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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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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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Felmlee DJ, Coilly A, Chung RT, Samuel D, Baumert TF. New perspectives for preventing hepatitis C virus liver graft infection. THE LANCET. INFECTIOUS DISEASES 2016; 16:735-745. [PMID: 27301929 PMCID: PMC4911897 DOI: 10.1016/s1473-3099(16)00120-1] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 01/29/2016] [Accepted: 02/15/2016] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20-30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be used synergistically with DAAs to prevent or treat graft infection.
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Affiliation(s)
- Daniel J Felmlee
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Hepatology Research Group, Peninsula School of Medicine and Dentistry, University of Plymouth, Plymouth, UK
| | - Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France
| | - Raymond T Chung
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; University Paris-Sud, UMR-S 1193, Villejuif, France; Inserm Unit 1193, Villejuif F-94800, France.
| | - Thomas F Baumert
- Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
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Kaido T. Selection Criteria and Current Issues in Liver Transplantation for Hepatocellular Carcinoma. Liver Cancer 2016; 5:121-7. [PMID: 27386430 PMCID: PMC4906426 DOI: 10.1159/000367749] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Liver transplantation (LT) is an ideal treatment for hepatocellular carcinoma (HCC) because it not only resects HCCs but it also replaces the underlying damaged liver with normal tissue. However, the selection criteria are still a matter of debate. After the introduction of the Milan criteria, some expanded criteria focusing on tumor size and number have been proposed. In addition, new expanded criteria considering tumor biology have been proposed using tumor markers and (18)F-fluorodeoxyglucose positron emission tomography. This review summarizes the selection criteria in LT for HCC and introduces current issues focusing on the treatment for hepatitis C virus infection and the significance of sarcopenia in this field.
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Affiliation(s)
- Toshimi Kaido
- *Toshimi Kaido, MD, PhD, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan), Tel. +81 75 751 4323, E-Mail:
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Kawaoka T, Takahashi S, Kawakami Y, Tsuge M, Hiramatsu A, Imamura M, Hyogo H, Aikata H, Ishiyama K, Tashiro H, Ohdan H, Tanaka J, Chayama K. Sustained virological response to antiviral therapy improves survival rate in patients with recurrent hepatitis C virus infection after liver transplantation. Hepatol Res 2015; 45:1047-54. [PMID: 25376902 DOI: 10.1111/hepr.12447] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 10/28/2014] [Accepted: 10/28/2014] [Indexed: 02/08/2023]
Abstract
AIM Previous European and North American studies analyzed the relationship between survival rate and sustained virological response (SVR) to interferon (IFN) therapy in patients with recurrent hepatitis C viral (HCV) infection after liver transplantation (LT). The present study was designed to define the same relationship in Japanese patients who had undergone LT. METHODS Forty-seven patients (genotype 1, 40; genotype 2, 7) with recurrent HCV after LT were treated with pegylated interferon (PEG IFN) or IFN/ribavirin (RBV). In possible, within 3 months after LT, patients started treatment with PEG IFN-α-2b or IFN-α-2b s.c. once weekly combined with RBV (200 mg/day). RESULTS The SVR rate was 51% (24/47) for all patients, 42.5% (17/40) for genotype 1 and 100% (7/7) for genotype 2. The median follow-up period was 71 months (range, 24-152). The survival rate of 24 patients who achieved SVR was 95% at 5 years and 92% at 10 years. These rates were significantly better than those of 23 patients who did not achieve SVR (82% at 5 years, 58% at 10 years) (P = 0.027). Two patients of the SVR group died during follow up (due to hepatocellular carcinoma in one and chronic rejection in one), while six non-SVR patients died during the same period (three died due to liver failure by recurrent HCV). CONCLUSION SVR following IFN therapy contributes to improvement of survival rate in patients with recurrent post-LT HCV infection.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Shoichi Takahashi
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Kohei Ishiyama
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hirotaka Tashiro
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
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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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Roche B, Coilly A, Roque-Afonso AM, Samuel D. Interferon-Free Hepatitis C Treatment before and after Liver Transplantation: The Role of HCV Drug Resistance. Viruses 2015; 7:5155-68. [PMID: 26404355 PMCID: PMC4584308 DOI: 10.3390/v7092864] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 09/09/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection progressing to cirrhosis within five years in 20% to 30% of them. Obtaining a sustained virological response (SVR) greatly improves overall and graft survival. Until 2011, standard antiviral therapy using PEGylated interferon (PEG-IFN) and ribavirin (RBV) was the only effective therapy, with an SVR rate around 30% in this setting. For patients infected with genotype 1, first generation NS3/4A protease inhibitors (PIs), boceprevir (BOC) or telaprevir (TVR), associated with PEG-IFN and RBV for 48 weeks have increased the SVR rates to 60% in non-transplant patients. However, tolerability and drug-drug interactions with calcineurin inhibitors (CNI) are both limiting factors of their use in the liver transplant setting. Over recent years, the efficacy of antiviral C therapy has improved dramatically using new direct-acting antiviral (DAA) agents without PEG-IFN and/or RBV, leading to SVR rates over 90% in non-transplant patients. Results available for transplant patients showed a better efficacy and tolerability and less drug-drug interactions than with first wave PIs. However, some infrequent cases of viral resistance have been reported using PIs or NS5A inhibitors pre- or post-LT that can lead to difficulties in the management of these patients.
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Affiliation(s)
- Bruno Roche
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.
- Hepatinov, Villejuif, F-94800, France.
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.
- Hepatinov, Villejuif, F-94800, France.
| | - Anne-Marie Roque-Afonso
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France
- Hepatinov, Villejuif, F-94800, France
- AP-HP Hôpital Paul-Brousse, Laboratoire de Virologie, Villejuif F-94800, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Univ. Paris-Sud, UMR-S 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant-Couturier, Villejuif, F-94800, France.
- Inserm, UMR-S 1193, Université Paris-Saclay, Villejuif F-94800, France.
- Hepatinov, Villejuif, F-94800, France.
