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Adekunle RO, Rodrigues M, Durand CM. Evaluating Challenges in Access To Transplantation for Persons with HIV. Curr HIV/AIDS Rep 2025; 22:26. [PMID: 40113607 PMCID: PMC11926053 DOI: 10.1007/s11904-025-00735-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/07/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE OF REVIEW Antiretroviral therapy has significantly improved the life expectancy of people with HIV (PWH), leading to an increased prevalence of comorbidities such as end-stage organ diseases. PWH with end-stage disease face a significantly higher risk of mortality compared to those without HIV, highlighting the urgent need to improve access to organ transplantation for this vulnerable group. This review examines barriers to organ transplantation for PWH, utilizing a modified five A's model (acceptability, availability, accessibility, affordability, accommodation). RECENT FINDINGS Despite comparable post-transplant outcomes to the general population, PWH are less likely to receive organ transplants. The HIV Organ Policy and Equity (HOPE) Act has expanded the donor pool by permitting organ transplants from donors with HIV to recipients with HIV. However, factors limiting expansion include policy, logistical constraints, and HIV-related stigma. Despite pivotal advancements in HIV organ transplantation, multilevel challenges continue to limit access for PWH. Addressing these barriers is essential to ensuring equitable access to this life-saving therapy.
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Affiliation(s)
- Ruth O Adekunle
- Division of Infectious Diseases, Medical University of South Carolina, 135 Rutledge Avenue, 12th Floor, MSC 752, Charleston, SC, 29425, USA.
| | - Moreno Rodrigues
- Department of Medicine, Johns Hopkins University School of Medicine, 2000 E. Monument Street Room 103, Baltimore, MD, 21205, USA
| | - Christine M Durand
- Department of Medicine, Johns Hopkins University School of Medicine, 2000 E. Monument Street Room 103, Baltimore, MD, 21205, USA.
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2
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Aslam S, Hussain S, Haydel B, Florman SS, Gilbert AJ, Pereira MR, Elias N, Hand J, Mekeel K, Schnickel G, Shah M, Ajmera V, Tobian AAR, Odim J, Massie A, Segev DL, Durand CM, Rana M. Breaking barriers: successful outcomes of hepatitis C virus D +/R - Transplants in HIV + Recipients. Am J Transplant 2025:S1600-6135(25)00090-5. [PMID: 39956322 DOI: 10.1016/j.ajt.2025.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/05/2025] [Accepted: 02/11/2025] [Indexed: 02/18/2025]
Abstract
Transplantation from donors with hepatitis C virus (HCV) viremia to recipients without HCV-viremia (HCV D+/R-) is common, but no data exist for recipients with HIV or donors with HCV/HIV coinfection. We assessed outcomes of HCV D+/R- transplants within 3 HIV Organ Policy Equity Act studies of HIV+ abdominal transplantation to recipients with HIV between 2017 and 2023. Eighteen kidney and 6 liver transplant recipients with HIV received organs from 19 donors with HCV viremia, including 7 with HCV/HIV coinfection. Median recipient age was 58 years, 96% were male, and median waitlist time was 1 year. All recipients had undetectable HIV RNA at time of transplant with median cluster of differentiation 4 count 499 cells/mm3. HCV/HIV-coinfected donors had median cluster of differentiation 4 count 210 cells/mm3, and 4 of the 7 had detectable HIV RNA. HCV treatment with direct-acting antivirals was initiated at median 33 days after transplant and sustained virologic response was achieved in 23 of the 23 treated recipients without HCV-related adverse events; data unavailable for 1 participant. Kaplan-Meier survival analysis demonstrated 100% 1-year and 96% 3-year survival. Graft survival was 96% at 1 and 3 years. HCV D+/R- abdominal transplantation, including donors with HCV/HIV coinfection, demonstrates favorable patient and graft survival in recipients with HIV and is a viable strategy to increase organ utilization.
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Affiliation(s)
- Saima Aslam
- Department of Medicine, University of California San Diego, La Jolla, California, USA.
| | - Sarah Hussain
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Brandy Haydel
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, New York, USA
| | - Sander S Florman
- Recanati-Miller Transplantation Institute, The Mount Sinai Hospital, New York, New York, USA
| | - Alexander J Gilbert
- Division of Nephrology, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Marcus R Pereira
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, New York, USA
| | - Nahel Elias
- Departments of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Jonathan Hand
- Division of Infectious Disease, Ochsner Health, New Orleans, Los Angeles, USA
| | - Kristin Mekeel
- Department of Surgery, University of California San Diego, La Jolla, California, USA
| | - Gabriel Schnickel
- Department of Surgery, University of California San Diego, La Jolla, California, USA
| | - Mita Shah
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Veeral Ajmera
- Department of Medicine, University of California San Diego, La Jolla, California, USA
| | - Aaron A R Tobian
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jonah Odim
- Division of Allergy Immunology of Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
| | - Allan Massie
- Department of Surgery, NYU Langone Health, New York, New York, USA
| | - Dorry L Segev
- Department of Surgery, NYU Langone Health, New York, New York, USA
| | - Christine M Durand
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Meenakshi Rana
- Division of Infectious Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Rossotti R, Merli M, Mazzarelli C, De Carlis RM, Travi G, Vecchi M, Viganò R, Lauterio A, Raimondi A, Belli LS, De Carlis LG, Puoti M. Similar survival but higher and delayed hepatocellular carcinoma recurrence in HIV-positive compared to negative cirrhotics undergoing liver transplantation. Dig Liver Dis 2023; 55:268-275. [PMID: 35644890 DOI: 10.1016/j.dld.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. AIMS To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. METHODS Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. RESULTS Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). CONCLUSIONS Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.
