifesaving significance of transplantation. Many factors involving the donor, recipient and virus have been evaluated throughout the literature, although few have been fully elucidated and implemented in actual clinical practice. Antiviral therapy has been recognized as a cornerstone of HCV infection control; however, experience and success are diminished following transplantation in a challenging cohort of patients with liver cirrhosis. Current therapeutic protocols surpass those used previously, both in sustained viral response and side-effect profile. In this article we review the most relevant and contemporary scientific evidence regarding hepatitis C infection and liver transplantation, with special attention dedicated to novel, more efficient and safer antiviral regimens.
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Coilly A, Roche B, Duclos-Vallée JC, Samuel D. Management of post transplant hepatitis C in the direct antiviral agents era. Hepatol Int 2015; 9:192-201. [PMID: 25820797 DOI: 10.1007/s12072-015-9621-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 02/23/2015] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the main indications for liver transplantation. Viral recurrence occurs in all patients with detectable serum HCV RNA at the time of transplantation leading to cirrhosis in 20-30% of patients within 5 years. Viral eradication using antiviral therapy has been shown to improve patient and graft survival. Pegylated interferon (PEG-IFN) and ribavirin (RBV) antiviral therapy achieved SVR in around 30% of transplant recipients. In the non-transplant setting, first generation NS3/4 protease inhibitors, boceprevir or telaprevir associated with PEG-IFN and RBV, has improved the SVR rates to 75% in genotype 1 infected patients. However, tolerability and drug-drug interactions with calcineurin inhibitors are both limiting factors of their use in transplant recipients. In the non-transplant patients, using new direct-acting antiviral therapy has dramatically improved the efficacy of antiviral C therapy over recent years leading to SVR rates over 90% in phase II and III clinical trials, without PEG-IFN and/or RBV. Preliminary results in transplant patients showed better efficacy, better tolerability and less drug-drug interactions.
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Affiliation(s)
- Audrey Coilly
- Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, 12, Avenue Paul Vaillant-Couturier, 94800, Villejuif, France,
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Jeong SW, Choi Y, Kim JW. Management of viral hepatitis in liver transplant recipients. Clin Mol Hepatol 2014; 20:338-44. [PMID: 25548738 PMCID: PMC4278063 DOI: 10.3350/cmh.2014.20.4.338] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 12/15/2014] [Indexed: 12/15/2022] Open
Abstract
Recurrence of viral hepatitis after liver transplantation (LT) can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB) using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV). Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.
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Affiliation(s)
- Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Mohammad RA, Bulloch MN, Chan J, Deming P, Love B, Smith L, Dong BJ, GI Liver Nutrition and Infectious Diseases Practice and Research Networks of the American College of Clinical Pharmacy. Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection: Joint Opinion of the GI/Liver/Nutrition and Infectious Diseases Practice and Research Networks of the American College of Clinical Pharmacy. Pharmacotherapy 2014; 34:1341-54. [PMID: 25359244 DOI: 10.1002/phar.1512] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The objective of this opinion paper was to identify and describe potential clinical pharmacists' services for the prevention and management of patients infected with the hepatitis C virus (HCV). The goals of this paper are to guide the establishment and development of pharmacy services for patients infected with HCV and to highlight HCV research and educational opportunities. Recommendations were based on the following: a review of published data on clinical pharmacist involvement in the treatment and management of HCV-infected patients; a consensus of clinical pharmacists who provide direct patient care to HCV-infected patients and practice in different pharmacy models, including community-based and academic settings; and a review of published guidelines and literature focusing on the treatment and management of HCV infections. The recommendations provided in this opinion paper define the areas of clinical pharmacist involvement and clinical pharmacy practice in the treatment and management of patients with HCV. Clinical pharmacists can promote preventive measures and education about reducing HCV transmission, improve medication adherence, assist in monitoring clinical and adverse effects, recommend treatment strategies to minimize adverse effects and drug interactions, and facilitate medication acquisition and logistics that positively improve patient outcomes and reduce the health care system costs.
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Affiliation(s)
- Rima A Mohammad
- Department of Clinical, Social, and Administrative Sciences, University of Michigan College of Pharmacy, Ann Arbor, Michigan; Department of Inpatient Pharmacy Services, University of Michigan Health System, University Hospital, Ann Arbor, Michigan
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Burton JR, O'Leary JG, Verna EC, Saxena V, Dodge JL, Stravitz RT, Levitsky J, Trotter JF, Everson GT, Brown RS, Terrault NA. A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy. J Hepatol 2014; 61:508-14. [PMID: 24801415 PMCID: PMC4394742 DOI: 10.1016/j.jhep.2014.04.037] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 04/21/2014] [Accepted: 04/24/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited. METHODS This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12). RESULTS The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p<0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8g/dl and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related. CONCLUSIONS The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.
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Affiliation(s)
- James R Burton
- University of Colorado, Denver, Aurora, CO, United States
| | | | | | - Varun Saxena
- University of California at San Francisco, San Francisco, CA, United States
| | - Jennifer L Dodge
- University of California at San Francisco, San Francisco, CA, United States
| | | | | | | | | | | | - Norah A Terrault
- University of California at San Francisco, San Francisco, CA, United States.