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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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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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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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11
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Optimizing outcome of recurrent hepatitis C virus genotype 4 after living donor liver transplantation: moving forward by looking back. Transplant Proc 2015; 46:822-7. [PMID: 24767357 DOI: 10.1016/j.transproceed.2013.11.152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Revised: 11/08/2013] [Accepted: 11/27/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE Recurrence of HCV after LDLT is almost universal. Different factors affect response to treatment. Few data are available regarding outcome of recurrent HCV genotype 4. The purpose of this study is to improve outcome of recurrent HCV genotype 4 after LDLT. METHODS An IRB approved chart review of 243 patients transplanted for ESLD, HCV genotype 4 over 4 years were reviewed. Protocol liver biopsies were taken 6 months after transplant. Patients received pegylated interferon and ribavirin in case of histological recurrence. Five patients had FCH were excluded. RESULTS Thirty-seven patients were included. Sustained Virological Response (SVR) was achieved in 29 (78.3%). Patients with Metavir fibrosis stage (F0) and (F1) had SVR in 5/5 (100%) and 20/24 (83.3%). Two patients with F1 had to stop treatment because of thrombocytopenia and 2 were non responders. Three out of 6 patients (50%) with (F2) had SVR, 2 were non responders and one had to discontinue treatment because of severe depression. One of 2 patients (50%) with F3 had SVR and the other patient decompensated within 4 months before treatment and died. CONCLUSION Protocol biopsies allow early detection of inflammatory changes in the graft before fibrosis occurs. Early treatment of recurrent HCV genotype 4 after LDLT results in better response.
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12
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Jiménez-Pérez M, González-Grande R, Rando-Muñoz FJ. Management of recurrent hepatitis C virus after liver transplantation. World J Gastroenterol 2014; 20:16409-16417. [PMID: 25469009 PMCID: PMC4248184 DOI: 10.3748/wjg.v20.i44.16409] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 08/27/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is the leading cause of death from liver disease and the leading indication for liver transplantation (LT) in the United States and Western Europe. LT represents the best therapeutic alternative for patients with advanced chronic liver disease caused by HCV or those who develop hepatocarcinoma. Reinfection by HCV of the graft is universal and occurs in 95% of transplant patients. This reinfection can compromise graft function and patient survival. In a few cases, the histological recurrence is minimal and non-progressive; however, in most patients it follows a more rapid course than in immunocompetent persons, and frequently evolves into cirrhosis with graft loss. In fact, the five-year and ten-year survival of patients transplanted because of HCV are 75% and 68%, respectively, compared with 85% and 78% in patients transplanted for other reasons. There is also a pattern of recurrence that is very severe, but rare (< 10%), called fibrosing cholestatic hepatitis, which often involves rapid graft loss. Patients who present a negative HCV viremia after antiviral treatment have better survival. Many studies published over recent years have shown that antiviral treatment of post-transplant HCV hepatitis carried out during the late phase is the best option for improving the prognosis of these patients. Until 2011, PEGylated interferon plus ribavirin was the standard of care, resulting in a sustained virological response in around 30% of recipients. The addition of protease inhibitors, such as boceprevir or telaprevir, to the standard of care, or the use of other direct-acting antiviral drugs may involve therapeutic changes in the context of HCV recurrence. This may result a better prognosis for these patients, particularly those with severe recurrence or factors predicting rapid progression of fibrosis. However, the use of these agents in LT still requires clarification in terms of safety and efficacy.
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MESH Headings
- Antiviral Agents/adverse effects
- Antiviral Agents/therapeutic use
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/surgery
- Carcinoma, Hepatocellular/virology
- Drug Therapy, Combination
- End Stage Liver Disease/diagnosis
- End Stage Liver Disease/mortality
- End Stage Liver Disease/surgery
- End Stage Liver Disease/virology
- Hepatitis C, Chronic/complications
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/drug therapy
- Hepatitis C, Chronic/immunology
- Hepatitis C, Chronic/mortality
- Humans
- Immunocompromised Host
- Immunosuppressive Agents/adverse effects
- Liver Neoplasms/diagnosis
- Liver Neoplasms/mortality
- Liver Neoplasms/surgery
- Liver Neoplasms/virology
- Liver Transplantation/adverse effects
- Liver Transplantation/mortality
- Recurrence
- Risk Factors
- Time Factors
- Treatment Outcome
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14
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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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15
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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16
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Harada N, Tamura S, Sugawara Y, Togashi J, Ishizawa T, Kaneko J, Aoki T, Sakamoto Y, Hasegawa K, Tanaka T, Yamashiki N, Kokudo N. Impact of donor and recipient single nucleotide polymorphisms of IL28B rs8099917 in living donor liver transplantation for hepatitis C. PLoS One 2014; 9:e90462. [PMID: 24599320 PMCID: PMC3944011 DOI: 10.1371/journal.pone.0090462] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Accepted: 01/31/2014] [Indexed: 02/06/2023] Open
Abstract
Single nucleotide polymorphisms of interleukin-28B (IL28B) rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV)-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR) and sustained virologic response (SVR) were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT) in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG) corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.
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Affiliation(s)
- Nobuhiro Harada
- Division of Artificial Organ and Transplantation, The University of Tokyo Hospital, Tokyo, Japan
| | - Sumihito Tamura
- Division of Artificial Organ and Transplantation, The University of Tokyo Hospital, Tokyo, Japan
| | - Yasuhiko Sugawara
- Division of Artificial Organ and Transplantation, The University of Tokyo Hospital, Tokyo, Japan
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
| | - Junichi Togashi
- Division of Artificial Organ and Transplantation, The University of Tokyo Hospital, Tokyo, Japan
| | - Takeaki Ishizawa
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Junichi Kaneko
- Division of Artificial Organ and Transplantation, The University of Tokyo Hospital, Tokyo, Japan
| | - Taku Aoki
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan
| | - Tomohiro Tanaka
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
| | - Noriyo Yamashiki
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
| | - Norihiro Kokudo
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, The University of Tokyo Hospital, Tokyo, Japan
- Organ Transplantation Service, The University of Tokyo Hospital, Tokyo, Japan
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17
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Coilly A, Roche B, Duclos-Vallée JC, Samuel D. Management of HCV transplant patients with triple therapy. Liver Int 2014; 34 Suppl 1:46-52. [PMID: 24373078 DOI: 10.1111/liv.12406] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection. Between 20 and 30% of patients have developed cirrhosis at 5 years post-LT. The outcome of transplant patients with cirrhosis on the graft is severe, with a rate of decompensation at 1 year of approximately 40%. To date, retransplantation is the only option in patients with decompensated liver disease. Until 2011, standard antiviral therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV), was the only effective therapy. Obtaining a sustained virological response (SVR) in patients with LT greatly improves overall and graft survival but this only occurs in 30% of transplanted patients. Direct acting antivirals (DAAs) such as protease inhibitors (PI), polymerase or other non-structural proteins inhibitors represent a new era in HCV associated liver disease. Although their use in the field of LT will certainly be essential there are some limitations because of safety and tolerance. One limitation is the potential interaction with calcineurin inhibitors. We describe the results of triple therapy with boceprevir (BOC) or telaprevir (TVR) for efficacy and safety and comment on future therapeutic strategies in liver transplant recipients.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Univ Paris-Sud, UMR-S 785, Villejuif, France; Inserm, Unité 785, Villejuif, France; Hepatinov, Villejuif, France
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18
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New insights in recurrent HCV infection after liver transplantation. Clin Dev Immunol 2013; 2013:890517. [PMID: 23710205 PMCID: PMC3655463 DOI: 10.1155/2013/890517] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Revised: 03/17/2013] [Accepted: 03/31/2013] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.