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Affiliation(s)
- Roberto Rossotti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
| | - Marco Merli
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Chiara Mazzarelli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Riccardo Maria De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanna Travi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marta Vecchi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Raffaella Viganò
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Alessandro Raimondi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luca Saverio Belli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luciano Gregorio De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; School of Medicine, University of Milan-Bicocca, Milan, Italy
| | - Massimo Puoti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; School of Medicine, University of Milan-Bicocca, Milan, Italy
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4
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Saeed H, Cano EJ, Khan MQ, Yetmar ZA, Smith B, Rizza SA, Badley AD, Mahmood M, Leise MD, Cummins NW. Changing Landscape of Liver Transplantation in the Post-DAA and Contemporary ART Era. Life (Basel) 2022; 12:1755. [PMID: 36362910 PMCID: PMC9693252 DOI: 10.3390/life12111755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 07/30/2023] Open
Abstract
Combination anti-retroviral therapy has drastically improved solid organ transplantation outcomes in persons living with HIV. DAA therapy has led to the successful eradication of HCV. While recent data have suggested improvement in outcomes in HIV/HCV-coinfected liver transplant recipients, temporal trends in patient survival within pre- and post-DAA eras are yet to be elucidated. The UNOS database was utilized to identify deceased donor liver transplant recipients between 1 January 2000 and 30 September 2020 and stratify them by HIV and HCV infection status. A total of 85,730 patients met the inclusion criteria. One-year and five-year patient survival improved (93% and 80%, respectively) for all transplants performed post-2015. For HIV/HCV-coinfected recipients, survival improved significantly from 78% (pre-2015) to 92% (post-2015). Multivariate regression analyses identified advanced recipient age, Black race, diabetes mellitus and decompensated cirrhosis as risk factors associated with higher one-year mortality. Liver transplant outcomes in HIV/HCV-coinfected liver transplant recipients have significantly improved over the last quinquennium in the setting of the highly effective combination of ART and DAA therapy. The presence of HIV, HCV, HIV/HCV-coinfection and active HCV viremia at the time of transplant do not cause higher mortality risk in liver transplant recipients in the current era.
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Affiliation(s)
- Huma Saeed
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
| | - Edison J. Cano
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
| | - Mohammad Qasim Khan
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA
| | - Zachary A. Yetmar
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
| | - Byron Smith
- Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55902, USA
| | - Stacey A. Rizza
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA
| | - Andrew D. Badley
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA
| | - Maryam Mahmood
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
| | - Michael D. Leise
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, USA
| | - Nathan W. Cummins
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA
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5
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Liver Outcome in Renal Transplant Recipients Who Acquired Hepatitis C Infection From an Infected Graft: Study Based on Liver Biopsy Findings. Transplant Direct 2022; 8:e1342. [PMID: 35651584 PMCID: PMC9148688 DOI: 10.1097/txd.0000000000001342] [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: 04/05/2022] [Revised: 04/18/2022] [Accepted: 04/19/2022] [Indexed: 11/25/2022] Open
Abstract
Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts.
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6
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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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7
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Kumar RN, Stosor V. Advances in Liver Transplantation for Persons with Human Immunodeficiency Infection. Curr Infect Dis Rep 2022; 24:39-50. [PMID: 35308580 PMCID: PMC8922075 DOI: 10.1007/s11908-022-00776-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 02/06/2023]
Affiliation(s)
- Rebecca N. Kumar
- Division of Infectious Diseases and Travel Medicine, Georgetown University Medical Center, Washington, DC USA
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611 USA
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8
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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: 8] [Impact Index Per Article: 2.0] [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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9
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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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10
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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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11
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Yamamoto H, Sugawara Y, Sambommatsu Y, Shimata K, Yoshii D, Isono K, Honda M, Yamashita T, Matsushita S, Inomata Y, Hibi T. Living donor domino liver transplantation in a hepatitis C virus/human immunodeficiency virus-coinfected hemophilia patient: a case report. Surg Case Rep 2020; 6:184. [PMID: 32728812 PMCID: PMC7391454 DOI: 10.1186/s40792-020-00944-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 07/15/2020] [Indexed: 11/10/2022] Open
Abstract
Background Outcome of the liver transplantation (LT) is worse in hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients compared to patients infected with HCV alone. We report the world’s first case of living donor domino liver transplantation (LDDLT) using a familial amyloid polyneuropathy (FAP) liver in a coinfected recipient with HCV-related liver cirrhosis. Case presentation The recipient was a 43-year-old male with a CD4 cell count of 52/μL and undetectable HIV-RNA at the time of LT. He received a domino liver graft from a 41-year-old female with FAP. No acute cellular rejection or infection occurred after LT. HCV recurrence was confirmed histologically on the posttransplant day 34. Peginterferon/ribavirin therapy resulted in non-response; however, the patient achieved a sustained viral response with sofosbuvir (SOF)/ledipasvir (LDV). Currently, HCV and HIV testing are negative, and symptomatic de novo amyloidosis has not occurred. Conclusions LDDLT allows successful LT in HCV/HIV-coinfected patients; posttransplant HCV recurrence can be successfully treated with anti-viral therapy.
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Affiliation(s)
- Hidekazu Yamamoto
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
| | - Yasuhiko Sugawara
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Yuzuru Sambommatsu
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Keita Shimata
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Daiki Yoshii
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Kaori Isono
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Masaki Honda
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
| | - Taro Yamashita
- Department of Neurology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, 860-8556, Japan
| | - Shuzo Matsushita
- Center for AIDS Research, Kumamoto University, Kumamoto, 860-8556, Japan
| | - Yukihiro Inomata
- Department of Surgery, Kumamoto Rosai Hospital, Kumamoto, 866-8533, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
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12
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Abstract
: With current antiretroviral therapy, the lifespan of newly diagnosed persons with HIV (PWH) approaches that of uninfected persons. However, metabolic abnormalities related to both the disease and the virus itself, along with comorbidities of aging, have resulted in end-organ disease and organ failure as a major cause of morbidity and mortality. Solid organ transplantation is a life-saving therapy for PWH who have organ failure, and the approval of the HIV Organ Policy Equity Act has opened and expanded opportunities for PWH to donate and receive organs. The current environment of organ transplantation for PWH will be reviewed and future directions of research and treatment will be discussed.
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Affiliation(s)
| | - Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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13
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Morales MK, Lambing T, Husson J. Review: Evaluation and Management of the HIV/HCV Co-Infected Kidney or Liver Transplant Candidate. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020. [DOI: 10.1007/s40506-020-00220-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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14
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Eman P, Chacon E, Gupta M, Berger JC, Shah MB, El Haddad HE, El-Husseini A, Dela Cruz AC, Grigorian A, Mei X, Gedaly R. Long term outcomes of patients transplanted for hepatocellular carcinoma with human immunodeficiency virus infection. HPB (Oxford) 2019; 21:1009-1016. [PMID: 30765199 DOI: 10.1016/j.hpb.2019.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 12/18/2018] [Accepted: 01/03/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND We aimed to study outcomes in HIV + patients with HCC in the US following Liver Transplantation (LT) using the UNOS dataset. METHODS The database was queried from 2003 to 2016 for patients undergoing LT with HCC, HIV+, and HCC/HIV+. RESULTS Out of 17,397 LT performed for HCC during the study period, 113 were transplanted for HCC with HIV infection (91 isolated livers). Patients transplanted for HCC/HIV+ were younger (55.54 ± 5.89 vs 58.80 ± 7.37, p < 0.001), had lower total bilirubin (1.20 vs 1.60, p = 0.042) significantly lower BMI (25.35 ± 4.43 vs 28.39 ± 5.17, p < 0.001) and were more likely to be co-infected with HBV (25.3% vs 8.2% p < 0.001) than those transplanted for HCC alone. HCC/HIV + patients were found to have a 3.8 fold increased risk of peri-operative mortality at 90 days after matching. HCC/HIV + recipients had 54% decreased long-term survival within the HCC cohort. Our initial analysis of overall graft and patient survival found significant differences between HCC/HIV and HCC/HIV + recipients. However, these variances were lost after case-matching. Recurrence and disease free survival were similar in HCC alone vs HCC/HIV + recipients. CONCLUSIONS Our analysis suggests that excellent outcomes can be achieved in selected patients with HCC/HIV+.
