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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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2
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Aregay A, Engel B, Port K, Vondran FWR, Bremer B, Niehaus C, Khera T, Richter N, Jaeckel E, Cornberg M, Taubert R, Wedemeyer H. Distinct Immune Imprints of Post-Liver Transplantation Hepatitis C Persist Despite Viral Clearance. Liver Transpl 2021; 27:887-899. [PMID: 33641215 DOI: 10.1002/lt.26031] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 01/21/2021] [Accepted: 01/27/2021] [Indexed: 01/13/2023]
Abstract
Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C-X-Cmotif chemokine 10 (CXCL10), caspase 8, C-C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain-containing protein 1 (CDCP1), interleukin (IL)-18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor-beta, CXCL6, osteoprotegerin, IL10, fms-related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase-type plasminogen activator, neurotrophin-3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV-specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy-induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.
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Affiliation(s)
- Amare Aregay
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Bastian Engel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Kerstin Port
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Florian W R Vondran
- Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Birgit Bremer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Christian Niehaus
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Tanvi Khera
- Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany
| | - Nicolas Richter
- Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
| | - Elmar Jaeckel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research, DZIF, partner-site Hannover-Braunschweig, Hannover, Germany.,Centre for individualized infection medicine (CIIM), Hannover, Germany
| | - Richard Taubert
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.,Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.,Integrated Research and Treatment Centre Transplantation, Hannover Medical School, Hannover, Germany.,German Centre for Infection Research, DZIF, partner-site Hannover-Braunschweig, Hannover, Germany
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3
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Nicastro E, Norsa L, Di Giorgio A, Indolfi G, D'Antiga L. Breakthroughs and challenges in the management of pediatric viral hepatitis. World J Gastroenterol 2021; 27:2474-2494. [PMID: 34092970 PMCID: PMC8160618 DOI: 10.3748/wjg.v27.i20.2474] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/04/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) major causes of advanced liver disease and mortality worldwide. Although regarded as benign infections in children, their persistence through adulthood is undoubtedly of concern. Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment, which is currently far from being curative. Herein we describe direct-acting antivirals available for pediatric HCV (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) and their real-world use. A critical review of the HBV pediatric classification is provided. Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population, including capsid assembly modulators, antigen secretion inhibitors, silencing RNAs, and immune modifiers. Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.
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Affiliation(s)
- Emanuele Nicastro
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
| | - Lorenzo Norsa
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
| | - Angelo Di Giorgio
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
| | - Giuseppe Indolfi
- Department of Neurofarba, Meyer Children's University Hospital of Florence, Florence 50137, Italy
| | - Lorenzo D'Antiga
- Department of Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo 24127, Italy
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Delman AM, Ammann AM, Shah SA. The current status of virus-positive liver transplantation. Curr Opin Organ Transplant 2021; 26:160-167. [PMID: 33595981 DOI: 10.1097/mot.0000000000000850] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW The last 2 years have seen significant developments in virus-positive liver transplantation. This review provides an updated account of the transplantation of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV-positive livers, with a specific focus on studies published in the last 18 months. RECENT FINDINGS The advent of highly efficacious direct acting antiviral agents, nucleos(t)ide analogues and a continued organ shortage have led to the well tolerated utilization of HCV, HBV and HIV-positive organs. There has been a significant increase in the transplantation of HCV seropositive and NAT+ organs into HCV-negative recipients, without compromising patient or graft survival. Early reports of HBV core antibody (HBVcAb), HBV surface antigen (HBVsAg) positive and NAT+ donors are growing in the USA with promising results. Similarly, small studies have described the use of HIV-positive to HIV-positive liver transplantation without concerns for superinfection. SUMMARY HCV, HBV and HIV-positive liver transplantations can be accomplished safely and are associated with equivalent outcomes when paired with appropriate recipients. The practice of virus positive liver transplantation should be encouraged to combat the ongoing organ shortage.
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Affiliation(s)
- Aaron M Delman
- The Department of Surgery, University of Cincinnati
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS) Research Group, The Department of Surgery at The University of Cincinnati, Cincinnati, Ohio, USA
| | - Allison M Ammann
- The Department of Surgery, University of Cincinnati
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS) Research Group, The Department of Surgery at The University of Cincinnati, Cincinnati, Ohio, USA
| | - Shimul A Shah
- The Department of Surgery, University of Cincinnati
- Cincinnati Research on Outcomes and Safety in Surgery (CROSS) Research Group, The Department of Surgery at The University of Cincinnati, Cincinnati, Ohio, USA
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Roche B, Coilly A, Samuel D. Management of Transplant Patients Infected with HCV. HEPATITIS C: CARE AND TREATMENT 2021:153-173. [DOI: 10.1007/978-3-030-67762-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Ismail MS, Hassan M, Khaderi SA, Yousry WA, Kamal El-Din MM, Bahaa El-Din MM, El Sayed OA, Kaseb AO, Goss JA, Kanwal F, Jalal PK. Clinical efficacy of direct-acting antiviral therapy for recurrent hepatitis C virus infection after liver transplantation in patients with hepatocellular carcinoma. World J Hepatol 2020; 12:628-640. [PMID: 33033569 PMCID: PMC7522560 DOI: 10.4254/wjh.v12.i9.628] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 06/03/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Recurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Direct-acting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown.
AIM To demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients.
METHODS A total of 106 LT recipients given DAAs for recurrent HCV infection from 2015 to 2019 were identified (68 with and 38 without HCC). Descriptive statistics and logistic regression models were used to estimate the multivariate odds ratios and respective 95% confidence intervals for predictors of treatment failure and HCC recurrence.
RESULTS Six patients (6%) experienced DAA therapy failure post-LT and 100 (94%) had a sustained virologic response at follow-up week 12. A high alanine transaminase level > 35 U/L at treatment week 4 was a significant predictor of treatment failure. Relapse to pre-LT DAA therapy is a predictor of post-LT HCC recurrence, P = 0.04. DAA relapse post-LT was also associated with post-transplantation HCC recurrence, P = 0.05.
CONCLUSION DAAs are effective and safe in the treatment of recurrent HCV infection in LT recipients with history of HCC. Relapse to pre- and post-LT DAA therapy is associated with post-transplantation HCC recurrence.
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Affiliation(s)
- Mohamed Saleh Ismail
- Division of Gastroenterology, Baylor College of Medicine, Houston, TX 77030, United States
- Department of Internal medicine, Gastroenterology and Hepatology, Ain Shams University, Cairo 11566, Egypt
- Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX 77030, United States
| | - Manal Hassan
- Division of Gastroenterology, Baylor College of Medicine, Houston, TX 77030, United States
- Department of Epidemiology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Saira Aijaz Khaderi
- Division of Gastroenterology, Baylor College of Medicine, Houston, TX 77030, United States
- Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX 77030, United States
| | - Wael Ahmed Yousry
- Department of Internal medicine, Gastroenterology and Hepatology, Ain Shams University, Cairo 11566, Egypt
| | - Maha Mohsen Kamal El-Din
- Department of Internal medicine, Gastroenterology and Hepatology, Ain Shams University, Cairo 11566, Egypt
| | | | - Osama Aboelfotoh El Sayed
- Department of Internal medicine, Gastroenterology and Hepatology, Ain Shams University, Cairo 11566, Egypt
| | - Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - John Alan Goss
- Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX 77030, United States
| | - Fasiha Kanwal
- Division of Gastroenterology, Baylor College of Medicine, Houston, TX 77030, United States
| | - Prasun Kumar Jalal
- Division of Gastroenterology, Baylor College of Medicine, Houston, TX 77030, United States
- Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX 77030, United States
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7
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Araujo A, Valenzuela-Granados V, Lopes AB, Michalczuk MT, Mantovani A, Alvares-da-Silva MR. Sofosbuvir-based antiviral therapy in patients with recurrent HCV infection after liver transplant: A real-life experience. Ann Hepatol 2020; 18:450-455. [PMID: 31028014 DOI: 10.1016/j.aohep.2018.09.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 09/16/2018] [Accepted: 09/28/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Recurrent HCV infection after liver transplant (LT) has a negative impact on graft and patient survival. The aim of this study is to describe the efficacy and safety of sofosbuvir (SOF-based) regimens in the treatment of recurrent HCV after liver transplant (LT). MATERIALS AND METHODS This retrospective study included 68 adults with recurrent HCV infection after LT, treated with different SOF-based regimens between March 2015 and December 2016. The choice of regimens, their duration and use of ribavirin (RBV) was made by the treating physician. The efficacy of antiviral treatment was assessed based on the sustained viral response obtained 12 weeks after the end of treatment (SVR12), according to an intention-to-treat analysis. RESULTS The most frequent HCV genotypes were 1 and 3 (n=35, 51.4% and n=31, 45.6%, respectively). Only 22 patients were treatment naïve (32.3%) and 7 had cirrhosis (10.2%). SOF+daclatasvir (DCV) was the most commonly used regimen (n=63, 92.6%). Most patients used RBV (n=56, 82.3%) and were treated for 12 weeks (n=66, 97%). Overall SVR12 was 95.5% (65/68 patients). Three patients had virologic failure. Three patients had serious adverse events, however, no one discontinued treatment prematurely. RBV-related anaemia was the most frequent adverse event (n=34, 50%). Four patients had severe cellular graft rejection after HCV elimination, while immunosuppression remained stable. CONCLUSION SOF-based therapy is highly effective and safe to treat HCV recurrence after LT. Cellular graft rejection following the successful treatment of HCV needs further investigation.
