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Nabatchikova EA, Abdurakhmanov DT, Rozina TP, Nikulkina EN, Tanaschuk EL, Moiseev SV. Delisting and clinical outcomes of liver transplant candidates after hepatitis C virus eradication: A long-term single-center experience. Clin Res Hepatol Gastroenterol 2021; 45:101714. [PMID: 33930587 DOI: 10.1016/j.clinre.2021.101714] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/05/2021] [Accepted: 04/10/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Previous short-term studies have reported on liver function improvements and delisting among liver transplantation (LT) candidates with hepatitis C virus (HCV) and decompensated liver cirrhosis after successful antiviral therapy. This study aimed to evaluate the long-term impact of HCV eradication on liver function, portal hypertension, probability of delisting, and clinical outcomes in patients awaiting LT. METHODS Forty-five LT candidates with decompensated HCV cirrhosis were prospectively observed after HCV eradication by direct-acting antiviral therapy. The median follow-up (FU) time was 24 months. RESULTS Twenty-six (57.8%) patients were delisted due to clinical improvement. Multivariate analysis revealed male gender (hazard ratio (HR) 3.28; p = 0.022), baseline Child - Turcotte - Pugh class C (HR 4.81; p = 0.003), and delta prothrombin index <2% between baseline and the time of sustained virological response (HR 3.82; p = 0.01) as independent risk factors for non-delisting. During a median FU of 21 months after delisting, hepatocellular carcinoma (HCC) developed in 2 (7.7%) patients. Among non-delisted patients, HCC developed in 6 (31.6%) cases, variceal bleeding developed in 3 (15.8%) patients, and spontaneous bacterial peritonitis developed in 2 (10.5%) patients. CONCLUSION HCV eradication lead to the delisting of more than 50% of patients, but did not eliminate the HCC risk, and close monitoring of patients should continue after the end of treatment.
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Affiliation(s)
- Ekaterina A Nabatchikova
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia.
| | - Dzhamal T Abdurakhmanov
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia
| | - Teona P Rozina
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia; The Department of Internal Diseases, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, 27-1 Lomonosov prospect, Moscow, 119192, Russia
| | - Elena N Nikulkina
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia
| | - Elena L Tanaschuk
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia
| | - Sergey V Moiseev
- The Department of Internal, Occupational Diseases and Rheumatology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya st., Moscow, 119991, Russia; The Department of Internal Diseases, Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, 27-1 Lomonosov prospect, Moscow, 119192, Russia
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Wellington J, Ma A, Kottilil S, Ravichandran B, Husson J, Bruno D, Wilson E. Outcomes in Hepatitis C Positive Liver Transplantation: Timing of Direct-Acting Antiviral Treatment and Impact on Graft Fibrosis. Viruses 2021; 13:v13091831. [PMID: 34578412 PMCID: PMC8473279 DOI: 10.3390/v13091831] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/31/2021] [Accepted: 09/08/2021] [Indexed: 12/11/2022] Open
Abstract
Liver transplantation for hepatitis C virus (HCV)-related disease has the lowest five-year graft survival among all liver transplant recipients. Graft failure due to accelerated fibrosis from unrestrained HCV replication is common. Optimal timing of HCV treatment with direct-acting antiviral agents remains unknown. We compared HCV liver transplant recipients successfully treated for HCV before transplant to those treated within 1 year of transplant to determine if graft fibrosis, measured by Fib-4 scores, differs with timing of treatment. Fib-4 scores less than or equal to 1.45 defined minimal fibrosis and greater than 1.45 defined greater than minimal fibrosis. We identified 117 liver transplant recipients: 52 treated before transplantation and 65 treated within 1 year of transplantation. Overall, 34% of recipients had minimal fibrosis, and the likelihood of having minimal fibrosis following treatment and liver transplantation did not differ by timing of treatment. The odds ratio of having greater than minimal fibrosis was 0.65 (95% CI 0.30, 1.42) among those treated within 1 year after transplantation compared to those treated before transplantation (p-value 0.28). Importantly, nearly 2/3 of these patients had evidence of fibrosis progression one year after sustained virologic response, supporting recommendations for early antiviral-based treatment to prevent accumulation of HCV-related disease.