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Affiliation(s)
- Pedro Eman
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, USA
| | - Eduardo Chacon
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, USA
| | - Meera Gupta
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, USA
| | - Jonathan C Berger
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, USA
| | - Malay B Shah
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, USA
| | - Hanine E El Haddad
- Department of Medicine, Division of Infectious Diseases, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Amr El-Husseini
- Department of Medicine, Division of Nephrology, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Anna C Dela Cruz
- Department of Medicine, Division of Gastroenterology, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Alla Grigorian
- Department of Medicine, Division of Gastroenterology, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Xiaonan Mei
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, USA
| | - Roberto Gedaly
- Department of Surgery - Transplant Division, University of Kentucky, College of Medicine, Lexington, KY, 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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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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17
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Hepatic Failure Due to Cholestatic Hepatitis C in an Immunosuppressed Patient Treated With Elbasvir and Grazeprevir. ACG Case Rep J 2018; 5:e6. [PMID: 29392153 PMCID: PMC5772065 DOI: 10.14309/crj.2018.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/15/2017] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C-induced cholestatic hepatitis is a well-known fatal complication of postorthotropic liver transplantation and prolonged immunosuppression. Recent studies on direct-acting antiviral agents have shown promising results in terms of morbidity and mortality of this condition in postorthotropic liver, heart, and renal transplant patients. However, hepatitis C-induced cholestatic hepatitis remains a highly fatal condition in non-transplant patients. We report the first-ever use of the oral direct-acting antiviral combination, elbasvir and grazeprevir, in the treatment of a non-liver transplant patient with cholestatic hepatitis.
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18
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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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19
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Araiz JJ, Serrano MT, García-Gil FA, Lacruz EM, Lorente S, Sánchez JI, Suarez MA. Intention-to-treat survival analysis of hepatitis C virus/human immunodeficiency virus coinfected liver transplant: Is it the waiting list? Liver Transpl 2016; 22:1186-96. [PMID: 27114030 DOI: 10.1002/lt.24474] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Accepted: 04/08/2016] [Indexed: 01/13/2023]
Abstract
In human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, the accelerated severity of liver disease, associated comorbidities, and mortality on the waiting list could change the possibility and results of liver transplantation (LT). Intention-to-treat survival analysis (ITTA) can accurately estimate the applicability and efficacy of LT. The primary objective of this study was to compare the survival of patients with HCV with and without HIV infection. We analyzed a cohort of 199 patients with HCV infection enrolled for LT between 1998 and 2015; 17 were also infected with HIV. The patients with HCV/HIV coinfection had higher mortality on the waiting list than those with HCV monoinfection (35.3% versus 4.6%; P < 0.001). ITTA at 1, 3, and 4 years was 75%, 64%, and 57% for HCV monoinfection and 52%, 47%, and 39% for HCV/HIV coinfection, respectively (Wilcoxon test P < 0.05). The ITTA at 1, 3, 6, and 12 months was 96%, 91%, 87%, and 75% for HCV monoinfection and 76%, 70%, 64%, and 52% for HCV/HIV coinfection, respectively (log-rank P < 0.05; Wilcoxon test P < 0.01). A Cox regression analysis was carried out including all variables with predictive value in the univariate analysis, showing that only donor age > 70 years (hazard ratio [HR] = 3.12; P < 0.05), United Network for Organ Sharing status 1 (HR = 10.1; P < 0.01), Model for End-Stage Liver Disease (HR = 1.13; P < 0.001), and HIV coinfection (HR = 2.65; P < 0.05) had independent negative predictive value for survival. In conclusion, our study indicates that HIV coinfection is a factor in mortality prior to transplantation and associated with higher mortality on the waiting list. Liver Transplantation 22 1186-1196 2016 AASLD.
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Affiliation(s)
- Juan J Araiz
- Transplant Procurement Management, University Hospital Lozano Blesa, Zaragoza, Spain.,Intensive Care Unit, University Hospital Lozano Blesa, Zaragoza, Spain.,Department of Medicine, University Hospital Lozano Blesa, Zaragoza, Spain
| | - M Trinidad Serrano
- Department of Medicine, University Hospital Lozano Blesa, Zaragoza, Spain.,Liver Unit, Department of Gastroenterology, University Hospital Lozano Blesa, Zaragoza, Spain.,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | - Francisco A García-Gil
- Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain.,Hepatic Surgery Unit, Department of Surgery, University Hospital Lozano Blesa, Zaragoza, Spain.,Department of Surgery, University of Zaragoza, Zaragoza, Spain
| | - Elena M Lacruz
- Intensive Care Unit, University Hospital Lozano Blesa, Zaragoza, Spain
| | - Sara Lorente
- Liver Unit, Department of Gastroenterology, University Hospital Lozano Blesa, Zaragoza, Spain.,Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | - José I Sánchez
- Intensive Care Unit, University Hospital Lozano Blesa, Zaragoza, Spain
| | - Miguel A Suarez
- Intensive Care Unit, University Hospital Lozano Blesa, Zaragoza, Spain.,Department of Medicine, University Hospital Lozano Blesa, Zaragoza, Spain
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20
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Successful Treatment of Mitochondrial Toxicity in an HIV-Positive Patient After Liver Transplantation. Transplant Proc 2016; 47:2771-4. [PMID: 26680091 DOI: 10.1016/j.transproceed.2015.10.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 10/01/2015] [Indexed: 11/20/2022]
Abstract
Liver transplantation in patients infected with the human immunodeficiency virus (HIV) has been increasingly performed with reasonable outcomes; however, medical management of both immunosuppression and antiretroviral therapy can be challenging owing to drug toxicities and interactions. Nucleoside reverse transcriptase inhibitors (NRTIs), a common backbone of highly active antiretroviral therapy (HAART), were the first class of effective antiretroviral drugs developed. NRTIs are commonly used for posttransplant HAART therapy and have a rare but fatal complication of mitochondrial toxicity, manifesting as severe lactic acidosis, hepatic steatosis, and lipoatrophy. Herein, we have reported on the first known successful treatment of severe mitochondrial toxicity secondary to NRTIs in an HIV-infected transplant recipient.
