|
1
|
Shetty A, Lee M, Valenzuela J, Saab S. Cost effectiveness of hepatitis C direct acting agents. Expert Rev Pharmacoecon Outcomes Res 2024; 24:589-597. [PMID: 38665122 DOI: 10.1080/14737167.2024.2348053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 04/23/2024] [Indexed: 05/04/2024]
Abstract
INTRODUCTION Introduction of direct acting antivirals (DAA) has transformed treatment of chronic hepatitis C (HCV) and made the elimination of HCV an achievable goal set forward by World Health Organization by 2030. Multiple barriers need to be overcome for successful eradication of HCV. Availability of pan-genotypic HCV regimens has decreased the need for genotype testing but maintained high efficacy associated with DAAs. AREAS COVERED In this review, we will assess the cost-effectiveness of DAA treatment in patients with chronic HCV disease, with emphasis on general, cirrhosis, and vulnerable populations. EXPERT OPINION Multiple barriers exist limiting eradication of HCV, including cost to treatment, access, simplified testing, and implementing policy to foster treatment for all groups of HCV patients. Clinically, DAAs have drastically changed the landscape of HCV, but focused targeting of vulnerable groups is needed. Public policy will continue to play a strong role in eliminating HCV. While we will focus on the cost-effectiveness of DAA, several other factors regarding HCV require on going attention, such as increasing public awareness and decreasing social stigma associated with HCV, offering universal screening followed by linkage to treatment and improving preventive interventions to decrease spread of HCV.
Collapse
Affiliation(s)
- Akshay Shetty
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Michelle Lee
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Julia Valenzuela
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California at Los Angeles, Los Angeles, CA, USA
| |
Collapse
|
|
2
|
Sintusek P, Thanapirom K, Komolmit P, Poovorawan Y. Eliminating viral hepatitis in children after liver transplants: How to reach the goal by 2030. World J Gastroenterol 2022; 28:290-309. [PMID: 35110951 PMCID: PMC8771616 DOI: 10.3748/wjg.v28.i3.290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/12/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis infections are a great burden in children who have received liver transplant. Hepatotropic viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long term. Immunological reactions due to viral hepatitis infections are associated with or can mimic graft rejection, rendering the condition difficult to manage. Prevention strategies using vaccinations are agreeable to patients, safe, cost-effective and practical. Hence, strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver transplant. Although a vaccine has been developed to prevent hepatitis C and E viruses, its use is not licensed worldwide. Consequently, eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral therapy. Good hygiene and sanitation are also important to prevent hepatitis A and E infections. Donor blood products and liver grafts should be screened for hepatitis B, C and E in children who are undergoing liver transplantation. Future research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and E. Moreover, novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.
Collapse
Affiliation(s)
- Palittiya Sintusek
- The Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
- Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Liver Fibrosis and Cirrhosis Research Unit, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| |
Collapse
|
|
3
|
Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
Collapse
Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| |
Collapse
|
|
4
|
Elzorkany K, Kora MAE, Wahed ASA, Zaghla HES, Zahran AM, Yassein YS, El Naggar AZ, Essa A, Gadallah AA. Assessment of Renal Function in Post-Liver Transplant HCV-Positive Patients Treated with Direct Acting Antivirals. Int J Nephrol Renovasc Dis 2020; 13:351-358. [PMID: 33273842 PMCID: PMC7705253 DOI: 10.2147/ijnrd.s275721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/21/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose Direct acting antiviral agents (DAAs) have greatly improved the clearance of hepatitis C virus (HCV) infection. The effect of DAAs on renal function in post-liver transplant HCV-positive patients remains questionable, especially considering the possibility of drug interactions between immunosuppressants and DAAs. Patients and methods A retrospective observational study included 84 post-liver transplant patients with HCV infection. Patients were divided into two groups: group I received sofosbuvir plus ribavirin for 24 weeks, group II received sofosbuvir plus daclatasvir for 12 weeks. Laboratory data and eGFR were determined before, at the end, and 6 months after completion of treatment. Results The treatment was well tolerated with 100% sustained virologic response (SVR 12). There was no statistically significant difference between the two groups regarding clinical and laboratory data before treatment. Mean eGFR significantly reduced from 87.36 mL/min to 76.16 mL/min in group I (P=0.001). However, within 6 months after treatment, mean eGFR recovered to 81.51 mL/min, which was not significant when compared to baseline eGFR (P=0.09). Mean eGFR in group II showed non-significant change. There were no significant changes in immunosuppressive drug levels and eGFR in either group of patients, who received either ciclosporin or tacrolimus before and at the end of treatment. Conclusion DDAs in post-liver transplant patients with HCV infection were well tolerated and associated with stable renal function. Moreover, sofosbuvir plus daclatasvir regimen showed relatively better renal safety compared to sofosbuvir plus ribavirin.