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Affiliation(s)
- Alexandre Araujo
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | | | - Antonio B Lopes
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Matheus T Michalczuk
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Augusto Mantovani
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Mario R Alvares-da-Silva
- Division of Gastroenterology and Hepatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; World Gastroenterology Organisation Porto Alegre Hepatology Training Center, Porto Alegre, RS, Brazil; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
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8
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Cieciura T, Hryniewiecka E, Foroncewicz B, Strzelczyk Z, Ciszek M, Paczek L. Long-Term Follow-up of Liver Transplant Recipients Treated With Direct-Acting Antiviral Agents for Hepatitis C Recurrence After Transplantation. Transplant Proc 2020; 52:2468-2471. [PMID: 32241638 DOI: 10.1016/j.transproceed.2020.01.097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 01/26/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LTX) with direct-acting antiviral agents (DAA) is effective and leads to sustained viral response (SVR) in most cases. Long-term effect of HCV elimination on LTX function is not clear. The aim of the study was to evaluate the long-term influence of DAA with HCV on the liver function in LTX recipients. METHODS The study included 120 LTX patients with HCV recurrence. Before starting DAA therapy, all patients underwent liver biopsy and elastography. Biochemical tests and HCV viremia were assessed at baseline, 4, 12, and 24 weeks and 24 months after the end of treatment (EOT). The study protocol conformed with the Declaration of Helsinki. RESULTS In the HCV genotype 1 (G1) group, 106 patients were treated with ledipasvir/sofosbuvir with ribavirin (RBV), and 3 patients received paritaprevir/ritonavir/ombitasvir/dasabuvir/RBV. All HCV genotype 3 (G3) patients were treated with sofosbuvir/RBV; all HCV genotype 4 (G4) patients were treated with paritaprevir/ombitasvir/RBV. The efficacy of the treatment defined as SVR at week 12 after EOT (SVR12) was 97.3% in G1 group, 75% in G3, and 100% in G4 group. Median alanine (ALT) and aspartate (AST) transaminase before therapy were 44.0 IU/mL and 42.5 IU/mL, respectively. Median ALT and AST at 24 months after EOT were 17 IU/mL and 22 IU/mL, respectively. The lack of transaminases normalization was observed in 10 patients 24 months after EOT. CONCLUSION The efficacy of DAA therapy of HCV recurrence after LTX is as high as that reported in randomized clinical trials. It is also associated with the improvement of liver function tests during long-term follow-up.
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Affiliation(s)
- Tomasz Cieciura
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Hryniewiecka
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Bartosz Foroncewicz
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Ziemowit Strzelczyk
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - Michal Ciszek
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - Leszek Paczek
- Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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9
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Sise ME, Strohbehn IA, Chute DF, Gustafson J, Van Deerlin VM, Smith JR, Gentile C, Wojciechowski D, Williams WW, Elias N, Chung RT. Preemptive Treatment With Elbasvir and Grazoprevir for Hepatitis C-Viremic Donor to Uninfected Recipient Kidney Transplantation. Kidney Int Rep 2020; 5:459-467. [PMID: 32280841 PMCID: PMC7136432 DOI: 10.1016/j.ekir.2020.01.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 01/03/2020] [Accepted: 01/06/2020] [Indexed: 01/25/2023] Open
Abstract
Introduction Long wait times for kidney transplants have prompted investigation into strategies to decrease the discarding of potentially viable organs. Recent reports suggest that kidneys from hepatitis C virus (HCV)-infected donors may be transplanted into HCV-naive donors followed by direct-acting antiviral therapy. Methods This was a pilot clinical trial to transplant kidneys from HCV-infected donors into HCV-naive recipients with preemptive use of elbasvir and grazoprevir for 12 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy. Secondary outcomes were safety, quality of life, and early viral kinetics. Results A total of 33 patients were screened, and 8 underwent kidney transplantation from a HCV-viremic donors from August 2017 to March 2019. The median donor kidney donor profile index was 31% (range, 29%-65%), and patients who underwent transplantation waited a median of 6.5 months (range, 1-19 months). None had detectable HCV viremia beyond 2 weeks post-transplantation, and all achieved sustained virologic response 12 weeks after therapy (SVR12). There were no study-related severe adverse events. One patient experienced early graft loss due to venous thrombosis, whereas the remaining 7 patients had excellent allograft function at 6 months. Conclusion Preemptive elbasvir and grazoprevir eliminated HCV infection in HCV-naive patients who received a kidney transplant from an HCV-infected donor.
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Affiliation(s)
- Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Ian A Strohbehn
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Donald F Chute
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jenna Gustafson
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Vivianna M Van Deerlin
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Jennifer R Smith
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Caren Gentile
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - David Wojciechowski
- Division of Nephrology, University of Texas Southwestern, Dallas, Texas, USA
| | - Winfred W Williams
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nahel Elias
- Department of Surgery, Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Raymond T Chung
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts, USA
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10
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Laub M, Harris M, Sanoff S, Berg C, Byrns J. Effects of Sofosbuvir-Based Hepatitis C Treatment Regimens on Calcineurin Inhibitor Dosing in Liver and Kidney Transplant Recipients. EXP CLIN TRANSPLANT 2019; 19:142-148. [PMID: 31875466 DOI: 10.6002/ect.2019.0289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Available data have suggested that directacting antivirals for hepatitis C virus may decrease calcineurin inhibitor concentrations. In this study, our aim was to determine the effects of hepatitis C directacting antivirals on calcineurin inhibitor doses and trough levels. MATERIALS AND METHODS This retrospective, singlecenter study included 52 abdominal transplant recipients treated with sofosbuvir-based regimens between 2014 and 2017. The primary outcome was percent change in calcineurin inhibitor troughs and total daily doses between the week before treatment with direct-acting antivirals, days 21 to 35 oftreatment, and days 21 to 35 aftertreatment. Secondary outcomes included sustained virologic response and biopsyproven acute rejection rates. RESULTS The median percent difference in calcineurin inhibitor troughs from pretreatment to during treatment was -20.5% (interquartile range, -36.2% to 13.1%) and from pretreatment to posttreatment was -13.5% (interquartile range, -33.7% to 10.7%). Corresponding percent changes in calcineurin inhibitor doses were 0% (interquartile range, 0%-0%) and 0% (interquartile range, -10.5% to 33.3%), respectively. Patients on tacrolimus experienced statistically significant changes in troughs but not doses. During treatment, 65% of patients required no dose change, 23% underwent a dose increase, and 12% had a dose decrease. The sustained virologic response rate was 98%, and the biopsy-proven acute rejection rate was 0%. CONCLUSIONS Hepatitis C direct-acting antiviraltherapy may decrease calcineurin inhibitor levels, but this was not associated with clinically different dosing requirements or rejection rates.
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Affiliation(s)
- Melissa Laub
- From the Augusta University Medical Center Department of Pharmacy, Augusta, GA, USA
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11
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Sise ME, Wojciechowski D, Chute DF, Gustafson J, Chung RT, Williams WW, Elias N. Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation. Artif Organs 2019; 43:913-920. [PMID: 31001828 PMCID: PMC6733639 DOI: 10.1111/aor.13473] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 04/10/2019] [Accepted: 04/11/2019] [Indexed: 12/29/2022]
Abstract
Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)-infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV-infected donors has increased significantly. With the development of direct-acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct-acting antiviral therapy to treat HCV infection in HCV-uninfected transplant recipients of kidneys from HCV-viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct-acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.
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Affiliation(s)
- Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts
| | - David Wojciechowski
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts
| | - Donald F Chute
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts
| | - Jenna Gustafson
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts
| | - Raymond T Chung
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts
| | - Winfred W Williams
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts
| | - Nahel Elias
- Department of Surgery, Division of Transplant Surgery, Massachusetts General Hospital, Boston, Massachusetts
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12
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International Liver Transplantation Society Asian Consensus on the Management of Hepatitis C Virus Infection in Resource Limited Setting-From Noncirrhotic to Decompensated Disease and After Liver Transplantation. Transplantation 2019; 103:733-746. [PMID: 30335692 DOI: 10.1097/tp.0000000000002453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia. METHODS To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions. RESULTS An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article. CONCLUSIONS With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.
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13
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Sise ME, Strohbehn IA, Bethea E, Gustafson JL, Chung RT. Balancing the risk and rewards of utilizing organs from hepatitis C viremic donors. Curr Opin Organ Transplant 2019; 24:351-357. [PMID: 31090648 PMCID: PMC7093034 DOI: 10.1097/mot.0000000000000651] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW Owing to long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of hepatitis C viremic-deceased donor organs are under investigation in kidney, liver, heart, and lung transplantation. RECENT FINDINGS Direct-acting antiviral medications for hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early posttransplant direct-acting antiviral therapy, 100% of uninfected recipients of hepatitis C viremic organs have been cured of infection after transplantation. SUMMARY In this manuscript, we review the risks and rewards of utilizing hepatitis C viremic organs for transplantation.