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19
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Joshi D, Carey I, Agarwal K. Review article: the treatment of genotype 1 chronic hepatitis C virus infection in liver transplant candidates and recipients. Aliment Pharmacol Ther 2013; 37:659-71. [PMID: 23432320 DOI: 10.1111/apt.12260] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 12/20/2012] [Accepted: 02/03/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recently, the therapeutic landscape with regard to anti-HCV therapy has changed dramatically. The new directly acting anti-virals (DAAs) have demonstrated improved sustained virological response (SVR) compared with pegylated-interferon and ribavirin. AIM To examine and present the latest data with regard to anti-viral therapy in genotype 1 HCV-positive transplant candidates and recipients. METHODS An electronic search using Medline was performed. Search terms included 'HCV, DAA and protease inhibitor' in combination with 'treatment pre-transplantation' and 'treatment post-transplantation'. RESULTS Patients with advanced fibrosis and cirrhosis have inferior SVR rates compared with patients with minimal fibrosis. A low accelerating dose regimen (LADR) of pegylated interferon and ribavirin (PR) appears to be a safe therapeutic option. Side effects also appear to be more pronounced in patients with advanced disease. Data from the large registration studies with triple therapy (boceprevir or telaprevir plus PR) demonstrated improved SVR rates even in patients with advanced disease, although virological relapse rates were highest amongst these patients. In transplant recipients, initial data are being reported on the use of triple therapy, and although no SVR data are available, promising results are accruing. The drug-drug interactions appear to be manageable. Side effects in particular anaemia appear to be markedly increased in the posttransplant setting. CONCLUSIONS The use of the new DAAs in patients with advanced fibrosis/cirrhosis pretransplant and posttransplant appears possible, with manageable side effects and drug-drug interactions, and improved early virological response rates. We recommend that these patients are managed in centres with the appropriate expertise.
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Affiliation(s)
- D Joshi
- Institute of Liver Studies, King's College Hospital, London, UK.
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20
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Lee SW, Bae SH. Management of Hepatitis C Viral Infection Pre- and Post-liver Transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2013. [DOI: 10.4285/jkstn.2013.27.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Sung Won Lee
- Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Si Hyun Bae
- Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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21
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An update on the management of hepatitis C: guidelines for protease inhibitor-based triple therapy from the Latin American Association for the Study of the Liver. Ann Hepatol 2013. [PMID: 23559487 DOI: 10.1016/s1665-2681(19)31404-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
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22
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Gonzalez HC, Jafri SM, Gordon SC. Role of liver biopsy in the era of direct-acting antivirals. Curr Gastroenterol Rep 2013; 15:307. [PMID: 23319086 DOI: 10.1007/s11894-012-0307-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
An accurate assessment of the degree of fibrosis or presence of cirrhosis is critical both for the appropriate management of, and to provide prognosis for, patients with chronic hepatitis C infection. In the new era of direct acting antivirals, large numbers of patients may enter therapy, and although liver biopsy remains the gold standard, it is not practical in all settings. In recent years, a variety of noninvasive methods have been developed that may obviate the need for liver biopsy in most settings. Indirect laboratory formulas, tests, panels of biomarkers and imaging modalities may accurately stage the degree of fibrosis in hepatitis C monoinfection, hepatitis C/HIV coinfection, and post-transplant recurrent hepatitis C.
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23
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Coilly A, Roche B, Samuel D. Current management and perspectives for HCV recurrence after liver transplantation. Liver Int 2013; 33 Suppl 1:56-62. [PMID: 23286847 DOI: 10.1111/liv.12062] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection. Between 20 and 30% of patients develop cirrhosis within 5 years post-LT. The outcome of transplant patients with cirrhosis on the graft is severe, with a rate of decompensation at 1 year of around 40%. To date, retransplantation is the only option for patients who develop decompensation. Until 2011, standard antiviral therapy, using pegylated interferon (PEG-IFN) and ribavirin (RBV), was the only effective therapy. Obtaining a sustained virological response (SVR) in the setting of LT greatly improves overall and graft survival, but this only concerns 30% of transplanted patients. Direct-acting antivirals (DAA) such as protease inhibitors, polymerase or other non-structural proteins inhibitors represent a new era in HCV-associated liver disease. Although their use in the field of liver transplantation seems to be essential, there are some limitations due to safety and tolerance. One limitation is the potential interaction with calcineurin inhibitors. We describe the preliminary results of triple therapy with boceprevir or telaprevir in terms of efficacy and safety in liver transplant recipients.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
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24
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Living-donor liver transplantation and hepatitis C. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2013; 2013:985972. [PMID: 23401640 PMCID: PMC3564275 DOI: 10.1155/2013/985972] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Accepted: 01/01/2013] [Indexed: 12/19/2022]
Abstract
Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompression. In areas with low deceased-donor organ availability like Japan, living-donor liver transplantation (LDLT) is similarly indicated for HCV cirrhosis as deceased-donor liver transplantation (DDLT) in Western countries and accepted as an established treatment for HCV-cirrhosis, and the results are equivalent to those of DDLT. To prevent graft failure due to recurrent hepatitis C, antiviral treatment with pegylated-interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. In contrast to DDLT, many Japanese LDLT centers have reported modified treatment regimens as best efforts to secure first graft, such as aggressive preemptive antiviral treatment, escalation of dosages, and elongation of treatment duration.
