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Lam C, Landry S, Moussa G, Sakr D, Varinot G, Mousseau K, Martel D, Frenette AJ, Ambaraghassi G, Rouleau D, Cantarovich M, Klein MB, Sheehan NL, Lemire B. Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review. Transplant Direct 2023; 9:e1441. [PMID: 36733439 PMCID: PMC9886517 DOI: 10.1097/txd.0000000000001441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 12/01/2022] [Accepted: 12/03/2022] [Indexed: 01/28/2023] Open
Abstract
The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.
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Affiliation(s)
- Cindy Lam
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Sébastien Landry
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Ghina Moussa
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Dania Sakr
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Gabriel Varinot
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
| | - Katherine Mousseau
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
| | - Dominic Martel
- Département de pharmacie, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada
- Centre de recherche du CHUM, Montréal, QC, Canada
- Unité hospitalière de recherche, d’enseignement et de soins sur le sida, CHUM, Montréal, QC, Canada
| | - Anne Julie Frenette
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Département de pharmacie, Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada
| | - Georges Ambaraghassi
- Service de microbiologie, Département de médecine de laboratoire, CHUM, Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada
| | - Danielle Rouleau
- Centre de recherche du CHUM, Montréal, QC, Canada
- Unité hospitalière de recherche, d’enseignement et de soins sur le sida, CHUM, Montréal, QC, Canada
- Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada
| | | | - Marina B. Klein
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
- Division of Infectious Diseases, Department of Medicine, MUHC, Montréal, QC, Canada
| | - Nancy L. Sheehan
- Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
| | - Benoît Lemire
- Department of Pharmacy, McGill University Health Centre (MUHC), Montréal, QC, Canada
- Chronic Viral Illness Service, Department of Medicine MUHC, Montréal, QC, Canada
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McCain JD, Chascsa DM. Special Considerations in the Management of HIV and Viral Hepatitis Coinfections in Liver Transplantation. Hepat Med 2022; 14:27-36. [PMID: 35514530 PMCID: PMC9063796 DOI: 10.2147/hmer.s282662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 04/07/2022] [Indexed: 11/26/2022] Open
Abstract
Modern therapies for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus have become so effective that patients treated for these conditions can have normal life-expectancies. Suitable livers for transplantation remain a scarce and valuable resource. As such, significant efforts have been made to expand donation criteria at many centers. This constant pressure, coupled with the increasing effectiveness of antiviral therapies, has meant that more and more patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) may be considered appropriate donors in the right circumstances. Patients with these infections are also more likely to be considered appropriate transplantation recipients than in the past. The treatment of HBV, HCV, and HIV after liver transplantation (LT) can be challenging and complicated by viral coinfections. The various pharmaceutical agents used to treat these infections, as well as the immunosuppressants used post-LT must be carefully balanced for maximum efficacy, and to avoid resistance and drug–drug interactions.
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Affiliation(s)
- Josiah D McCain
- Department of Gastroenterology & Hepatology, Mayo Clinic, Phoenix, AZ, USA
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Shimada S, Ivanics T, Kitajima T, Shamaa T, Rizzari M, Collins K, Yoshida A, Abouljoud M, Moonka D, Zhang J, Lu M, Nagai S. Improvements in liver transplant outcomes in patients with HCV/HIV coinfection after the introduction of direct‐acting antiviral therapies. Transpl Infect Dis 2022; 24:e13808. [DOI: 10.1111/tid.13808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/25/2022] [Accepted: 02/06/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Shingo Shimada
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Tommy Ivanics
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Toshihiro Kitajima
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Tayseer Shamaa
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Michael Rizzari
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Kelly Collins
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
| | - Dilip Moonka
- Division of Gastroenterology and Hepatology Henry Ford Hospital Detroit MI USA
| | - Jiaqi Zhang
- Department of Public Health Sciences Henry Ford Hospital Detroit MI USA
| | - Mei Lu
- Department of Public Health Sciences Henry Ford Hospital Detroit MI USA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery Henry Ford Hospital Detroit MI USA
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Fan X, Fang J, Wu X, Poulsen K, Miyata T, Kim A, Yu L, Wang X, Zhang X, Zhang K, Han Q, Liu Z. Effect of HIV infection on pre- and post-liver transplant mortality in patients with organ failure. HIV Med 2021; 22:662-673. [PMID: 33964108 DOI: 10.1111/hiv.13113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Organ failure (OF), a leading cause of death in HIV-positive individuals, is common in patients undergoing liver transplantation (LT). We examined the impact of HIV infection on pre- and post-LT mortalities in cirrhotic patients stratified by the number and type of OFs. METHODS We performed a cross-sectional study and a retrospective cohort study using the US National Inpatient Sample (NIS) and the United Network for Organ Sharing (UNOS) registry data, respectively. Patients who had not yet undergone LT from the NIS database (2010-2014) and patients undergoing LT from the UNOS database (2003-2016) were included in the study. RESULTS Analysis of patients (201 348) from the NIS database showed that one [adjusted odds ratio (aOR) 1.531; 95% confidence interval (CI) 1.160-2.023], two (aOR 1.624; 95% CI 1.266-2.083) or three or more OFs (aOR 1.349; 95% CI 1.165-1.562) were associated with higher pre-LT mortality in HIV-infected patients compared with HIV-negative patients with the corresponding number of OFs. In patients without OF, HIV infection was not associated with increased pre-LT mortality. UNOS data for patients undergoing LT (38 942) showed that the presence of two or more OFs was associated with increased post-LT 1-year mortality in HIV-infected patients compared with non-HIV-infected patients with the corresponding number of OFs (aOR 2.342; 95% CI 1.576-3.480). However, in patients with no OF or only one OF, HIV infection was not associated with increased post-LT 1-year mortality (aOR 1.372; 95% CI 0.911-2.068). CONCLUSIONS The results of this study emphasize the importance of preventing OF development, and justify LT for HIV-infected patients with no or only one OF.
