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1
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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2
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Garbuzenko DV. [The role of antiviral therapy in the management of patients with liver cirrhosis associated with chronic HBV and HCV infection]. Vopr Virusol 2021; 66:331-339. [PMID: 34738448 DOI: 10.36233/0507-4088-70] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 11/04/2021] [Indexed: 12/12/2022]
Abstract
The formation of the liver cirrhosis (LC) is an unfavorable event of the natural history of chronic liver diseases being accompanied by complications that often cause a fatal outcome. The study of the effectiveness of drugs that affect various etiopathogenetic mechanisms of this condition is an urgent problem of modern hepatology.The aim of the review was to show the role of antiviral therapy (AVT) in the management of patients with LC associated with chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection.PubMed database, Google Scholar search engine, Cochrane Systematic Reviews, eLIBRARY.RU electronic scientific library, as well as the reference lists of articles were used to search for scientific articles. The relevant objectives of the review of the publications were identified for the period since 2000 up to 2021 by the search queries as following: «liver cirrhosis», «liver fibrosis», «chronic HBV infection», «chronic HCV infection», «portal hypertension», «treatment». The inclusion criteria were restricted to the management of patients with LC associated with chronic HBV and HCV infection.Current guidelines recommend indefinite treatment of patients with HBV-associated LC with nucleos(t)ide analogues regardless of serum HBV DNA levels, while the modern concept of using direct-acting antiviral drug combinations has become the standard treatment for HCV-associated cirrhosis. Studies have shown the ability of AVT to inhibit and reverse fibrotic processes in LC associated with chronic HBV and HCV infection. It has also been reported that HBV/HCV eradication prior to orthotopic liver transplantation improves long-term overall survival.This, in turn, can reduce the severity of portal hypertension and decrease the risk of associated complications, as well as normalize liver function. Thus, ensuring the availability of drugs for those in need of AVT will not only help prevent the development of LC, but also improve the quality of life and increase its expectancy of patients suffering from this disease.
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Affiliation(s)
- D V Garbuzenko
- FSBEI HE «South Ural State Medical University» of the Ministry of the Health of Russia
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3
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Ioannou GN, Feld JJ. What Are the Benefits of a Sustained Virologic Response to Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection? Gastroenterology 2019; 156:446-460.e2. [PMID: 30367836 DOI: 10.1053/j.gastro.2018.10.033] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 09/26/2018] [Accepted: 10/03/2018] [Indexed: 02/06/2023]
Abstract
Direct-acting antiviral (DAA) regimens are safe and effective at eradicating hepatitis C virus (HCV) infection. Unfortunately, DAAs remain expensive, so treatment of all HCV-infected patients would substantially affect health care costs. It is therefore important to continue to assess the hepatic and extrahepatic benefits of a DAA-induced sustained virologic response (SVR). A DAA-induced SVR reduces a patient's risk of cirrhosis and hepatocellular carcinoma and extrahepatic manifestations of HCV infection; there are also data to indicate that an SVR can reduce mortality. SVR is a relevant clinical end point, but further analyses are required to confirm its importance among diverse HCV-infected populations and to document the public health benefits of HCV elimination at the population level. We review the evidence for the benefits associated with SVRs in different clinical settings and challenges to data collection.
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Affiliation(s)
- George N Ioannou
- Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Department of Medicine, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington; Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, Washington.
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Sandra Rotman Centre for Global Health, University of Toronto, Toronto, Ontario, Canada
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4
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Sáez-González E, Vinaixa C, San Juan F, Hontangas V, Benlloch S, Aguilera V, Rubín A, García M, Prieto M, López-Andujar R, Berenguer M. Impact of hepatitis C virus (HCV) antiviral treatment on the need for liver transplantation (LT). Liver Int 2018; 38:1022-1027. [PMID: 29105320 DOI: 10.1111/liv.13618] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 10/26/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Therapies for hepatitis C virus (HCV) infection have revolutionized the treatment of patients with chronic HCV infection. The effect of these therapies on the epidemiology of liver transplantation (LT) has yet to be elucidated. AIM To establish whether the indications for LT have changed as a result of the introduction of new therapies for HCV. MATERIALS AND METHODS We conducted a retrospective study based on a prospectively maintained registry of patients who undergo LT at La Fe Hospital in Valencia from 1997 to 2016. An analysis of outcome measures over time stratified by LT indications was performed. RESULTS From January 1997 to December 2016, 2379 patients were listed for LT. Of these, 1113 (47%) were listed for HCV cirrhosis±hepatocellular carcinoma (HCC). This percentage varied significantly over time declining from 48.8% in the 1997-2009 initial period (IFN-based regimens) to 33% in the 2014-2016 final period (DAAs regimens) (P = .03). However, during that period, the proportion of those included in the waiting list (WL) due to HCV-HCC increased significantly (P = .001). In addition, among HCV-positive waitlisted patients with decompensated cirrhosis without HCC, the proportion of those with an HCV-alcohol mixed etiology also increased significantly over time (P = .001). Of all HCV-positive waitlisted patients, 203 were eventually removed from the WL due to either clinical improvement (n = 77) or more frequently worsening/death (n = 126). CONCLUSIONS The proportion of patients wait-listed for LT for decompensated HCV cirrhosis has significantly decreased over time. These changes are possibly related to the large-scale use of direct-acting antivirals.
