RESUMEN
Improvements in downstaging therapies have expanded the indications for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients with more advanced disease are now considered candidates due to advancements in radiation therapy, combination therapies, and immunotherapy. Combination stereotactic body radiation therapy (SBRT) and trans-arterial chemoembolization (TACE) has been shown to be superior to the historic treatment, sorafenib, in patients with macrovascular invasion. These patients are now candidates for LT with stable disease after LRT. Patients with ruptured HCC and prolonged stability have also been shown to have acceptable outcomes. The role of neoadjuvant immunotherapy needs to be further defined and has the potential to further improve tumor control prior to transplant.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Quimioembolización Terapéutica/métodosRESUMEN
BACKGROUND: No reliable or standardized system exists for measuring the size of deceased donor livers to determine whether they will fit appropriately into intended recipients. METHODS: This retrospective, single-center study evaluated the efficacy of Tampa General Hospital's size-matching protocol for consecutive, deceased donor liver transplantations between October 2021 and November 2022. Our protocol uses cross-sectional imaging at the time of organ offer to compare the donor's right hepatic lobe size with the recipient's right hepatic fossa. Outcomes were analyzed, including large-for-size syndrome, small-for-size syndrome, early allograft dysfunction, primary nonfunction, graft survival, and patient survival. RESULTS: We included 171 patients in the study. The donor liver physically fit in all the patients except one whose pretransplant imaging was outdated. One patient (0.6%) had large-for-size syndrome, none had small-for-size syndrome, 15 (10%) had early allograft dysfunction, and none had primary nonfunction. There were 11 (7%) patient deaths and 11 (7%) graft failures. CONCLUSION: Our measurement system is fast and effective. It reliably predicts whether the donor liver will fit in the intended recipient and is associated with low rates of early allograft dysfunction.
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Trasplante de Hígado , Humanos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Donadores Vivos , Hígado/diagnóstico por imagen , Trasplante Homólogo , Supervivencia de Injerto , Resultado del TratamientoRESUMEN
Solid organ transplant recipients (SOTRs) are at high risk for infections including SARS-CoV-2, primarily due to use of immunosuppressive therapies that prevent organ rejection. Furthermore, these immunosuppressants are typically associated with suboptimal responses to vaccination. While COVID-19 vaccines have reduced the risk of COVID-19-related morbidity and mortality in SOTRs, breakthrough infection rates and death remain higher in this population compared with immunocompetent individuals. Approaches to enhancing response in SOTRs, such as through administration of additional doses and heterologous vaccination, have resulted in increased seroresponse and antibody levels. In this article, safety and immunogenicity of mRNA COVID-19 vaccines in SOTRs are explored by dose. Key considerations for clinical practice and the current vaccine recommendations for SOTRs are discussed within the context of the dynamic COVID-19 vaccination guideline landscape. A thorough understanding of these topics is essential for determining public health and vaccination strategies to help protect immunocompromised populations, including SOTRs.
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COVID-19 , Trasplante de Órganos , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Vacunación , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes , Inmunidad , Anticuerpos AntiviralesRESUMEN
OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.
RESUMEN
During the early wave of the COVID-19 pandemic, the Scientific Registry of Transplant Recipients (SRTR) designated a "black out" period between March 12, 2020, and June 12, 2020, for transplant outcomes reporting. We discuss the implications and potential bias it has introduced as it may selectively favor the outcomes for certain regions and harm other regions due to varied effects of different waves of COVID-19 infections across the United States.
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COVID-19 , Trasplante de Órganos , Obtención de Tejidos y Órganos , Trasplantes , COVID-19/epidemiología , Humanos , Pandemias , Sistema de Registros , Receptores de Trasplantes , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3âmonths post-LT, and ≥3âmonths post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3âmonths post-LT, and ≥3âmonths post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3âmonths after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.