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Affiliation(s)
- X Fan
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - J Fang
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - X Wu
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - K Poulsen
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - T Miyata
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - A Kim
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - L Yu
- Department of Inflammation and Immunity, Center for Liver Disease Research, Cleveland Clinic, Cleveland, OH, USA
| | - X Wang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - X Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - K Zhang
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Q Han
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Z Liu
- Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Fengdong New Town (International) Hospital, Xi'an, Shaanxi, China
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"Raising HOPE": Improved Outcomes for HIV/HCV-coinfected Liver Transplant Recipients in the Direct-acting Antiviral Era. Transplant Direct 2021; 7:e707. [PMID: 34124343 PMCID: PMC8191686 DOI: 10.1097/txd.0000000000001154] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 03/15/2021] [Indexed: 12/11/2022] Open
Abstract
The 2013 HIV Organ Policy Equity Act has increased liver transplantation (LT) in HIV+ patients; however, transplant centers may remain reluctant to perform LT in HIV/hepatitis C virus (HCV)-coinfected patients due to inferior outcomes. We aimed to assess how direct-acting antivirals (DAAs) have impacted HIV+/HCV+-coinfected LT recipient outcomes.
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Peters MG, Kottilil S, Terrault N, Amara D, Husson J, Huprikar S, Florman S, Sulkowski MS, Durand CM, Luetkemeyer AF, Rogers R, Grab J, Haydel B, Blumberg E, Dove L, Emond J, Olthoff K, Smith C, Fishbein T, Masur H, Stock PG. Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant. Am J Transplant 2021; 21:1780-1788. [PMID: 33277801 PMCID: PMC8096639 DOI: 10.1111/ajt.16427] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/30/2020] [Accepted: 11/24/2020] [Indexed: 01/25/2023]
Abstract
Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4 years and post-LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.
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Affiliation(s)
- Marion G. Peters
- Department of Medicine, University of California, San Francisco, CA
| | | | - Norah Terrault
- Department of Medicine, University of Southern California, Los Angeles, CA
| | - Dominic Amara
- Department of Surgery, University of California, San Francisco, CA
| | | | | | - Sander Florman
- Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY
| | | | | | | | - Rodney Rogers
- Department of Surgery, University of California, San Francisco, CA
| | - Joshua Grab
- Department of Medicine, University of California, San Francisco, CA
| | - Brandy Haydel
- Recanati/Miller Transplantation Institute, Mount Sinai Hospital, New York, NY
| | - Emily Blumberg
- Department of Medicine, University of Pennsylvania, Philadelphia PA
| | - Lorna Dove
- Department of Medicine, Columbia University, New York, NY
| | - Jean Emond
- Department of Surgery, Columbia University, New York, NY
| | - Kim Olthoff
- Department of Surgery, University of Pennsylvania, Philadelphia PA
| | - Coleman Smith
- Medstar Georgetown Transplant Institute, Georgetown University, Georgetown, DC
| | - Thomas Fishbein
- Medstar Georgetown Transplant Institute, Georgetown University, Georgetown, DC
| | - Henry Masur
- Department of Critical Care Medicine, National Institutes of Health, Bethesda MD
| | - Peter G. Stock
- Department of Surgery, University of California, San Francisco, CA
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7
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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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Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis. HPB (Oxford) 2020; 22:900-910. [PMID: 31734238 DOI: 10.1016/j.hpb.2019.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 09/15/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND To address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT). METHODS All patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS). RESULTS The LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062). CONCLUSION This was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.
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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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Abstract
Human immunodeficiency virus (HIV) has become a chronic disease with a near normal life span resulting in increased risk of organ failure. HIV organ transplantation is a proven and accepted intervention in appropriately selected cases. HIV-positive organ transplantation into HIV-positive recipients is in its nascent stages. Hepatitis C virus, high rates of organ rejection, and immune dysregulation are significant remaining barriers to overcome. This article provides an overview of the transplantation needs in the HIV population focusing on kidney and liver transplants.
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Affiliation(s)
- Alan J Taege
- Department of Infectious Disease, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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Mohazzab-Torabi S, Dolatimehr F, Sharafi H, Safi-Abadi M, Rezaee-Zavareh MS, Bayatpour E, Karimi-Sari H, Alavian SM. Treatment of HCV Infection with Direct-Acting Antiviral Agents in Patients with HIV/HCV Co-Infection: A Systematic Review. HEPATITIS MONTHLY 2018; In Press. [DOI: 10.5812/hepatmon.82971] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
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Abutaleb A, Sherman KE. A changing paradigm: management and treatment of the HCV/HIV-co-infected patient. Hepatol Int 2018; 12:500-509. [PMID: 30238230 PMCID: PMC6471674 DOI: 10.1007/s12072-018-9896-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 09/06/2018] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) treatment in HIV/HCV co-infected individuals has renewed relevance given the ongoing opioid crisis and rise of new HIV and HCV infections associated with injection drug use. Patients co-infected with HIV and HCV demonstrate increased rates of hepatic fibrosis, progression to liver failure, and liver-related mortality. HIV co-infection does not impact outcomes of current HCV treatments, and patients should be treated the same as HCV mono-infected persons, though attention to drug:drug interactions is required. In this review, we discuss the mechanisms mediating injury to the liver in HIV mono-infection and HIV/HCV co-infection, and present the landmark trials of HCV treatment in HIV-infected individuals.
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Affiliation(s)
- Ameer Abutaleb
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore, MD, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland, Baltimore, MD, USA
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
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Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients After Liver Transplantation: Results From the ANRS CO23 CUPILT Study. Transplantation 2018; 102:119-126. [PMID: 28846559 DOI: 10.1097/tp.0000000000001928] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation. METHODS Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort. Their antiviral treatment combined SOF, daclatasvir with or without ribavirin (n = 10/n = 6), or SOF, ledipasvir with or without ribavirin (n = 2/n = 11). RESULTS The median delay between liver transplantation and treatment initiation was 37.5 months (interquartile range [IQR], 14.4-99.2). The breakdown of HCV genotypes was G1, 22 patients (75.9%); G3, 3 patients (10.3%); and G4, 4 patients (13.8%). The treatment indications were HCV recurrence (≥ F1 n = 23) or fibrosing cholestatic hepatitis (n = 6). Before starting SOF, the HCV viral load and CD4 count were 6.7 log10 IU/mL (IQR, 5.9-7.2) and 342 cells/mm (IQR, 172-483), respectively. At week 4, the HCV viral load was less than 15 IU/mL in 12 (42.9%) patients. The overall sustained virological response 12 was 96.6%. No significant drug-drug interactions were observed. CONCLUSIONS SOF-based treatment regimens produced excellent results in HIV/HCV coinfected patients after liver transplantation, suggesting an important change in their prognosis.