Collapse
Affiliation(s)
- Khaled Elzorkany
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt.,Internal Medicine Department, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mahmoud Abd-Elaziz Kora
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | - Aliaa Sabry Abdel Wahed
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt
| | - Hassan El-Sayed Zaghla
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt
| | - Ahmed Mohamed Zahran
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | - Yassein Salah Yassein
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | | | - Abdallah Essa
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | | |
Collapse
|
|
5
|
Liver and Kidney Recipient Selection of Hepatitis C Virus Viremic Donors: Meeting Consensus Report From the 2019 Controversies in Transplantation. Transplantation 2020; 104:476-481. [PMID: 31634329 DOI: 10.1097/tp.0000000000003014] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The development of multiple highly effective and safe direct-acting antivirals to treat hepatitis C virus (HCV) has resulted in greater ease and confidence in managing HCV infection in transplant recipients that in turn has impacted the solid organ transplant community as well. In the United States, the opioid epidemic has increased the number of overdose deaths with a concomitant increase in younger HCV viremic donors after brain death being identified. At the same time, a decrease in HCV viremic transplant candidates has led to a growing interest in exploring the use of HCV viremic liver and kidney donor allografts in HCV-negative recipients. To date, experience with the use of HCV viremic liver and kidney allografts in HCV-negative recipients is limited to a few small prospective research trials, case series, and case reports. There are also limited data on recipient and donor selection for HCV viremic liver and kidney allografts. In response to this rapidly changing landscape in the United States, experts in the field of viral hepatitis and liver and kidney transplantation convened a meeting to review current data on liver and kidney recipient selection and developed consensus opinions related specifically to recipient and donor selection of HCV viremic liver and kidney allografts.
Collapse
|
|
6
|
Kapila N, Khalloufi KA, Flocco G, Menon KN, Lindenmeyer C, Reino D, Vanatta JM, Ebaid S, Tzakis A, Zervos XB. Transplantation of HCV Viremic Livers into HCV Viremic Recipients Followed by Direct-acting Antiviral Therapy. J Clin Transl Hepatol 2019; 7:122-126. [PMID: 31293911 PMCID: PMC6609846 DOI: 10.14218/jcth.2019.00014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 04/26/2019] [Accepted: 05/15/2019] [Indexed: 12/19/2022] Open
Abstract
Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor. Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression. Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation. Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.
Collapse
Affiliation(s)
- Nikhil Kapila
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
| | | | - Gianina Flocco
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - K.V. Narayanan Menon
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | | | - Diego Reino
- Department of Transplant, Cleveland Clinic Florida, Weston, FL, USA
| | - Jason M. Vanatta
- Department of Transplant, Cleveland Clinic Florida, Weston, FL, USA
| | - Samer Ebaid
- Department of Transplant, Cleveland Clinic Florida, Weston, FL, USA
| | - Andreas Tzakis
- Department of Transplant, Cleveland Clinic Florida, Weston, FL, USA
| | - Xaralambos Bobby Zervos
- Department of Transplant, Cleveland Clinic Florida, Weston, FL, USA
- *Correspondence to: Xaralambos Bobby Zervos, Department of Transplant, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331, USA. Tel: +1-954-659-5133, Fax: +1-954-659-6731, E-mail:
| |
Collapse
|
|
7
|
Gountas I, Sypsa V, Papatheodoridis G, Souliotis K, Athanasakis K, Razavi H, Hatzakis A. Economic evaluation of the hepatitis C elimination strategy in Greece in the era of affordable direct-acting antivirals. World J Gastroenterol 2019; 25:1327-1340. [PMID: 30918426 PMCID: PMC6429341 DOI: 10.3748/wjg.v25.i11.1327] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 02/20/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral (DAA) treatment coverage, to compute the total costs (including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in Greece.