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Antivirales/administración & dosificación , Carcinoma Hepatocelular/cirugía , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Anciano , Bencimidazoles/administración & dosificación , Carbamatos/administración & dosificación , Carcinoma Hepatocelular/virología , Esquema de Medicación , Combinación de Medicamentos , Femenino , Fluorenos/administración & dosificación , Hepatitis C Crónica/complicaciones , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Humanos , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pirrolidinas/administración & dosificación , Quinoxalinas/administración & dosificación , Estudios Retrospectivos , Sofosbuvir/administración & dosificación , Sulfonamidas/administración & dosificación , Respuesta Virológica SostenidaRESUMEN
Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, and associated with a high mortality if untreated. CCA is locally aggressive and located in close proximity to vital structures i.e. the portal vein and hepatic artery. A complete extirpation of the tumor including microscopically detectable disease R0 resection offers the best possibility of long-term survival in patients with CCA. As such, the surgical approach to achieve a R0 resection is dictated by the location of the tumor and the presence of underlying liver disease. The present article focuses on the general principles of the multidisciplinary treatment of hilar and intrahepatic CCA.
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Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/terapia , Tumor de Klatskin/terapia , Grupo de Atención al Paciente , Adulto , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Femenino , Arteria Hepática/patología , Humanos , Tumor de Klatskin/mortalidad , Tumor de Klatskin/patología , Masculino , Persona de Mediana Edad , Vena Porta/patologíaAsunto(s)
Carcinoma Hepatocelular/diagnóstico , Detección Precoz del Cáncer/tendencias , Hepatitis B/complicaciones , Neoplasias Hepáticas/diagnóstico , Hígado/patología , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/virología , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/virología , Tamizaje Masivo/tendencias , Vigilancia de la Población/métodosRESUMEN
BACKGROUND: Malignant primary pediatric hepatic tumors (MPPHTs) are rare and account for approximately 1% of all childhood malignancies. In recent years, liver transplantation has emerged as a viable treatment options for select patients with MPPHTs. STUDY DESIGN: We performed a single-center retrospective study using a prospective database to compare outcomes of pediatric liver transplant recipients, with and without cancer, between January 2000 and December 2014. RESULTS: One hundred fifty-three children underwent 173 liver transplantations during the study period. Of these, 21 (12%) children received 23 (13.3%) transplants for unresectable MPPHTs: 16 hepatoblastomas (HBs), 3 embryonal cell sarcomas (ECS), and 2 hepatocellular carcinomas (HCCs). There was no significant difference in 1-, 3-, and 10-year patient and graft survival rates between MPPHT and non-MPPHT patients (95.2%, 81.2%, 81.2%, and 95.2%, 72,2%, 72.2% for MPPHT vs 92.7%, 89.8%, 87.6% and 85.4%, 81.1%, 75% for the non-MPPHT group, respectively) (p > 0.05). Rates of 1-, 5-, and 10-year disease-free survival for MPPHT patients were 76%, 76%, and 76%, respectively. Median age at transplantation for MPPHT patients was 3.1 years (range 58 days to 17 years), median listing time was 81 days, and median wait list time was 15 days. Eight (38%) children had 2 tumors or more and 4 of 16 (25%) HB patients had metastatic disease at presentation. All children received neoadjuvant treatment, with radiographic response in 19 of 21 patients. Presence of metastatic HB at presentation, International Society of Pediatric Oncology Epithelial Liver (SIOPEL) high risk status, and persistently elevated alpha fetoprotein levels after neoadjuvant chemotherapy might be risk factors for tumor recurrence and decreased survival. CONCLUSIONS: Liver transplantation is an excellent option for select patients with unresectable MPPHTs, with outcomes comparable to those after transplantation for nonmalignant causes.