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25
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Kawaoka T, Takahashi S, Takaki S, Hiramatsu A, Waki K, Hiraga N, Miki D, Tsuge M, Imamura M, Kawakami Y, Aikata H, Ochi H, Onoe T, Tashiro H, Ohdan H, Chayama K. Interleukin-28B single nucleotide polymorphism of donors and recipients can predict viral response to pegylated interferon/ribavirin therapy in patients with recurrent hepatitis C after living donor liver transplantation. J Gastroenterol Hepatol 2012; 27:1467-72. [PMID: 22432893 DOI: 10.1111/j.1440-1746.2012.07129.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM Interleukin-28B (IL28B) single nucleotide polymorphism (SNP) influences viral response (VR) to interferon (IFN) therapy in patients with hepatitis C. We studied the relationship between VR and the IL28B polymorphism (rs8099917) in patients on long-term pegylated IFN plus ribavirin (PEGIFN/RBV) therapy for recurrent hepatitis C after living-donor liver transplantation (LDLT). METHODS Thirty-five patients with recurrent hepatitis C after LDLT were treated with PEGIFN/RBV. We evaluated the effect of IL28B SNP on the outcome in 20 patients infected with hepatitis C virus genotype 1 who completed IFN therapy. RESULTS The sustained VR (SVR) rate was 54% (19/35) for all patients; 46% (13/28) for genotype 1. The SVR rate of donors' TT group (major genotype) was higher than that of donors' TG+GG group (minor genotype) (73% vs 20%), while that of recipients' TT group was similar to that of recipients' TG+GG group (64% vs 50%). With regard to the combined effect of donors' and recipients' IL28B SNP, the SVR rates of TT:TT (donors':recipients'), TT:TG+GG, TG+GG:any group were 81%, 50%, and 20%, respectively. The VR rate of TT:TT, TT:TG+GG and TG+GG:any group at 12 weeks were 28%, 0%, and 0%; those at 48weeks were 70%, 50%, 20%, and those at the end of treatment were 100%, 50%, 20%, respectively. The multivariate analysis identified IL28B of donors:recipients (TT:TT) as the only independent determinant of SVR (odds ratio 15.0, P=0.035). CONCLUSION Measurement of donors' and recipients' IL28B SNP can predict the response to PEGIFN/RBV therapy, and the donors' IL28B SNP might be a more significant predictor than that of the recipients.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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26
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Carbone M, Lenci I, Baiocchi L. Prevention of hepatitis C recurrence after liver transplantation: An update. World J Gastrointest Pharmacol Ther 2012; 3:36-48. [PMID: 22966482 PMCID: PMC3437445 DOI: 10.4292/wjgpt.v3.i4.36] [Citation(s) in RCA: 3] [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: 05/18/2011] [Revised: 06/20/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries. Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation, being associated with accelerated progression to cirrhosis, graft loss and death. Graft and patient survival is reduced in liver transplant recipients with recurrent Hepatitis C virus (HCV) infection compared to HCV-negative recipients. Many variables may impact on recurrent HCV liver disease. Overall, excess immunosuppression is believed to be a key factor; however, no immunosuppressive regimen has been identified to be more beneficial or less harmful. Donor age limitations, exclusion of moderately to severely steatotic livers and minimization of ischemic times could be a potential strategy to minimize the severity of HCV disease in transplanted subjects. After transplantation, antiviral therapy based on pegylated IFN alpha with or without ribavirin is associated with far less results than that reported for immunocompetent HCV-infected patients. New findings in the field of immunotherapy and genomic medicine applied to this context are promising.
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Affiliation(s)
- Marco Carbone
- Marco Carbone, Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, United Kingdom
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27
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Berenguer M, Charco R, Manuel Pascasio J, Ignacio Herrero J. Spanish society of liver transplantation (SETH) consensus recommendations on hepatitis C virus and liver transplantation. Liver Int 2012; 32:712-31. [PMID: 22221843 DOI: 10.1111/j.1478-3231.2011.02731.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2011] [Accepted: 11/23/2011] [Indexed: 02/06/2023]
Abstract
In November 2010, the Spanish Society of Liver Transplantation (Sociedad Española de Trasplante Hepático, SETH) held a consensus conference. One of the topics of debate was liver transplantation in patients with hepatitis C. This document reviews (i) the natural history of post-transplant hepatitis C, (ii) factors associated with post-transplant prognosis in patients with hepatitis C, (iii) the role of immunosuppression in the evolution of recurrent hepatitis C and response to antiviral therapy, (iv) antiviral therapy, both before and after transplantation, (v) follow-up of patients with recurrent hepatitis C and (vi) the role of retransplantation.
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Affiliation(s)
- Marina Berenguer
- Spanish Society of Liver Transplantation (Sociedad Española de Trasplante Hepático, SETH)
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28
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Jafri SR, Gordon SC. Is there still a role for liver biopsy in managing hepatitis C virus infections? Clin Liver Dis (Hoboken) 2012; 1:32-35. [PMID: 31186843 PMCID: PMC6499258 DOI: 10.1002/cld.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2010] [Revised: 12/20/2010] [Accepted: 01/10/2011] [Indexed: 02/04/2023] Open
Affiliation(s)
- Syed‐Mohammed R. Jafri
- From the Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI
| | - Stuart C. Gordon
- From the Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, MI
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29
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Marubashi S, Umeshita K, Asahara T, Fujiwara K, Haga H, Hashimoto T, Hatakeyama K, Ichida T, Kanematsu T, Kitajima M, Kiyosawa K, Makuuchi M, Miyagawa S, Satomi S, Soejima Y, Takada Y, Tanaka N, Teraoka S, Monden M. Steroid-free living donor liver transplantation for HCV--a multicenter prospective cohort study in Japan. Clin Transplant 2012; 26:857-67. [PMID: 22507465 DOI: 10.1111/j.1399-0012.2012.01627.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2012] [Indexed: 12/29/2022]
Abstract
This prospective, non-randomized, multicenter cohort study analyzed the safety and efficacy of a steroid-free immunosuppressive (IS) protocol for hepatitis C virus (HCV)-positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assigned the steroid-free IS protocol (Fr group) and 29 the traditional steroid-containing IS protocol (St group). Serum HCV RNA levels increased over time and were higher in the St group until postoperative day 90 (POD 14, p=0.013). Preemptive anti-HCV therapy was started in a higher percentage of recipients (59.3%) in the Fr group than in the St group (31.0%, p=0.031), mainly due to early HCV recurrence. The incidence of HCV recurrence at one yr was lower in the Fr group (22.2%) than in the St group (41.4%; p=0.066). The incidence of acute cellular rejection was similar between groups. New onset diabetes after transplant, cytomegalovirus infection, and renal dysfunction were significantly less frequent in the Fr group than in the St group (p=0.022, p<0.0001, p=0.012, respectively). The steroid-free IS protocol safely reduced postoperative morbidity and effectively suppressed both the HCV viral load in the early post-transplant period and HCV recurrence in HCV-positive LDLT recipients.