AIM To estimate the required interventions and subsequent costs to achieve HCV elimination in Greece.
METHODS A previously validated mathematical model was adapted to the Greek HCV-infected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HCV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs (direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price scenarios.
RESULTS Without the implementation of awareness or screening campaigns, approximately 20000 patients would be diagnosed and treated with DAAs by 2030. This strategy would result in a 19.6% increase in HCV-related mortality in 2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by 78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros (€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very cost-effective. Furthermore, HCV elimination strategy would save €560-895 million by 2035.
CONCLUSION Without large screening programs, elimination of HCV cannot be achieved. The HCV elimination strategy is feasible and cost-saving despite the uncertainty of the future cost of DAAs in Greece.
Collapse
Affiliation(s)
- Ilias Gountas
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
- Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases, Athens 11527, Greece
| | - Vana Sypsa
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens 11527, Greece
| | - Kyriakos Souliotis
- Faculty of Social and Political Sciences, University of Peloponnese, Korinthos 20100, Greece
| | - Kostas Athanasakis
- Department of Health Economics, National School of Public Health, Athens 11521, Greece
| | - Homie Razavi
- Center for Disease Analysis, Lafayette, CO 80026, United States
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
- Hellenic Scientific Society for the Study of AIDS and Sexually Transmitted Diseases, Athens 11527, Greece
| |
Collapse
|
|
8
|
Bethea ED, Samur S, Kanwal F, Ayer T, Hur C, Roberts MS, Terrault N, Chung RT, Chhatwal J. Cost Effectiveness of Transplanting HCV-Infected Livers Into Uninfected Recipients With Preemptive Antiviral Therapy. Clin Gastroenterol Hepatol 2019; 17:739-747.e8. [PMID: 30138735 PMCID: PMC6382534 DOI: 10.1016/j.cgh.2018.08.042] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/26/2018] [Accepted: 08/13/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Guidelines do not recommend transplanting hepatitis C virus (HCV)-infected livers into HCV-uninfected recipients. Direct-acting antivirals (DAAs) can be used to treat donor-derived HCV infection. However, the added cost of DAA therapy is a barrier. We evaluated the cost effectiveness of transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy. METHODS A previously validated Markov-based mathematical model was adapted to simulate a virtual trial of HCV-negative patients on the liver transplant waitlist. The model compared long-term clinical and economic outcomes in patients willing to accept only HCV-negative livers vs those willing to accept any liver (HCV negative or HCV positive). Recipients of HCV-positive livers received 12 weeks of preemptive DAA therapy. The model incorporated data from the United Network for Organ Sharing and published sources. RESULTS For patients with a model for end-stage liver disease (MELD) score ≥ 22, accepting any liver vs waiting for only HCV-negative livers was cost effective, with incremental cost-effectiveness ratios ranging from $56,100 to $91,700/quality-adjusted life-year. For patients with a MELD score of 28 (the median MELD score of patients undergoing transplantation in the United States), accepting any liver was cost effective at an incremental cost-effectiveness ratio of $62,600/quality-adjusted life year. In patients with low MELD scores, which may not accurately reflect disease severity, accepting any liver was cost effective, irrespective of MELD score. CONCLUSIONS Using a Markov-based mathematical model, we found transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy to be a cost-effective strategy that could improve health outcomes.