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Affiliation(s)
- Esteban Sáez-González
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Carmen Vinaixa
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Fernando San Juan
- Unit of Hepato-Biliary-Pancreatic Surgery and Transplantation, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Vanesa Hontangas
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Salvador Benlloch
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Networking Biomedical Research Centre in Hepatic and Digestive Diseases (CIBEREHD), Valencia, Spain
| | - Victoria Aguilera
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Networking Biomedical Research Centre in Hepatic and Digestive Diseases (CIBEREHD), Valencia, Spain
| | - Angel Rubín
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - María García
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Martín Prieto
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Networking Biomedical Research Centre in Hepatic and Digestive Diseases (CIBEREHD), Valencia, Spain
| | - Rafa López-Andujar
- Unit of Hepato-Biliary-Pancreatic Surgery and Transplantation, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Marina Berenguer
- Department of Gastroenterology, Hepatology and Liver Transplantation Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Instituto de Investigación Sanitaria (IIS La Fe), Hospital Universitari i Politècnic La Fe, Valencia, Spain.,Networking Biomedical Research Centre in Hepatic and Digestive Diseases (CIBEREHD), Valencia, Spain.,Department of Medicine, Universitat de València, Valencia, Spain
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5
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Aravinthan AD, Barbas AS, Doyle AC, Tazari M, Sapisochin G, Cattral MS, Ghanekar A, McGilvray ID, Selzner M, Greig PD, Bhat M, Selzner N, Grant DR, Lilly LB, Renner EL. Characteristics of liver transplant candidates delisted following recompensation and predictors of such delisting in alcohol-related liver disease: a case-control study. Transpl Int 2017; 30:1140-1149. [DOI: 10.1111/tri.13008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 04/29/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Aloysious D. Aravinthan
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
- Nottingham Digestive Diseases Centre; University of Nottingham and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre; Nottingham University Hospitals NHS Trust; Nottingham UK
| | - Andrew S. Barbas
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Adam C. Doyle
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Mahmood Tazari
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Gonzalo Sapisochin
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Mark S. Cattral
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Anand Ghanekar
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Ian D. McGilvray
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Markus Selzner
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Paul D. Greig
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Mamatha Bhat
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Nazia Selzner
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - David R. Grant
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Leslie B. Lilly
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
| | - Eberhard L. Renner
- Multiorgan Transplant Program; Toronto General Hospital; University of Toronto; Toronto ON Canada
- Department of Medicine; Max Rady College of Medicine/Rady Faculty of Health Sciences; University of Manitoba; Winnipeg MB Canada
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6
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Little EC, Berenguer M. The New Era of Hepatitis C: Therapy in Liver Transplant Recipients. Clin Liver Dis 2017; 21:421-434. [PMID: 28364822 DOI: 10.1016/j.cld.2016.12.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) is the leading cause of end-stage liver disease in both Europe and the United States and is the most common reason for liver transplant. In the absence of antiviral therapy, recurrent infection is the norm with subsequent graft hepatitis and impaired survival. Whether it may be better to postpone therapy in patients in whom higher risk of failure and toxicity is coupled with lower chance of liver function improvement likely depends on several factors, including waiting time, center allocation policy, presence of hepatocellular carcinoma and local prevalence of anti-HCV-positive donors.
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Affiliation(s)
- Ester Coelho Little
- Banner Transplant Institute, 1441 North 12th Street, Second floor, Phoenix, AZ 85006, USA; Banner University Medical Center Phoenix, Phoenix, AZ, USA
| | - Marina Berenguer
- Servicio de Medicina Digestivo (Torre F-5), La Fe University Hospital, Ciberehd*, University of Valencia, Avda Fernando Abril Martorell n 106, Valencia 46026, Spain.