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International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Candidates. Transplantation 2018; 101:945-955. [PMID: 28437387 DOI: 10.1097/tp.0000000000001708] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Parra M, Laufer N, Manrique JM, Jones LR, Quarleri J. Phylogenetic Diversity in Core Region of Hepatitis C Virus Genotype 1a as a Factor Associated with Fibrosis Severity in HIV-1-Coinfected Patients. BIOMED RESEARCH INTERNATIONAL 2017; 2017:1728456. [PMID: 29259976 PMCID: PMC5702417 DOI: 10.1155/2017/1728456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 10/19/2017] [Indexed: 02/06/2023]
Abstract
High hepatitis C virus (HCV) genetic diversity impacts infectivity/pathogenicity, influencing chronic liver disease progression associated with fibrosis degrees and hepatocellular carcinoma. HCV core protein is crucial in cell-growth regulation and host-gene expression. Liver fibrosis is accelerated by unknown mechanisms in human immunodeficiency virus-1- (HIV-1-) coinfected individuals. We aimed to study whether well-defined HCV-1a core polymorphisms and genetic heterogeneity are related to fibrosis in a highly homogeneous group of interferon-treated HIV-HCV-coinfected patients. Genetic heterogeneity was weighed by Faith's phylogenetic diversity (PD), which has been little studied in HCV. Eighteen HCV/HIV-coinfected patients presenting different liver fibrosis stages before anti-HCV treatment-initiation were recruited. Sampling at baseline and during and after treatment was performed up to 72 weeks. At inter/intrahost level, HCV-1a populations were studied using molecular cloning and Sanger sequencing. Over 400 complete HCV-1a core sequences encompassing 573 positions of C were obtained. Amino acid substitutions found previously at positions 70 and 91 of HCV-1b core region were not observed. However, HCV genetic heterogeneity was higher in mild than in severe fibrosis cases. These results suggest a potential utility of PD as a virus-related factor associated with chronic hepatitis C progression. These observations should be reassessed in larger cohorts to corroborate our findings and assess other potential covariates.
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Affiliation(s)
- Micaela Parra
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 11, C1121ABG Buenos Aires, Argentina
- Laboratorio de Virología y Genética Molecular (LVGM), Facultad de Ciencias Naturales y Ciencias de la Salud Sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, Chubut, 9100 Trelew, Argentina
| | - Natalia Laufer
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 11, C1121ABG Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina
| | - Julieta M. Manrique
- Laboratorio de Virología y Genética Molecular (LVGM), Facultad de Ciencias Naturales y Ciencias de la Salud Sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, Chubut, 9100 Trelew, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina
| | - Leandro R. Jones
- Laboratorio de Virología y Genética Molecular (LVGM), Facultad de Ciencias Naturales y Ciencias de la Salud Sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, Chubut, 9100 Trelew, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina
| | - Jorge Quarleri
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 11, C1121ABG Buenos Aires, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina
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Abstract
HIV-infected persons who achieve undetectable viral loads on antiretroviral therapy currently have near-normal lifespans. Liver disease is a major cause of non-AIDS-related deaths, and as a result of longer survival, the prevalence of end-stage renal disease in HIV is increasing. HIV-infected persons undergoing organ transplantation generally achieve comparable patient and graft survival rates compared to their HIV-uninfected counterparts, despite a nearly threefold increased risk of acute rejection. However, the ongoing shortage of suitable organs can limit transplantation as an option, and patients with HIV have higher waitlist mortality than others. One way to solve this problem would be to expand the donor pool to include HIV-infected individuals. The results of a South Africa study involving 27 HIV-to-HIV kidney transplants showed promise, with 3- and 5-year patient and graft survival rates similar to those of their HIV-uninfected counterparts. Similarly, individual cases of HIV-to-HIV liver transplantation from the United Kingdom and Switzerland have also shown good results. In the United States, HIV-to-HIV kidney and liver transplants are currently permitted only under a research protocol. Nevertheless, areas of ambiguity exist, including streamlining organ allocation practices, optimizing HIV-infected donor and recipient selection, managing donor-derived transmission of a resistant HIV strain, determining optimal immunosuppressive and antiretroviral regimens, and elucidating the incidence of rejection in HIV-to-HIV solid organ transplant recipients.
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17
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Guaraldi G, Rossotti R, Verucchi G, Tavio M, Pasulo L, Beghetto B, Dolci G, Nardini G, Badia L, Magliano A, Moioli MC, Puoti M. Successful Pre- and Posttransplant Sofosbuvir-Based Anti-Hepatitis C Virus Treatment in Persons Living With Human Immunodeficiency Virus Infection. Open Forum Infect Dis 2017; 4:ofx065. [PMID: 28584851 PMCID: PMC5451199 DOI: 10.1093/ofid/ofx065] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Accepted: 05/16/2017] [Indexed: 02/07/2023] Open
Abstract
This retrospective study reports the data of sofosbuvir-based anti-hepatitis C virus treatment in 24 candidates and 24 recipients of liver transplantation coinfected with human immunodeficiency virus. Sustained virologic response was cumulatively 85% (90% and 100% in those treated with optimal schedules pre- and posttransplant, respectively).
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Affiliation(s)
| | | | | | - Marcello Tavio
- Azienda Ospedaliera Universitaria Ospedali Riuniti, Ancona, Italy; and
| | - Luisa Pasulo
- Gastroenterology Department ASST Papa Giovanni XXIII, Bergamo, Italy
| | | | - Giovanni Dolci
- Infectious Diseases Departments of University of Modena, Italy
| | - Giulia Nardini
- Infectious Diseases Departments of University of Modena, Italy
| | | | - Anna Magliano
- Azienda Ospedaliera Universitaria Ospedali Riuniti, Ancona, Italy; and
| | | | - Massimo Puoti
- ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
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18
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Warren-Gash C, Childs K, Thornton A, Bhagani S, Demma S, Srivastava A, Leen C, Agarwal K, Rodger AJ, Sabin CA. Cirrhosis and liver transplantation in patients co-infected with HIV and hepatitis B or C: an observational cohort study. Infection 2017; 45:215-220. [PMID: 28054251 PMCID: PMC5374166 DOI: 10.1007/s15010-016-0976-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 12/19/2016] [Indexed: 12/11/2022]
Abstract
This study assessed the likelihood of referral for liver transplantation assessment in a prospective cohort of patients co-infected with HIV and hepatitis B or C with complications of cirrhosis. There were 141 co-infected patients from 11 UK centres with at least one complication of cirrhosis recorded (either decompensation or hepatocellular carcinoma) out of 772 identified with cirrhosis and/or HCC. Only 23 of these 141 (16.3%) were referred for liver transplantation assessment, even though referral is recommended for co-infected patients after the first decompensation episode.