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Affiliation(s)
- Meghan E. Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital
| | - Ian A. Strohbehn
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Emily Bethea
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Jenna L. Gustafson
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Raymond T. Chung
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
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14
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Sise ME, Chute DF, Gustafson JL, Wojciechowski D, Elias N, Chung RT, Williams WW. Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients. Hemodial Int 2019; 22 Suppl 1:S71-S80. [PMID: 29694722 DOI: 10.1111/hdi.12650] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Long wait times for kidney transplant and the high risk of mortality on dialysis have prompted investigation into strategies to increase organ allocation and decrease discard rates of potentially viable kidneys. Organs from hepatitis C virus (HCV) antibody positive donors are often rejected; nearly 500 HCV-infected kidneys are discarded annually in the United States. Due the opioid epidemic, the number of HCV-infected donors has increased because of a rise in both new HCV infections and drug-related deaths. In the past 5 years, HCV has been transformed into a curable illness with direct-acting antiviral therapies (DAAs) that are effective in >95% of patients treated and are extremely well tolerated. Recent data has shown several direct-acting antiviral combinations are safe and effective after kidney transplant, and can achieve the same high cure rate seen in the general population and without increasing the rate of acute rejection. Because of this, strategies to decrease discard of HCV-infected organs have been devised. Two recent studies have transplanted HCV-uninfected dialysis patients with kidneys from donors actively infected with HCV; recipients were treated with DAA in the peri-transplant period. More research is needed to determine the safety and efficacy of this approach, but it has the potential to dramatically increase the donor pool of available kidneys, shorten waitlist times and ultimately decreases mortality in patients waiting for kidney transplant.
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Affiliation(s)
- Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Donald F Chute
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jenna L Gustafson
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - David Wojciechowski
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nahel Elias
- Department of Transplant Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Winfred W Williams
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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15
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Coilly A, Roche B, Samuel D. Management of HCVInfection After Liver Transplantation. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:753-764. [DOI: 10.1002/9781119211419.ch50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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16
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Xue W, Liu K, Qiu K, Shen Y, Pan Z, Hu P, Peng M, Chen M, Ren H. A systematic review with meta-analysis: Is ribavirin necessary in sofosbuvir-based direct-acting antiviral therapies for patients with HCV recurrence after liver transplantation? Int J Infect Dis 2019; 83:56-63. [PMID: 30959250 DOI: 10.1016/j.ijid.2019.03.038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 03/29/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES With the appearance of direct-acting antiviral agents (DAAs), sofosbuvir (SOF)-based DAAs are recommended for patients with hepatitis C virus (HCV) recurrence after liver transplantation (LT). Whether ribavirin (RBV) is needed by patients after LT in combination with SOF-based DAAs remains to be determined. This meta-analysis was conducted to evaluate the necessity of RBV with SOF-based DAAs for post-LT patients. METHODS PubMed, Web of Science, Cochrane Library and EMBASE databases were systematically searched for eligible studies from the databases' inceptions until November 2018. We accepted the studies that included HCV recurrence in post-LT patients who were treated with SOF-based DAAs ± RBV, and evaluated the rate of sustained virological response 12 weeks (SVR12) after the end of treatment. RESULTS Twelve studies, comprising a total of 1466 LT recipients, were included in this study. The pooled SVR12 of these patients was 91% (95% CI: 84% to 95%). There was no statistical difference of SVR12 in the patients treated with SOF-based DAAs + RBV versus -RBV group (risk ratio [RR] = 0.97; 95% CI: 0.92 to 1.03; P = 0.35) by different therapy duration (P = 0.26), with different targets of DAAs (P = 0.13) and in different regions (P = 0.34) but a tendency for a higher incidence of anemia in the +RBV group than in the -RBV group (RR = 5.18; 95% CI: 3.41 to 7.86; p < 0.00001). CONCLUSION The addition of RBV may not contribute to a higher SVR rate and could increase the incidence of anemia, so RBV is not necessary in SOF-based DAAs for patients with HCV recurrence after LT.
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Affiliation(s)
- Wei Xue
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Kai Liu
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Medical Laboratory, The People's Hospital of Leshan, Leshan, China
| | - Ke Qiu
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; West China Hospital, Sichuan University, Chengdu, China
| | - Yanxi Shen
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhaojun Pan
- Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Peng Hu
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingli Peng
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Min Chen
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Hong Ren
- The Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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17
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Liu J, Ma B, Cao W, Li M, Bramer WM, Peppelenbosch MP, Pan Q. Direct-acting antiviral agents for liver transplant recipients with recurrent genotype 1 hepatitis C virus infection: Systematic review and meta-analysis. Transpl Infect Dis 2019; 21:e13047. [PMID: 30615227 PMCID: PMC6850617 DOI: 10.1111/tid.13047] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 12/18/2018] [Accepted: 12/23/2018] [Indexed: 12/15/2022]
Abstract
Background Comprehensive evaluation of safety and efficacy of different combinations of direct‐acting antivirals (DAAs) in liver transplant recipients with genotype 1 (GT1) hepatitis C virus (HCV) recurrence remains limited. Therefore, we performed this systematic review and meta‐analysis in order to evaluate the clinical outcome of DAA treatment in liver transplant patients with HCV GT1 recurrence. Methods Studies were included if they contained information of 12 weeks sustained virologic response (SVR12) after DAA treatment completion as well as treatment related complications for liver transplant recipients with GT1 HCV recurrence. Results We identified 16 studies comprising 885 patients. The overall pooled estimate proportion of SVR12 was 93% (95% confidence interval (CI): 0.89, 0.96), with moderate heterogeneity observed (τ2 = 0.01, P < 0.01, I2=75%). High tolerability was observed in liver transplant recipients reflected by serious adverse events (sAEs) with pooled estimate proportion of 4% (95% CI: 0.01, 0.07; τ2 = 0.02, P < 0.01, I2 = 81%). For subgroup analysis, a total of five different DAA regimens were applied for treating these patients. Sofosbuvir/Ledipasvir (SOF/LDV) led the highest pooled estimate SVR12 proportion, followed by Paritaprevir/Ritonavir/Ombitasivir/Dasabuvir (PrOD), Daclatasvir (DCV)/Simeprevir (SMV) ± Ribavirin (RBV), and SOF/SMV ± RBV, Asunaprevir (ASV)/DCV. There was a tendency for favoring a higher pooled SVR12 proportion in patients with METAVIR Stage F0‐F2 of 97% (95% CI: 0.93, 0.99) compared to 85% (95% CI: 0.79, 0.90) for stage F3‐F4 (P < 0.01). There was no significant difference between LT recipients treated with or without RBV (P = 0.23). Conclusions Direct‐acting antiviral treatment is highly effective and well‐tolerated in liver transplant recipients with recurrent GT1 HCV infection.
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Affiliation(s)
- Jiaye Liu
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China.,Erasmus MC Cancer Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Buyun Ma
- Erasmus MC Cancer Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Wanlu Cao
- Erasmus MC Cancer Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Meng Li
- Erasmus MC Cancer Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Wichor M Bramer
- Department of Medical Library, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Maikel P Peppelenbosch
- Erasmus MC Cancer Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Qiuwei Pan
- Biomedical Research Center, Northwest Minzu University, Lanzhou, China.,Erasmus MC Cancer Institute, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
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18
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Abstract
Liver transplantation has become an important treatment modality for patients with end-stage liver disease/cirrhosis, acute liver failure, and hepatocellular carcinoma. Although surgical techniques and immunosuppressive regimens for liver transplantation have improved significantly over the past 20 years, infectious complications continue to contribute to the morbidity and mortality in this patient population. The use of standardized screening protocols for both donors and recipients, coupled with targeted prophylaxis against specific pathogens, has helped to mitigate the risk of infection in liver transplant recipients. Patients with chronic liver disease and cirrhosis have immunological deficits that place them at increased risk for infection while awaiting liver transplantation. The patient undergoing liver transplantation is prone to develop healthcare-acquired infections due to multidrug-resistant organisms that could potentially affect patient outcomes after transplantation. The complex nature of liver transplant surgery that involves multiple vascular and hepatobiliary anastomoses further increases the risk of infection after liver transplantation. During the early post-transplantation period, healthcare-acquired bacterial and fungal infections are the most common types of infection encountered in liver transplant recipients. The period of maximal immunosuppression that occurs at 1–6 months after transplantation can be complicated by opportunistic infections due to both primary infection and reactivation of latent infection. Severe community-acquired infections can complicate the course of liver transplantation beyond 12 months after transplant surgery. This chapter provides an overview of liver transplantation including indications, donor-recipient selection criteria, surgical procedures, and immunosuppressive therapies. A focus on infections in patients with chronic liver disease/cirrhosis and an overview of the specific infectious complications in liver transplant recipients are presented.