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Affiliation(s)
- Jennifer Wellington
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Correspondence:
| | - Andrew Ma
- Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (S.K.); (J.H.); (E.W.)
| | - Bharath Ravichandran
- Department of Pharmacy, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Jennifer Husson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (S.K.); (J.H.); (E.W.)
| | - David Bruno
- Division of Transplant Surgery, University of Maryland Medical Center, Baltimore, MD 21201, USA;
| | - Eleanor Wilson
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (S.K.); (J.H.); (E.W.)
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Lim N, Singh D, Jackson S, Lake JR. Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus (HCV) Liver Transplant Recipients Treated with Pretransplant Direct-Acting Antiviral (DAA) Therapy. Gastrointest Tumors 2020; 7:134-143. [PMID: 33173777 DOI: 10.1159/000510341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 07/17/2020] [Indexed: 12/27/2022] Open
Abstract
Background Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain. Objective We aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT. Methods The study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017. We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group). Results One hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group. Kaplan-Meier estimates of being HCC free were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively; p = 0.08. There was no difference observed for HCC recurrence between the DAA and IFN groups. In a multivariate Cox proportional hazards model, DAA use increased the risk of post-LT HCC recurrence (HR 5.2, 95% CI 0.9-29.81, p = 0.07). Conclusions A strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC.
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Affiliation(s)
- Nicholas Lim
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Dupinder Singh
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Scott Jackson
- Fairview Health Services, Minneapolis, Minnesota, USA
| | - John R Lake
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
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Solid organ transplantation of viral hepatitis C positive donor organs into viral hepatitis C negative recipients. Curr Opin Organ Transplant 2019; 23:257-263. [PMID: 29432255 DOI: 10.1097/mot.0000000000000504] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW Strategies are needed to reduce waitlist mortality and increase transplantation rates. Advances in hepatitis C therapy has allowed the transplant community to look toward utilization of grafts from hepatitis C viremic donors to expand the organ pool. Use of such grafts for hepatitis C-negative patients is being evaluated and debated, and early trial data are emerging. RECENT FINDINGS Both hepatitis C antibody-positive/nucleic acid test-negative and viremic donors are currently underutilized. Outcomes for viral hepatitis C (HCV) viremic transplant recipients are improving in the setting of direct-acting antiviral therapy. Optimization of graft utilization from HCV 'positive' donors and expansion to use of viremic donors for HCV-negative recipients will likely reduce waitlist mortality and result in net overall reduction in healthcare expenditures. SUMMARY Herein, we provide a review of recent advancements relating to hepatitis C in solid organ transplant and outline future directions. A primary future focus will be data collection of outcomes of transplantation of grafts from HCV 'viremic' donors to nonviremic recipients in formal clinical trial protocols.
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Daniel KE, Said A. Considerations When Treating Hepatitis C in a Cirrhotic Transplant Candidate. Curr Gastroenterol Rep 2018; 20:20. [PMID: 29623506 DOI: 10.1007/s11894-018-0626-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW This review examines the issues in determining the decision to treat a HCV-positive patient who is a liver transplant (LT) candidate with highly effective and well-tolerated direct-acting antiviral (DAA) therapies. RECENT FINDINGS Cure of HCV with DAA can improve liver function and allow delisting in some patients. Beyond a threshold of hepatic impairment (likely MELD score > 16 to 20), patients may experience a decline in MELD score with HCV cure without improvement in liver-related complications resulting in decreased opportunity to receive a LT. Eradicating HCV from patients who need LT regardless also deprives them of the option of receiving HCV-positive donor organs. Patients with MELD > 16 or Child-Pugh B/C may also have reduced cure rates of HCV, increased risk of hepatic decompensation, and adverse events with DAA pre-LT compared to post-LT DAA therapy. Preliminary data demonstrates increase risk of hepatocellular carcinoma (HCC) recurrence after treatment with DAA with subsequent studies raising doubts about this association. Patients with HCV cirrhosis on the LT waiting list with MELD score > 16, CTP-B/C, and HCC are best treated after LT with better response, tolerability, and the ability to receive organs from a larger donor pool that includes HCV-positive donors. Larger, prospective studies are needed to assess whether increased HCC recurrence after DAA is a true effect.
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Affiliation(s)
- Kimberly E Daniel
- Gastroenterology and Hepatology Fellow, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Adnan Said
- Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health and Madison VAMC, Madison, WI, USA.