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7
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Anand AC. Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation? J Clin Exp Hepatol 2017; 7:42-54. [PMID: 28348470 PMCID: PMC5357718 DOI: 10.1016/j.jceh.2017.01.116] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 01/31/2017] [Indexed: 12/12/2022] Open
Abstract
Treatment of hepatitis C virus (HCV) with newer directly acting antivirals (DAAs) and lead to sustained viral response (SVR) in majority of patients and SVR has been documented to be associated with reversal of liver cirrhosis. The improved SVR rates and safety profiles of DAAs have led to the treatment of patients with decompensated cirrhosis awaiting liver transplantation (LT). Several clinical trials of DAAs in decompensated HCV patients have recently demonstrated SVR rates above 80%, which have been associated with significant improvements, in the Child-Pugh-Turcotte scores/or model for end-stage liver disease scores in a proportion of patients. Moreover, it has been shown that HCV RNA becomes negative after 2-4 weeks of treatment, and those who are transplanted after becoming HCV RNA negative will be have very low the risk of HCV recurrence after transplantation. Some of the patients may have reached the "point of no return" and may proceed to worsening of decomposition over time. To avoid the risk of worsening, there is an additional option of treating these patients after LT should they develop recurrent HCV infection. Currently there are no guidelines as to select patients who would benefit from treatment prior to LT as opposed to those who will be better off being treated after the transplant surgery. The article discusses a possible approach for such selection.
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Key Words
- CSA, cyclosporine A
- CTP, Child–Turcotte–Pugh staging
- DAA, directly acting antivirals
- DCV, daclatasvir
- DDLT, deceased donor liver transplant
- DSB, dasabuvir
- EBV, elbasvir
- FCH, fibrosing cholestatic hepatitis
- GRZ, grazoprevir
- GT, genotype
- HCV, hepatitis C virus
- IU, international units
- LDLT, living donor liver transplant
- LDV, ledipasvir
- LT, liver transplantation
- MELD, model for end-stage liver disease RNA
- OMB, ombitasvir
- PTV, paritaprevir
- Peg-IFN, pegylated interferon alfa
- RBV, ribavirin
- SMV, simeprevir
- SOF, sofosbuvir
- SVR, sustained virological response, (SVR 12 signifies SVR at 12 weeks)
- TAC, tacrolimus
- VLP, velpatasvir
- decompensated cirrhosis
- directly acting antivirals
- hepatitis C virus infection
- liver transplantation
- rt, ritonavir
- sustained virological response
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Affiliation(s)
- Anil C. Anand
- Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
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8
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van der Meer AJ, Berenguer M. Reversion of disease manifestations after HCV eradication. J Hepatol 2016; 65:S95-S108. [PMID: 27641991 DOI: 10.1016/j.jhep.2016.07.039] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Revised: 07/29/2016] [Accepted: 07/29/2016] [Indexed: 12/13/2022]
Abstract
Chronic infection with the hepatitis C virus (HCV) may lead to hepatic fibrosis and eventually cirrhosis, at which stage, patients have a substantial risk of liver failure, hepatocellular carcinoma (HCC) and liver-related death. Moreover, HCV infection is associated with several extrahepatic manifestations which impact the quality of life and increase the non-liver-related mortality rate. For patients with compensated liver disease, interferon (IFN)-based antiviral therapy has been a treatment option for over two decades. Long-term follow-up studies indicated that among those with sustained virological response (SVR) the extend of hepatic fibrosis can regress and that their risk of cirrhosis-related complications (including HCC) is reduced, also in case of cirrhosis. Recent population-based studies extended these observations for solid extrahepatic outcomes, such as end-stage renal failure and cardiovascular events. Most importantly, SVR has been associated with prolonged overall survival. These results highlight the importance of the development of new direct-acting antivirals (DAAs), by which almost all patients are able to eradicate HCV in a comfortable manner. Based on the excellent first experiences with the DAAs, physicians gained confidence to use these drugs among patients with decompensated cirrhosis on a more regular basis as well. This was not possible with interferon therapy. Also in this high risk population the DAAs show high SVR rates with improvements in biochemical parameters of liver function shortly after therapy, especially in case of SVR. In fact, some patients could actually be removed from the liver transplantation waiting list due to clinical improvement following DAA therapy. How these short-term results translate into a prolonged (long-term) survival has yet to be determined, as well as which patients with decompensated liver disease are likely or not to benefit from viral eradication. Here we review the current data regarding the beneficial clinical outcome with antiviral therapy as well the remaining uncertainties in this field, both for patients with compensated liver disease and patients with decompensated liver disease.