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21
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Long-term Outcomes After Liver Transplantation Among Human Immunodeficiency Virus-Infected Recipients. Transplantation 2016; 100:141-6. [PMID: 26177090 DOI: 10.1097/tp.0000000000000829] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Early outcomes after human immunodeficiency virus (HIV) + liver transplantation (LT) are encouraging, but data are lacking regarding long-term outcomes and comparisons with matched HIV- patients. METHODS We examined outcomes among 180 HIV+ LT, and compared outcomes to matched HIV- counterfactuals (Scientific Registry of Transplant Recipients 2002-2011). Iterative expanding radius matching (1:10) on recipient age, race, body mass index, hepatitis C virus (HCV), model for end-stage liver disease score, and acute rejection; and donor age and race, cold ischemia time, and year of transplant. Patient survival and graft survival were estimated using Kaplan-Meier methodology and compared using log-rank and Cox proportional hazards. Subgroup analyses were performed by transplant era (early: 2002-2007 vs. modern: 2008-2011) and HCV infection status. RESULTS Compared to matched HIV- controls, HIV+ LT recipients had a 1.68-fold increased risk for death (adjusted hazard ratio [aHR], 1.68, 95% confidence interval [95% CI], 1.28-2.20; P < 0.001), and a 1.70-fold increased risk for graft loss (aHR, 1.70; 95% CI, 1.31-2.20; P < 0.001). These differences persisted independent of HCV infection status. However, in the modern transplant era risk for death (aHR, 1.11; 95% CI, 0.52-2.35; P = 0.79) and graft loss (aHR, 0.89; 95% CI, 0.42-1.88; P = 0.77) were similar between monoinfected and uninfected LT recipients. In contrast, independent of transplant era, coinfected LT recipients had increased risk for death (aHR, 2.24; 95% CI, 1.43-3.53; P < 0.001) and graft loss (aHR, 2.07; 95% CI, 1.33-3.22; P = 0.001) compared to HCV+ alone LT recipients. CONCLUSIONS These results suggest that outcomes among monoinfected HIV+ LT recipients have improved over time. However, outcomes among HIV+ LT recipients coinfected with HCV remain concerning and motivate future survival benefit studies.
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22
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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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23
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Schafer JJ, Gill TK, Sherman EM, McNicholl IR. ASHP Guidelines on Pharmacist Involvement in HIV Care. Am J Health Syst Pharm 2016; 73:468-94. [PMID: 26892679 DOI: 10.2146/ajhp150623] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Jason J Schafer
- Department of Pharmacy Practice, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA
| | - Taylor K Gill
- Internal Medicine, Via Christi Hospitals Wichita, Wichita, KS
| | - Elizabeth M Sherman
- College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, and South Broward Community Health Services, Memorial Healthcare System, Hollywood, FL
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24
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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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25
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Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection. AIDS 2016; 30:93-8. [PMID: 26731756 DOI: 10.1097/qad.0000000000000887] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Recurrent hepatitis C virus (HCV) infection contributes to unfavourable outcomes in HIV/HCV coinfected liver transplant recipients. Direct-acting antiviral (DAA) therapies for HCV offer an opportunity to improve patient and allograft survival in this patient population. We evaluated treatment outcomes with sofosbuvir (SOF)-based DAA therapy among HIV/HCV coinfected liver transplant recipients. DESIGN Single centre prospective cohort study. METHODS We identified eight HIV/HCV coinfected liver transplant recipients who were prospectively followed in the Northwestern University Viral Hepatitis Registry and who received SOF-based DAA therapy. We evaluated responses to therapy, including sustained HCV viral response 12 weeks after therapy completion (SVR12) and adverse effects. RESULTS Seven recipients (87.5%) completed 12 weeks of SOF-based therapy: SOF/simeprevir for genotype 1 (n = 6), SOF/ribavirin for genotype 2 (n = 1). Of persons who completed therapy, all achieved SVR12. Strategies for the management of expected and observed drug interactions consequent to the addition of simeprevir to preexisting complex medication regimens included modifications of HIV antiretroviral regimens (n = 4) and tacrolimus dosing (n = 4) and frequent monitoring of tacrolimus trough levels. Minor adverse effects were observed after DAA initiation. One episode of allograft rejection and one death occurred that were deemed unlikely related to HCV therapy. CONCLUSION High rates of HCV treatment success and no treatment-limiting adverse effects were observed in this HIV/HCV liver transplant cohort. Complex drug interactions were successfully managed in the context of multidisciplinary specialty care. Further studies are needed to assess the long-term effects of DAA therapy on patient and allograft survival among HIV/HCV coinfected liver transplant recipients.
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26
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Joshi D, Agarwal K. Role of liver transplantation in human immunodeficiency virus positive patients. World J Gastroenterol 2015; 21:12311-12321. [PMID: 26604639 PMCID: PMC4649115 DOI: 10.3748/wjg.v21.i43.12311] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 08/04/2015] [Accepted: 10/26/2015] [Indexed: 02/06/2023] Open
Abstract
End-stage liver disease (ESLD) is a leading cause of morbidity and mortality amongst human immunodeficiency virus (HIV)-positive individuals. Chronic hepatitis B and hepatitis C virus (HCV) infection, drug-induced hepatotoxicity related to combined anti-retro-viral therapy, alcohol related liver disease and non-alcohol related fatty liver disease appear to be the leading causes. It is therefore, anticipated that more HIV-positive patients with ESLD will present as potential transplant candidates. HIV infection is no longer a contraindication to liver transplantation. Key transplantation outcomes such as rejection and infection rates as well as medium term graft and patient survival match those seen in the non-HIV infected patients in the absence of co-existing HCV infection. HIV disease does not seem to be negatively impacted by transplantation. However, HIV-HCV co-infection transplant outcomes remain suboptimal due to recurrence. In this article, we review the key challenges faced by this patient cohort in the pre- and post-transplant period.