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19
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Pham TT, Keast SL, Farmer KC, Thompson DM, Rathbun RC, Nesser NJ, Holderread BP, Skrepnek GH. Sustained Virologic Response and Costs Associated with Direct-Acting Antivirals for Chronic Hepatitis C Infection in Oklahoma Medicaid. J Manag Care Spec Pharm 2018; 24:664-676. [PMID: 29952711 PMCID: PMC10398076 DOI: 10.18553/jmcp.2018.24.7.664] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Outcomes involving newer direct-acting antiviral (DAA) hepatitis C virus (HCV) regimens have not been studied extensively among the Medicaid population. OBJECTIVE To assess clinical (treatment failure) and economic outcomes for chronic HCV-infected Oklahoma Medicaid members following treatment with DAAs and to measure associations with patient, treatment, and clinical characteristics. METHODS This cross-sectional study used Oklahoma Medicaid pharmacy and medical claims data for adult members who used a newer DAA agent and had reported a successful or failed sustained virological response rate 12 weeks after therapy completion (SVR12) from January 1, 2014, to June 30, 2016. Multivariable logistic and gamma regressions assessed predictors of SVR12 failure and costs controlling for member demographics (i.e., age, sex, race, rural residence); type of DAA and adherence; clinical characteristics (e.g., comorbid conditions, advanced liver disease); and the implementation of changes to a prior authorization program. RESULTS Of 934 Medicaid members eligible for treatment with DAAs between January 1, 2014, and June 30, 2016, 906 received DAA treatment, 40.6% (368/906) had reported SVR12 outcomes, and 59.4% (n = 538) did not have a reported SVR recorded. Of those with reported SVR12 outcomes, patients were 53.1 ± 9.7 years of age, 51.1% were male, 8.4% had SVR12 failure, and each member had mean costs of $140,283 ± $52,779. Multivariable analyses indicated higher odds of SVR12 failure was independently associated with cirrhosis (OR [decompensated] = 6.69 and OR [compensated] = 3.52, P < 0.001), while males had higher odds of failure than females (OR = 3.34, P < 0.010). No significant difference in SVR12 failure was noted, according to DAA type or a medication adherence threshold of > 95%. Ledipasvir/sofosbuvir was independently associated with lower costs (exp[b] = 0.81; P < 0.001) compared with sofosbuvir, while higher costs were associated with decompensated cirrhosis (exp[b] = 1.22; P < 0.001) and treatment failure (exp[b] = 1.18, P < 0.010). In an analysis including members without reported SVR12 outcomes, decompensated and compensated cirrhosis had lower odds (P < 0.001) of no reported SVR12 from ambulatory clinic settings. CONCLUSIONS Almost 60% of Medicaid members receiving DAA treatment did not have a final reported SVR12 outcome. Among those with viral load measurements, treatment success was high and both decompensated and compensated cirrhosis were independently associated with significantly higher odds of treatment failure. Addressing a loss to follow-up among HCV patients and curtailing the development of cirrhosis to improve treatment success may warrant interventions that improve access to care and remove barriers that impede treatment initiation and completion. DISCLOSURES No outside funding supported this study. Pham, Keast, Holderread, Nesser, and Skrepnek disclose either employment by the Oklahoma Health Care Authority or contractual work for this employer. Pham discloses fellowship funding from Purdue Pharma unrelated to this study. Keast and Skrepnek disclose research grant funding from Gilead Sciences and Abbvie. Holderread also reports grant funding from Gilead Sciences and fees from PRIME Education. Thompson, Farmer, and Rathbun have nothing to disclose.
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Affiliation(s)
- Timothy T Pham
- 1 University of Oklahoma College of Pharmacy, Oklahoma City
| | | | - Kevin C Farmer
- 1 University of Oklahoma College of Pharmacy, Oklahoma City
| | - David M Thompson
- 2 University of Oklahoma College of Public Health, Oklahoma City
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20
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Manzardo C, Londoño MC, Castells LL, Testillano M, Luis Montero J, Peñafiel J, Subirana M, Moreno A, Aguilera V, Luisa González-Diéguez M, Calvo-Pulido J, Xiol X, Salcedo M, Cuervas-Mons V, Manuel Sousa J, Suarez F, Serrano T, Ignacio Herrero J, Jiménez M, Fernandez JR, Giménez C, Del Campo S, Esteban-Mur JI, Crespo G, Moreno A, de la Rosa G, Rimola A, Miro JM. Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study. Am J Transplant 2018; 18:2513-2522. [PMID: 29963780 DOI: 10.1111/ajt.14996] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 06/04/2018] [Accepted: 06/22/2018] [Indexed: 01/25/2023]
Abstract
Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients.
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Affiliation(s)
| | - Maria C Londoño
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - LLuís Castells
- CIBEREHD, Barcelona, Spain.,Liver Unit, Internal Medicine Department, Hospital Vall d'Hebrón, Universitat Autónoma de Barcelona, Barcelona, Spain
| | | | - José Luis Montero
- CIBEREHD, Barcelona, Spain.,Hospital Universitario Reina Sofía-IMIBIC Córdoba, Cordoba, Spain
| | - Judit Peñafiel
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Marta Subirana
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Ana Moreno
- Hospital Universitario Ramón y Cajal-IRYCIS, Madrid, Spain
| | | | | | | | - Xavier Xiol
- Hospital de Bellvitge-IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | | | | | | | - Trinidad Serrano
- CIBEREHD, Barcelona, Spain.,Hospital Universitario Lozano Blesa, ISS Aragón, Zaragoza, Spain
| | - Jose Ignacio Herrero
- CIBEREHD, Barcelona, Spain.,Clínica Universidad de Navarra, IdiSNA, Pamplona, Spain
| | | | - José R Fernandez
- Servicio de Digestivo, Hospital Universitario Cruces, Barakaldo, Barakaldo
| | | | | | - Juan I Esteban-Mur
- CIBEREHD, Barcelona, Spain.,Liver Unit, Internal Medicine Department, Hospital Vall d'Hebrón, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Asunción Moreno
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Antoni Rimola
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.,CIBEREHD, Barcelona, Spain
| | - Jose M Miro
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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21
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Saab S, Challita Y, Chen PH, Jimenez MA, Lee AD, Saab EG, Ahn T, Choi G, Durazo FA, El-Kabany MM, Han SHB, Grotts J, Agopian VG, Busuttil RW. Elimination of Hepatitis C in Liver Transplant Recipients. J Clin Transl Hepatol 2018; 6:247-250. [PMID: 30271735 PMCID: PMC6160303 DOI: 10.14218/jcth.2017.00079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 02/20/2018] [Accepted: 02/26/2018] [Indexed: 12/11/2022] Open
Abstract
Background and Aims: Recurrent hepatitis C (HCV) disease in liver transplant (LT) recipients is associated with significant morbidity and mortality. With the availability of noninterferon-based therapy, eliminating HCV may be achievable in LT recipients. Methods: We studied all consecutive recipients who underwent LT at the University of California Los Angeles between January 2005 and June 2017. We collected data on date of transplant and last follow-up, as well as laboratory values. We also recorded type and timing of antiviral therapy relative to LT. Analyses were performed to assess the proportion of LT recipients who are viremic after transplant. Results: Six hundred thirty-four patients underwent LT with a diagnosis of HCV. There was a statistically significant trend for patients to be cured before (p < 0.001) and after liver transplantation (p < 0.001) for the study period of 2014 to 2016 relative to 2005 and 2013, respectively. Of the 634 recipients eligible for therapy, 8% and 74% were treated within 12 months of transplant for the study periods 2005 to 2013 and 2014 to 2016, respectively. There was a significant decrease between the two study periods in the proportion of patients undergoing re-LT 1 year after the original LT: 5.5% (n = 28/510) and 1.5% (n = 2/124) respectively for study periods 2005 to 2013 and 2014 to 2016 respectively (p = 0.011). Conclusions: The proportion of LT recipients who are viremic has decreased over time. Eliminating HCV in LT recipients is feasible after the introduction of direct-acting agents. Curing HCV should translate to improved clinical outcomes in LT recipients who were transplanted for HCV infection with longer follow-up. Preliminary results suggest the decreased need for transplant in the direct-acting agents era.
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Affiliation(s)
- Sammy Saab
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
- *Correspondence to: Sammy Saab, Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA. Tel: +1-310-206-6705, Fax: +1-310-206-4197, E-mail:
| | - Youssef Challita
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
| | - Phillip H. Chen
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Melissa A. Jimenez
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Alex D. Lee
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Elena G. Saab
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Timothy Ahn
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Gina Choi
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Francisco A. Durazo
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Mohamed M. El-Kabany
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Steven-Huy B. Han
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Jonathan Grotts
- Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
| | - Vatche G. Agopian
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
| | - Ronald W. Busuttil
- Department of Surgery at the University of California at Los Angeles, Los Angeles, California, USA
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22
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Hong CM, Liu CH, Su TH, Yang HC, Chen PJ, Chen YW, Kao JH, Liu CJ. Real-world effectiveness of direct-acting antiviral agents for chronic hepatitis C in Taiwan: Real-world data. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2018; 53:569-577. [PMID: 30316726 DOI: 10.1016/j.jmii.2018.09.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 09/12/2018] [Accepted: 09/18/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND/PURPOSE Treatment of chronic hepatitis C (CHC) has entered a new era since the introduction of direct-acting antiviral agents (DAAs). Numerous clinical trials have shown that treatment response as well as tolerability of DAAs are superior to those of conventional therapy with pegylated interferon and ribavirin. However, the results of clinical trials may not be directly applied to real-world practice. Therefore our study tried to investigate the effectiveness of various DAA regimens in Taiwanese patients with chronic hepatitis C. METHODS We performed a retrospective study on 400 CHC patients. The primary endpoint was undetectable HCV RNA (an HCV RNA level of <25 IU/mL) at 12 weeks posttreatment (SVR12). The results were stratified by different DAAs and HCV genotypes. RESULTS Genotype 1b was the major genotype (297, 74.3%), followed by genotype 2 (65, 16.3%). The patients were treated according to HCV genotype, clinical practice and reimbursement guidelines. The SVR12 rates of 57 patients treated with sofosbuvir and ribavirin, 107 treated with ledipasvir/sofosbuvir with or without ribavirin, 60 treated with daclatasvir/asunaprevir with or without ribavirin, 129 treated with ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin, 12 treated with sofosbuvir/daclatasvir with or without ribavirin, and 35 treated with elbasvir/grazoprevir were 98.2%, 97.2%, 85.0%, 97.7%, 100.0%, and 100.0%, respectively. CONCLUSIONS The overall SVR12 rates in our study were comparable with those in previous pivotal trials. DAAs are generally safe. The interaction of HBV and HCV during DAA therapy and the observation of de novo HCC development and HCC recurrence during or after DAAs warrants additional studies.