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Affiliation(s)
- Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - Marina Berenguer
- Hepatology and Liver Transplant Unit and Ciberehd, La Fe Univ. Hospital and Univ. Valencia, Spain
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9
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Belli LS, Berenguer M, Cortesi PA, Strazzabosco M, Rockenschaub SR, Martini S, Morelli C, Donato F, Volpes R, Pageaux GP, Coilly A, Fagiuoli S, Amaddeo G, Perricone G, Vinaixa C, Berlakovich G, Facchetti R, Polak W, Muiesan P, Duvoux C. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study. J Hepatol 2016; 65:524-31. [PMID: 27212241 DOI: 10.1016/j.jhep.2016.05.010] [Citation(s) in RCA: 245] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Revised: 04/30/2016] [Accepted: 05/04/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. METHODS 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015. RESULTS The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24weeks, 27.6% and 10.3% at 48weeks, 33.3% and 19.2% at 60weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p<0.0001) and 2 points for Child-Pugh (CP) (delta-CP, p<0.0001). Three variables emerged from the most parsimonious multivariate competing risk model as predictors of inactivation for clinical improvement, namely, baseline MELD classes (MELD 16-20: HR=0.120; p=0.0005, MELD >20:HR=0.042; p<0.0001), delta MELD (HR=1.349; p<0.0001) and delta albumin (HR=0.307; p=0.0069) both assessed after 12weeks of DAA therapy. CONCLUSIONS This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained. LAY SUMMARY The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, "direct acting antivirals" or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5.
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Affiliation(s)
- Luca Saverio Belli
- Department of Gastroenterology and Hepatology, Liver Unit, Niguarda Hospital, Milan, Italy.
| | - Marina Berenguer
- Hepatology & Liver Transplantation Unit, Hospital Universitari I Politècnic La Fe, University of Valencia & Ciberhed, Valencia, Spain
| | - Paolo Angelo Cortesi
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | - Mario Strazzabosco
- Digestive Disease Section and International Centre for Digestive Health, School of Medicine and Surgery, University of Milano Bicocca and Yale University Liver Center, Department of Medicine, New Haven, USA
| | | | - Silvia Martini
- LiverTransplantation Center, Gastrohepatology Unit, Molinette Hospital, AOU Città della Salute e della Scienza di Torino, Turin, Italy
| | - Cristina Morelli
- Liver and Multi-organ Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Francesca Donato
- Division of Digestive Diseases, 'Maggiore' University Hospital, Milan, Italy
| | | | - Georges-Philippe Pageaux
- Department of Hepatology, Gastroenterology, and Liver Transplantation, Centre Hospitalier Universitaire (CHU) Saint Eloi, Montpellier, France
| | - Audrey Coilly
- Centre Hepato-Biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Sud University, Villejuif, France
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Giuliana Amaddeo
- Department of Hepatology and Liver Transplant Unit, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est University, Creteil, France
| | - Giovanni Perricone
- Department of Gastroenterology and Hepatology, Liver Unit, Niguarda Hospital, Milan, Italy
| | - Carmen Vinaixa
- Hepatology & Liver Transplantation Unit, Hospital Universitari I Politècnic La Fe, University of Valencia & Ciberhed, Valencia, Spain
| | - Gabriela Berlakovich
- Division of Transplantation, Department of Surgery, University of Vienna, Vienna, Austria
| | - Rita Facchetti
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | - Wojciech Polak
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC, University Medical Center Rotterdam, The Netherlands
| | - Paolo Muiesan
- Department of HPB Surgery & Liver Transplantation, University of Birmingham, UK
| | - Christophe Duvoux
- Department of Hepatology and Liver Transplant Unit, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Est University, Creteil, France
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10
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Herzer K, Gerken G. When and How to Treat HCV Infection with the New Antivirals before or after Liver Transplantation. Visc Med 2016; 32:258-262. [PMID: 27722162 PMCID: PMC5040937 DOI: 10.1159/000446976] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection is one of the primary causes of hepatocellular carcinoma and liver transplantation (LT). Graft loss due to hepatitis C (HCV) recurrence is a serious problem after LT. Thus, the approval of interferon-free direct-acting antiviral (DAA) regimens has important implications in the LT setting. The findings of controlled trials have confirmed the safety and the excellent efficacy of most DAA combinations, and these findings have been confirmed by reports of high rates of sustained virologic response in the real-life setting. However, data from patients with decompensated cirrhosis who are on the LT waiting list are still scarce and, when available, suggest cautious consideration of whether HCV treatment before LT is beneficial in all cases. Progression of cirrhosis and refractory decompensation result in severely decreasing response rates, the risk of resistance, and reduced Model for End-Stage Liver Disease (MELD) scores despite clinical deterioration, making LT more difficult to achieve. On the other hand, treating HCV recurrence after LT is feasible with most of the available DAA combinations. Thus, an important topic of current debate is the establishment of predictors and conditions that can determine whether HCV treatment is best before or after LT. This review article comprehends and discusses recent data and challenges on the treatment of HCV infection in the liver transplant setting.