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Dall’Agata M, Gramenzi A, Biselli M, Bernardi M. Hepatitis C virus reinfection after liver transplantation: Is there a role for direct antiviral agents? World J Gastroenterol 2014; 20:9253-9260. [PMID: 25071318 PMCID: PMC4110555 DOI: 10.3748/wjg.v20.i28.9253] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 03/27/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatitis C virus (HCV) infection following liver transplantation (LT) is almost universal and can accelerate graft cirrhosis in up to 30% of patients. The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge, considering the shortage of donor organs and the accelerated progression of HCV in LT recipients. Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients, even though the combination is not as effective as it is in immunocompetent patients. A sustained virological response in the setting of LT improves patient and graft survival, but this is only achieved in 30%-45% of patients and the treatment is poorly tolerated. To improve the efficacy of pre- and post-transplant antiviral therapy, a new class of potent direct-acting antiviral agents (DAAs) has been developed. The aim of this review is to summarize the use of DAAs in LT HCV patients. PubMed, Cochrane Library, MEDLINE, EMBASE, Web of Science and clinical trial databases were searched for this purpose. To date, only three clinical studies on the topic have been published and most of the available data are in abstract form. Although a moderately successful early virological response has been reported, DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness. Moreover, the ongoing nature of data, the lack of randomized studies, the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable. In conclusion, large well-designed clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.
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Hunyady B, Gervain J, Horváth G, Makara M, Pár A, Szalay F, Telegdy L, Tornai I. [Diagnosis, treatment, and follow-up of hepatitis C-virus related liver disease. Hungarian national consensus guideline]. Orv Hetil 2014; 155 Suppl:3-24. [PMID: 24631886 DOI: 10.1556/oh.2013.29893] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.
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Affiliation(s)
- Béla Hunyady
- Somogy Megyei Kaposi Mór Oktató Kórház Belgyógyászati Osztály Kaposvár Tallián Gyula u. 20-32. 7400 Pécsi Tudományegyetem, Általános Orvostudományi Kar I. Belgyógyászati Klinika Pécs
| | - Judit Gervain
- Szent György Egyetemi Oktató Kórház I. Belgyógyászat és Molekuláris Diagnosztikai Laboratórium Székesfehérvár
| | - Gábor Horváth
- Szent János Kórház és Észak-budai Egyesített Kórházak Hepatológiai Szakrendelés Budapest
| | - Mihály Makara
- Egyesített Szent István és Szent László Kórház Budapest
| | - Alajos Pár
- Pécsi Tudományegyetem, Általános Orvostudományi Kar I. Belgyógyászati Klinika Pécs
| | - Ferenc Szalay
- Semmelweis Egyetem, Általános Orvostudományi Kar I. Belgyógyászati Klinika Budapest
| | | | - István Tornai
- Debreceni Egyetem, Általános Orvostudományi Kar, Orvos- és Egészségtudományi Centrum Belgyógyászati Intézet Debrecen
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Hibi T, Nishida S, Sageshima J, Levi DM, Ruiz P, Roth D, Martin P, Okabayashi K, Burke GW, Ciancio G, Tzakis AG. Excessive immunosuppression as a potential cause of poor survival in simultaneous liver/kidney transplantation for hepatitis C. Transpl Int 2014; 27:606-16. [PMID: 24606223 DOI: 10.1111/tri.12303] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 08/26/2013] [Accepted: 03/03/2014] [Indexed: 02/06/2023]
Abstract
Appropriate recipient selection of simultaneous liver/kidney transplantation (SLKT) remains controversial. In particular, data on liver graft survival in hepatitis C virus-infected (HCV+) SLKT recipients are lacking. We conducted a single-center, retrospective study of HCV+ SLKT recipients (N = 25) in comparison with HCV- SLKT (N = 26) and HCV+ liver transplantation alone (LTA, N = 296). Despite backgrounds of HCV+ and HCV- SLKT being similar, HCV+ SLKT demonstrated significantly impaired 5-year liver graft survival of 35% (HCV- SLKT, 79%, P = 0.004). Compared with HCV+ LTA, induction immunosuppression was more frequently used in HCV+ SLKT. Five-year liver graft survival rate for HCV+ SLKT was significantly lower than that for LTA (35% vs. 74%, respectively, P < 0.001). Adjusted hazard ratio of liver graft loss in HCV+ SLKT was 4.9 (95% confidence interval 2.0-12.1, P = 0.001). HCV+ SLKT recipients were more likely to succumb to recurrent HCV and sepsis compared with LTA (32% vs. 8.8%, P < 0.001 and 24% vs. 8.8%, P = 0.030, respectively). Ten HCV+ SLKT recipients underwent anti-HCV therapy for recurrent HCV; only 1 achieved sustained virological response. HCV+ SLKT is associated with significantly decreased long-term prognosis compared with HCV- SLKT and HCV+ LTA.
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Affiliation(s)
- Taizo Hibi
- Miami Transplant Institute, University of Miami Leonard M. Miller School of Medicine and Jackson Memorial Hospital, Miami, Florida, USA; DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine and Jackson Memorial Hospital, Miami, Florida, USA; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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