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Affiliation(s)
- Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Wen Chen
- Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Chun-Jen Liu
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
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23
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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.
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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
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24
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Agarwal K, Castells L, Müllhaupt B, Rosenberg WMC, McNabb B, Arterburn S, Camus G, McNally J, Stamm LM, Brainard DM, Mani Subramanian G, Mariño Z, Dufour JF, Forns X. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol 2018; 69:603-607. [PMID: 29886154 DOI: 10.1016/j.jhep.2018.05.039] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 05/02/2018] [Accepted: 05/29/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant. METHODS Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naïve with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. RESULTS A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naïve, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. CONCLUSIONS Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis. LAY SUMMARY Sofosbuvir/velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.
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Affiliation(s)
- Kosh Agarwal
- Institute of Liver Studies, King's College Hospital NHS Trust Foundation, London, UK
| | - Lluís Castells
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, CIBEREHD, Univerisitat Autònoma de Barcelona, Barcelona, Spain
| | - Beat Müllhaupt
- Department for Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | | | | | | | | | | | | | | | | | - Zoe Mariño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Xavier Forns
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain.
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25
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Mansour M, Hill L, Kerr J. Safety and effectiveness of direct acting antivirals for treatment of hepatitis C virus in patients with solid organ transplantation. Transpl Infect Dis 2018; 20:e12972. [PMID: 30080955 DOI: 10.1111/tid.12972] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 07/22/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND The direct acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection have sustained virologic response (SVR) rates of greater than 90% in most patients. However, data evaluating DAA use in transplant patients are limited. The goal of this study was to evaluate the effectiveness and safety of HCV treatment in this high-risk population. METHODOLOGY This single-center retrospective study included liver, kidney, lung, and/or heart transplant patients who were treated for HCV infection with DAAs. The primary objective was to identify drug-drug interactions between DAAs and immunosuppressants by comparing immunosuppression dosages and levels at baseline and week 4 of HCV treatment. As secondary objectives, we described the percentage of patients with new or worsening rejection and/or graft dysfunction during HCV treatment, and the percentage of study patients who achieved SVR. RESULTS Of the 108 patients included, the majority had liver (76%) or kidney (13%) transplants. Simeprevir plus sofosbuvir was the most commonly prescribed HCV treatment (33.9%) and tacrolimus was the most common immunosuppressant (91%). We did not detect a statistically significant difference in immunosuppression dosages or levels during HCV treatment. Furthermore, only one patient (<1%) experienced rejection and five patients (4.6%) had six episodes of graft dysfunction while on DAAs. Efficacy was high with 98% of patients achieving SVR. CONCLUSION DAAs appear to be safe and effective for HCV treatment in patients with a history of liver and/or kidney transplantation. More data are needed to evaluate DAAs in lung and/or heart transplant patients.
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Affiliation(s)
- Marlina Mansour
- Department of Pharmacy Services, UC San Diego Health, La Jolla, California
| | - Lucas Hill
- Department of Hepatology, UC San Diego Health, San Diego, California
| | - Janice Kerr
- Abdominal Transplantation, UC San Diego Health, La Jolla, California
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26
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Nogueras López F, López Garrido A, Ortega Suazo EJ, Vadillo Calles F, Valverde López F, Espinosa Aguilar MD. Therapy With Direct-Acting Antiviral Agents for Hepatitis C in Liver Transplant Recipients. Transplant Proc 2018; 50:631-633. [PMID: 29579872 DOI: 10.1016/j.transproceed.2017.09.057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 09/21/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND Recurrent infection with the hepatitis C virus (HCV) after liver transplantation (LT) is associated with decreased graft and patient survival. Direct-acting antiviral (DAA) therapies have changed the landscape of HCV due to their excellent safety profile and cure rates. Our aim was to evaluate the efficacy and tolerability of antiviral therapy in recurrent HCV after LT with DAA therapy. METHODS Our retrospective analysis included 46 LT recipients with HCV recurrence. Patients received therapy with DAA therapy between November 2014 and May 2016. Stage of fibrosis was documented by transient elastography (FibroScan). RESULTS Thirty-three of the patients were men (71.7%), with a mean age of 59.6 years. Most patients were infected with HCV genotype 1 (71.7%) (1a = 7, 1b = 26) or genotype 3 (19.6%). Cirrhosis was present in 10 (21.7%). The most frequent immunosuppression regimen was tacrolimus + mycophenolate mofetil (MMF) (41.3%). Most patients received sofosbuvir + simeprevir (SOF+SMV) (n = 13, 28.3%) and sofosbuvir + daclatasvir (SOF+DCV) (n = 15, 32.6%). A virologic response at posttreatment week 12 was detected in 93.8% of the patients. Two patients failed treatment (1 had resistance-associated variants [RAVs] Y93H in NS5A). Three patients died due to chronic rejection, acute arterial thrombosis, and spontaneous bacterial peritonitis. Adverse events were observed in 23 patients (50%). The most common events were asthenia in 17 (37%) and headache in 6 (13%) patients. One patient discontinued treatment due to serious adverse events attributable to the drug's interaction with tacrolimus. CONCLUSIONS DAAs are safe and effective for use in treating HCV recurrence after LT, with results similar to those seen in the general population, including patients with cirrhosis.
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Affiliation(s)
- F Nogueras López
- Department of Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain.
| | - A López Garrido
- Department of Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - E J Ortega Suazo
- Department of Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - F Vadillo Calles
- Department of Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - F Valverde López
- Department of Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
| | - M D Espinosa Aguilar
- Department of Hepatology, "Virgen de las Nieves" University Hospital, Granada, Spain
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27
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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.
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28
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Kogiso T, Tokushige K. Key roles of hepatologists in successful liver transplantation. Hepatol Res 2018; 48:608-621. [PMID: 29722107 DOI: 10.1111/hepr.13183] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 04/18/2018] [Accepted: 04/21/2018] [Indexed: 12/14/2022]
Abstract
Liver transplantation (LT) has been carried out for acute liver failure, end-stage liver disease, and congenital metabolic disease in more than 7000 cases in Japan. Liver transplantation has been established as a treatment option, and survival rates have improved. In 2016, a new registration/allocation policy and a new scoring system for deceased donor LT were established. The management of perioperative patients and preoperative therapy for liver failure, nutrition, and preventing infection were upgraded. Moreover, methods for preventing disease recurrence, and treating hepatitis C and B have been developed and are particularly crucial for good outcomes in LT. Treatment of the complications of obesity, lifestyle-related diseases, and malignancy is also required post-LT. Managing patients after LT contributes to better survival and quality of life. The role of hepatologists is becoming broader and more important.
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Affiliation(s)
- Tomomi Kogiso
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Katsutoshi Tokushige
- Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan
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29
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The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2017.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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30
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Beinhardt S, Al-Zoairy R, Kozbial K, Stättermayer AF, Maieron A, Stauber R, Strasser M, Zoller H, Graziadei I, Rasoul-Rockenschaub S, Trauner M, Ferenci P, Hofer H. Long-term follow-up of ribavirin-free DAA-based treatment in HCV recurrence after orthotopic liver transplantation. Liver Int 2018; 38:1188-1197. [PMID: 29197145 DOI: 10.1111/liv.13652] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 11/18/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Excellent efficacy and safety profile of second-generation DAA combinations improved treatment of chronic hepatitis C (HCV) as well as in HCV recurrence after orthotopic liver transplantation (OLT). The need of ribavirin addition is under debate as anaemia and decreased renal function are prevalent in transplant cohorts. The aim of this study was thus to assess safety and long-term efficacy of RBV-free DAA combinations in HCV-recurrent patients after OLT. PATIENTS & METHODS A total of 62 OLT recipients (male: 50%/81%; age: 60.7 ± 8.5 years [mean ± SD]; GT - 1: 48, GT - 3: 9, GT - 4: 5; cirrhosis: 34%/55% [7%/21% decompensated], fibrosing cholestatic hepatitis: 1%/2%) received RBV-free treatment with second-generation DAA combinations: sofosbuvir (SOF)/daclatasvir (DCV): 42%/68%, SOF/simeprevir (SMV): 10%/16%, SOF/ledipasvir (LDV): 6%/10% and PrOD: 4%/7%. RESULTS Data of at least 96 weeks of FUP after treatment cessation (mean: 120; up to 167 weeks) were analysed. All patients showed on-treatment response. By intention-to-treat (ITT) analysis, SVR12 was 97% (60/62, GT-1a: 11/11 [100%]; 1b: 33/34 [97%]; 1g: 1/1 [100%]; subtype not specified: 2/2 [100%]; GT3a: 9/9 [100%]; GT4: 4/5 [80%]) compared to SVR96 of 89% (55/62). No late relapses occurred. In total, 16 severe adverse events occurred, including two newly diagnosed carcinoma (lung cancer, hepatocellular carcinoma). Six patients died; one at treatment week 24 (HCV-RNA undetectable) and five during treatment-free FUP and after achieving SVR (SVR4: N = 1, SVR12: N = 3, after SVR96: N = 1 respectively). Reasons for death were: multi-organ failure (N = 4), impaired graft function (N = 1) and unknown (N = 1). CONCLUSION RBV-free DAA combinations for the treatment of HCV recurrence after OLT are highly efficacious and well tolerated. Our long-term data show that viral eradication is durable but not necessarily translated into beneficial long-term clinical outcome.