Collapse
Affiliation(s)
- Emily D Bethea
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Sumeyye Samur
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Turgay Ayer
- Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Chin Hur
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Mark S Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Norah Terrault
- University of California San Francisco Medical Center, Gastroenterology and Hepatology Division, San Francisco, California
| | - Raymond T Chung
- Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jagpreet Chhatwal
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts.
| |
Collapse
|
|
9
|
Axelrod DA, Schnitzler MA, Alhamad T, Gordon F, Bloom RD, Hess GP, Xiao H, Nazzal M, Segev DL, Dharnidharka VR, Naik AS, Lam NN, Ouseph R, Kasiske BL, Durand CM, Lentine KL. The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes. Am J Transplant 2018; 18:2473-2482. [PMID: 29701909 PMCID: PMC6409105 DOI: 10.1111/ajt.14895] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 04/14/2018] [Accepted: 04/17/2018] [Indexed: 02/06/2023]
Abstract
Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.34 1.852.10 , P < .0001) and death (aHR 1.47 1.681.91 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.34 0.671.32 , P = .25) or graft failure (aHR 0.32 0.641.26 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.19 0.430.95 , P = .04) and graft loss by 46% (0.27 0.541.07 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.
Collapse
Affiliation(s)
- D A Axelrod
- Lahey Hospital & Medical Center, Burlington, MA, USA
| | - M A Schnitzler
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO, USA
| | - T Alhamad
- Washington University, St. Louis, MO, USA
| | - F Gordon
- Lahey Hospital & Medical Center, Burlington, MA, USA
| | - R D Bloom
- University of Pennsylvania, Philadelphia, PA, USA
| | - G P Hess
- Symphony Health, Conshohocken, PA, USA
| | - H Xiao
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO, USA
| | - M Nazzal
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO, USA
| | - D L Segev
- Johns Hopkins University, Baltimore, MD, USA
| | | | - A S Naik
- University of Michigan, Ann Arbor, MI, USA
| | - N N Lam
- University of Alberta, Edmonton, AB, Canada
| | - R Ouseph
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO, USA
| | - B L Kasiske
- Hennepin County Medical Center, Minneapolis, MN, USA
| | - C M Durand
- Johns Hopkins University, Baltimore, MD, USA
| | - K L Lentine
- Saint Louis University Center for Abdominal Transplantation, St. Louis, MO, USA
| |
Collapse
|
|
10
|
Shaffer AA, Thomas AG, Bowring MG, Van Pilsum Rasmussen SE, Cash A, Kucirka LM, Alqahtani SA, Gurakar A, Sulkowski MS, Cameron AM, Segev DL, Durand CM. Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey. Transpl Infect Dis 2018; 20:e12982. [PMID: 30144258 DOI: 10.1111/tid.12982] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 06/14/2018] [Accepted: 08/12/2018] [Indexed: 12/18/2022]
Abstract
With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.
Collapse
Affiliation(s)
- Ashton A Shaffer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Alvin G Thomas
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina
| | - Mary Grace Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Ayla Cash
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Lauren M Kucirka
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Saleh A Alqahtani
- Department of Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ahmet Gurakar
- Department of Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark S Sulkowski
- Department of Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Christine M Durand
- Department of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
11
|
Krzeczkowska A, Flowers P, Chouliara Z, Hayes P, Dickson A. 'It's been a long haul, a big haul, but we've made it': hepatitis C virus treatment in post-transplant patients with virus recurrence: An interpretative phenomenological analysis. Health Psychol Open 2018; 5:2055102918792673. [PMID: 30094056 PMCID: PMC6080080 DOI: 10.1177/2055102918792673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
The lived experience of both interferon-based and new interferon-free treatments in patients with hepatitis C virus remains understudied. To explore their journey through hepatitis C virus treatment, we interviewed seven post-transplant patients with recurrent hepatitis C virus. Three themes were identified using interpretative phenomenological analysis. Participants reported an ongoing sense of ontological uncertainty characterized by lack of control over their condition and treatment. Furthermore, an apposition of scepticism and hope accompanying each stage of hepatitis C virus treatment was described. A staged approach to psychological intervention tailored to the needs of the patient and their associated 'stage' of hepatitis C virus treatment was recommended.