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Trapani S, Rizzato L, Masiero L, Ricci A, Morabito V, Peritore D, Fiaschetti P, Del Sordo E, Cacciotti AR, Montemurro A, Nanni Costa A. Hepatitis C Virus Positive Patients on the Waiting List for Liver Transplantation: Turnover and Characteristics of the Population on the Eve of the Therapeutic Revolution With Direct-Acting Antivirals. Transplant Proc 2017; 49:658-666. [PMID: 28457366 DOI: 10.1016/j.transproceed.2017.02.039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Antivirals direct acting (DAA) for hepatitis C virus (HCV) have brought a revolution in the field of transplantation. It is likely to think that in the future patients on the waiting list for liver transplantation (LT) will no longer be registered for HCV-related cirrhosis but for liver disease from other causes. On the eve of this change, we show a snapshot of the Italian waiting list for LT. METHODS From October 1, 2012 to September 30, 2013, we estimated the total number of patients on the liver waiting list as intention to treat (ITT), the number of incident cases, and the delistings, particularly in the HCV positive (HCV+) population. Gender, median age, etiology and prognosis of liver disease, presence of hepatocellular carcinoma (HCC), reason for delisting, mean waiting time for LT, and rate of death on waiting list were evaluated. RESULTS In the time period, there were 517 new patients who were HCV+ (median age, 53 years): 255 (49.3%) mono-infected with HCV, 236 (45.7%) co-infected with HCV and hepatitis B virus (HBV), 11 (2.1%) co-infected with HCV and human immunodeficiency virus (HIV), and 15 (2.9%) co-infected with HCV, HBV, and HIV. The median model for end-stage liver disease (MELD) score at listing was 17 and HCC was present in 206 (39.8%) cases. HCV+ patients delisted were 442 (61.9%), 355 (80.3%) for LT. The mean waiting time to transplantation was 1.9 months; the percentage of death was 7.6%. CONCLUSIONS This snapshot of the waiting list for LT in the year before the advent of DAA drugs will allow us to assess whether and how they will change the waiting list for LT when we start to look at the impact of new therapies on the waiting list.
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Affiliation(s)
- S Trapani
- Italian National Transplant Center, Rome, Italy.
| | - L Rizzato
- Italian National Transplant Center, Rome, Italy
| | - L Masiero
- Italian National Transplant Center, Rome, Italy
| | - A Ricci
- Italian National Transplant Center, Rome, Italy
| | - V Morabito
- Italian National Transplant Center, Rome, Italy
| | - D Peritore
- Italian National Transplant Center, Rome, Italy
| | | | - E Del Sordo
- Italian National Transplant Center, Rome, Italy
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Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting. Transplantation 2017; 101:2739-2745. [PMID: 28795982 DOI: 10.1097/tp.0000000000001907] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. METHODS This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. RESULTS A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. CONCLUSIONS LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.
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Brown K. Maximizing donors with viral hepatitis in the current era. Liver Transpl 2017; 23:S44-S49. [PMID: 28846183 DOI: 10.1002/lt.24863] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 08/11/2017] [Accepted: 08/24/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Kimberly Brown
- Department of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI
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Donato MF, Morelli C, Romagnoli R, Invernizzi F, Mazzarelli C, Iemmolo RM, Montalbano M, Lenci I, Bhoori S, Pieri G, Berardi S, Caraceni P, Martini S. Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre- to post-liver transplant: a real-life strategy. Liver Int 2017; 37:678-683. [PMID: 27865034 DOI: 10.1111/liv.13322] [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: 06/10/2016] [Accepted: 11/12/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) re-infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre- to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV-RNA undetectability at the time of transplant. METHODS From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One hundred patients were transplanted and 31 patients (31%) treated with SOF/R bridging therapy were studied. RESULTS Liver transplant indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA positive (median HCV-RNA 58 IU/mL). One recipient had a virological breakthrough at week 4 post-transplant; one died, on treatment, 1-month post-transplant for sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute cellular rejection occurred in three recipients. On September 2016, 30 recipients (97%) were alive with a median follow-up of 18 months (range 13-25). CONCLUSIONS In patients with suboptimal virological response at LT, a bridging SOF/R regimen helps avoiding post-transplant graft reinfection.