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Affiliation(s)
- Shigeru Marubashi
- Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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30
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Strader DB, Seeff LB. A brief history of the treatment of viral hepatitis C. Clin Liver Dis (Hoboken) 2012; 1:6-11. [PMID: 31186837 PMCID: PMC6490695 DOI: 10.1002/cld.1] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Doris B. Strader
- Division of Gastroenterology and Hepatology, Fletcher Allen Health Care, University of Vermont College of Medicine, Burlington, VT
| | - Leonard B. Seeff
- Hill Group, Bethesda, MD,Food and Drug Administration, Silver Spring, MD
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31
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Abstract
Liver disease caused by the hepatitis C virus is the main indication for liver transplantation in Western countries. However, HCV re-infection post-transplantation is constant and recent data confirm that it significantly impairs patient and graft survival. Chronic HCV infection develops in 75-90% of patients, and 5-30% ultimately progress to cirrhosis within 5 years. Because of the impact of HCV recurrence on graft and patient survival, several treatment strategies have been evaluated. Antiviral therapy could be administered before transplantation to suppress viral replication and reduce the risk of recurrence. However, this approach is applicable in around 50% of patients and tolerance is poor, particularly in patients with decompensated cirrhosis. Pre-emptive therapy in the early post-transplant period is limited by the high rate of side effects. Frequently, antiviral therapy is initiated when HCV recurs to obtain viral eradication and/or reduce disease progression. Treatment of established graft lesions with Pegylated Interferon (PEG-IFN) and Ribavirin (RBV) combination therapy results in a sustained virological response (SVR) in around 30% of patients. The new classes of potent and direct antiviral agents (DAA) will certainly improve the results of pre- and post-transplant antiviral therapy. However, at the present time, no data are available on the use of these drugs in patients with decompensated cirrhosis or post-transplant hepatitis.
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Affiliation(s)
- Bruno Roche
- Centre Hepato-Biliaire, AP-HP Hopital Paul Brousse, Villejuif, France. France
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32
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Stickel F, Helbling B, Heim M, Geier A, Hirschi C, Terziroli B, Wehr K, De Gottardi A, Negro F, Gerlach T. Critical review of the use of erythropoietin in the treatment of anaemia during therapy for chronic hepatitis C. J Viral Hepat 2012; 19:77-87. [PMID: 22239497 DOI: 10.1111/j.1365-2893.2011.01527.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient.
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Affiliation(s)
- F Stickel
- Department of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, Switzerland.
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Kawaoka T, Aikata H, Miyaki D, Murakami E, Azakami T, Takaki S, Nagaoki Y, Hashimoto Y, Katamura Y, Hiramatsu A, Waki K, Hiraga N, Miki D, Tsuge M, Imamura M, Kawakami Y, Takahashi S, Ochi H, Tashiro H, Ohdan H, Chayama K. Eradication of hepatitis C virus genotype 1 after liver transplantation by interferon therapy before surgery: Report of three patients with analysis of interleukin-28 polymorphism, hepatitis C virus core region and interferon-sensitivity determining region. Hepatol Res 2011; 41:1126-31. [PMID: 22032680 DOI: 10.1111/j.1872-034x.2011.00853.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The achievement of sustained viral response (SVR) with interferon (IFN) therapy before liver transplantation (LT) is difficult due to liver dysfunction, pancytopenia and frequent side-effects. Here, we report eradication of hepatitis C virus (HCV) genotype 1 after LT in three patients by IFN therapy before surgery. All three patients achieved virological response (VR), namely, fall in serum HCV RNA titer below the detection limit of real-time polymerase chain reaction (PCR) during IFN administration. However, HCV RNA rebound after cessation of treatment in all three patients; namely, they could not achieve SVR despite treatment with pegylated (PEG) IFN plus ribavirin. All three patients had wild-type amino acids (a.a.) at either aa70 or aa91 in the core region. Genotyping of IL-28 single nucleotide polymorphisms (rs8099917) showed TT genotype in two patients and TG genotype in one. All three patients developed multiple hepatocellular carcinomas during the clinical course, and requested living donor LT using liver grafts from their relatives. The patients were treated with IFN to immediately before LT, at which time they remained negative for HCV RNA in serum by real-time PCR. The three patients were followed-up for 14-15 months after LT, during which they remained negative for HCV RNA despite no further IFN therapy. In conclusion, it is possible to eradicate HCV after LT by inducing VR with continuous IFN therapy to before LT in spite of viral and host evidences reflecting low susceptibility to IFN treatment.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Medicine and Molecular Science, Division of Frontier Medical Science Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Hiroshima, Japan
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Limaye AR, Firpi RJ. Management of recurrent hepatitis C infection after liver transplantation. Clin Liver Dis 2011; 15:845-58. [PMID: 22032532 DOI: 10.1016/j.cld.2011.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Recurrence of hepatitis C virus remains a near-universal phenomenon after liver transplantation (LT) and is responsible for the high morbidity and low survival seen in these patients. The severity of recurrent disease varies depending on multiple factors, only some of which are modifiable. Antiviral therapy is associated with improved outcomes, but viral clearance is only attainable in a small percentage of this patient population. This patient population is in need of new therapeutic options, and it remains to be seen whether direct-acting antiviral agents will be the answer to this ongoing therapeutic question.