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Affiliation(s)
- Sandra Beinhardt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine 2, Division of Gastroenterology and Hepatology, Universitätsklinikum, St. Pölten, Austria
| | - Ramona Al-Zoairy
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Karin Kozbial
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Albert F Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Andreas Maieron
- Department of Internal Medicine 2, Division of Gastroenterology and Hepatology, Universitätsklinikum, St. Pölten, Austria.,Department of Gastroenterology, Hospital Elisabethinen, Linz, Austria
| | - Rudolf Stauber
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Michael Strasser
- Department of Gastroenterology and Hepatology, Paracelsus Medical University Salzburg, Salzburg, Austria
| | - Heinz Zoller
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Ivo Graziadei
- Department of Internal Medicine, Landeskrankenhaus Hall, Hall/Tirol, Austria
| | | | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Harald Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Klinikum Wels-Grieskirchen, Wels, Austria
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31
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Campos-Varela I, Agudelo EZ, Terrault NA. Outcomes of antiviral treatment in hepatitis C virus liver transplant patients off immunosuppression in the direct acting antivirals era: A case series. Clin Transplant 2018; 32:e13303. [PMID: 29851150 DOI: 10.1111/ctr.13303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2018] [Indexed: 11/28/2022]
Abstract
BACKGROUND Clearance of hepatitis C virus (HCV) under antiviral therapy, including direct-acting antivirals (DAAs), has been associated with higher risk of rejection. Whether patients who are not on immunosuppression (IS) during DAA therapy are at higher risk of rejection is unknown. METHODS Four transplant recipients who were off IS and treated with DAA therapy were identified. RESULTS All patients were genotype 1 infection and treated for 12 weeks with sofosbuvir/ledipasvir/ribavirin. At the time of DAA therapy, patients were off IS for a median of 9.5 years. Time from liver transplant (LT) to treatment was 12.9 years. Median baseline ALT was 70 IU/L, at follow-up week 12 was 18 IU/L. No signs of rejection were observed during DAA therapy or follow-up after the end of therapy. All 4 patients obtained sustained virological response. CONCLUSION Direct-acting antivirals therapy in HCV patients off IS post-LT can be successfully undertaken without the need to restart IS.
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Affiliation(s)
- Isabel Campos-Varela
- Universidade de Santiago de Compostela (CLINURSID), Santiago de Compostela, Spain.,Department of Internal Medicine, Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Eliana Z Agudelo
- Department of Medicine, University of California, San Francisco, CA, USA.,Department of Surgery, University of California, San Francisco, CA, USA
| | - Norah A Terrault
- Department of Medicine, University of California, San Francisco, CA, USA.,Department of Surgery, University of California, San Francisco, CA, USA
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32
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Efficacy And Safety of Sofosbuvir Based Regimens For Treatment of Hepatitis C Recurrence After Living Donor Liver Transplantation: An Experience From India. J Clin Exp Hepatol 2018; 8:121-124. [PMID: 29892173 PMCID: PMC5992320 DOI: 10.1016/j.jceh.2017.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 08/24/2017] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on "real world" experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. MATERIAL AND METHODS Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin (n = 58), Sofosbuvir + Ledipasvir ± Ribavirin (n = 5), Sofosbuvir + Daclatasvir ± Ribavirin (n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). RESULTS A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin < 8 g/dl; two patients complained fatigue in absence of anemia. CONCLUSION Sofosbuvir based regimens are safe and highly effective in treatment of HCV recurrence after LDLT.
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33
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Anty R, Favre G, Coilly A, Rossignol E, Houssel-Debry P, Duvoux C, De Ledinghen V, Di Martino V, Leroy V, Radenne S, Kamar N, Canva V, D'Alteroche L, Durand F, Dumortier J, Lebray P, Besch C, Tran A, Canivet CM, Botta-Fridlund D, Montialoux H, Moreno C, Conti F, Silvain C, Perré P, Habersetzer F, Abergel A, Debette-Gratien M, Dharancy S, Esnault VLM, Fougerou-Leurent C, Cagnot C, Diallo A, Veislinger A, Danjou H, Samuel D, Pageaux GP, Duclos-Vallée JC. Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study. Aliment Pharmacol Ther 2018; 47:1682-1689. [PMID: 29665081 DOI: 10.1111/apt.14639] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/09/2018] [Accepted: 03/07/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.
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Aiza-Haddad I, Ballesteros-Amozurrutia A, Borjas-Almaguer OD, Castillo-Barradas M, Castro-Narro G, Chávez-Tapia N, Chirino-Sprung RA, Cisneros-Garza L, Dehesa-Violante M, Flores-Calderón J, Flores-Gaxiola A, García-Juárez I, González-Huezo MS, González-Moreno EI, Higuera-de la Tijera F, Kershenobich-Stalnikowitz D, López-Méndez E, Malé-Velázquez R, Marín-López E, Mata-Marín JA, Méndez-Sánchez N, Monreal-Robles R, Moreno-Alcántar R, Muñoz-Espinosa L, Navarro-Alvarez S, Pavia-Ruz N, Pérez-Ríos AM, Poo-Ramírez JL, Rizo-Robles MT, Sánchez-Ávila JF, Sandoval-Salas R, Torre A, Torres-Ibarra R, Trejo-Estrada R, Velarde-Ruiz Velasco JA, Wolpert-Barraza E, Bosques-Padilla F. The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 83:275-324. [PMID: 29803325 DOI: 10.1016/j.rgmx.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/17/2017] [Accepted: 11/02/2017] [Indexed: 12/12/2022]
Abstract
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
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Affiliation(s)
| | | | - O D Borjas-Almaguer
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - G Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - L Cisneros-Garza
- Centro de Enfermedades Hepáticas del Hospital San José, Monterrey, Nuevo León, México
| | | | - J Flores-Calderón
- Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | | | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - E I González-Moreno
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | | | - E López-Méndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática, Guadalajara, Jalisco, México
| | | | - J A Mata-Marín
- Hospital de Infectología del Centro Médico Nacional «La Raza», Ciudad de México, México
| | | | - R Monreal-Robles
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - L Muñoz-Espinosa
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - N Pavia-Ruz
- Hospital Infantil de México «Federico Gómez», Ciudad de México, México
| | - A M Pérez-Ríos
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J L Poo-Ramírez
- Clínica San Jerónimo de Salud Hepática y Digestiva, Ciudad de México, México
| | | | - J F Sánchez-Ávila
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - A Torre
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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Durand CM, Bowring MG, Thomas AG, Kucirka LM, Massie AB, Cameron A, Desai NM, Sulkowski M, Segev DL. The Drug Overdose Epidemic and Deceased-Donor Transplantation in the United States: A National Registry Study. Ann Intern Med 2018; 168:702-711. [PMID: 29710288 PMCID: PMC6205229 DOI: 10.7326/m17-2451] [Citation(s) in RCA: 157] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The epidemic of drug overdose deaths in the United States has led to an increase in organ donors. OBJECTIVE To characterize donors who died of overdose and to analyze outcomes among transplant recipients. DESIGN Prospective observational cohort study. SETTING Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017. PARTICIPANTS 138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers. MEASUREMENTS The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score-weighted standardized risk differences (sRDs). RESULTS A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV) (18.3%), and increased-infectious risk donors (IRDs) (56.4%). Standardized 5-year patient survival was similar for ODD organ recipients compared with TDD organ recipients (sRDs ranged from 3.1% lower to 3.9% higher survival) and MDD organ recipients (sRDs ranged from 2.1% to 5.2% higher survival). Standardized 5-year graft survival was similar between ODD and TDD grafts (minimal difference for kidneys and lungs, marginally lower [sRD, -3.2%] for livers, and marginally higher [sRD, 1.9%] for hearts). Kidney discard was higher for ODDs than TDDs (sRD, 5.2%) or MDDs (sRD, 1.5%); standardization for HCV and IRD status attenuated this difference. LIMITATION Inability to distinguish between opioid and nonopioid overdoses. CONCLUSION In the United States, transplantation with ODD organs has increased dramatically, with noninferior outcomes in transplant recipients. Concerns about IRD behaviors and hepatitis C among donors lead to excess discard that should be minimized given the current organ shortage. PRIMARY FUNDING SOURCE National Institutes of Health.