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Affiliation(s)
- Kerstin Herzer
- Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Essen, Germany, Essen, Germany
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
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11
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Llaneras J, Castells L, Santos B, Crespo M, Puig T, Esteban J, Esteban R. Removal from liver transplantation list of a hepatitis C virus-HIV co-infected patient after successful treatment with sofosbuvir and daclatasvir. Transpl Infect Dis 2016; 18:442-445. [DOI: 10.1111/tid.12538] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2015] [Revised: 10/07/2015] [Accepted: 02/03/2016] [Indexed: 11/27/2022]
Affiliation(s)
- J. Llaneras
- Liver Unit; Internal Medicine Department; Hospital Universitari Vall Hebron, Barcelona; Univeristat Autònoma de Barcelona; Barcelona Spain
| | - L. Castells
- Liver Unit; Internal Medicine Department; Hospital Universitari Vall Hebron, Barcelona; Univeristat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Instituto de Salud Carlos III; Madrid Spain
| | - B. Santos
- Liver Unit; Internal Medicine Department; Hospital Universitari Vall Hebron, Barcelona; Univeristat Autònoma de Barcelona; Barcelona Spain
| | - M. Crespo
- Infectious Disease Unit; Internal Medicine Department; Hospital Universitari Vall Hebron; Barcelona Spain
| | - T. Puig
- HIV Unit; Internal Medicine Department; Hospital Universitari Arnau de Vilanova de Lleida; Universitat de Lleida; Lleida Spain
| | - J.I. Esteban
- Liver Unit; Internal Medicine Department; Hospital Universitari Vall Hebron, Barcelona; Univeristat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Instituto de Salud Carlos III; Madrid Spain
| | - R. Esteban
- Liver Unit; Internal Medicine Department; Hospital Universitari Vall Hebron, Barcelona; Univeristat Autònoma de Barcelona; Barcelona Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd); Instituto de Salud Carlos III; Madrid Spain
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12
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Puri P, Saraswat VA, Dhiman RK, Anand AC, Acharya SK, Singh SP, Chawla YK, Amarapurkar DN, Kumar A, Arora A, Dixit VK, Koshy A, Sood A, Duseja A, Kapoor D, Madan K, Srivastava A, Kumar A, Wadhawan M, Goel A, Verma A, Shalimar, Pandey G, Malik R, Agrawal S. Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016. J Clin Exp Hepatol 2016; 6:119-45. [PMID: 27493460 PMCID: PMC4963318 DOI: 10.1016/j.jceh.2016.07.001] [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: 12/12/2022] Open
Abstract
India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.
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Key Words
- ALT, alanine aminotransferase
- ANC, absolute neutrophil count
- AST, aspartate aminotransferase
- CH-C, chronic hepatitis C
- CTP, Child-Turcotte-Pugh
- DAA, directly acting antiviral agents
- DCV, daclatasvir
- EIA, enzyme immunoassay
- ESRD, end-stage renal disease
- EVR, early virological response
- FCH, fibrosing cholestatic hepatitis
- GT, genotype
- HCV
- HCV, hepatitis C virus
- HCWs, healthcare workers
- HIV, human immunodeficiency virus
- INASL, Indian National Association for Study of the Liver
- IU, international units
- LDV, ledipasvir
- LT, liver transplantation
- NS, nonstructural protein
- NSI, needlestick injury
- PCR, polymerase chain reaction
- Peg-IFNα, pegylated interferon alfa
- RBV, ribavirin
- RVR, rapid virological response
- SOF, sofosbuvir
- SVR, sustained virological response
- ULN, upper limit of normal
- anti-HCV, antibody to HCV
- antiviral therapy
- chronic hepatitis
- hepatitis C virus
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Affiliation(s)
- Pankaj Puri
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Anil C. Anand
- Department of Gastroenterology and Hepatology, Indraprastha Apollo Hospital, New Delhi 110076, India
| | - Subrat K. Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack 753007, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | | | - Ajay Kumar
- Department of Gastroenterology and Hepatology, Fortis Escorts Liver and Digestive Diseases Institute, New Delhi 110076, India
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Banaras Hindu University, Varanasi 221005, India
| | - Abraham Koshy
- Department of Hepatology, Lakeshore Hospital, Cochin 682304, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana 141001, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad 500004, India
| | - Kaushal Madan
- Department of Gastroenterology, Artemis Hospital, Gurgaon 122001, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Manav Wadhawan
- Department of Gastroenterology and Hepatology, Fortis Escorts Liver and Digestive Diseases Institute, New Delhi 110076, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Abhai Verma
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Gaurav Pandey
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Rohan Malik
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Swastik Agrawal
- Department of Gastroenterology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, India
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13
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Abstract
BACKGROUND Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated liver cirrhosis is a major indication for liver transplantation. This concise review gives an overview about current interferon (IFN)-free treatment options before and after liver transplantation in HBV- or HCV-associated liver disease. METHODS A PubMed database search using the terms hepatitis B, hepatitis C, cirrhosis, and liver transplantation was performed to identify significant clinical studies as well as national and international guidelines. RESULTS Studies investigating IFN-free treatment in patients with decompensated HBV as well as in HCV-associated cirrhosis are scarce. Hepatic recompensation during antiviral therapy seems more frequent in patients with HBV than in those with HCV-associated cirrhosis. Graft hepatitis B or C is characterized by an accelerated and unfavorable course. Graft infection prophylaxis is safe and efficacious in HBV-related liver transplantation. Eradication of HCV prior to liver transplantation prevents HCV graft infection, and IFN-free treatment of established HCV graft infection is safe and associated with high sustained virologic response rates. CONCLUSION Patients with HBV-associated cirrhosis should be treated prior to liver transplantation, and receive a continuing graft infection prophylaxis thereafter. Patients with HCV-associated decompensated cirrhosis may be considered as candidates for antiviral therapy prior to liver transplantation or may be treated subsequently.