Asunto(s)
Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Adolescente , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Niño , Preescolar , Femenino , Hepatoblastoma/patología , Hepatoblastoma/cirugía , Humanos , Lactante , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias de Células Germinales y Embrionarias/cirugía , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
More than one third of patients with chronic lung disease undergoing lung transplantation have pre-existing Abs against lung-restricted self-Ags, collagen type V (ColV), and k-α1 tubulin (KAT). These Abs can also develop de novo after lung transplantation and mediate allograft rejection. However, the mechanisms leading to lung-restricted autoimmunity remain unknown. Because these self-Ags are normally sequestered, tissue injury is required to expose them to the immune system. We previously showed that respiratory viruses can induce apoptosis in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), the key mediators of self-tolerance. Therefore, we hypothesized that lung-tissue injury can lead to lung-restricted immunity if it occurs in a setting when Tregs are impaired. We found that human lung recipients who suffer respiratory viral infections experienced a decrease in peripheral Tregs. Pre-existing lung allograft injury from donor-directed Abs or gastroesophageal reflux led to new ColV and KAT Abs post respiratory viral infection. Similarly, murine parainfluenza (Sendai) respiratory viral infection caused a decrease in Tregs. Intratracheal instillation of anti-MHC class I Abs, but not isotype control, followed by murine Sendai virus infection led to development of Abs against ColV and KAT, but not collagen type II (ColII), a cartilaginous protein. This was associated with expansion of IFN-γ-producing CD4(+) T cells specific to ColV and KAT, but not ColII. Intratracheal anti-MHC class I Abs or hydrochloric acid in Foxp3-DTR mice induced ColV and KAT, but not ColII, immunity, only if Tregs were depleted using diphtheria toxin. We conclude that tissue injury combined with loss of Tregs can lead to lung-tissue-restricted immunity.
Asunto(s)
Rechazo de Injerto/inmunología , Lesión Pulmonar/inmunología , Trasplante de Pulmón , Pulmón/inmunología , Infecciones por Respirovirus/inmunología , Virus Sendai/inmunología , Linfocitos T Reguladores/inmunología , Animales , Autoanticuerpos/sangre , Autoantígenos/inmunología , Proliferación Celular , Células Cultivadas , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , RatonesRESUMEN
BACKGROUND: The decision for a simultaneous liver and kidney transplantation (SLKT) is fraught with controversy. The aim of this study was to compare SLKT with liver transplantation alone (LTA) in patients with pretransplantation renal failure. STUDY DESIGN: A retrospective review comparing patients undergoing SLKT and LTA (with renal failure) between January 2000 and December 2014 was performed. RESULTS: Of 1,129 liver transplantations, 132 had renal failure pretransplantation; 52 had SLKT and 80 recipients had LTA. Model for End-Stage Liver Disease score and BMI were lower in the SLKT group (p = 0.001). Simultaneous liver and kidney transplantation patients had better overall survival rates at 1 and 5 years compared with LTA (92.3% and 81.6% vs 73.3% and 64.3% respectively; p < 0.01). Graft survival was also superior in patients undergoing SLKT vs LTA. Six of 52 (11.5%) SLKT patients had final positive cross match, but only 1 of 52 (1.9%) kidney grafts was lost to rejection. In the SLKT group, 9 of 52 (17.3%) patients required dialysis post transplantation, but only 2 remained on dialysis beyond 30 days. All patients in the LTA group were on dialysis pretransplantation and significantly more patients (52 of 80 [65%]) required dialysis post LTA (p ≤ 0.0001); 31 of 80 (38.8%) were dialysis dependent for more than 30 days or died on dialysis within 30 days. Two LTA recipients were subsequently listed for kidney transplant. CONCLUSIONS: Patients with end-stage liver disease on dialysis who undergo liver transplantation have significantly better survival when SLKT is performed. In selected patients, SLKT is an appropriate use of a scarce resource, but better prognostic indicators for selection of patients are still needed.
Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Riñón/métodos , Trasplante de Hígado/métodos , Insuficiencia Renal/cirugía , Adulto , Anciano , Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/mortalidad , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Trasplante de Riñón/mortalidad , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Insuficiencia Renal/complicaciones , Insuficiencia Renal/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: A new era in organ donation with national redistricting is being proposed. With these proposals, costs of organ acquisition are estimated to more than double. Traditionally, organ recoveries occur in the donor hospital setting, incurring premium hospital expenses. The aim of the study was to determine organ recovery costs and organ yield for donor recoveries performed at an organ procurement organization (OPO) facility. STUDY DESIGN: In 2001, we established an OPO facility and in 2008 began transferring the donor expeditiously when brain death was declared. The OPO donor and hospital costs on a per donor basis were calculated. Donation after cardiac death donors cannot be transferred and were included in the hospital cost analysis. RESULTS: From January 2009 to December 2014, nine hundred and sixty-three donors originating in our OPO had organs recovered and transplanted. Seven hundred and sixty-six (79.5%) donors were transferred to the OPO facility 8.6 hours (range 0.6 to 23.6 hours) after declaration of brain death. Donor recovery cost was 51% less when donors were transferred to the OPO facility ($16,153 OPO recovery vs $33,161 hospital recovery; p < 0.0001). Organ yield was 27.5% better (3.43 organs) from OPO-recovered donors vs an organ yield of 2.69 from hospital-recovered donors (p < 0.0001). Standard criteria donor organ yield from our OPO was 6% higher than the national average (3.92 vs 3.7 nationally; p = 0.012) and expanded criteria donor organ yield was 18% higher (2.2 vs 1.87 nationally; p = 0.03). CONCLUSIONS: An OPO facility for donor organ recovery increases efficiency and organ yield, reduces costs, and minimizes organ acquisition charge. As we face new considerations with broader sharing, increased efficiencies, cost. and organ use should be considered.