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Affiliation(s)
- Maria Francesca Donato
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Cristina Morelli
- U.O. Medicina Interna e delle Insufficienze d'Organo-Azienda Ospedaliera-Universitaria, Policlinico S. Orsola-Malpighi di Bologna, Bologna, Italy
| | - Renato Romagnoli
- Liver Transplantation Center, General Surgery Unit 2U, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
| | - Federica Invernizzi
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Chiara Mazzarelli
- Hepatology Unit and Liver Transplantation Surgery, Niguarda Hospital, Milan, Italy
| | - Rosa Maria Iemmolo
- Liver and Multivisceral Transplant Center, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Marzia Montalbano
- Infectious Diseases and General Surgery, National Institute for Infectious Diseases Spallanzani, Rome, Italy
| | - Ilaria Lenci
- Gastroenterology Unit and Experimental Medicine and Surgery, University of Tor Vergata, Rome, Italy
| | - Sherrie Bhoori
- Surgery and Liver Transplantation Unit, IRCCS National Institute of Cancer, Milan, Italy
| | - Giulia Pieri
- Division of Hepatology, IRCCS AO San Martino IST, Genova, Italy
| | - Sonia Berardi
- U.O. Medicina Interna e delle Insufficienze d'Organo-Azienda Ospedaliera-Universitaria, Policlinico S. Orsola-Malpighi di Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Silvia Martini
- Liver Transplantation Center, Gastrohepatology Unit, AOU Città della Salute e della Scienza di Torino, Turin, Italy
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Poordad F, Lawitz E, Gutierrez JA, Guerrero J, Speeg K, Swenson ES. An HCV-positive recipient of an HCV-positive donor liver successfully treated before and immediately after liver transplant with daclatasvir, sofosbuvir, and ribavirin. Clin Case Rep 2017; 5:371-375. [PMID: 28396749 PMCID: PMC5378822 DOI: 10.1002/ccr3.841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Accepted: 10/31/2016] [Indexed: 01/14/2023] Open
Abstract
This case suggests that initiation of HCV therapy immediately after liver transplantation with well‐tolerated, all‐oral regimens may achieve a virologic cure in HCV‐positive recipients, thus preventing post‐transplant HCV recurrence and associated disease progression. This strategy may broaden utilization of HCV‐positive donor livers, potentially including HCV‐negative transplant recipients.
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Affiliation(s)
- Fred Poordad
- Texas Liver Institute San Antonio Texas USA; Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Eric Lawitz
- Texas Liver Institute San Antonio Texas USA; Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Julio A Gutierrez
- Texas Liver Institute San Antonio Texas USA; Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Juan Guerrero
- Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Kermit Speeg
- Department of Transplant Hepatology University of Texas Health Science San Antonio Texas USA
| | - Eugene S Swenson
- Bristol-Myers Squibb Research and Development Wallingford Connecticut USA
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11
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Park JY. Strategy for Hepatitis C Treatment in Liver Transplant Settings. KOREAN JOURNAL OF TRANSPLANTATION 2016. [DOI: 10.4285/jkstn.2016.30.4.149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Jun Yong Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Yonsei University Health System, Seoul, Korea
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12
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Njei B, McCarty TR, Fortune BE, Lim JK. Optimal timing for hepatitis C therapy in US patients eligible for liver transplantation: a cost-effectiveness analysis. Aliment Pharmacol Ther 2016; 44:1090-1101. [PMID: 27640785 DOI: 10.1111/apt.13798] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2016] [Revised: 08/12/2016] [Accepted: 08/20/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal for those with ongoing viraemia and is associated with higher rates of allograft failure and death. However, the optimal timing of HCV treatment for patients awaiting transplant remains unclear. AIM To evaluate the comparative cost-effectiveness of treating HCV pre-LT vs. post-LT (pre-emptive or after HCV recurrence). METHODS A Markov state-transition model was created to simulate the progression of a cohort of HCV-genotype 1 or 4 cirrhotic patients from the time of transplant listing until death. We then used this model to study the cost-effectiveness of ledipasvir-sofosbuvir (LDV/SOF) with ribavirin for 12 weeks, administered for three separate treatment strategies: (i) pre-LT; (ii) post-LT preemptively prior to HCV recurrence; or (iii) post-LT after HCV recurrence. RESULTS In the base-case analysis using a median model for end-stage liver disease (MELD) score <25 at the time of transplant, we found that pre-LT treatment of HCV led to more QALYs for fewer dollars compared to other strategies. Analysis limited to living donor LT recipients revealed that pre-LT treatment was also the most cost-effective strategy. When the analysis was repeated for MELD ≥25, decompensated disease (Child-Pugh class B or C), and hepatocellular carcinoma cases, preemptive post-LT strategy was more cost-effective. CONCLUSIONS Treatment of HCV prior to liver transplantation appears to be the most cost-effective strategy for patients with a MELD score <25. For patients with a MELD ≥25 or decompensated cirrhosis, preemptive post-liver transplantation treatment before HCV recurrence is the most cost-effective strategy.