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Affiliation(s)
- Charlotte Warren-Gash
- Institute of Health Informatics, University College London, London, UK.
- The Farr Institute of Health Informatics Research, 222 Euston Road, London, NW1 2DA, UK.
| | - Kate Childs
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Alicia Thornton
- Research Department of Infection and Population Health, University College London, London, UK
| | - Sanjay Bhagani
- Department of Infectious Diseases, Royal Free London NHS Foundation Trust, London, UK
| | - Shirin Demma
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
- Hepatology Unit, Department of Experimental and Clinical Medicine, University of Catania, Catania, Italy
| | - Ankur Srivastava
- Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Clifford Leen
- Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK
| | - Kosh Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Alison J Rodger
- Research Department of Infection and Population Health, University College London, London, UK
- Department of Infectious Diseases, Royal Free London NHS Foundation Trust, London, UK
| | - Caroline A Sabin
- Research Department of Infection and Population Health, University College London, London, UK
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19
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Talavera Pons S, Boyer A, Lamblin G, Chennell P, Châtenet F, Nicolas C, Sautou V, Abergel A. Managing drug-drug interactions with new direct-acting antiviral agents in chronic hepatitis C. Br J Clin Pharmacol 2017; 83:269-293. [PMID: 27530469 PMCID: PMC5237698 DOI: 10.1111/bcp.13095] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 07/21/2016] [Accepted: 07/26/2016] [Indexed: 12/16/2022] Open
Abstract
Several direct-acting antiviral agents (DAAs) have marketing authorization in Europe and in the USA and have changed the landscape of hepatitis C treatment: each DAA has its own metabolism and drug-drug interactions (DDIs), and managing them is a challenge. To compile the pharmacokinetics and DDI data of the new DAA and to provide a guide for management of DDI. An indexed MEDLINE search was conducted using the keywords: DAA, hepatitis C, simeprevir, daclatasvir, ledipasvir, sofosbuvir, 3D regimen (paritaprevir/ritonavir, ombitasvir, dasabuvir), DDI and pharmacokinetics. Data were also collected from hepatology, and infectious disease and clinical pharmacology conferences abstracts. Food can play a role in the absorption of DAAs. Most of the interactions are linked to metabolism (cytochrome P450-3 A4 [CYP3A4]) or hepatic and/or intestinal transporters (organic anion-transporting polypeptide and P-glycoprotein [P-gp]). To a lesser extent other pathways can be involved such as breast cancer resistance protein transporter or UDP-glucuronosyltransferase metabolism. DDI are more likely to occur with 3D regimen, daclatasvir, simeprevir and ledipasvir, as they are all both substrates and inhibitors of P-gp and/or CYP3A4, than with sofosbuvir. They can increase concentrations of coadministered drugs and their concentrations may be influenced by P-gp or CYP3A4 inducers or inhibitors. Overdosage or low dosage can be encountered with potent inducers or inhibitors of CYP3A4 or drugs with a narrow therapeutic range. The key to interpret DDI data is a good understanding of the pharmacokinetic profiles of the drugs involved. Their ability to inhibit CYP450-3A4 and transporters (hepatic and/or intestinal) can have significant clinical consequences.
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Affiliation(s)
| | - Anne Boyer
- Service de Pharmacie Centre Hospitalier UniversitaireClermont‐FerrandFrance
| | - Geraldine Lamblin
- Service de Médecine Digestive et Hépato‐biliaire Centre Hospitalier Universitaire EstaingClermont‐FerrandFrance
| | - Philip Chennell
- Service de Pharmacie Centre Hospitalier UniversitaireClermont‐FerrandFrance
- EA 4676 C‐BiosenssUniversité d'AuvergneClermont‐FerrandCedexFrance
| | | | - Carine Nicolas
- Service de Médecine Digestive et Hépato‐biliaire Centre Hospitalier Universitaire EstaingClermont‐FerrandFrance
| | - Valérie Sautou
- Service de Pharmacie Centre Hospitalier UniversitaireClermont‐FerrandFrance
- EA 4676 C‐BiosenssUniversité d'AuvergneClermont‐FerrandCedexFrance
| | - Armand Abergel
- Service de Médecine Digestive et Hépato‐biliaire Centre Hospitalier Universitaire EstaingClermont‐FerrandFrance
- Unité Mixte de Recherche Université d'Auvergne, CNRS 6284University of Clermont‐FerrandFrance
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20
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Rockstroh JK, Ingiliz P, Petersen J, Peck-Radosavljevic M, Welzel TM, Van der Valk M, Zhao Y, Jimenez-Exposito MJ, Zeuzem S. Daclatasvir plus sofosbuvir, with or without ribavirin, in real-world patients with HIV-HCV coinfection and advanced liver disease. Antivir Ther 2016; 22:225-236. [PMID: 27845298 DOI: 10.3851/imp3108] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2016] [Indexed: 01/12/2023]
Abstract
BACKGROUND HIV-HCV-coinfected patients respond just as well to modern direct-acting antiviral HCV therapy as HCV-monoinfected patients. However, clinical data for all-oral HCV treatments are sparse in HIV-HCV-coinfected patients with an advanced stage of liver cirrhosis. METHODS A subanalysis of efficacy and safety for a daclatasvir (DCV) and sofosbuvir (SOF) regimen, with or without ribavirin (RBV), was undertaken in HIV-HCV-coinfected patients with advanced liver disease and no other treatment options enrolled into a European DCV compassionate use programme. RESULTS Fifty five HIV-HCV (mostly genotypes 1, 3, 4) coinfected patients were treated with DCV+SOF with (n=16) or without RBV (n=39), mostly for 24 weeks. Patients were predominantly (95%) cirrhotic (50% were Child-Pugh class B or C) and were receiving a wide range of antiretrovirals; 40% were injection drug users and 25% were receiving oral opioid substitution. Sustained virological response at post-treatment week 12 (SVR12) by modified intention-to-treat analysis (n=52) was 92% overall (95% CI 81.5, 97.9), and was similar with (94% [95% CI 69.8, 99.8]) or without RBV (92% [95% CI 77.5, 98.2]). Only one patient relapsed (Child-Pugh class B). The overall SVR12 rate after excluding non-virological failures (n=49) was 98% (95% CI 89.1, 99.9). Four patients discontinued treatment for adverse events and one died during treatment (not treatment-related). No patient lost opioid maintenance or required a change of antiretrovirals due to drug-drug interactions. CONCLUSIONS DCV+SOF, with or without RBV, showed high SVR12 rates and was well tolerated in this real-world cohort of HIV-HCV-coinfected patients with very advanced liver disease. ClinicalTrials.gov ID NCT02097966 (Study AI444-237).