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Affiliation(s)
- Christine M Durand
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Mary G Bowring
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Alvin G Thomas
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Lauren M Kucirka
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Allan B Massie
- Johns Hopkins University School of Medicine and Johns Hopkins School of Public Health, Baltimore, Maryland (A.B.M.)
| | - Andrew Cameron
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Niraj M Desai
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Mark Sulkowski
- Johns Hopkins University School of Medicine, Baltimore, Maryland (C.M.D., M.G.B., A.G.T., L.M.K., A.C., N.M.D., M.S.)
| | - Dorry L Segev
- Johns Hopkins University School of Medicine and Johns Hopkins School of Public Health, Baltimore, Maryland, and Scientific Registry of Transplant Recipients, Minneapolis, Minnesota (D.L.S.)
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Suda G, Ogawa K, Morikawa K, Sakamoto N. Treatment of hepatitis C in special populations. J Gastroenterol 2018; 53:591-605. [PMID: 29299684 PMCID: PMC5910474 DOI: 10.1007/s00535-017-1427-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 12/19/2017] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy. In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.
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Affiliation(s)
- Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
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Shaffer AA, Durand CM. Solid Organ Transplantation for HIV-Infected Individuals. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2018; 10:107-120. [PMID: 29977166 DOI: 10.1007/s40506-018-0144-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Purpose of Review The prevalence of end-stage organ disease is increasing among HIV-infected (HIV+) individuals. Individuals with well-controlled HIV on antiretroviral therapy (ART), without active opportunistic infections or cancer, and with specified minimum CD4 cell counts are appropriate transplant candidates. Infectious disease clinicians can improve access to transplantation for these patients and optimize management pre- and post-transplant. Recent Findings Clinical trials and registry-based studies demonstrate excellent outcomes for select HIV+ kidney and liver transplant recipients with similar patient and graft survival as HIV-uninfected patients. Elevated allograft rejection rates have been observed in HIV+ individuals; this may be related to a dysregulated immune system or drug interactions. Lymphocyte-depleting immunosuppression has been associated with lower rejection rates without increased infections using national registry data. Hepatitis C virus (HCV) coinfection has been associated with worse outcomes, however improvements are expected with direct-acting antivirals. Summary Solid organ transplantation should be considered for HIV+ individuals with end-stage organ disease. Infectious disease clinicians can optimize ART to avoid pharmacoenhancers, which interact with immunosuppression. The timing of HCV treatment (pre- or post-transplant) should be discussed with the transplant team. Finally, organs from HIV+ donors can now be considered for HIV+ transplant candidates, within research protocols.
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Affiliation(s)
- Ashton A Shaffer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD
| | - Christine M Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
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Kwo P, Fried MW, Reddy KR, Soldevila-Pico C, Khemichian S, Darling J, Zamor PJ, Napoli AA, Anduze-Faris B, Brown RS. Daclatasvir and sofosbuvir treatment of decompensated liver disease or post-liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real-world cohort. Hepatol Commun 2018; 2:354-363. [PMID: 29619415 PMCID: PMC5880197 DOI: 10.1002/hep4.1156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/08/2017] [Accepted: 01/11/2018] [Indexed: 12/12/2022] Open
Abstract
We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child‐Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12‐month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks. Sustained virologic response (SVR) at posttreatment week 12 (SVR12) was measured. Assessments adhered to local standards. One patient (prior Child‐Pugh class C who improved to class B) enrolled by exemption was included in the overall data but not the class C cohort efficacy/safety data. Of the 77 treated patients, including 62 liver transplant recipients (genotype 1, n = 43, 69%; genotype 3, n = 16, 26%) and 14 patients with Child‐Pugh class C cirrhosis (genotype 1, n = 4, 29%; genotype 3, n = 10, 71%), 63 (82%) completed treatment. SVR12 rates by modified intention‐to‐treat analysis (excluding nonvirologic failures lost to follow‐up and withdrawal [consent/no reason]) in the overall, liver transplant, and Child‐Pugh class C cohorts were 84% (n = 64/76), 90% (n = 56/62), and 62% (n = 8/13), respectively. Rates increased to 96% (n = 64/67), 97% (n = 56/58), and 89% (n = 8/9), respectively, in patients with available virologic data (including early discontinuations); 22/23 patients with genotype 3 (96%) achieved SVR12. Single cases of virologic nonresponse and relapse (both in liver transplant recipients with genotype 1) and viral breakthrough (Child‐Pugh class C; genotype 3) occurred. Six patients died, 10 had adverse events leading to discontinuation, and 30 experienced serious adverse events. Conclusion: Daclatasvir plus sofosbuvir, with/without ribavirin, provided high SVR12 rates and was generally well tolerated in patients with life‐threatening disease and high unmet needs. (Hepatology Communications 2018;2:354‐363)
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Affiliation(s)
- Paul Kwo
- Division of Gastroenterology and Hepatology Stanford University School of Medicine Palo Alto CA
| | - Michael W Fried
- Department of Medicine University of North Carolina School of Medicine Chapel Hill NC
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology University of Pennsylvania Philadelphia PA
| | | | - Saro Khemichian
- Department of Medicine, Keck School of Medicine University of Southern California Los Angeles CA
| | - Jama Darling
- Department of Medicine University of North Carolina School of Medicine Chapel Hill NC
| | | | | | | | - Robert S Brown
- Department of Medicine Weill Cornell Medicine New York NY
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International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 2018; 101:956-967. [PMID: 28437388 DOI: 10.1097/tp.0000000000001704] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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40
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Nookala AU, Crismale J, Schiano T, Te H, Ahn J, Robertazzi S, Rodigas C, Satoskar R, Kc M, Hassan M, Smith C. Direct-acting antiviral regimens are safe and effective in the treatment of hepatitis C in simultaneous liver-kidney transplant recipients. Clin Transplant 2018; 32:e13198. [PMID: 29323755 DOI: 10.1111/ctr.13198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2018] [Indexed: 01/17/2023]
Abstract
Hepatitis C (HCV) remains the single most common etiology of end-stage liver disease leading to simultaneous liver/kidney transplant (SLKT) and has worse post-transplant survival compared to non-HCV patients. We aim to assess the effectiveness and tolerance of the all-oral direct-acting antiviral (DAA) agents with or without ribavirin (RBV) in the treatment of HCV recurrence post-SLKT. Thirty-four patients were studied retrospectively, composed predominantly of treatment-naïve (73.5%) non-Caucasian (61.8%) males (82.4%) infected with genotype 1a (64.7%). 94.1% reached a sustained virologic response (SVR) after 24 weeks (32/34 patients), without difference between 12 and 24 weeks of therapy. 64.7% had no clinical side effects. Three deaths occurred, all unrelated to treatment. One patient had liver rejection; tacrolimus was increased and prednisone was initiated while HCV treatment was continued and the patient ultimately achieved SVR. No liver graft losses. No kidney rejection or losses. We demonstrated that DAA combinations with or without RBV result in a remarkable SVR rate and tolerated in the majority of the studied SLKT patients. It is safe to wait to treat until post-kidney transplant and therefore increase the donor pool for these patients. Our cohort is ethnically diverse, making our results generalizable.
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Affiliation(s)
| | | | | | - Helen Te
- University of Chicago Medicine, Chicago, IL, USA
| | - Joseph Ahn
- Oregon Health and Sciences University, Portland, OR, USA
| | | | - Colleen Rodigas
- MedStar Georgetown Transplant Institute, Washington, DC, USA
| | - Rohit Satoskar
- MedStar Georgetown Transplant Institute, Washington, DC, USA
| | - Mandip Kc
- University of Minnesota, Minneapolis, MN, USA
| | | | - Coleman Smith
- MedStar Georgetown Transplant Institute, Washington, DC, USA
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Chute DF, Chung RT, Sise ME. Direct-acting antiviral therapy for hepatitis C virus infection in the kidney transplant recipient. Kidney Int 2018; 93:560-567. [PMID: 29325996 DOI: 10.1016/j.kint.2017.10.024] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/12/2017] [Accepted: 10/05/2017] [Indexed: 12/26/2022]
Abstract
Hepatitis C virus infection (HCV) is a common comorbidity in patients who have undergone kidney transplantation and is associated with increased morbidity and mortality compared with recipients who do not have chronic HCV infection. Because interferon-α-based therapies can precipitate acute rejection, they are relatively contraindicated after kidney transplantation. Thus, the majority of kidney transplant recipients with HCV remain untreated. There are now all-oral, interferon-free direct-acting antiviral therapies for HCV infection that are extremely effective and well tolerated in the general population. Recent reports in the literature demonstrate that direct-acting antiviral therapies effectively cured HCV in 406 of 418 kidney transplant recipients (97%); the majority were treated with sofosbuvir-based regimens. Smaller numbers of kidney transplant recipients have been treated with paritaprevir-ritonavir, ombitasvir and dasabuvir, elbasvir-grazoprevir, or glecaprevir-pibrentasvir with excellent success. Direct-acting antiviral therapies were well tolerated and did not increase the rate of acute rejection. The latest advances include approval of regimens that can treat patients with advanced allograft dysfunction (eGFR < 30 ml/min per 1.73 m2) and "pan-genotypic" regimens that have activity against all 6 major genotypes of HCV. This review summarizes what is known about the epidemiology of HCV infection in kidney transplant recipients, and presents the landscape of direct-acting antiviral therapies and areas in need of further investigation.