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Affiliation(s)
- Alpna R Limaye
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida College of Medicine, Gainesville, USA
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Living donor liver transplantations in HIV- and hepatitis C virus-coinfected hemophiliacs: experience in a single center. Transplantation 2011; 91:1261-4. [PMID: 21593704 DOI: 10.1097/tp.0b013e3182193cf3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Although almost all human immunodeficiency virus (HIV)-infected Japanese hemophiliacs are coinfected with hepatitis C virus (HCV), the outcome of living donor liver transplantation (LDLT) in such patients in terms of survival rate, perioperative complications, and recovery of coagulation activity is poorly understood. PATIENTS AND METHODS Six HIV-positive hemophiliacs underwent LDLT for HCV-associated advanced cirrhosis. The mean CD4 T-cell count at transplantation was 376±227/μL. RESULTS The 1-, 3-, and 5-year survival rates were 66%, 66%, and 50%, respectively. Fatal perioperative bleeding related to hemophilia was not observed. Two patients died within 6 months after transplantation due to graft failure. HIV infection was well controlled in all patients who survived longer than 6 months. Two patients (genotype 2a and 2+3a) achieved a sustained viral response and both of them were alive at the end of follow-up period, whereas one patient (genotype 1a+1b) died of decompensated cirrhosis 4 years after transplantation due to recurrent HCV infection. CONCLUSIONS HIV/HCV-coinfected hemophiliacs can safely undergo LDLT. Hemophilia was clinically cured after successful transplantation. A good outcome can be expected as long as postoperative hepatitis C is controlled with interferon/ribavirin combination therapy.
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Ponziani FR, Gasbarrini A, Pompili M, Burra P, Fagiuoli S. Management of hepatitis C virus infection recurrence after liver transplantation: an overview. Transplant Proc 2011; 43:291-5. [PMID: 21335208 DOI: 10.1016/j.transproceed.2010.09.102] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis C virus (HCV) infection is the major indication for liver transplantation worldwide. Its recurrence is virtually universal. Once reinfection is established, progression to cirrhosis occurs in 25%-30% of recipients within 5 years. Several studies have attempted to identify the ideal antiviral treatment for liver transplant recipients. At present, the management of recurrent HCV infection in liver transplant recipients is based on widely accepted indications, which represent a reliable guide to identify the "ideal" candidate for therapy, when therapy should be started, and what is to be expected in terms of side effects and response to treatment.
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Affiliation(s)
- F R Ponziani
- Department of Internal Medicine, Catholic University, Rome, Italy.
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Roche B, Samuel D. Is early antiviral therapy for recurrent hepatitis C after liver transplantation superior to later treatment? The answer is no. Liver Transpl 2011; 17:488-91. [PMID: 21455930 DOI: 10.1002/lt.22297] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Kishi Y, Hasegawa K, Sugawara Y, Kokudo N. Hepatocellular carcinoma: current management and future development-improved outcomes with surgical resection. Int J Hepatol 2011; 2011:728103. [PMID: 21994868 PMCID: PMC3170840 DOI: 10.4061/2011/728103] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Revised: 04/16/2011] [Accepted: 04/24/2011] [Indexed: 12/13/2022] Open
Abstract
Currently, surgical resection is the treatment strategy offering the best long-term outcomes in patients with hepatocellular carcinoma (HCC). Especially for advanced HCC, surgical resection is the only strategy that is potentially curative, and the indications for surgical resection have expanded concomitantly with the technical advances in hepatectomy. A major problem is the high recurrence rate even after curative resection, especially in the remnant liver. Although repeat hepatectomy may prolong survival, the suitability may be limited due to multiple tumor recurrence or background liver cirrhosis. Multimodality approaches combining other local ablation or systemic therapy may help improve the prognosis. On the other hand, minimally invasive, or laparoscopic, hepatectomy has become popular over the last decade. Although the short-term safety and feasibility has been established, the long-term outcomes have not yet been adequately evaluated. Liver transplantation for HCC is also a possible option. Given the current situation of donor shortage, however, other local treatments should be considered as the first choice as long as liver function is maintained. Non-transplant treatment as a bridge to transplantation also helps in decreasing the risk of tumor progression or death during the waiting period. The optimal timing for transplantation after HCC recurrence remains to be investigated.
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Affiliation(s)
- Yoji Kishi
- Division of Surgery, Depatments of Hepatobiliary Pancreatic Surgery and Artificial Organ and Transplantation, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kiyoshi Hasegawa
- Division of Surgery, Depatments of Hepatobiliary Pancreatic Surgery and Artificial Organ and Transplantation, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan,*Kiyoshi Hasegawa:
| | - Yasuhiko Sugawara
- Division of Surgery, Depatments of Hepatobiliary Pancreatic Surgery and Artificial Organ and Transplantation, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Norihiro Kokudo
- Division of Surgery, Depatments of Hepatobiliary Pancreatic Surgery and Artificial Organ and Transplantation, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Kawaoka T, Hiraga N, Takahashi S, Takaki S, Mitsui F, Tsuge M, Nagaoki Y, Kimura Y, Hashimoto Y, Katamura Y, Hiramatsu A, Waki K, Imamura M, Kawakami Y, Aikata H, Tashiro H, Ohdan H, Chayama K. Prolongation of interferon therapy for recurrent hepatitis C after living donor liver transplantation: analysis of predictive factors of sustained virological response, including amino acid sequence of the core and NS5A regions of hepatitis C virus. Scand J Gastroenterol 2010; 45:1488-96. [PMID: 20662615 DOI: 10.3109/00365521.2010.505657] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The aim of the present retrospective study was to evaluate the therapeutic efficacy and predictive factors of prolongation of treatment with peginterferon (PEGIFN) combined with ribavirin (RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT). METHODS Fifty-three patients underwent LDLT due to HCV-related end-stage liver disease. Sixteen patients were removed from the study as a result of early death (n=14), no recurrence of HCV (n=1) and refusal of antiviral therapy (n=1). Therapy is ongoing in another 10 patients. The remaining 27 patients were available to establish the efficacy of IFN therapy. HCV genotype was 1b in 24 patients. All patients with genotype 1b were treated with IFN therapy for at least 48 weeks after HCV RNA levels had become undetectable. Amino acid substitutions in the HCV core region and NS5A region were analyzed by direct sequencing before LDLT. RESULTS The rate of sustained virological response (SVR) was 37.0% (10/27). SVR rate in patients with genotype 1 was 29.2% (7/24) and 100% (3/3) in patients with genotype 2. Most patients with genotype 1b whose HCV RNA reached undetectable levels achieved SVR (87.5%; 7/8). However, mutation of the HCV core region and number of ISDR mutations were not associated with SVR rate in LDLT in our study. CONCLUSIONS Prolonged IFN therapy for more than 48 weeks after HCV RNA reached undetectable levels might prevent virological relapse of HCV.