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Affiliation(s)
- Martin-Walter Welker
- Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
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14
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Ferrarese A, Zanetto A, Gambato M, Bortoluzzi I, Nadal E, Germani G, Senzolo M, Burra P, Russo FP. Liver transplantation for viral hepatitis in 2015. World J Gastroenterol 2016; 22:1570-1581. [PMID: 26819523 PMCID: PMC4721989 DOI: 10.3748/wjg.v22.i4.1570] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.
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15
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Coilly A, Roche B, Duclos-Vallée JC, Samuel D. News and challenges in the treatment of hepatitis C in liver transplantation. Liver Int 2016; 36 Suppl 1:34-42. [PMID: 26725895 DOI: 10.1111/liv.13017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 11/02/2015] [Indexed: 02/13/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the main causes of end-stage liver disease and indications for liver transplantation (LT) worldwide. HCV infection always recurs on the graft in patients who undergo LT with detectable serum HCV RNA, leading to cirrhosis in 20-30% within 5 years after transplantation. Achieving a sustained virological response (SVR) greatly improves patient and graft survival. Recently, the efficacy of therapy has radically changed and improved based on new direct acting antiviral agents (DAAs) without pegylated-interferon (PEG-IFN) and/or ribavirin (RBV), leading to SVR rates of more than 90% in transplanted patients. The safety profile in this population is also good, with limited drug-drug interactions. However, there are very few data on patients on the waiting list. Even when the results of combined DAAs are good (>80%), SVR rates are lower than in patients without cirrhosis. This review reports recent available data on the treatment of HCV infection in the transplant setting and discusses new dilemmas and challenges.
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Affiliation(s)
- Audrey Coilly
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France.,Univ. Paris-Sud, Univ. Paris-Saclay, Villejuif, F-94800, France.,Unité 1193, Inserm, Villejuif, F-94800, France.,Hepatinov, Villejuif, F-94800, France
| | - Bruno Roche
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France.,Unité 1193, Inserm, Villejuif, F-94800, France.,Hepatinov, Villejuif, F-94800, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France.,Univ. Paris-Sud, Univ. Paris-Saclay, Villejuif, F-94800, France.,Unité 1193, Inserm, Villejuif, F-94800, France.,Hepatinov, Villejuif, F-94800, France
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France.,Univ. Paris-Sud, Univ. Paris-Saclay, Villejuif, F-94800, France.,Unité 1193, Inserm, Villejuif, F-94800, France.,Hepatinov, Villejuif, F-94800, France
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16
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Fung J. Era of direct acting antivirals in chronic hepatitis C: Who will benefit? World J Hepatol 2015; 7:2543-2550. [PMID: 26523206 PMCID: PMC4621468 DOI: 10.4254/wjh.v7.i24.2543] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 09/07/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
In the era of highly effective direct acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) infection, where eradication is almost ensured with minimal side effects, all hepatitis C carriers should benefit theoretically. In the real world setting however, only a small proportion will benefit at this time point due to the multiple barriers to accessing therapy. Given that universal treatment is unlikely, treatment with DAAs will likely be restricted to those with the highest health benefits, and for those who can afford the high expense of a treatment course. Those with the highest unmet needs include those who have failed previous interferon-based therapy or who are interferon-ineligible with evidence of active disease, those with advance liver disease, and those with recurrence of hepatitis C after liver transplantation. In the future, the focus should be on increasing access to treatment for those infected with CHC.