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Affiliation(s)
| | | | - Jörg Petersen
- IFI-Medizin GmbH and the Asklepios Klinik St Georg, Hamburg, Germany
| | - Markus Peck-Radosavljevic
- Medical University of Vienna, Vienna, Austria.,Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria
| | - Tania M Welzel
- Universitätsklinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany
| | - Marc Van der Valk
- Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Yue Zhao
- Bristol-Myers Squibb, Global Biostatistics, Hopewell, NJ, USA
| | | | - Stefan Zeuzem
- Universitätsklinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany
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21
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Sede M, Parra M, Manrique JM, Laufer N, Jones LR, Quarleri J. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2016; 43:186-196. [PMID: 27234841 DOI: 10.1016/j.meegid.2016.05.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Revised: 05/13/2016] [Accepted: 05/23/2016] [Indexed: 02/07/2023]
Abstract
Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses.
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Affiliation(s)
- Mariano Sede
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG Buenos Aires, Argentina
| | - Micaela Parra
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG Buenos Aires, Argentina
| | - Julieta M Manrique
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Laboratorio de Virología y Genética Molecular, Facultad de Ciencias Naturales sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, 9100 Trelew, Chubut, Argentina
| | - Natalia Laufer
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG Buenos Aires, Argentina
| | - Leandro R Jones
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Laboratorio de Virología y Genética Molecular, Facultad de Ciencias Naturales sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, 9100 Trelew, Chubut, Argentina.
| | - Jorge Quarleri
- Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG Buenos Aires, Argentina.
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22
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Sepúlveda-Crespo D, Jiménez JL, Gómez R, De La Mata FJ, Majano PL, Muñoz-Fernández MÁ, Gastaminza P. Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2016; 13:49-58. [PMID: 27562210 DOI: 10.1016/j.nano.2016.08.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 07/11/2016] [Accepted: 08/11/2016] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is a major biomedical problem worldwide. Although new direct antiviral agents (DAAs) have been developed for the treatment of chronic HCV infection, the potential emergence of resistant virus variants and the difficulties to implement their administration worldwide make the development of novel antiviral agents an urgent need. Moreover, no effective vaccine is available against HCV and transmission of the virus still occurs particularly when prophylactic measures are not taken. We used a cell-based system to screen a battery of polyanionic carbosilane dendrimers (PCDs) to identify compounds with antiviral activity against HCV and show that they inhibit effective virus adsorption of major HCV genotypes. Interestingly, one of the PCDs irreversibly destabilized infectious virions. This compound displays additive effect in combination with a clinically relevant DAA, sofosbuvir. Our results support further characterization of these molecules as nanotools for the control of hepatitis C virus spread.
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Affiliation(s)
- Daniel Sepúlveda-Crespo
- Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - José Luis Jiménez
- Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Gómez
- Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco Javier De La Mata
- Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain
| | - Pedro L Majano
- Molecular Biology Unit, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain; CIBERehd, Instituto de Salud Carlos III, Madrid, Spain
| | - Ma Ángeles Muñoz-Fernández
- Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV-HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; Plataforma de Laboratorio, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain
| | - Pablo Gastaminza
- Centro Nacional De Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Campus Cantoblanco, Madrid, Spain.
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23
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Calmy A, van Delden C, Giostra E, Junet C, Rubbia Brandt L, Yerly S, Chave JP, Samer C, Elkrief L, Vionnet J, Berney T. HIV-Positive-to-HIV-Positive Liver Transplantation. Am J Transplant 2016; 16:2473-8. [PMID: 27109874 DOI: 10.1111/ajt.13824] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 04/08/2016] [Accepted: 04/09/2016] [Indexed: 01/25/2023]
Abstract
Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug-resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV-positive donors for transplants specifically allocated to HIV-positive recipients.
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Affiliation(s)
- A Calmy
- HIV Unit, Geneva University Hospitals, Geneva, Switzerland
| | - C van Delden
- Transplant Infectious Diseases Unit, Geneva University Hospitals, Geneva, Switzerland
| | - E Giostra
- Division of Transplantation, Geneva University Hospitals, Geneva, Switzerland
| | - C Junet
- Private Practice, Geneva, Switzerland
| | - L Rubbia Brandt
- Division of Pathology, Geneva University Hospitals, Geneva, Switzerland
| | - S Yerly
- Virology Laboratory, Geneva University Hospitals, Geneva, Switzerland
| | - J-P Chave
- Private Practice, Lausanne, Switzerland
| | - C Samer
- Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland
| | - L Elkrief
- Division of Transplantation, Geneva University Hospitals, Geneva, Switzerland
| | - J Vionnet
- Division of Gastroenterology and Division of Transplantation, CHUV, Lausanne, Switzerland
| | - T Berney
- Division of Transplantation, Geneva University Hospitals, Geneva, Switzerland
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24
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Londoño MC, Manzardo C, Rimola A, Ruiz P, Costa J, Forner A, Ambrosioni J, Agüero F, Laguno M, Lligoña A, Moreno A, Miró JM. IFN-free therapy for HIV/HCV-coinfected patients within the liver transplant setting. J Antimicrob Chemother 2016; 71:3195-3201. [PMID: 27402009 DOI: 10.1093/jac/dkw270] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Revised: 05/17/2016] [Accepted: 06/01/2016] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVES IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV-coinfected liver transplant recipients, the results are even poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting. METHODS Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT [fibrosing cholestatic hepatitis (n = 1), fibrosis stage ≥F3 (n = 2) and decompensated cirrhosis (n = 4)]. Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks. RESULTS Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events. CONCLUSIONS IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population.