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Affiliation(s)
- Tomokazu Kawaoka
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan
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Antiviral treatment for hepatitis C virus infection after liver transplantation. HEPATITIS RESEARCH AND TREATMENT 2010; 2010:475746. [PMID: 21151523 PMCID: PMC2989693 DOI: 10.1155/2010/475746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Revised: 08/13/2010] [Accepted: 10/06/2010] [Indexed: 12/16/2022]
Abstract
A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary.
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Kaido T, Uemoto S. Does living donation have advantages over deceased donation in liver transplantation? J Gastroenterol Hepatol 2010; 25:1598-603. [PMID: 20880167 DOI: 10.1111/j.1440-1746.2010.06418.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) is the best treatment option for patients with end-stage liver disease. Living donor LT (LDLT) has developed as an alternative to deceased donor LT (DDLT) in order to overcome the critical shortage of deceased organ donations, particularly in Asia. LDLT offers several advantages over DDLT. The major advantage of LDLT is the reduction in waiting time mortality. Especially among patients with hepatocellular carcinoma (HCC), LDLT can shorten the waiting time and lower the dropout rate. The Hong Kong group reported that median waiting time was significantly shorter for LDLT than for DDLT. Intention-to-treat survival rates of HCC patients with voluntary live donors were significantly higher than those of patients without voluntary live donors. In contrast, a multicenter adult-to-adult LDLT retrospective cohort study reported that LDLT recipients displayed a significantly higher rate of HCC recurrence than DDLT recipients, although LDLT recipients had shorter waiting times than DDLT recipients. The advantage of LDLT involves the more liberal criteria for HCC compared with those for DDLT. Various preoperative interventions including nutritional treatment can also be planned for both the donor and recipient in LDLT. Conversely, LDLT has marked unfavorable characteristics in terms of donor risks. Donor morbidity is not infrequent and the donor mortality rate is estimated at around 0.1-0.3%. In conclusion, living donation is not necessarily advantageous over deceased donation in LT. Taking the advantages and disadvantages of each option into consideration, LDLT and DDLT should both be used to facilitate effective LT for patients requiring transplant.
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Affiliation(s)
- Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
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Aytaman A, Kaufman M, Terrault NA. Management of posttransplant hepatitis C infection. Curr Opin Organ Transplant 2010; 15:301-9. [PMID: 20445452 DOI: 10.1097/mot.0b013e3283398237] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE OF REVIEW Chronic hepatitis C virus (HCV) infection is the leading cause of liver transplantation. Outcome of HCV-associated liver transplantation has been worse than transplantation from other causes. This is mostly related to universal recurrence of HCV in the allograft leading to graft and patient loss or retransplantation. Current antiviral therapies (AVTs) are inadequate and ineffective in the vast majority of the patients with intolerable side effects in most. However, a sustained virologic response (SVR) is associated with improved graft and patient survival. New specifically targeted AVTs for HCV (STAT-C) agents in development will significantly improve the success of AVT. This review focuses on recent data in peritransplant management of HCV with special emphasis on predictors of outcome, diagnosis, prevention and control of reinfection with newer treatments on the horizon. RECENT FINDINGS In the immediate pretransplant setting, AVT should be considered in select patients to eradicate the virus. Careful donor selection, immunosuppression (IMS) modulation with steroid and calcineurin inhibitor (CNI) minimization, avoidance of T-cell-depleting treatments and acute rejection episodes, and control of metabolic syndrome can improve allograft outcomes and improve the response to AVT. AVT prior to significant damage to the allograft is strongly recommended. SUMMARY With modified novel IMS protocols, careful donor selection, and AVT prior to significant damage to the allograft we can improve the outcome of posttransplant hepatitis C infection. Albeit there are no available data on new antiviral agents, STAT-Cs will have a significant impact in this setting in the near future.
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Affiliation(s)
- Ayse Aytaman
- VA New York Harbor HCS Brooklyn, Brooklyn, New York 11209, USA.
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Masuzaki R, Yamashiki N, Sugawara Y, Yoshida H, Tateishi R, Tamura S, Kaneko J, Hasegawa K, Kokudo N, Makuuchi M, Omata M. Assessment of liver stiffness in patients after living donor liver transplantation by transient elastography. Scand J Gastroenterol 2010; 44:1115-20. [PMID: 19562623 DOI: 10.1080/00365520903078810] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Recurrence of hepatitis and progression of fibrosis are major problems in liver transplantation (LT) for patients with hepatitis C. Liver stiffness measurement (LSM) by transient elastography correlates well with histologic liver fibrosis stages in chronic liver diseases. The aim of this study was to evaluate the usefulness of transient elastography for the assessment of fibrosis in patients after living donor LT. MATERIAL AND METHODS Seventy-nine patients who visited our institution, and in whom LSM was successfully evaluated, were enrolled in the study. The patients were divided into three groups according to positivity for hepatitis C antibody and hepatitis B surface antigen as the hepatitis C virus (HCV) group (n=37), the hepatitis B virus (HBV) group (n=10), and the NBNC (negative for both hepatitis B and C) group (n=32). The correlation between LSM and histologic fibrosis stage was assessed in 36 patients. LSM was also compared with regard to the effect of interferon therapy in HCV patients. RESULTS The median value for liver stiffness was 6.8 kPa and the median time from LT was 3.1 years. In patients who underwent liver biopsy, stiffness was significantly correlated with the stages of fibrosis (p<0.001, rho = 0.848). In patients who received interferon therapy after LT, the LSM decreased over time in those with a sustained virological response, whereas LSM increased in patients without a response. CONCLUSION Transient elastography may be an appropriate non-invasive procedure to sequentially assess the progression of liver fibrosis in patients after LT.