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Obtención de Tejidos y Órganos/organización & administración , Bancos de Muestras Biológicas/economía , Muerte Encefálica , Control de Costos , Arquitectura y Construcción de Instituciones de Salud/economía , Costos de Hospital , Humanos , Transferencia de Pacientes/economía , Estudios Retrospectivos , Recolección de Tejidos y Órganos/economíaRESUMEN
Immune responses to HLA and tissue-restricted self-antigens (SAgs) have been proposed to play a role in the pathogenesis of renal allograft (KTx) rejection. However, ABO incompatible (ABOi) KTx recipients (KTxR) following depletion of antibodies (Abs) to blood group antigens had fewer rejections. To determine the mechanisms, pre- and post-transplant sera from ABOi (n=18) and ABO-compatible (ABOc) (n=45) KTxR were analyzed for Abs against HLA class I and II by LABScreen single antigen assay. The development of Abs to SAgs was measured by ELISA. Immunity to Collagen IV (Col-IV) and cytokines induced were measured by ELISPOT. While 8/45 (18%) ABOc KTxR developed new donor specific antibodies to HLA (DSA) following transplantation, 0/18 ABOi KTxR developed DSA. ABOi KTxR failed to develop Abs to kidney SAgs (Col-IV and fibronectin (FN)). In contrast, 7 ABOc KTxR developed Abs to both Col-IV and FN. Col-IV stimulation of lymphocytes from ABOc KTxR demonstrated increased IFNγ, IL-17 and decreased IL-10. In contrast ABOi recipients following stimulation with antigens resulted in more IL10 and reduced IFN-γ and IL17 production. At one year, the GFR in ABOi KTxR were significantly better (p<0.04) than ABOc KTxR. De novo DSA and immune responses to SAgs are reduced or absent in ABOi KTxR which we propose leads to less acute rejection and better long term function following ABOi KTx.
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Incompatibilidad de Grupos Sanguíneos/inmunología , Rechazo de Injerto/inmunología , Trasplante de Riñón , Adulto , Anticuerpos/sangre , Autoantígenos/inmunología , Células Cultivadas , Colágeno Tipo IV/inmunología , Citocinas/metabolismo , Ensayo de Immunospot Ligado a Enzimas , Fibronectinas/inmunología , Estudios de Seguimiento , Tasa de Filtración Glomerular , Supervivencia de Injerto , Antígenos HLA/inmunología , Humanos , Activación de Linfocitos , Persona de Mediana EdadRESUMEN
Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self-antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney-associated self-antigens develop following pediatric renal transplantation. We investigated post-transplant development of Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney-associated self-antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post-transplant. No samples had Abs to kidney-associated self-antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney-associated self-antigen post-transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation--a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.
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Autoanticuerpos/inmunología , Colágeno Tipo IV/inmunología , Fibronectinas/inmunología , Trasplante de Riñón/efectos adversos , Receptor de Angiotensina Tipo 1/inmunología , Insuficiencia Renal/inmunología , Adolescente , Autoantígenos/inmunología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Rechazo de Injerto , Humanos , Lactante , Riñón/inmunología , Masculino , Periodo Posoperatorio , Insuficiencia Renal/sangre , Insuficiencia Renal/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.
