RESUMEN
Liver transplantation has evolved into a mature clinical field but scarcity of usable organs poses a unique challenge. Expanding the donor pool requires novel approaches for protecting hepatic physiology and cellular homeostasis. Here we define hepatocellular injury during transplantation, with an emphasis on modifiable cell death pathways as future therapeutics.
RESUMEN
Living liver donation (LLD) has been suggested as a potential solution to reduce the waitlist mortality for liver transplantation (LT) recipients by facilitating living donor liver transplantation (LDLT). Ensuring both donor and recipient safety is a critical aspect of LDLT. An accurate understanding of the complexity and extend of safety outcomes of the donor is imperative to maintain the high-quality standard this medical program requires. This review seeks to outline safety outcome parameters of interest for donors. Early postoperative mortality is very low with no significant differences comparing left lobe to right lobe LLD. Complications most commonly are biliary (leakage or strictures), bleeding, respiratory or pulmonary, gastrointestinal or infectious. Return to full-time work and quality of life are essential parameters in the mid and long term. As evidence continues to accumulate, outcomes may evolve with the expansion of minimal invasive surgery practice and currently laparoscopic approach is recommended in large experienced centers. By offering safer operations that require fewer incisions or liver resections, living liver donations can be further encouraged, and the perception of the procedure can be improved. Rational consideration of the safety of the donor and in-depth discussion and evaluation with the patient is of utmost importance.
RESUMEN
Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3-, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42-0.93 [ p <0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22-0.74 [ p <0.05]). There were no differences in the 1-, 3-, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p =0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56-1.68 [ p >0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.
Asunto(s)
Colangitis Esclerosante , Hepatitis Autoinmune , Análisis de Intención de Tratar , Trasplante de Hígado , Donadores Vivos , Listas de Espera , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Femenino , Masculino , Donadores Vivos/estadística & datos numéricos , Estudios Retrospectivos , Persona de Mediana Edad , Listas de Espera/mortalidad , Adulto , Resultado del Tratamiento , Colangitis Esclerosante/cirugía , Colangitis Esclerosante/mortalidad , Colangitis Esclerosante/complicaciones , Hepatitis Autoinmune/cirugía , Hepatitis Autoinmune/mortalidad , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/diagnóstico , Cirrosis Hepática Biliar/cirugía , Cirrosis Hepática Biliar/mortalidad , Enfermedades Autoinmunes/cirugía , Enfermedades Autoinmunes/mortalidad , Anciano , Factores de Tiempo , Supervivencia de InjertoRESUMEN
The 2023 Joint Annual Congress of the International Liver Transplantation Society, European Liver and Intestine Transplant Association, and Liver Intensive Care Group of Europe were held in Rotterdam, the Netherlands, from May 3 to 6, 2023. This year, all speakers were invited to attend the Congress in person for the first time since the COVID-19 pandemic. The congress was attended by 1159 registered delegates from 54 countries representing 5 continents, with the 10 countries comprising the bulk of the delegates. Of the 647 abstracts initially submitted, 542 were eventually presented at the meeting, coming from 38 countries (mainly North America, Europe, and Asia) and 85% of them (462 abstracts) came from only 10 countries. Fifty-three (9.8%) abstracts, originated from 17 countries, were submitted under the Basic/Translational Scientific Research category, a similar percentage as in 2022. Abstracts presented at the meeting were classified as (1) ischemia and reperfusion injury, (2) machine perfusion, (3) bioengineering and liver regeneration, (4) transplant oncology, (5) novel biomarkers in liver transplantation, (6) liver immunology (rejection and tolerance), and (7) artificial intelligence and machine learning. Finally, we evaluated the number of abstracts commented in the Basic and Translational Research Committee-International Liver Transplantation Society annual reports over the past 5 y that resulted in publications in peer-reviewed journals to measure their scientific impact in the field of liver transplantation.
Asunto(s)
Trasplante de Hígado , Investigación Biomédica Traslacional , Trasplante de Hígado/tendencias , Humanos , Investigación Biomédica Traslacional/organización & administración , Investigación Biomédica Traslacional/tendencias , COVID-19/epidemiología , SARS-CoV-2/inmunología , Sociedades Médicas , Congresos como AsuntoRESUMEN
BACKGROUND: Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. METHODS: Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. RESULTS: Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. CONCLUSION: Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.
Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Constricción Patológica , Estudios Retrospectivos , Donadores Vivos , Donantes de Tejidos , Muerte , Muerte EncefálicaRESUMEN
OBJECTIVE: To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA: In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS: All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS: Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION: With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.
Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Trasplante de Hígado/métodos , Donadores Vivos , Supervivencia de Injerto , Estudios Retrospectivos , Donantes de Tejidos , Muerte , Muerte Encefálica , HígadoRESUMEN
The incidence and geographical distribution of cancers in children are dramatically different from the adult population. Consequent to improvements in postcancer survival, there is a progressive increase in the number of patients requiring liver transplantation (LT) who are in remission from pretransplant malignancy (PTM). Conventionally, however, PTM has been considered a relative contraindication to LT. Furthermore, with improving post-LT survival now extending beyond decades, the cumulative effect of immunosuppression and the increasing risk of de novo cancers need to be acknowledged. A working group was formed to evaluate, discuss, and retrieve all the evidence and provide guidelines with regards to best practices surrounding nonhepatic cancer in the pediatric LT (PLT) population. Further subsections of research included (a) extrahepatic solid tumors, leukemia, lymphoma, and other hematological disturbances before PLT and (b) malignancies following PLT (including posttransplant lymphoproliferative disorders). This guidance provides a collection of evidence-based expert opinions, consensus, and best practices on nonhepatic cancers in PLT.
Asunto(s)
Trasplante de Hígado , Neoplasias , Adulto , Niño , Consenso , Humanos , Terapia de Inmunosupresión/efectos adversos , Incidencia , Trasplante de Hígado/efectos adversos , Neoplasias/epidemiología , Neoplasias/etiología , Factores de RiesgoRESUMEN
PURPOSE: Extrahepatic portal vein obstruction (EHPVO) is a major cause of non-cirrhotic portal hypertension in children. Surgical procedures for EHPVO include portosystemic shunts (PSS) and meso-Rex bypass (MRB). We conducted a systematic review and meta-analysis to compare the effectiveness of MRB versus PSS in EHPVO patients. METHODS: A systematic literature search was performed using four databases. Articles reporting EHPVO and comparing patients who received MRB and PSS were included in the analysis. RESULTS: We retrieved 851 papers, of which five observational studies met the inclusion criteria. There was no difference in shunt complications, mortality, or gastrointestinal bleeding after surgery between MRB and PSS in the meta-analysis. MRB had increased shunt complications compared with PSS in the non-comparative studies. MRB had a potential advantage over PSS in long-term prognosis in one comparative study. Overall, the quality of the evidence was low. CONCLUSIONS: Based on available data, our meta-analysis indicates that MRB does not increase shunt complications, mortality, or gastrointestinal bleeding after surgery. The present study did not reveal superiority for either MRB or PSS. The paucity of well conducted trials in this area justifies future multicenter studies and studies that examine long-term outcomes.
Asunto(s)
Várices Esofágicas y Gástricas , Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Niño , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Humanos , Hipertensión Portal/cirugía , Vena Porta/cirugía , Derivación Portosistémica QuirúrgicaRESUMEN
BACKGROUND: Optimal diagnostic and surgical approaches for patients with bile duct injuries (BDI) remain debated. This study reviews results from a standardized approach to management of high-grade BDIs at a North American center. DESIGN: Patients undergoing surgical repair for BDIs over a 15-year period were included. Post-operative outcomes and biliary patency rates were calculated using imaging, laboratory values, and patient interviews. RESULTS: A total of 107 consecutive patients underwent repair for BDIs. Bismuth grade I/II injuries were identified in 46 patients (41%), grade III/IV in 41 (38%), grade V in 11 patients (10%), and 9 (10%) were unclassified. BDI anatomy was commonly identified using magnetic resonance imaging (MRI) (75%). Concomitant arterial injuries were identified in 30 (28 with formal angiography). Fifteen had early repairs (within 4 days) and remainder interval repairs (median: 65 days). Hepp-Couinaud repair was method of choice (83%). Estimated primary biliary patency was 100% at 30 days and 87% at 5 years. CONCLUSION: With appropriate referral to a specialist, surgical reconstruction of BDIs can have excellent outcomes, even with accompanying arterial injuries. Based on our experience, MR as first imaging modality and supplemental angiography served as the optimal diagnostic strategy. Delayed repair, using Hepp-Couinaud technique, with selective liver resection results in high long-term patency rates.