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27
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Teicher E, Boufassa F, Vittecoq D, Antonini TM, Tateo MG, Coilly A, Roque-Afonso AM, Kassis-Chikhani N, Lambotte O, Ichai P, Samuel D, Duclos-Vallee JC. Infectious complications after liver transplantation in human immunodeficiency virus-infected recipients. Transpl Infect Dis 2015; 17:662-70. [PMID: 26192379 DOI: 10.1111/tid.12422] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 06/15/2015] [Accepted: 07/05/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND Few studies have investigated infections in human immunodeficiency virus (HIV)-infected liver transplant patients. The aim of this study was to describe the prevalence, time of onset, mortality of infectious complications, other than hepatitis C virus (HCV), and to identify risk factors for their development in a large single-center cohort of HIV-infected liver transplant patients. METHODS We studied 109 consecutive HIV-infected patients who underwent liver transplantation (LT) between 1999 and 2010 and followed until December 2012. RESULTS The median age was 44 years (interquartile range [IQR] 41-49), 82.6% were male, and the median follow-up was 45.7 months (IQR 14-65). The major indications for LT were HCV cirrhosis (61%) and hepatocellular carcinoma (19%). Forty patients (37%) developed at least 1 infection during the first year after LT. Twenty-eight (26%) patients had an episode of bacteremia. Five (4.6%) patients developed a cytomegalovirus infection. Fungal infections occurred in 5 (4.5%) patients. Four (3.6%) patients developed an HIV-related opportunistic infection. A total of 43 (39.4%) patients died during follow-up. Mortality related to infection occurred in 9 (7%) cases, and 20 (42.5%) patients died because of HCV recurrence. No patients died from opportunistic infections. Model for end-stage liver disease (MELD) score >17 was associated with a 2-fold higher risk (hazard ratio 1.96; 95% confidence interval 1.01-3.80) of developing infectious complications. CONCLUSIONS Infections are not a major cause of mortality after LT in HIV patients and opportunistic infections of acquired immunodeficiency syndrome are infrequent. A MELD score >17 increased the risk of developing post-LT infectious complications. Recurrence of HCV infection remains a major cause of mortality.
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Affiliation(s)
- E Teicher
- Service de Médecine Interne Immunologie Clinique et Maladies Infectieuses, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,DHU Hepatinov, Villejuif, France
| | - F Boufassa
- Centre for research in Epidemiology and Population Health - U1018, Inserm, Le Kremlin-Bicêtre, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France
| | - D Vittecoq
- Service de Médecine Interne Immunologie Clinique et Maladies Infectieuses, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France
| | - T M Antonini
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,DHU Hepatinov, Villejuif, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France.,Unité 1193, Inserm, Villejuif, France
| | - M-G Tateo
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France
| | - A Coilly
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,DHU Hepatinov, Villejuif, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France.,Unité 1193, Inserm, Villejuif, France
| | - A-M Roque-Afonso
- Univ Paris-Sud, Le Kremlin-Bicêtre, France.,Unité 1193, Inserm, Villejuif, France.,Département de Microbiologie et Virologie, AP-HP Hôpital Paul-Brousse, Villejuif, France
| | - N Kassis-Chikhani
- Département de Microbiologie et Virologie, AP-HP Hôpital Paul-Brousse, Villejuif, France
| | - O Lambotte
- Univ Paris-Sud, Le Kremlin-Bicêtre, France
| | - P Ichai
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,DHU Hepatinov, Villejuif, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France.,Unité 1193, Inserm, Villejuif, France
| | - D Samuel
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,DHU Hepatinov, Villejuif, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France.,Unité 1193, Inserm, Villejuif, France
| | - J-C Duclos-Vallee
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,DHU Hepatinov, Villejuif, France.,Univ Paris-Sud, Le Kremlin-Bicêtre, France.,Unité 1193, Inserm, Villejuif, France
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28
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Abstract
PURPOSE OF REVIEW To review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients. RECENT FINDINGS The prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required. SUMMARY Liver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.
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29
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Sawinski D, Goldberg DS, Blumberg E, Abt PL, Bloom RD, Forde KA. Beyond the NIH Multicenter HIV Transplant Trial Experience: Outcomes of HIV+ Liver Transplant Recipients Compared to HCV+ or HIV+/HCV+ Coinfected Recipients in the United States. Clin Infect Dis 2015; 61:1054-62. [PMID: 26082506 DOI: 10.1093/cid/civ471] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 06/07/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The effectiveness of liver transplant (LT) in human immunodeficiency virus (HIV) and HIV/hepatitis C virus (HCV) coinfected recipients in the United States is unknown. We investigated (i) the effect of HIV on US patient and allograft LT outcomes, compared to HCV+ and HIV/HCV uninfected recipients and (ii) whether LT at centers that participated in the National Institutes of Health (NIH) Solid Organ Transplantation in HIV Trial, reflecting experience and a standardized approach to patient selection, impacted outcomes. METHODS A retrospective cohort study of primary LT recipients transplanted 27 February 2002 through 31 December 2013, categorized by serostatus: HCV+ (n = 20 829), HIV+ (n = 72), HIV+/HCV+ (n = 160), and HIV-/HCV- uninfected (n = 22 926) as reference. Survival was determined using Cox regression, stratified according to center NIH trial participation. RESULTS HCV (hazard ratio [HR] 1.46, 95% confidence interval [CI], 1.41-1.52) and HIV/HCV coinfection (HR 2.62, 95% CI, 2.06-3.33) were associated with mortality; HIV monoinfection was not (HR 1.37, 95% CI, .86-2.18). This was unchanged after stratification on NIH trial participation, although mortality was higher in NIH-enrolling (HIV+: HR 1.65, 95% CI, .93-2.92; HIV+/HCV+: HR 3.15, 95% CI, 2.32-4.28) than in non-enrolling centers (HIV+: HR 1.03, 95% CI, .43-2.47, HIV+/HCV+: HR 2.55, 95% CI, 1.64-3.96). Although allograft loss was higher in HIV/HCV coinfected recipients transplanted at enrolling (HR 2.64, 9%% CI, 1.91-3.64) vs nonenrolling centers (HR 2.22, 95% CI, 1.41-3.49), there was no difference in HIV and HCV monoinfected patients. CONCLUSIONS HIV+ LT recipient outcomes were superior to HCV+ or HIV/HCV coinfected recipients. Despite a standardized approach and plausibly more experience with HIV patients, transplantation at NIH study center did not improve outcomes.