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Affiliation(s)
- B Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.,Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
| | - T R McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - B E Fortune
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - J K Lim
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
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Alavian SM, Hajarizadeh B, Bagheri Lankarani K, Sharafi H, Ebrahimi Daryani N, Merat S, Mohraz M, Mardani M, Fattahi MR, Poustchi H, Nikbin M, Nabavi M, Adibi P, Ziaee M, Behnava B, Rezaee-Zavareh MS, Colombo M, Massoumi H, Bizri AR, Eghtesad B, Amiri M, Namvar A, Hesamizadeh K, Malekzadeh R. Recommendations for the Clinical Management of Hepatitis C in Iran: A Consensus-Based National Guideline. HEPATITIS MONTHLY 2016; 16:e40959. [PMID: 27799966 PMCID: PMC5075356 DOI: 10.5812/hepatmon.guideline] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 07/31/2016] [Indexed: 02/07/2023]
Abstract
CONTEXT Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. EVIDENCE ACQUISITION The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. RESULTS Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. CONCLUSIONS Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.
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Affiliation(s)
- Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Corresponding Author: Seyed Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran. Tel: +98-2181264070, E-mail:
| | - Behzad Hajarizadeh
- Viral Hepatitis Clinical Research Program, The Kirby Institute, The University of New South Wales (UNSW Australia), Sydney, Australia
| | | | - Heidar Sharafi
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
| | | | - Shahin Merat
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Minoo Mohraz
- Iranian Research Center for HIV/AIDS (IRCHA), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Masoud Mardani
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Mohamad Reza Fattahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, IR Iran
| | - Hossein Poustchi
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran
| | - Mehri Nikbin
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
| | - Mahmood Nabavi
- Department of Infectious Diseases and Tropical Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Peyman Adibi
- Department of Gastroenterology and Hepatology, Isfahan University of Medical Sciences, Isfahan, IR Iran
| | - Masood Ziaee
- Hepatitis Research Center, Birjand University of Medical Sciences, Birjand, IR Iran
| | - Bita Behnava
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
| | - Mohammad Saeid Rezaee-Zavareh
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
- Student’s Research Committee, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Massimo Colombo
- Department of Medicine, Gastroenterology Division 1, AM and A Migliavacca Center for the Study of Liver Disease, Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Hatef Massoumi
- New York Associates in Gastroenterology, Bronx, New York, USA
| | - Abdul Rahman Bizri
- Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | | | - Majid Amiri
- Gastroenterology and Hepatology Department, Gouin Hospital, Clichy, France
| | - Ali Namvar
- Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, IR Iran
| | - Khashayar Hesamizadeh
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Diseases (MELD) Center, Tehran, IR Iran
| | - Reza Malekzadeh
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran
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Poordad F, Schiff ER, Vierling JM, Landis C, Fontana RJ, Yang R, McPhee F, Hughes EA, Noviello S, Swenson ES. Daclatasvir with sofosbuvir and ribavirin for hepatitis C virus infection with advanced cirrhosis or post-liver transplantation recurrence. Hepatology 2016; 63:1493-505. [PMID: 26754432 PMCID: PMC5069651 DOI: 10.1002/hep.28446] [Citation(s) in RCA: 341] [Impact Index Per Article: 37.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 01/07/2016] [Indexed: 12/16/2022]
Abstract
UNLABELLED Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open-label ALLY-1 study assessed the safety and efficacy of a 60-mg once-daily dosage of daclatasvir (pan-genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24-week follow-up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on-treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child-Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%-92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child-Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%-99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment-related serious adverse events. CONCLUSION The pan-genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post-liver transplantation recurrence or advanced cirrhosis.