Collapse
|
|
12
|
Chhatwal J, Samur S, Bethea ED, Ayer T, Kanwal F, Hur C, Roberts MS, Terrault N, Chung RT. Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study. Hepatology 2018; 67:2085-2095. [PMID: 29222916 PMCID: PMC5991982 DOI: 10.1002/hep.29723] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 10/30/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Under current guidelines, hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the LT waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: (1) willing to accept any (HCV-negative or HCV-positive) liver versus (2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when Model for End-Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life-years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. CONCLUSION Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).
Collapse
Affiliation(s)
- Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Sumeyye Samur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA
| | - Emily D. Bethea
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Turgay Ayer
- Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX,Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Chin Hur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Mark S. Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA,University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Norah Terrault
- University of California San Francisco Medical Center, San Francisco, CA
| | - Raymond T. Chung
- Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| |
Collapse
|
|
13
|
Chhatwal J, Kanwal F. Cost-effectiveness and Decision Analysis in Clinical Gastroenterology and Hepatology: From Evidence to Informed Decision Making. Clin Gastroenterol Hepatol 2018; 16:459-461. [PMID: 29246695 DOI: 10.1016/j.cgh.2017.12.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 12/04/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Harvard Medical School, Boston, Massachusetts
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston Veterans Affairs Health Services Research, Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| |
Collapse
|
|
14
|
Rupp C, Hippchen T, Neuberger M, Sauer P, Pfeiffenberger J, Stremmel W, Gotthardt DN, Mehrabi A, Weiss KH. Successful combination of direct antiviral agents in liver-transplanted patients with recurrent hepatitis C virus. World J Gastroenterol 2018; 24:1353-1360. [PMID: 29599610 PMCID: PMC5871830 DOI: 10.3748/wjg.v24.i12.1353] [Citation(s) in RCA: 7] [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: 01/30/2018] [Revised: 03/02/2018] [Accepted: 03/18/2018] [Indexed: 02/07/2023] Open
Abstract
AIM To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection.
METHODS Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV. Ten patients were treated with SOF + DAC ± RBV. Fiveteen patients were treated with fixed-dose combination of SOF + LDV ± RBV. One patient was treated with SOF + SIM + RBV. Three patients with relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk in all cases. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medications.
RESULTS The majority of patients were IFN-experienced (29/39, 74.4%) and had a history of hepatocellular carcinoma (26/39, 66.7%) before liver transplantation. Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were significantly higher, as compared to all other therapy regimens (P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period.
CONCLUSION Our cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5A and NS5B inhibitors.