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Affiliation(s)
- Deirdre Sawinski
- Department of Medicine, Renal Electrolyte and Hypertension Division
| | - David S Goldberg
- Department of Medicine, Division of Gastroenterology Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine
| | | | - Peter L Abt
- Department of Surgery, University of Pennsylvania, Philadelphia
| | - Roy D Bloom
- Department of Medicine, Renal Electrolyte and Hypertension Division
| | - Kimberly A Forde
- Department of Medicine, Division of Gastroenterology Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine
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30
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Miro JM, Stock P, Teicher E, Duclos-Vallée JC, Terrault N, Rimola A. Outcome and management of HCV/HIV coinfection pre- and post-liver transplantation. A 2015 update. J Hepatol 2015; 62:701-11. [PMID: 25450714 DOI: 10.1016/j.jhep.2014.10.032] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 10/15/2014] [Accepted: 10/23/2014] [Indexed: 01/13/2023]
Abstract
Liver transplantation is increasingly performed in selected HIV-infected patients in most developed countries, with excellent results reported in patients with liver diseases unrelated to HCV. In contrast, survival in HCV/HIV-coinfected liver recipients is poorer than in HCV-monoinfected patients, due to more aggressive recurrence of HCV and consequent graft loss and death. Results from American, French, and Spanish cohort studies showed a 5-year survival rate of only 50-55%. Therefore, it is debated whether liver transplantation should be offered to HCV/HIV-coinfected patients. Studies have shown that the variables more consistently associated with poor outcome are: (1) the use of old or HCV-positive donors, (2) dual liver-kidney transplantation, (3) recipients with very low body mass index and (4) less site experience. However, the most effective factor influencing transplantation outcome is the successful treatment of HCV recurrence with anti-HCV. Survival is 80% in patients whose HCV infection resolves. Unfortunately, the rates of sustained virological response with pegylated-interferon plus ribavirin in coinfected recipients are low, particularly for genotype 1 (only 10%). Here we present a non-systematic review of the literature based on our own experience in different liver transplant scenarios. This review covers selection criteria in HIV-infected patients, pre- and post-LT management, donor selection, anti-HCV treatment, drug interactions with antiretrovirals and anti-HCV direct antiviral agents, hepatocellular carcinoma, and liver retransplantation. Recommendations are rated. Finally, we explain how the introduction of new effective and more tolerable direct antiviral agents may improve significantly the outcome of HCV/HIV-coinfected liver recipients.
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Affiliation(s)
- Jose M Miro
- Infectious Diseases Service, Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
| | - Peter Stock
- Department of Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Elina Teicher
- Département Médecine Interne et Infectiologie, AP-HP Hôpital Kremlin Bicêtre, Le Kremlin Bicêtre, DHU Hepatinov, France
| | - Jean-Charles Duclos-Vallée
- AP-HP Hôpitaux de Paris, Centre Hépato-Biliaire, Univ. Paris-Sud, UMR-S 785, Inserm, Unité 785, DHU Hepatinov, Villejuif, France
| | - Norah Terrault
- Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA
| | - Antoni Rimola
- Liver Unit, Hospital Clinic - IDIBAPS, CIBEREHD, Barcelona, Spain
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31
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Castells L, Rimola A, Manzardo C, Valdivieso A, Montero JL, Barcena R, Abradelo M, Xiol X, Aguilera V, Salcedo M, Rodriguez M, Bernal C, Suarez F, Antela A, Olivares S, Del Campo S, Laguno M, Fernandez JR, de la Rosa G, Agüero F, Perez I, González-García J, Esteban-Mur JI, Miro JM. Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: a prospective cohort study. J Hepatol 2015; 62:92-100. [PMID: 25127748 DOI: 10.1016/j.jhep.2014.07.034] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 07/22/2014] [Accepted: 07/28/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly.
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Affiliation(s)
- Lluis Castells
- Hospital Vall d'Hebrón, Universitat Autónoma de Barcelona, Barcelona, Spain; CIBEREHD, Barcelona, Spain
| | - Antoni Rimola
- CIBEREHD, Barcelona, Spain; Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | | | | | - Rafael Barcena
- Hospital Universitario Ramón y Cajal-IRYCIS, Madrid, Spain
| | | | - Xavier Xiol
- Hospital de Bellvitge-IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | | | | | | | - Carmen Bernal
- Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | | | - Antonio Antela
- Hospital Universitario de Santiago de Compostela, La Coruña, Spain
| | | | | | | | - José R Fernandez
- Hospital de Cruces, University of the Basque Country, Bilbao, Spain
| | | | - Fernando Agüero
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Iñaki Perez
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Juan I Esteban-Mur
- Hospital Vall d'Hebrón, Universitat Autónoma de Barcelona, Barcelona, Spain; CIBEREHD, Barcelona, Spain
| | - Jose M Miro
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
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Miro J, Agüero F, Duclos-Vallée JC, Mueller N, Grossi P, Moreno A. Infections in solid organ transplant HIV-infected patients. Clin Microbiol Infect 2014; 20 Suppl 7:119-30. [DOI: 10.1111/1469-0691.12754] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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33
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Saab S, Gordon SC, Park H, Sulkowski M, Ahmed A, Younossi Z. Cost-effectiveness analysis of sofosbuvir plus peginterferon/ribavirin in the treatment of chronic hepatitis C virus genotype 1 infection. Aliment Pharmacol Ther 2014; 40:657-75. [PMID: 25065960 DOI: 10.1111/apt.12871] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Revised: 04/15/2014] [Accepted: 06/20/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND Sofosbuvir, an oral NS5B nucleotide polymerase inhibitor, is indicated for the treatment of patients infected with hepatitis C virus (HCV). AIM To evaluate the long-term health economic outcomes of sofosbuvir + pegylated interferon alfa/ribavirin (pegIFN/RBV) compared with current treatments in patients infected with HCV genotype 1 in the US. METHODS A decision-analytic Markov model was developed to estimate health outcomes, number needed to treat and short-term and long-term economic outcomes, including incremental cost-effectiveness ratios and cost per sustained virological response (SVR), for several sofosbuvir-comparator regimen pairings for a cohort of 10 000 patients. It considered three patient cohorts: treatment-naïve, treatment-experienced and treatment-naïve human immunodeficiency virus (HIV) co-infected. Subgroup analyses were conducted for treatment-naïve patients with and without cirrhosis. RESULTS Reductions in the incidence of new cases of liver-disease complications with sofosbuvir + pegIFN/RBV compared with pegIFN/RBV, boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV were 64-82%, 50-68%, 43-58% and 33-56%, respectively. Sofosbuvir + pegIFN/RBV was typically associated with the lowest 1-year cost per SVR. When considering the lifetime incremental cost per quality-adjusted life-year gained, sofosbuvir + pegIFN/RBV was the most cost-effective treatment option assessed. Sofosbuvir + pegIFN/RBV generally dominated (less costly and more effective than) boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV. CONCLUSION Sofosbuvir + pegIFN/RBV yields more favourable future health and economic outcomes than current treatment regimens for patients across all levels of treatment experience and cirrhosis stage, as well as for individuals with or without HIV co-infection.