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Affiliation(s)
- Fred Poordad
- The Texas Liver InstituteUniversity of Texas Health Science CenterSan AntonioTX
| | - Eugene R. Schiff
- Schiff Center for Liver DiseasesUniversity of Miami Miller School of MedicineMiamiFL
| | - John M. Vierling
- Division of Abdominal TransplantationBaylor College of MedicineHoustonTX
| | - Charles Landis
- Division of Gastroenterology and Hepatology, Department of MedicineUniversity of WashingtonSeattleWA
| | - Robert J. Fontana
- University Division of Gastroenterology, Department of Internal MedicineUniversity of Michigan Medical CenterAnn ArborMI
| | - Rong Yang
- Bristol‐Myers SquibbLawrence TownshipNJ
| | - Fiona McPhee
- Discovery VirologyBristol‐Myers Squibb Research and DevelopmentWallingfordCT
| | | | | | - Eugene S. Swenson
- Discovery VirologyBristol‐Myers Squibb Research and DevelopmentWallingfordCT
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15
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Al-hamoudi WK. Management of hepatitis c genotype 4 in the liver transplant setting. Saudi J Gastroenterol 2016; 22:173-82. [PMID: 27184634 PMCID: PMC4898085 DOI: 10.4103/1319-3767.182453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 08/17/2015] [Indexed: 12/20/2022] Open
Abstract
End-stage liver disease secondary to hepatitis C virus (HCV) infection is the major indication for orthotopic liver transplantation (OLT) worldwide. The percentage of HCV patients infected with genotype 4 (G4) among recipients of OLT varies depending on geographic location. In the Middle East, including Saudi Arabia, G4 infection is the most common genotype among transplant recipients. Due to the low prevalence of HCV-G4 in Europe and the United States, this genotype has not been adequately studied in prospective trials evaluating treatment outcomes and remains the least studied variant. The aim of this review is to summarize the natural history and treatment outcome of HCV-G4 following liver transplantation, with particular attention to new HCV therapies. This review incorporates all published studies and abstracts including HCV-G4 patients.
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Affiliation(s)
- Waleed K. Al-hamoudi
- Department of Medicine, Gastroenterology Unit, College of Medicine, Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
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16
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Perumpail RB, Hahambis TA, Aggarwal A, Younossi ZM, Ahmed A. Treatment strategies for chronic hepatitis C prior to and following liver transplantation. World J Hepatol 2016; 8:69-73. [PMID: 26783422 PMCID: PMC4705454 DOI: 10.4254/wjh.v8.i1.69] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/30/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related liver disease is the leading indication for liver transplantation (LT) worldwide. However, HCV is an independent predictor of lower survival following LT, and recurrence of HCV post-LT is virtually universal. The historic standard of care during the interferon era of HCV therapy was expectant management-initiation of antiviral therapy in the setting of documented disease progression following LT. With the advent of new direct acting antiviral (DAA) therapies for HCV, the paradigm of expectant treatment for recurrent HCV infection post-LT is shifting. The safety, tolerability, and efficacy of DAAs, even among the sickest patients with advanced liver disease, enables treatment of HCV in the pre-transplant setting among LT waitlist registrants. Finally, emerging data are supportive of preemptive therapy with DAAs in liver transplant recipients as the preferred approach. Expectant management of HCV following LT can rarely be justified in the modern era of HCV therapy.
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Infectious Considerations in the Pre-Transplant Evaluation of Cirrhotic Patients Awaiting Orthotopic Liver Transplantation. Curr Infect Dis Rep 2016; 18:4. [PMID: 26743200 DOI: 10.1007/s11908-015-0514-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The incidence of end-stage liver disease (ESLD) is increasing and many of these patients may be considered for orthotopic liver transplantation. As patients with ESLD are at risk of a number of infections, infectious disease physicians should be aware of the management of these infections in order to provide optimal patient care and ensure transplantation success. We present a review of the literature pertaining to infectious disease considerations in the liver transplant candidate. It highlights several topics with recent developments including the management of hepatitis C virus infection prior to transplantation, treatment of hepatitis B virus infection, colonization and infection with multidrug resistant organisms, and management of spontaneous bacterial peritonitis.
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18
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Barsa JE, Branch AD, Schiano TD. A pleasant dilemma to have: to treat the HCV patient on the waiting list or to treat post-liver transplantation? Clin Transplant 2015; 29:859-65. [DOI: 10.1111/ctr.12596] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2015] [Indexed: 12/13/2022]
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