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Affiliation(s)
- Maria-Carlota Londoño
- Liver Unit, Hospital Clínic Barcelona, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Christian Manzardo
- Infectious Disease Service, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Antoni Rimola
- Liver Unit, Hospital Clínic Barcelona, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Pablo Ruiz
- Liver Unit, Hospital Clínic Barcelona, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Josep Costa
- Microbiology Service (CDB), Hospital Clínic Barcelona, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Alejandro Forner
- Liver Unit, Hospital Clínic Barcelona, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Juan Ambrosioni
- Infectious Disease Service, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Fernando Agüero
- Infectious Disease Service, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Montserrat Laguno
- Infectious Disease Service, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Anna Lligoña
- Addictive Behavior Unit, Hospital Clínic Barcelona, Barcelona, Spain
| | - Asunción Moreno
- Infectious Disease Service, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Jose-Maria Miró
- Infectious Disease Service, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
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25
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Hull M, Shafran S, Wong A, Tseng A, Giguère P, Barrett L, Haider S, Conway B, Klein M, Cooper C. CIHR Canadian HIV Trials Network Coinfection and Concurrent Diseases Core Research Group: 2016 Updated Canadian HIV/Hepatitis C Adult Guidelines for Management and Treatment. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2016; 2016:4385643. [PMID: 27471521 PMCID: PMC4947683 DOI: 10.1155/2016/4385643] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 12/15/2015] [Indexed: 12/13/2022]
Abstract
Background. Hepatitis C virus (HCV) coinfection occurs in 20-30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.
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Affiliation(s)
- Mark Hull
- British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, BC, Canada V6T 1Z4
| | | | - Alex Wong
- Regina Qu'Appelle Health Region, Regina, SK, Canada S4P 1E2
| | - Alice Tseng
- Toronto General Hospital, Toronto, ON, Canada M5G 2C4
| | | | - Lisa Barrett
- Dalhousie University, Halifax, NS, Canada B3H 4R2
| | | | - Brian Conway
- Vancouver Infectious Diseases Centre, Vancouver, BC, Canada V6Z 2C7
| | | | - Curtis Cooper
- The Ottawa Hospital, General Campus, G12, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6
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26
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Liver involvement in human immunodeficiency virus infection. Indian J Gastroenterol 2016; 35:260-73. [PMID: 27256434 DOI: 10.1007/s12664-016-0666-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 05/01/2016] [Indexed: 02/04/2023]
Abstract
The advances in management of patients with acquired immunodeficiency syndrome (AIDS) with highly effective anti-retroviral therapy (HAART) have resulted in increased longevity of patients with human immunodeficiency virus (HIV) infection. AIDS-related illnesses now account for less than 50 % of the deaths, and liver diseases have emerged as the leading cause of death in patients with HIV infection. Chronic viral hepatitis, drug-related hepatotoxicity, non-alcoholic fatty liver disease, and opportunistic infections are the common liver diseases that are seen in HIV-infected individuals. Because of the shared routes of transmission, co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are very common in HIV-infected persons. Hepatitis C is the most common viral hepatitis seen in HIV-infected patients. With the availability of directly acting agents, treatment outcome of HCV is comparable to that seen in non HIV-infected patients. Careful monitoring is required for drug interactions and drug-induced hepatotoxicity and modification of drugs should be done where necessary. The results of liver transplantation in select HIV-infected patients can be comparable with those of HIV-negative patients.
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Tanaka T, Akamatsu N, Kaneko J, Arita J, Tamura S, Hasegawa K, Sakamoto Y, Kokudo N. Daclatasvir and asunaprevir for recurrent hepatitis C following living donor liver transplantation with HIV co-infection. Hepatol Res 2016; 46:829-832. [PMID: 26508337 DOI: 10.1111/hepr.12614] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Revised: 10/05/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023]
Abstract
Antiviral treatment in liver transplant recipients co-infected with hepatitis C virus (HCV) and HIV remains a challenge. We herein report a case of HCV recurrence that was successfully treated using interferon-free anti-HCV therapy with daclatasvir and asunaprevir. A 48-year-old man underwent antiviral therapy with a 24-week course of daclatasvir and asunaprevir for biopsy-proven recurrent HCV 15 months after living donor liver transplantation, following non-response to pre-emptive antiviral treatment with pegylated interferon plus ribavirin. Anti-HIV and immunosuppressive regimens were modified safely. Renal function was feasibly preserved. The anti-HCV effect was remarkable with an undetectable viral load confirmed within 2 weeks, and this patient achieved a sustained virological response after 12 weeks of post-transplantation treatment. No serious adverse events were observed. This case indicates that daclatasvir and asunaprevir for recurrent HCV in a HIV co-infected recipient after liver transplantation is safe and effective.
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Affiliation(s)
- Tomohiro Tanaka
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Junichi Kaneko
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Junichi Arita
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Sumihito Tamura
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Yoshihiro Sakamoto
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo
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Puri P, Saraswat VA, Dhiman RK, Anand AC, Acharya SK, Singh SP, Chawla YK, Amarapurkar DN, Kumar A, Arora A, Dixit VK, Koshy A, Sood A, Duseja A, Kapoor D, Madan K, Srivastava A, Kumar A, Wadhawan M, Goel A, Verma A, Shalimar, Pandey G, Malik R, Agrawal S. Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016. J Clin Exp Hepatol 2016; 6:119-145. [PMID: 27493460 PMCID: PMC4963318 DOI: 10.1016/j.jceh.2016.07.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
India contributes significantly to the global burden of HCV. While the nucleoside NS5B inhibitor sofosbuvir became available in the Indian market in March 2015, the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only recently become available in the India. The introduction of these DAA in India at a relatively affordable price has led to great optimism about prospects of cure for these patients as not only will they provide higher efficacy, but combination DAAs as all-oral regimen will result in lower side effects than were seen with pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs has necessitated revision of INASL guidelines for the treatment of HCV published in 2015. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. The availability of combination DAA therapy has simplified therapy of HCV with decreased reliance of evaluation for monitoring viral kinetics or drug related side effects.