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Affiliation(s)
- S Saab
- Department of Medicine, University of California, Los Angeles, CA, USA
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34
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The Successful Use of Telaprevir to Treat Hepatitis C Recurrence After Liver Transplantation in an HIV Co-Infected Patient. Transplantation 2014; 97:e14-5. [DOI: 10.1097/01.tp.0000438633.06344.3a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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35
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Congly SE, Doucette KE, Coffin CS. Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation. World J Gastroenterol 2014; 20:414-424. [PMID: 24574710 PMCID: PMC3923016 DOI: 10.3748/wjg.v20.i2.414] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 10/22/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for human immunodeficiency virus (HIV) positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers. Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients co-infected with hepatitis B virus (HBV). However, liver transplantation in HIV positive patients with hepatitis C virus (HCV) has poorer outcomes overall, requiring careful selection of candidates. This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management. In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.
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36
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Takatsuki M, Soyama A, Eguchi S. Liver transplantation for HIV/hepatitis C virus co-infected patients. Hepatol Res 2014; 44:17-21. [PMID: 23607831 DOI: 10.1111/hepr.12132] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2013] [Revised: 04/07/2013] [Accepted: 04/07/2013] [Indexed: 12/26/2022]
Abstract
Since the introduction of antiretroviral therapy (ART) in the mid-1990s, AIDS-related death has been dramatically reduced, and hepatitis-C-virus (HCV)-related liver failure or hepatocellular carcinoma has currently become the leading cause of death in HIV/HCV co-infected patients. Liver transplantation may be one of the treatments of choices in such cases, but the indications for transplantation, perioperative management including both HIV and HCV treatments, immunosuppression and the prevention/treatment of infectious complications are all still topics of debate. With the improved understanding of the viral behaviors of both HIV and HCV and the development of novel strategies, especially to avoid drug interactions between ART and immunosuppression, liver transplantation has become a realistic treatment for HIV/HCV co-infected patients.
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Affiliation(s)
- Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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37
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Stosor V. Organ Transplantation in HIV Patients: Current Status and New Directions. Curr Infect Dis Rep 2013; 15:526-35. [PMID: 24142801 DOI: 10.1007/s11908-013-0381-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Combination antiretroviral therapy has resulted in longer life expectancies in persons living with HIV; however, end organ disease and death from organ failure have become growing issues for this population. With effective therapies for viral suppression, HIV is no longer considered an absolute contraindication to organ transplantation. Over the past decade, studies of transplantation in patients with HIV have had encouraging results such that patients with organ failure are pursuing transplantation. This review focuses on the current status of organ transplantation for HIV-infected persons.
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Affiliation(s)
- Valentina Stosor
- Divisions of Infectious Diseases and Organ Transplantation and Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 900, Chicago, IL, 60611, USA,
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38
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Eguchi S, Takatsuki M, Kuroki T. Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus co-infection: update in 2013. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:263-8. [PMID: 24027085 DOI: 10.1002/jhbp.31] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Because of the progress of anti-retroviral therapy (ART) for human immunodeficiency virus (HIV), mortality due to opportunistic infection resulting in AIDS has been remarkably reduced. However, meanwhile, half of those patients have died of end-stage liver cirrhosis due to hepatitis C virus (HCV) with liver cirrhosis and early occurrence of hepatocellular carcinoma. Recently, in 2013, non-cirrhotic portal hypertension due to ART drugs or still unknown mechanisms have become problematic with early progression of the disease in this patient population. Liver transplantation (LT) could be one treatment of choice in such cases, but the indications for LT perioperative management, including both HIV and HCV treatments and immunosuppression, are still challenging. In this review, we update the literature on HIV/HCV co-infection and LT as well as recent effort for modifying allocation system for those patients.
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Affiliation(s)
- Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
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39
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Dannhorn E, O’Beirne JP. Liver transplantation for HIV/HCV coinfection: where is the controversy? Future Virol 2013. [DOI: 10.2217/fvl.13.51] [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
Liver transplantation (LT) is an accepted mode of treatment for patients with chronic liver disease. Historically, patients with HIV were excluded from LT programs, but with the introduction of highly effective antiretroviral regimens, HIV is no longer a contraindication. LT outcomes for some liver diseases in HIV-positive patients are equivalent to those observed in non-HIV-positive patients. This is not the case for patients coinfected with HIV and HCV, however, where results at 5 years have led to suggestions that LT for coinfection should be abandoned. This article examines the role of LT for HIV/HCV and identifies groups of patients where transplantation is associated with good outcomes. We believe that the application of existing knowledge to patient selection and organ allocation could improve outcomes further, and with the advent of directly acting antivirals for HCV, LT for HIV/HCV coinfection will no longer be controversial.
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Affiliation(s)
| | - James P O’Beirne
- UCL Institute of Liver & Digestive Health, Royal Free Hospital, Pond Street, Hampstead, London, UK
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40
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Rodríguez-Torres M. Challenges in the treatment of chronic hepatitis C in the HIV/HCV-coinfected patient. Expert Rev Anti Infect Ther 2013. [PMID: 23199398 DOI: 10.1586/eri.12.107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) and HIV are common coinfections that convey a shortened lifespan, mostly related to liver disease. Treatment against HCV in the coinfected patient is notoriously more complex and challenging. There are no optimal treatment algorithms for HIV/HCV coinfected patients as efficacy of approved anti-HCV therapies is low with relevant side effects. The use of direct-acting antivirals for anti-HCV therapy has the potential to improve therapeutic efficacy, but also increase side effects and drug-drug interactions. In spite of all of this, the most important and significant fact is that chronic hepatitis C is potentially curable, and the eradication of the HCV infection is a crucial outcome in this population. The establishment of a productive collaboration among the regulatory agencies, the medical community and the pharmaceutical industry could lead to faster access to more effective HCV therapies for the coinfected patient and eventually stop the progression of liver disease in these patients.