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Affiliation(s)
- Donald F Chute
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Solomon SS, Sulkowski MS, Amrose P, Srikrishnan AK, McFall AM, Ramasamy B, Kumar MS, Anand S, Thomas DL, Mehta SH. Directly observed therapy of sofosbuvir/ribavirin +/- peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT). J Viral Hepat 2018; 25:37-46. [PMID: 28719029 PMCID: PMC5743582 DOI: 10.1111/jvh.12761] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 07/03/2017] [Indexed: 12/14/2022]
Abstract
We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Fifty participants were randomized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin (SOF+PR) for 12 weeks (Arm 1) vs sofosbuvir+ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on-treatment viral loads were performed. Median age was 46 years. All were male and 20% had significant fibrosis/cirrhosis. All self-reported history of injection drug use, 18% recent noninjection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25=88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25=60%; P=.05). Among those completing SOF+R, SVR12 was significantly less common in participants reporting ongoing substance use (36% vs 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible; however, achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct-acting antivirals is warranted.
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Affiliation(s)
- S S Solomon
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | - M S Sulkowski
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - P Amrose
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | - A K Srikrishnan
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | - A M McFall
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - B Ramasamy
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | - M S Kumar
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | - S Anand
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | - D L Thomas
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - S H Mehta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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44
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Lionetti R, Calvaruso V, Piccolo P, Mancusi RL, Mazzarelli C, Fagiuoli S, Montalbano M, Lenci I, Carrai P, Guaraldi G, Visco-Comandini U, Milana M, Biolato M, Loiacono L, Valente G, Craxì A, Angelico M, D'offizi G. Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study. Clin Transplant 2017; 32. [PMID: 29193356 DOI: 10.1111/ctr.13165] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). METHODS All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). RESULTS Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ± 7.2 years, 83.9% genotype 1, 81.6% cirrhosis); 52 (59.8%) received RBV. Overall, 79 obtained SVR12 (90.8%): 100% in F3 and 88.7% in cirrhotics (91.5% in Child-Pugh A, 83.3% in Child-Pugh B and C). According to the treatment group, SVR was 80% in DCV + SOF group and 98.1% in SOF + DCV + RBV. Two virological relapses occurred during follow-up in cirrhotic patients who received DCV + SOF. Four cirrhotic patients in DCV + SOF group and 1 in DCV + SOF + RBV group died on treatment. CONCLUSION An extended course of SOF plus DCV for 24 weeks, with or without RBV, is effective and well tolerated for the treatment of post-LT HCV recurrence with severe fibrosis.
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Affiliation(s)
- Raffaella Lionetti
- Infectious and Liver Diseases, Lazzaro Spallanzani National Infectious Disease Institute, Rome, Italy
| | | | - Paola Piccolo
- Department of Internal Medicine, San Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy.,Hepatology Unit, Tor Vergata University, Rome, Italy
| | | | - Chiara Mazzarelli
- Gastroenterology and Liver Unit, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Liver Unit, San Giovanni XXIII Hospital, Bergamo, Italy
| | - Marzia Montalbano
- Infectious and Liver Diseases, Lazzaro Spallanzani National Infectious Disease Institute, Rome, Italy
| | - Ilaria Lenci
- Hepatology Unit, Tor Vergata University, Rome, Italy
| | - Paola Carrai
- Liver Transplantation Unit, Pisa Hospital, Pisa, Italy
| | | | - Ubaldo Visco-Comandini
- Infectious and Liver Diseases, Lazzaro Spallanzani National Infectious Disease Institute, Rome, Italy
| | | | - Marco Biolato
- Liver Transplant Medicine, Fondazione Policlinico Gemelli Catholic University, Rome, Italy
| | - Laura Loiacono
- Infectious and Liver Diseases, Lazzaro Spallanzani National Infectious Disease Institute, Rome, Italy
| | | | - Antonio Craxì
- Gastroenterology Unit, University of Palermo, Palermo, Italy
| | | | - Gianpiero D'offizi
- Infectious and Liver Diseases, Lazzaro Spallanzani National Infectious Disease Institute, Rome, Italy
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45
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Sugawara Y, Hibi T. Direct-acting agents for hepatitis C virus before and after liver transplantation. Biosci Trends 2017; 11:606-611. [PMID: 29238003 DOI: 10.5582/bst.2017.01293] [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: 01/15/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains a widespread public health concern and many people are infected with HCV. HCV is one of the leading indications for liver transplantation. Direct-acting antiviral agents (DAAs) against HCV have changed the course of chronic HCV infection, however, making it a curable disease. DAA treatment may be initiated before or after liver transplantation. In the present review, we present the available data on DAA treatment of HCV in liver transplant recipients.
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Affiliation(s)
- Yasuhiko Sugawara
- Departments of Transplantation/Pediatric Surgery and Gastroenterology and Hepatology, Postgraduate School of Life Science, Kumamoto University
| | - Taizo Hibi
- Departments of Transplantation/Pediatric Surgery and Gastroenterology and Hepatology, Postgraduate School of Life Science, Kumamoto University
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46
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Kasarala G, Choi S, Lopez K, Britt RB, Boatright C, Tillmann HL. Curing hepatitis C virus (HCV) after organ transplantation: Increased risk of rejection following HCV elimination. Transpl Infect Dis 2017; 20. [PMID: 29064152 DOI: 10.1111/tid.12796] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 06/21/2017] [Accepted: 06/30/2017] [Indexed: 11/26/2022]
Affiliation(s)
- George Kasarala
- Division of Gastroenterology, Department of Medicine, East Carolina University, Greenville, NC, USA
| | - Steve Choi
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC, USA.,Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Katie Lopez
- Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Rachel B Britt
- Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Colleen Boatright
- Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Hans L Tillmann
- Division of Gastroenterology, Department of Medicine, East Carolina University, Greenville, NC, USA.,Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
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47
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Saxena V, Khungar V, Verna EC, Levitsky J, Brown RS, Hassan MA, Sulkowski MS, O’Leary JG, Koraishy F, Galati JS, Kuo AA, Vainorius M, Akushevich L, Nelson DR, Fried MW, Terrault N, Reddy K. Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV-TARGET study. Hepatology 2017; 66:1090-1101. [PMID: 28504842 PMCID: PMC5756478 DOI: 10.1002/hep.29258] [Citation(s) in RCA: 126] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 04/06/2017] [Accepted: 05/09/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. CONCLUSION In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).
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Affiliation(s)
- Varun Saxena
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Norah Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco
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48
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Russo FP, Zanetto A, Burra P. Timing for treatment of HCV recurrence after liver transplantation: the earlier the better. Transpl Int 2017; 29:694-7. [PMID: 26713429 DOI: 10.1111/tri.12739] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 12/18/2015] [Indexed: 12/18/2022]
Affiliation(s)
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy
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49
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ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients. J Hepatol 2017; 67:585-602. [PMID: 28323126 DOI: 10.1016/j.jhep.2017.03.006] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 03/01/2017] [Accepted: 03/09/2017] [Indexed: 02/07/2023]
Abstract
The advent of safe and highly effective direct-acting antiviral agents (DAAs) has had huge implications for the hepatitis C virus (HCV) transplant field, and changed our management of both patients on the waiting list and those with HCV graft re-infection after liver transplantation (LT). When treating HCV infection before LT, HCV re-infection of the graft can be prevented in nearly all patients. In addition, some candidates show a remarkable clinical improvement and may be delisted. Alternatively, HCV infection can be treated post-LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence, as was carried out in the past. In either case, some DAAs have a limited use because of their drug to drug interactions with various immunosuppressants as well as the many other drugs liver transplant recipients are often prescribed. In addition, some DAAs should be avoided in case of severe renal failure, which is not an unusual complication after LT. The present document provides a series of consensus statements on the LT issues that have not been extensively addressed previously. These statements have been developed to support physicians and other stakeholders in charge of LT candidates and recipients when deciding to treat HCV, especially in difficult situations.
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50
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Mendizabal M, Silva MO. Developing multicenter consortia in liver disease in Latin America: Challenges and opportunities. Liver Transpl 2017; 23:1210-1215. [PMID: 28590520 DOI: 10.1002/lt.24793] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Revised: 05/26/2017] [Accepted: 05/31/2017] [Indexed: 12/12/2022]
Abstract
The development of consortia has been useful for exploring challenging scenarios and uncharted territories in liver disease treatments. Several consortia already developed in the United States and Europe have become key factors in patient care decision-making processes and medical education, and they have also impacted policy makers' decisions. In Latin America, the situation is different. As a result of a combination of different factors, our region has not been able to develop networking advantages in research and education in liver diseases. Thus far, most of the initial experiences focused on the development of collaborative groups established to investigate a particular topic, which were dissolved once the questions were answered. It is the aim of this review to describe those difficulties we confront in developing multicenter liver consortia in Latin America, to identify those challenges we face, and also to describe the opportunities we have for improvement. Liver Transplantation 23 1210-1215 2017 AASLD.
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Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina.,Latin American Liver Research, on behalf of the Latin American Liver Research, Educational and Awareness Network, Pilar, Provincia de Buenos Aires, Argentina
| | - Marcelo O Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina.,Latin American Liver Research, on behalf of the Latin American Liver Research, Educational and Awareness Network, Pilar, Provincia de Buenos Aires, Argentina
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