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Key Words
- ALT, alanine aminotransferase
- ANC, absolute neutrophil count
- AST, aspartate aminotransferase
- CH-C, chronic hepatitis C
- CTP, Child-Turcotte-Pugh
- DAA, directly acting antiviral agents
- DCV, daclatasvir
- EIA, enzyme immunoassay
- ESRD, end-stage renal disease
- EVR, early virological response
- FCH, fibrosing cholestatic hepatitis
- GT, genotype
- HCV
- HCV, hepatitis C virus
- HCWs, healthcare workers
- HIV, human immunodeficiency virus
- INASL, Indian National Association for Study of the Liver
- IU, international units
- LDV, ledipasvir
- LT, liver transplantation
- NS, nonstructural protein
- NSI, needlestick injury
- PCR, polymerase chain reaction
- Peg-IFNα, pegylated interferon alfa
- RBV, ribavirin
- RVR, rapid virological response
- SOF, sofosbuvir
- SVR, sustained virological response
- ULN, upper limit of normal
- anti-HCV, antibody to HCV
- antiviral therapy
- chronic hepatitis
- hepatitis C virus
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Affiliation(s)
- Pankaj Puri
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Anil C. Anand
- Department of Gastroenterology and Hepatology, Indraprastha Apollo Hospital, New Delhi 110076, India
| | - Subrat K. Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack 753007, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | | | - Ajay Kumar
- Department of Gastroenterology and Hepatology, Fortis Escorts Liver and Digestive Diseases Institute, New Delhi 110076, India
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Banaras Hindu University, Varanasi 221005, India
| | - Abraham Koshy
- Department of Hepatology, Lakeshore Hospital, Cochin 682304, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College, Ludhiana 141001, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Dharmesh Kapoor
- Department of Gastroenterology, Global Hospital, Hyderabad 500004, India
| | - Kaushal Madan
- Department of Gastroenterology, Artemis Hospital, Gurgaon 122001, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital, New Delhi 110060, India
| | - Manav Wadhawan
- Department of Gastroenterology and Hepatology, Fortis Escorts Liver and Digestive Diseases Institute, New Delhi 110076, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Abhai Verma
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Gaurav Pandey
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Rohan Malik
- Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Swastik Agrawal
- Department of Gastroenterology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, India
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Solid Organ Transplantation in HIV+ Recipients: Italian Experience. Transplant Proc 2016; 48:424-30. [DOI: 10.1016/j.transproceed.2015.12.049] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/30/2015] [Indexed: 01/28/2023]
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Sollima S, Milazzo L, Torre A, Calvi E, Regalia E, Antinori S. Paritaprevir/ritonavir, ombitasvir, and dasabuvir for treatment of recurrent hepatitis C virus infection in the human immunodeficiency virus coinfected liver transplant recipient. Liver Transpl 2016; 22:252-3. [PMID: 26439308 DOI: 10.1002/lt.24353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 09/20/2015] [Accepted: 09/30/2015] [Indexed: 01/13/2023]
Affiliation(s)
- Salvatore Sollima
- III Division of Infectious Diseases, L. Sacco University Hospital, Milan, Italy
| | - Laura Milazzo
- III Division of Infectious Diseases, L. Sacco University Hospital, Milan, Italy
| | - Alessandro Torre
- III Division of Infectious Diseases, L. Sacco University Hospital, Milan, Italy
| | - Elisa Calvi
- III Division of Infectious Diseases, L. Sacco University Hospital, Milan, Italy
| | - Enrico Regalia
- Liver Unit, Department of Surgery, National Cancer Institute, IRCCS Foundation, Naples, Italy
| | - Spinello Antinori
- III Division of Infectious Diseases, L. Sacco University Hospital, Milan, Italy
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Maki H, Kaneko J, Akamatsu N, Arita J, Sakamoto Y, Hasegawa K, Tanaka T, Tamura S, Sugawara Y, Tsukada K, Kokudo N. Interleukin-2 receptor antagonist immunosuppression and consecutive viral management in living-donor liver transplantation for human immunodeficiency virus/hepatitis C-co-infected patients: a report of 2 cases. Clin J Gastroenterol 2016; 9:32-37. [PMID: 26661842 DOI: 10.1007/s12328-015-0621-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Accepted: 11/22/2015] [Indexed: 10/22/2022]
Abstract
Management of immunosuppression for human immunodeficiency virus/hepatitis C (HIV/HCV) in living-donor liver transplantation (LDLT) has not been established. We performed LDLT for two patients with HIV/HCV-co-infected end-stage liver disease. The immunosuppression protocol consisted of early calcineurin inhibitor-free and interleukin-2 receptor antagonist (IL2Ra) induction and methylprednisolone. Maintenance low-dose tacrolimus was started and anti-retroviral therapy for HIV was re-started 1 week after LDLT. Consecutively, pegylated interferon and ribavirin therapy were successfully added as pre-emptive therapy for HCV. HIV-RNA and HCV-RNA were undetectable on anti-retroviral therapy and HCV treatment at 17 and 8 months after LDLT, respectively, with normal liver function. This study is the first report of early calcineurin inhibitor-free and IL2Ra induction with methylprednisolone immunosuppression in LDLT for HIV/HCV-co-infected patients with a favorable outcome. Consecutive HIV/HCV treatment was well tolerated.
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Affiliation(s)
- Harufumi Maki
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomohiro Tanaka
- Organ Transplantation Service, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Sumihito Tamura
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yasuhiko Sugawara
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kunihisa Tsukada
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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Abstract
HCV coinfection has emerged as a major cause of non-AIDS-related morbidity and mortality in HIV-positive patients. As a consequence of the availability of modern combined antiretroviral therapy regimens, for optimally managed HIV/HCV-coinfected patients, the rates of liver fibrosis progression and the risk of liver-related events are increasingly similar to those of HCV-monoinfected patients. Moreover, our understanding of modulators of liver disease progression has greatly improved. In addition to immune status, endocrine, metabolic, genetic and viral factors are closely interrelated and might be important determinants of liver disease progression. In the last decade, a variety of serologic and radiographic tests for noninvasive liver disease staging have been extensively validated and are commonly used in HIV/HCV-coinfected patients. Sustained virologic response prevents end-stage liver disease, hepatocellular carcinoma, and death, with an even greater effect size in HIV-positive compared to HIV-negative patients. As interferon-free regimens achieve comparable rates of sustained virologic response in HIV-negative and HIV-positive patients, HIV/HCV-coinfected patients should from now on be referred to as a special, rather than a difficult-to-treat, population. Our comprehensive review covers all relevant aspects of HIV/HCV coinfection. Beginning with the changing epidemiology, it also provides new insights into the natural history of this condition and gives an overview on non-invasive techniques for the staging of liver disease. Furthermore, it outlines current recommendations for the treatment of acute hepatitis C and summarizes the unprecedented advances in the field of chronic hepatitis C therapy.
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Infectious Considerations in the Pre-Transplant Evaluation of Cirrhotic Patients Awaiting Orthotopic Liver Transplantation. Curr Infect Dis Rep 2016; 18:4. [PMID: 26743200 DOI: 10.1007/s11908-015-0514-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The incidence of end-stage liver disease (ESLD) is increasing and many of these patients may be considered for orthotopic liver transplantation. As patients with ESLD are at risk of a number of infections, infectious disease physicians should be aware of the management of these infections in order to provide optimal patient care and ensure transplantation success. We present a review of the literature pertaining to infectious disease considerations in the liver transplant candidate. It highlights several topics with recent developments including the management of hepatitis C virus infection prior to transplantation, treatment of hepatitis B virus infection, colonization and infection with multidrug resistant organisms, and management of spontaneous bacterial peritonitis.