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41
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Karnik GS, Shetty K. Management of recurrent hepatitis C in orthotopic liver transplant recipients. Infect Dis Clin North Am 2013; 27:285-304. [PMID: 23714341 DOI: 10.1016/j.idc.2013.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
End-stage liver disease and hepatocellular carcinoma from chronic hepatitis C are the most common indications for orthotopic liver transplantation and the incidence of both are projected to increase over the next decade. Recurrent hepatitis C virus infection of the allograft is associated with an accelerated progression to cirrhosis, graft loss, and death. This article presents an overview of the natural history of hepatitis C virus recurrence in liver transplant recipients and guidance on optimal management strategies.
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Affiliation(s)
- Geeta S Karnik
- Department of Infectious Diseases, Georgetown University Hospital, Washington, DC 20007, USA.
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42
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Blumberg EA, Rogers CC. Human immunodeficiency virus in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:169-78. [PMID: 23465009 DOI: 10.1111/ajt.12109] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- E A Blumberg
- Perelman School of Medicine of University of Pennyslvania, Philadelphia, PA, USA.
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43
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Taege A. Organ Transplantation and HIV Progress or Success? A Review of Current Status. Curr Infect Dis Rep 2013; 15:67-76. [PMID: 23242762 DOI: 10.1007/s11908-012-0309-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Advancements in the scientific understanding of human immunodeficiency virus (HIV) and care of those afflicted have progressed to make HIV a chronic disease and significantly extend the lives of HIV patients. Subsequently, an aging population has emerged, with the conditions inherent with advanced years, including organ failure. Organ transplantation is an accepted modality for organ failure; however, it was felt to be contraindicated in HIV patients because HIV was an ultimately fatal condition that would be hastened by additional immune suppression. Highly active antiretroviral therapy has dramatically altered that mind-set. After limited early experience and a recent large national trial, HIV organ transplantation has gained a degree of acceptance. This article will review the progress and unresolved issues.
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Affiliation(s)
- Alan Taege
- Department of Infectious Diseases, Cleveland Clinic, 9500 Euclid Ave / G-21, Cleveland, OH, 44195, USA,
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44
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Akamatsu N, Sugawara Y. Living-donor liver transplantation and hepatitis C. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2013; 2013:985972. [PMID: 23401640 PMCID: PMC3564275 DOI: 10.1155/2013/985972] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Accepted: 01/01/2013] [Indexed: 12/19/2022]
Abstract
Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompression. In areas with low deceased-donor organ availability like Japan, living-donor liver transplantation (LDLT) is similarly indicated for HCV cirrhosis as deceased-donor liver transplantation (DDLT) in Western countries and accepted as an established treatment for HCV-cirrhosis, and the results are equivalent to those of DDLT. To prevent graft failure due to recurrent hepatitis C, antiviral treatment with pegylated-interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. In contrast to DDLT, many Japanese LDLT centers have reported modified treatment regimens as best efforts to secure first graft, such as aggressive preemptive antiviral treatment, escalation of dosages, and elongation of treatment duration.
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Affiliation(s)
- Nobuhisa Akamatsu
- Department of Hepato-Biliary-Pancreatic Surgery, Saitama Medical Center, Saitama Medical University, 1981 Tsujido-cho, Kamoda, Kawagoe, Saitama 350-8550, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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45
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Samuel D, Duclos-Vallee JC. Liver transplantation in the human immunodeficiency virus-hepatitis C virus coinfected patient: time to sum up. Hepatology 2013; 57:409-11. [PMID: 23297070 DOI: 10.1002/hep.26123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Revised: 10/10/2012] [Accepted: 10/15/2012] [Indexed: 01/27/2023]
Affiliation(s)
- Didier Samuel
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
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46
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Nasta P, Cattelan AM, Maida I, Gatti F, Chiari E, Puoti M, Carosi G. Antiretroviral Therapy in HIV/HCV Co-Infection Italian Consensus Workshop. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/aid.2013.32017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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47
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48
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Brennan DC, Aguado JM, Potena L, Jardine AG, Legendre C, Säemann MD, Mueller NJ, Merville P, Emery V, Nashan B. Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms. Rev Med Virol 2012; 23:97-125. [PMID: 23165654 DOI: 10.1002/rmv.1733] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2012] [Revised: 09/07/2012] [Accepted: 09/20/2012] [Indexed: 12/11/2022]
Abstract
Recent evidence suggesting a potential anti-CMV effect of mTORis is of great interest to the transplant community. However, the concept of an immunosuppressant with antiviral properties is not new, with many accounts of the antiviral properties of several agents over the years. Despite these reports, to date, there has been little effort to collate the evidence into a fuller picture. This manuscript was developed to gather the evidence of antiviral activity of the agents that comprise a typical immunosuppressive regimen against viruses that commonly reactivate following transplant (HHV1 and 2, VZV, EBV, CMV and HHV6, 7, and 8, HCV, HBV, BKV, HIV, HPV, and parvovirus). Appropriate immunosuppressive regimens posttransplant that avoid acute rejection while reducing risk of viral reactivation are also reviewed. The existing literature was disparate in nature, although indicating a possible stimulatory effect of tacrolimus on BKV, potentiation of viral reactivation by steroids, and a potential advantage of mammalian target of rapamycin (mTOR) inhibition in several viral infections, including BKV, HPV, and several herpesviruses.
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49
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Gutiérrez-Moreno M, Bernal-Bellido C, Suárez-Artacho G, Álamo-MartÍnez J, Marín-Gómez L, Serrano-Díaz-Canedo J, Padillo-Ruiz F, Gómez-Bravo M. Spontaneous Clearance of HCV in HIV–Hepatitis C Virus Coinfected Liver Transplant Patients: Prospective Study. Transplant Proc 2012; 44:2100-2. [DOI: 10.1016/j.transproceed.2012.07.074] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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50
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Gastaca M, Aguero F, Rimola A, Montejo M, Miralles P, Lozano R, Castells L, Abradelo M, Mata MDL, San Juan Rodríguez F, Cordero E, Campo SD, Manzardo C, de Urbina JO, Pérez I, Rosa GDL, Miro JM. Liver retransplantation in HIV-infected patients: a prospective cohort study. Am J Transplant 2012; 12:2465-76. [PMID: 22703615 DOI: 10.1111/j.1600-6143.2012.04142.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.
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Affiliation(s)
- M Gastaca
- Hospital Universitario de Cruces, University of the Basque Country, Bilbao, Spain
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