Collapse
Affiliation(s)
- Christian Rupp
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
- Interdisciplinary Endoscopy Unit, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Theresa Hippchen
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Manuel Neuberger
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Peter Sauer
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
- Interdisciplinary Endoscopy Unit, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Jan Pfeiffenberger
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Wolfgang Stremmel
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Daniel Nils Gotthardt
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Karl-Heinz Weiss
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| |
Collapse
|
|
15
|
Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 2018; 68:526-549. [PMID: 28989095 PMCID: PMC5818315 DOI: 10.1016/j.jhep.2017.09.016] [Citation(s) in RCA: 514] [Impact Index Per Article: 73.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 09/24/2017] [Accepted: 09/25/2017] [Indexed: 01/27/2023]
Abstract
Patients who develop chronic fibrotic liver disease, caused by viral or metabolic aetiologies, are at a high risk of developing hepatocellular carcinoma (HCC). Even after complete HCC tumour resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent de novo HCC tumours, which progress into incurable, advanced-stage disease in most patients. Thus, early detection and prevention of HCC development is, in principle, the most impactful strategy to improve patient prognosis. However, a "one-size-fits-all" approach to HCC screening for early tumour detection, as recommended by clinical practice guidelines, is utilised in less than 20% of the target population, and the performance of screening modalities, including ultrasound and alpha-fetoprotein, is suboptimal. Furthermore, optimal screening strategies for emerging at-risk patient populations, such as those with chronic hepatitis C after viral cure, or those with non-cirrhotic, non-alcoholic fatty liver disease remain controversial. New HCC biomarkers and imaging modalities may improve the sensitivity and specificity of HCC detection. Clinical and molecular HCC risk scores will enable precise HCC risk prediction followed by tailoured HCC screening of individual patients, maximising cost-effectiveness and optimising allocation of limited medical resources. Several aetiology-specific and generic HCC chemoprevention strategies are evolving. Epidemiological and experimental studies have identified candidate chemoprevention targets and therapies, including statins, anti-diabetic drugs, and selective molecular targeted agents, although their clinical testing has been limited by the lengthy process of cancer development that requires long-term, costly studies. Individual HCC risk prediction is expected to overcome the challenge by enabling personalised chemoprevention, targeting high-risk patients for precision HCC prevention and substantially improving the dismal prognosis of HCC.
Collapse
Affiliation(s)
- Naoto Fujiwara
- Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, USA; Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Japan
| | - Scott L Friedman
- Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, USA
| | - Nicolas Goossens
- Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Yujin Hoshida
- Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, USA.
| |
Collapse
|
|
16
|
Strasser SI. Longterm outcome of the liver graft: A clinician's perspective-recurrent disease, the universal shifting. Liver Transpl 2017; 23:S64-S69. [PMID: 28779560 DOI: 10.1002/lt.24839] [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: 07/24/2017] [Accepted: 08/03/2017] [Indexed: 01/13/2023]
Affiliation(s)
- Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre, Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| |
Collapse
|
|
17
|
Golfieri L, Gitto S, Morelli MC, Pinna AD, Grandi S, Andreone P. Impact of hepatitis C virus infection on health-related quality of life before and after liver transplantation: a multidisciplinary point of view. Expert Rev Anti Infect Ther 2017; 15:759-765. [PMID: 28756716 DOI: 10.1080/14787210.2017.1362334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis C negatively changes patient quality of life even in the absence of advanced liver disease. The specific patterns of quality of life of hepatitis C positive patients waiting for transplant or after surgery are not widely studied. Areas covered: A significant percentage of infected patients show cognitive impairment, fatigue, and/or a 'brain fog', that cannot be explained by the liver disease. Depression can be diagnosed in one third of hepatitis C positive patients. Conflicting data are available regarding the possible role of Model for End-Stage Liver Disease score as predictor of impaired quality of life. In the first period after liver transplant, quality of life tends to increase at the pre-transplant period but in the medium and long-term period, it declines. The recurrence of hepatitis C infection represents a strong predictor of morbidity and mortality and can significantly affect the global quality of life of patients. Expert commentary: Hepatologists, surgeons and psychologists should collaborate to support infected patients in all phases of transplant including the long-term period after surgery. Education and information should be implemented especially regarding the positive role of new direct antivirals.
Collapse
Affiliation(s)
- Lucia Golfieri
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Stefano Gitto
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy
- c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Maria Cristina Morelli
- d Medicina Interna per il trattamento delle gravi insufficienze d'organo , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Antonio Daniele Pinna
- e Chirurgia Generale e Trapianti , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| | - Silvana Grandi
- a Dipartimento di Psicologia , Università di Bologna , Bologna , Italy
| | - Pietro Andreone
- b Centro di Ricerca per lo Studio delle Epatiti, Dipartimento di Scienze Mediche e Chirurgiche , Università di Bologna , Bologna , Italy
- c Programma Dipartimentale Innovazione Terapeutica Epatopatie Croniche Virali (ITEC), Dipartimento Ospedaliero dell'Apparato Digerente , Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola , Bologna , Italy
| |
Collapse
|