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17
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Ferenci P, Kozbial K, Mandorfer M, Hofer H. HCV targeting of patients with cirrhosis. J Hepatol 2015; 63:1015-22. [PMID: 26100497 DOI: 10.1016/j.jhep.2015.06.003] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 06/09/2015] [Accepted: 06/10/2015] [Indexed: 12/15/2022]
Abstract
Interferon (IFN)-free treatments are now the treatment of choice for patients with chronic hepatitis C. Previously difficult to treat patients by IFN-containing treatments can now be treated safely by IFN-free therapies. More than 90% of hepatitis C genotype 1 and 4 patients with compensated cirrhosis or after orthotopic liver transplantation (OLT) can be cured by sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the paritaprevir/ritona-vir/ombitasvir/±dasabuvir (3D) combination. Addition of ribavirin confers to a minimal, if any, benefit to increase SVR. The need for ribavirin is controversial and remains to be studied. The optimal length of treatment is still unknown, and an individual approach may be needed. Most patients require only 12weeks of therapy. The safety of these drugs is not fully explored in patients with decompensated cirrhosis (Child-Pugh C), who should not be treated with protease inhibitors. In cirrhosis hepatitis C virus eradication does not necessarily mean a cure of the disease and patients regularly require follow-up. Drug-drug interactions with immunosuppressant in patients after OLT are easier to manage but still require attention. Better drugs are needed for genotype 3 patients.
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Affiliation(s)
- Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
| | - Karin Kozbial
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Harald Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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18
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Aqel BA, Pungpapong S, Leise M, Werner KT, Chervenak AE, Watt KD, Murphy JL, Ryland K, Keaveny AP, McLemore R, Vargas HE. Multicenter experience using simeprevir and sofosbuvir with or without ribavirin to treat hepatitis C genotype 1 in patients with cirrhosis. Hepatology 2015; 62:1004-12. [PMID: 26096332 DOI: 10.1002/hep.27937] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 06/05/2015] [Indexed: 12/13/2022]
Abstract
UNLABELLED Interferon (IFN)-free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child-Pugh-Turcott [CPT]-B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12-58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69-85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. CONCLUSIONS The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short-term impact on MELD score. Long-term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population.
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Affiliation(s)
- Bashar A Aqel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
| | | | - Michael Leise
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - K Tuesday Werner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
| | - Amy E Chervenak
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | | | | | - Ryan McLemore
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
| | - Hugo E Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ
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19
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Puri P, Anand AC, Saraswat VA, Acharya SK, Dhiman RK, Sarin SK, Singh SP, Chawla YK, Aggarwal R, Amarapurkar D, Arora A, Dixit VK, Sood A, Shah S, Duseja A, Kapoor D, Shalimar, Madan K, Pande G, Nagral A, Kar P, Koshy A, Puri AS, Eapen C, Thareja S. Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection in 2015. J Clin Exp Hepatol 2015; 5:221-38. [PMID: 26628840 PMCID: PMC4632106 DOI: 10.1016/j.jceh.2015.09.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 09/17/2015] [Indexed: 12/12/2022] Open
Abstract
Overall prevalence of HCV infection in India has been estimated to be approximately 1.3% in the general population. Recent introduction of sofosbuvir in India at a relatively affordable price has led to great optimism about prospects of cure for these patients. This drug is likely to form the backbone of current and future treatment regimes for HCV infection, displacing pegylated interferon. Availability of directly acting antiviral drugs (DAAs) has necessitated revision of INASL guidelines for the treatment of HCV published in 2014, as has happened across the world. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. Since only one DAA, sofosbuvir, is available in India, only two sofosbuvir-based regimes are possible: either dual drug therapy in combination with ribavirin alone for 6 months or triple drug therapy in combination with ribavirin and pegylated interferon for 3 months. The utility of these regimes in various situations has been discussed. Availability of a few other newer DAAs, expected in 2016, is expected to lead to more widespread use of these agents. Current guidance will be updated once newer DAAs, newer evidence with DAAs and 'real-life experience' with use of DAAs accumulate in India.