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Anticuerpos Monoclonales/farmacología , Antígeno CD47/inmunología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Animales , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Antígeno CD47/biosíntesis , Carcinoma Hepatocelular/inmunología , Movimiento Celular/inmunología , Células Hep G2 , Humanos , Neoplasias Hepáticas/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones SCID , Fagocitosis/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: Perioperative factors can affect outcomes of liver transplantation (LT) in recipients with hepatitis C virus (HCV) infection. This study was conducted to investigate whether the immunomodulatory effects of packed red blood cells (PRBC) and platelets administered in the perioperative period might affect immune responses to HCV and thus outcomes in LT recipients. METHODS: Data for a total of 257 HCV LT recipients were analysed. Data on clinical demographics including perioperative transfusion (during and within the first 24 h), serum cytokine concentration, HCV-specific interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing cells, and outcomes including graft and patient survival were analysed. RESULTS: Patient survival was higher in HCV LT recipients who did not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n = 192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02); 5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an increased post-transplant viral load (P = 0.032) and increased incidence of advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10, IL-17, IL-1ß and IL-6, and decreased IFN-γ, and a significantly increased rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02), PRBC transfusion (P < 0.01) and platelets administration were associated with worse survival. CONCLUSIONS: Transfusion had a negative impact on LT recipients with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased IFN-γ, suggests that transfusion may be associated with the modulation of HCV-specific responses, increased fibrosis and poor transplant outcomes.
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Transfusión de Eritrocitos , Hepacivirus/inmunología , Hepatitis C/cirugía , Trasplante de Hígado , Transfusión de Plaquetas , Adulto , Anciano , Citocinas/sangre , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/mortalidad , Femenino , Supervivencia de Injerto , Hepatitis C/sangre , Hepatitis C/diagnóstico , Hepatitis C/inmunología , Hepatitis C/mortalidad , Humanos , Estimación de Kaplan-Meier , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas/efectos adversos , Transfusión de Plaquetas/mortalidad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Células Th17/inmunología , Células Th17/virología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction.
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Aloinjertos/patología , Autoantígenos/inmunología , Rechazo de Injerto/inmunología , Trasplante de Órganos , Complicaciones Posoperatorias/inmunología , Animales , Autoinmunidad , Microambiente Celular , Fibrosis , Rechazo de Injerto/etiología , Antígenos HLA/inmunología , Humanos , Inmunidad Celular , Inmunidad Humoral , Interleucina-17/inmunologíaRESUMEN
BACKGROUND: The IL-17 axis is implicated in pathogenesis of chronic rejection after human lung transplantation. Using a murine model of obliterative airway disease (OAD), we recently demonstrated that Abs to MHC class I antigens can induce immune responses to self-antigens that contributes to immunopathogenesis of chronic rejection. Using a murine model of OAD, we determined the role of IL-17 family members in induction of autoimmunity leading to OAD after ligation of MHC class I. METHODS: Anti-MHC class I or control antibodies (Abs) were administered intrabronchially to wild-type (WT) and IL-17a knock out (IL-17A-/-) C57BL/6. RESULTS: By day 30, anti-MHC I administered endobronchially in IL-17A-/- mice demonstrated significant reduction in cellular infiltration, a 36.8% reduction in CD4 T cells, 62.7% in CD11b macrophages, 37.5% in degree of fibrosis, 1.94 fold and 2.17 fold decrease in anti-KAT and anti-Col-V, respectively, when compared with wild-type mice. Analysis of lung infiltrating cells in anti-MHC I WT revealed increase in IL-17A (KAT:92+21,Col-V:103+19spm) and IL-17F (KAT:5.03%,Col-V:2.75%) secreting CD4+ T cells. However, administration of anti-MHC I in IL-17A-/- demonstrated increase only in IL-17F for KAT (13.70%) and Col-V (7.08%). Anti-IL-17(A-F) mAb administration after anti-MHC I abrogated OAD in both WT and IL-17A-/-. CONCLUSION: Our findings indicate that IL-17A and IL-17F secreted by CD4+Th17 cells specific to lung self-antigens are critical mediators of autoimmunity leading to the pathogenesis of OAD.