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CD4 T lymphocyte counts in patients undergoing splenectomy during living donor liver transplantation. Transpl Immunol 2015; 34:50-3. [PMID: 26655336 DOI: 10.1016/j.trim.2015.11.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 11/25/2015] [Accepted: 11/30/2015] [Indexed: 12/12/2022]
Abstract
UNLABELLED The role of splenectomy in increasing the CD4-positive T lymphocyte counts (hereafter: CD4 counts) and the CD4 to CD8 ratio have not yet been fully investigated, especially in the case of HIV-positive patients undergoing liver transplantation (LT). METHODS The change in the total lymphocyte counts of 32 patients who underwent one-stage splenectomy with living donor (LD) LT with (n=13) or without rituximab (RTX, n=19) therapy were examined to validate our cohort of ABO-incompatible LDLT with RTX. Subsequently, perioperative changes in CD4 counts and the CD 4 to CD8 ratio were measured in 13 patients who underwent ABO-incompatible LDLT/RTX with splenectomy. RESULTS (1) The administration of RTX did not significantly affect the total lymphocyte counts of patients after LDLT/splenectomy in any of the observation periods. (2) The CD4 counts were significantly higher at 2years after LDLT in comparison to the perioperative CD4 counts but not within the 3-month period (p=0.039). The CD4/CD8 ratio gradually decreased after LDLT/splenectomy under RTX treatment. CONCLUSIONS An immediate increase in the CD4 counts therefore cannot be expected after LDLT with splenectomy. The total lymphocyte and CD4 counts were rather stable in the peritransplant period even in ABO incompatible LDLT with RTX.
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Bello DD, Ita-Nagy F, Hand J, Dieterich D. Treatment of hepatitis C in coinfected patients. Future Virol 2015. [DOI: 10.2217/fvl.15.99] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
HCV and liver disease have emerged as major causes of morbidity and mortality in HIV-positive patients. Treating HCV in patients with HIV has been challenging up until a few years ago due to poorer outcomes with interferon-based therapies in this population. The direct-acting antiviral (DAA) agents offer a new era in the treatment of HCV for all patients regardless of HIV status. This article reviews multiple aspects of the care of the coinfected patient with a focus on the modern DAA agents. HCV clinical treatment trials involving HIV-positive patients and antiretroviral therapy/DAA drug–drug interactions are reviewed in detail.
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Affiliation(s)
- David Del Bello
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, PO Box 1123, Annenberg 21–42, New York, NY 10029, USA
| | - Fanny Ita-Nagy
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, PO Box 1123, Annenberg 21–42, New York, NY 10029, USA
| | - Jonathan Hand
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, PO Box 1123, Annenberg 21–42, New York, NY 10029, USA
| | - Douglas Dieterich
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, PO Box 1123, Annenberg 21–42, New York, NY 10029, USA
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36
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Righi E, Londero A, Carnelutti A, Baccarani U, Bassetti M. Impact of new treatment options for hepatitis C virus infection in liver transplantation. World J Gastroenterol 2015; 21:10760-10775. [PMID: 26478668 PMCID: PMC4600578 DOI: 10.3748/wjg.v21.i38.10760] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 07/12/2015] [Accepted: 09/15/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplant candidates and recipients with hepatitis C virus (HCV)-related liver disease greatly benefit from an effective antiviral therapy. The achievement of a sustained virological response before transplantation can prevent the recurrence of post-transplant HCV disease that occurs universally and correlates with enhanced progression to graft cirrhosis. Previous standard-of-care regimens (e.g., pegylated-interferon plus ribavirin with or without first generation protease inhibitors, boceprevir and telaprevir) displayed suboptimal results and poor tolerance in liver transplant recipients. A new class of potent direct-acting antiviral agents (DAA) characterized by all-oral regimens with minimal side effects has been approved and included in the recent guidelines for the treatment of liver transplant recipients with recurrent HCV disease. Association of sofosbuvir with ribavirin and/or ledipasvir is recommended in liver transplant recipients and patients with decompensated cirrhosis. Other regimens include simeprevir, daclatasvir, and combination of other DAA. Possible interactions should be monitored, especially in coinfected human immunodeficiency virus/HCV patients receiving antiretrovirals.
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Beinhardt S, Peck-Radosavljevic M, Hofer H, Ferenci P. Interferon-free antiviral treatment of chronic hepatitis C in the transplant setting. Transpl Int 2015; 28:1011-1024. [PMID: 25864369 DOI: 10.1111/tri.12577] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 03/03/2015] [Accepted: 04/02/2015] [Indexed: 12/16/2022]
Abstract
Interferon-based regimens with first-generation protease inhibitors have a limited efficacy and an unfavorable safety profile. Combination therapies with two or more second-generation direct-acting antivirals plus/minus ribavirin revolutionized treatment strategies in patients chronically infected with hepatitis C virus. In this rapidly evolving era, patients in the transplant setting benefit from interferon-free treatment regimens. Scientific societies can barely keep up with this development, making it necessary to update the clinical guidelines by the American and European Associations for the Study of Liver Diseases within short periods. This review presents and discusses the currently available data of the use of interferon-free treatment in the setting of liver transplantation. However, costs, different reimbursement strategies, and health-care options cannot be answered by guidelines and recommendations from scientific societies. Further investigator-initiated trials are needed to individualize treatment concepts.
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Affiliation(s)
- Sandra Beinhardt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Harald Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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38
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Zhang AY, Liu YM, Gong JP. Kupffer cells and liver transplantation. Shijie Huaren Xiaohua Zazhi 2015; 23:1917-1923. [DOI: 10.11569/wcjd.v23.i12.1917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Nowadays, liver transplantation is globally considered the most effective treatment for end-stage liver diseases. Ischemia-reperfusion (I/R) injury and immune rejection response (IRR) are the two major imperfections which severely affect the recipients' prognosis and survival rate without satisfactory clinical management strategies. Therefore, exploring effective methods to improve I/R injury and IRR have important clinical significance under circumstances of shortage of donor livers. Kupffer cells (KCs) are the largest population of antigen representing cells (APCs) which settle in the liver. As the first defensive line of the live, KCs exhibit various biological effects. However, the exact mechanisms responsible for the role of KCs in I/R injury and IRR remain elusive. We hereby review the current finding about the role of KCs in I/R injury and IRR.
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