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Key Words
- ALT, alanine aminotransferase
- ANC, absolute neutrophil count
- AST, aspartate aminotransferase
- CH-C, chronic hepatitis C
- CTP, Child-Turcotte Pugh
- DAA, directly acting antiviral agents
- EIA, enzyme immunoassay
- ESRD, end stage renal disease
- EVR, early virological response
- HCV
- HCV, hepatitis C virus
- HIV, human immunodeficiency virus
- IFN-α, interferon alfa
- INASL, Indian National Association for Study of the Liver
- PCR, polymerase chain reaction
- Peg-IFNα, pegylated interferon alfa
- RBV, ribavirin
- RVR, rapid virological response
- SOC, standard of care
- SVR, sustained virological response
- Sof, sofosbuvir
- ULN, upper limit of normal
- anti-HCV, antibody to HCV
- antiviral therapy
- chronic hepatitis
- hepatitis C virus
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Affiliation(s)
- Pankaj Puri
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | - Anil C. Anand
- Department of Gastroenterology and Hepatology, Indraprastha Apollo Hospital, New Delhi 110076, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Subrat K. Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Shiv K. Sarin
- Institute of Liver and Biliary Sciences, VasantKunj, New Delhi 110070, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack 753007, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | | | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Banaras Hindu University, Varanasi 221005, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana 141001, India
| | - Samir Shah
- Department of Gastroenterology, Global Hospital, Mumbai 400078, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad 500004, India
| | - Shalimar
- Department of Gastroenterology, Artemis Hospital, Gurgaon 122001, India
| | - Kaushal Madan
- Department of Gastroenterology, Artemis Hospital, Gurgaon 122001, India
| | - Gaurav Pande
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital, Mumbai 400026, India
| | - Premashis Kar
- Department of Gastroenterology, LNJP Hospital, and Maulana Azad Medical College, New Delhi 110002, India
| | - Abraham Koshy
- Department of Hepatology, Lakeshore Hospital, Cochin 682304, India
| | - Amarender S. Puri
- Department of Gastroenterology, GB Pant Hospital, New Delhi 110002, India
| | - C.E. Eapen
- Department of Gastroenterology, Christian Medical College, Vellore 632004, India
| | - Sandeep Thareja
- Department of Gastroenterology, Army Hospital (R & R), New Delhi 110010, India
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20
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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. [PMID: 26199060 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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21
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Abstract
INTRODUCTION The recent development of new direct acting antivirals constitutes a clinical revolution in the field of hepatitis C therapy. Different drugs with direct antiviral effects and very high potency have been developed, changing the current scenario and prognosis of hepatitis C-related liver disease. This review aims to clarify the current stage of the different antiviral strategies in patients with chronic hepatitis C infection by analyzing the specific efficacy of each combination. AREAS COVERED Data have been extracted from the most important published clinical trials, cumulative real-world experience reports and data from the most relevant studies presented in the last international meetings (European and American International Liver Congresses). In addition, data from the recently updated international guidelines have also been included. EXPERT OPINION Although there are many differences in health-care budgets among countries in the world which will surely compromise drug availability and treatment decisions, this review aims to give a general and brief recommendation to help treating physicians to choose the best option to treat hepatitis C.
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Affiliation(s)
- Zoe Mariño
- Liver Unit, Hospital Clinic, University of Barcelona, CIBERehd, IDIBAPS , C/Villarroel 170, 08036 Barcelona , Spain +1 34 93 2275400 ;
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22
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Abstract
Interferon-free regimes are now the treatment of choice for patients with chronic hepatitis C; previously patients who were 'difficult-to-treat' using interferon-containing treatments can now safely be treated with such therapies. More than 90% of patients infected with HCV genotype 1 or 4, compensated cirrhosis, or who have had liver transplantation, can be cured with the use of sofosbuvir combined with simeprevir, daclatasvir or ledipasvir, or by the combination of paritaprevir with ritonavir, ombitasvir and with or without dasabuvir. Addition of ribavirin seems to shorten treatment duration. However, the safety of these drugs is not fully explored in patients with decompensated cirrhosis (that is, those with Child-Pugh class C disease), and protease inhibitors should not be used in this group. The optimal use of interferon-free regimes in patients with renal failure or after kidney transplantation is currently being studied. However, new and improved drugs are needed to treat patients infected with HCV genotype 3. Unfortunately, the broad application of new HCV treatments is limited by their high costs. In this Review, I discuss the treatment of patients with hepatitis C with compensated and decompensated cirrhosis, before and after orthotopic liver transplantation and in patients with impaired kidney function.
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Affiliation(s)
- Peter Ferenci
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria
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23
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Beinhardt S, Peck-Radosavljevic M, Hofer H, Ferenci P. Interferon-free antiviral treatment of chronic hepatitis C in the transplant setting. Transpl Int 2015; 28:1011-24. [PMID: 25864369 DOI: 10.1111/tri.12577] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 03/03/2015] [Accepted: 04/02/2015] [Indexed: 12/16/2022]
Abstract
Interferon-based regimens with first-generation protease inhibitors have a limited efficacy and an unfavorable safety profile. Combination therapies with two or more second-generation direct-acting antivirals plus/minus ribavirin revolutionized treatment strategies in patients chronically infected with hepatitis C virus. In this rapidly evolving era, patients in the transplant setting benefit from interferon-free treatment regimens. Scientific societies can barely keep up with this development, making it necessary to update the clinical guidelines by the American and European Associations for the Study of Liver Diseases within short periods. This review presents and discusses the currently available data of the use of interferon-free treatment in the setting of liver transplantation. However, costs, different reimbursement strategies, and health-care options cannot be answered by guidelines and recommendations from scientific societies. Further investigator-initiated trials are needed to individualize treatment concepts.
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Affiliation(s)
- Sandra Beinhardt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Harald Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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