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Affiliation(s)
- Ryota Masuzaki
- Department of Gastroenterology, University of Tokyo, Japan
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45
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Tamura S, Sugawara Y, Yamashiki N, Kaneko J, Kokudo N, Makuuchi M. Pre-emptive antiviral therapy in living donor liver transplantation for hepatitis C: observation based on a single-center experience. Transpl Int 2009; 23:580-8. [PMID: 20028490 DOI: 10.1111/j.1432-2277.2009.01023.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Reports of large series in living donor liver transplantation (LDLT) for hepatitis C virus infection (HCV) are scarce. Between 1996 and 2008, 105 LDLTs were performed at the University of Tokyo for HCV. Rapid induction of antiviral treatment with interferon (IFN) and ribavirin (RBV) was attempted per protocol regardless of the clinical presentation of recurrent HCV (pre-emptive treatment approach). Treatment was continued for 12 months after serum HCV-RNA became negative (ETR: end-of-treatment response) and judged as a sustained viral response (SVR) after another 6 months of negative results without treatment. A fixed treatment period was not defined unless an ETR was achieved (no-stopping approach). Flexible dose adjustments were allowed. Ninety-five patients were eligible for pre-emptive therapy. Forty-three (45%) patients experienced an ETR, and 32 (34%) achieved SVR. Nonadherence to full-dose INF and RBV had little impact on the viral response. Evaluation using the Kaplan-Meier method to incorporate the cumulative time-dependent nature of the no-stopping approach estimated SVR rate at 53% by the fifth year. Survival rate at 5 years was 79% for the HCV recipients and did not differ significantly from our non-HCV series. In LDLT for HCV, pre-emptive IFN-RBV-based treatment with the application of no-stopping approach is feasible and effective.
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Affiliation(s)
- Sumihito Tamura
- Artificial Organ and Transplantation Division, University of Tokyo, Tokyo, Japan
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46
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Peveling-Oberhag J, Zeuzem S, Hofmann WP. Antiviral therapy of chronic hepatitis C in patients with advanced liver disease and after liver transplantation. Med Microbiol Immunol 2009; 199:1-10. [PMID: 19902246 DOI: 10.1007/s00430-009-0131-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2009] [Indexed: 12/12/2022]
Abstract
Chronic infection with the hepatitis C virus (HCV) represents one of the major causes for end-stage liver disease worldwide. Although liver transplantation offers an effective treatment, HCV reinfection of the transplanted graft is a critical and almost inevitable complication with major influence on graft- and patient survival. Pre-transplant antiviral therapy in advanced liver disease is limited by poor tolerance and only applicable to mildly decompensated patients but was able to show promising results in patients reaching negative viral load when undergoing transplantation. Prophylactic therapy with HCV antibodies during the anhepatic phase has not been shown to be effective in studies to date. Antiviral therapy after transplantation but before evidence of reinfection, so called pre-emptive treatment, is limited by frequent complications and a high rate of side effects. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic Hepatitis C. With a combination therapy of pegylated interferon and ribavirin, sustained virologic response rates of 25-45% are achieved. However, tolerability is often poor, and the need of dose reduction is frequent. To date, there is no general consensus on modality, timing and dosing of antiviral treatment of HCV in patients with advanced liver disease and after liver transplantation. More randomised, controlled trials are needed. Moreover, upcoming new treatment approaches, e.g. specifically targeted antiviral therapy for hepatitis C (STAT-C) with HCV-specific polymerase and protease inhibitors, may represent a therapeutic alternative.
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47
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Hasegawa K, Kokudo N. Surgical treatment of hepatocellular carcinoma. Surg Today 2009; 39:833-43. [PMID: 19784720 DOI: 10.1007/s00595-008-4024-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2008] [Accepted: 10/14/2008] [Indexed: 12/16/2022]
Abstract
Local tumor control is still the most important consideration in the treatment of hepatocellular carcinoma (HCC). Surgical treatments, including liver resection and liver transplantation are, and will remain, the first-line therapeutic strategies for local control in patients with primary HCC. Although aggressive liver resection is often performed for advanced HCC in patients with a large tumor, multiple tumors, or tumors with vascular invasion, liver transplantation is the preferred option, after taking into consideration age and tumor-related factors, when there is poor liver functional reserve. Preventing deterioration in liver function is the second priority in the treatment of HCC. When performing liver resection, extensive removal of noncancerous liver parenchyma during lobectomy or hemihepatectomy, should be avoided as much as possible. Anatomic resection, which refers to systematic elimination of the main tumor with its minute metastases, preserves liver function and is highly recommended. A treatment algorithm based on published evidence is now available, which helps us decide on the most suitable therapeutic option for individual patients, depending on the tumor characteristics and liver functional reserve.
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Affiliation(s)
- Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Affiliation(s)
- Marc G Ghany
- Department of Health and Human Services, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Dinges S, Morard I, Heim M, Dufour JF, Müllhaupt B, Giostra E, Clavien PA, Mentha G, Negro F. Pegylated interferon-alpha2a/ribavirin treatment of recurrent hepatitis C after liver transplantation. Transpl Infect Dis 2009; 11:33-9. [DOI: 10.1111/j.1399-3062.2008.00359.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Roche B, Samuel D. Liver transplantation in viral hepatitis: prevention of recurrence. Best Pract Res Clin Gastroenterol 2008; 22:1153-69. [PMID: 19187873 DOI: 10.1016/j.bpg.2008.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
End-stage liver disease caused by the hepatitis B and C viruses (HBV and HCV) are major indications for liver transplantation. Outcome depends largely on the prevention of allograft reinfection. The advent of long-term hepatitis B immune globulin administration and the introduction of new antiviral agents were a major breakthrough in the management of these patients. Today, survival after orthotopic liver transplantation (OLT) is similar to that of patients transplanted for HBsAg-negative liver disease, and the risk of recurrence is below 10%. In contrast, HCV reinfection is almost constant and significantly impairs patient and graft survival. Factors that may influence disease severity and consequently progression of HCV graft injury remain unclear. Pre-transplantation and prophylactic post-transplantation antiviral treatments are limited by low applicability and poor tolerance. Treatment of established graft lesions with combination therapy gave promising results, with sustained virological response in 25-45% of patients, but indications, modality and duration of treatment should be assessed.
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Affiliation(s)
- Bruno Roche
- Assistance Publique-Hopitaux de Paris, Hopital Paul Brousse, Centre Hepato-Biliaire, Villejuif, France
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