Asunto(s)
Enfermedades de los Conductos Biliares , Colecistectomía Laparoscópica , Conductos Biliares/diagnóstico por imagen , Conductos Biliares/cirugía , Colecistectomía/efectos adversos , Colecistectomía Laparoscópica/efectos adversos , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Postoperative diaphragmatic hernia (DH) is a rare but potentially life-threatening complication following pediatric liver transplantation (LT). In the current literature, a total of 49 such hernias have been reported in 17 case series. We present eight additional cases, three of which reoccurred after surgical correction, and review the current literature with a focus on recurrence. MATERIALS AND METHODS: The study sample included children (<18 years of age) who underwent LT between June 2013 and June 2020 at five large transplant centers and who subsequently presented with DH. During the study period, a total of 907 LT was performed. Eight DH were recognized, and risk factors were analyzed. RESULTS: For the eight children with DH, the mean age at LT was 28.0 (5-132) months. All patients with a DH received left lateral segment split grafts except one, who received a full left lobe. The mean weight at time of LT was 11.8 (6.6-34) kg. Two patients had a primary abdominal muscle closure, and six had a temporary silastic mesh closure. All eight children presented with a right posterolateral DH. The small bowel was herniated in the majority of cases. Symptoms reported included nausea, vomiting, and respiratory distress. Two patients were asymptomatic, and discovery was incidental. All patients underwent prompt primary surgical repair. Three DH hernias (37.5%) recurred despite successful surgical correction. CONCLUSION: DH following liver transplant with technical variant grafts may be underreported and is prone to recur despite surgical correction. A better understanding of the pathophysiology and more thorough reporting may help increase awareness. Early detection and prompt surgical management are the cornerstones of a successful outcome.
Asunto(s)
Hernia Diafragmática/etiología , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Niño , Preescolar , Hernia Diafragmática/diagnóstico , Hernia Diafragmática/cirugía , Humanos , Lactante , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/cirugía , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD). The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD), we aimed to understand how ischemia/reperfusion (I/R) injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration. METHODS: Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13) and DBD (n = 10) livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22) and DBD (n = 13) livers. RESULTS: When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05) and C22 ceramide (p<0.05) were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST) of DCD allografts had significantly increased. CONCLUSION: These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.
Asunto(s)
Trasplante de Hígado , Hígado/irrigación sanguínea , Donantes de Tejidos , Adulto , Anciano , Aloinjertos , Apoptosis , Muerte Encefálica , Femenino , Humanos , Hígado/patología , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Daño por Reperfusión , Resultado del TratamientoRESUMEN
Although mast cells have long been considered the integral effector cell in allergy and atopic disease, the paradigm of mast cell function is now evolving to incorporate data showing that mast cells make innumerable contributions to both protective and pathologic immune responses. Mast cells express cell surface molecules with costimulatory or co-inhibitory activity and produce a multitude of mediators that can direct dendritic cell (DC) or T-cell differentiation and function. In addition, mast cells exhibit a widespread distribution and are in close proximity to DCs and T cells at several critical sites. While there has been amazing progress in characterizing mast cell populations in vitro, only recently has the ability to monitor their in vivo effects become a reality. In this review, we discuss the evolution of our understanding of mast cell biology with an emphasis on their established and hypothesized roles in influencing T-cell differentiation and function. The fact that T-cell and mast cell interactions exist and are a normal component of most adaptive immune responses is one of the best illustrations of the now established concept that innate and adaptive immunity are not completely independent entities.
Asunto(s)
Autoinmunidad , Activación de Linfocitos , Mastocitos/inmunología , Linfocitos T/inmunología , Animales , Movimiento Celular , Células Dendríticas/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Humanos , Hipersensibilidad/inmunología , RatonesRESUMEN
Following intranasal inoculation, Vibrio cholerae KFV101 (DeltactxAB DeltahapA DeltahlyA DeltartxA) colonizes and stimulates tumor necrosis factor alpha and interleukin 1beta (IL-1beta) in mice, similar to what occurs with isogenic strain P4 (DeltactxAB), but is less virulent and stimulates reduced levels of IL-6, demonstrating a role for accessory toxins in pathogenesis. Morbidity is enhanced in C3H/HeJ mice, indicating that Toll-like receptor 4 is important for infection containment.