Liver transplantation in Latin America: reality and challenges.

Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant programs and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.

Patient Blood Management in Liver Transplant-A Concise Review.

Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.

Hierarchical Modeling of the Liver Vascular System.

The liver plays a key role in the metabolic homeostasis of the whole organism. To carry out its functions, it is endowed with a peculiar circulatory system, made of three main dendritic flow structures and lobules. Understanding the vascular anatomy of the liver is clinically relevant since various liver pathologies are related to vascular disorders. Here, we develop a novel liver circulation model with a deterministic architecture based on the constructal law of design over the entire scale range (from macrocirculation to microcirculation). In this framework, the liver vascular structure is a combination of superimposed tree-shaped networks and porous system, where the main geometrical features of the dendritic fluid networks and the permeability of the porous medium, are defined from the constructal viewpoint. With this model, we are able to emulate physiological scenarios and to predict changes in blood pressure and flow rates throughout the hepatic vasculature due to resection or thrombosis in certain portions of the organ, simulated as deliberate blockages in the blood supply to these sections. This work sheds light on the critical impact of the vascular network on mechanics-related processes occurring in hepatic diseases, healing and regeneration that involve blood flow redistribution and are at the core of liver resilience.

Mortality and evolution between community and hospital-acquired COVID-AKI.

BACKGROUND: Acute kidney injury (AKI) is associated with poor outcomes in COVID patients. Differences between hospital-acquired (HA-AKI) and community-acquired AKI (CA-AKI) are not well established. METHODS: Prospective, observational cohort study. We included 877 patients hospitalized with COVID diagnosis at two third-level hospitals in Mexico. Primary outcome was all-cause mortality at 28 days compared between COVID patients with CA-AKI and HA-AKI. Secondary outcomes included the need for KRT, and risk factors associated with the development of CA-AKI and HA-AKI. RESULTS: A total of 377 patients (33.7%) developed AKI. CA-AKI occurred in 202 patients (59.9%) and HA-AKI occurred in 135 (40.1%). Patients with CA-AKI had more significant comorbidities, including diabetes (52.4% vs 38.5%), hypertension (58.4% vs 39.2%), CKD (30.1% vs 14.8%), and COPD (5.9% vs 1.4%), than those with HA-AKI. Patients' survival without AKI was 87.1%, with CA-AKI it was 75.4%, and with HA-AKI it was 69.6%, log-rank test p < 0.001. Only age > 60 years (OR 1.12, 95% CI 1.06-1.18, p <0.001), COVID severity (OR 1.09, 95% CI 1.03-1.16, p = 0.002), the need in mechanical lung ventilation (OR 1.67, 95% CI 1.56-1.78, p <0.001), and HA-AKI stage 3 (OR 1.16, 95% CI 1.05-1.29, p = 0.003) had a significant increase in mortality. The presence of CKD (OR 1.48, 95% CI 1.391.56, p < 0.001), serum lymphocytes < 1000 µL (OR 1.03, 95% CI 1.00-1.07, p = 0.03), the need in mechanical lung ventilation (OR 1.06, 95% CI 1.02-1.11, p = 0.003), and CA-AKI stage 3 (OR 1.37, 95% CI 1.29-1.46, p < 0.001) were the only variables associated with a KRT start. CONCLUSIONS: We found that COVID patients who are complicated by CA-AKI have more comorbidities and worse biochemical parameters at the time of hospitalization than HA-AKI patients, but despite these differences, their probability of dying is similar.

The liver, a functionalized vascular structure.

The liver is not only the largest organ in the body but also the one playing one of the most important role in the human metabolism as it is in charge of transforming toxic substances in the body. Understanding the way its blood vasculature works is key. In this work we show that the challenge of predicting the hepatic multi-scale vascular network can be met thanks to the constructal law of design evolution. The work unveils the structure of the liver blood flow architecture as a combination of superimposed tree-shaped networks and porous system. We demonstrate that the dendritic nature of the hepatic artery, portal vein and hepatic vein can be predicted, together with their geometrical features (diameter ratio, duct length ratio) as the entire blood flow architectures follow the principle of equipartition of imperfections. At the smallest scale, the shape of the liver elemental systems-the lobules-is discovered, while their permeability is also predicted. The theory is compared with good agreement to anatomical data from the literature.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

Changes in frequency of delayed graft function in deceased donor renal transplant recipient in a tertiary care center in Mexico.

BACKGROUND: Delayed graft function (DGF) is defined as the need for dialysis within the first seven days of transplantation. The frequency of DGF has decreased in the last five years compared with the previous 20 years of the kidney transplant program at a Mexican referral hospital. OBJECTIVE: To determine the incidence and risk factors for DGF in the past five years (2009-2013). METHODS: We analyzed a retrospective cohort of renal transplant recipients from deceased donors at our hospital between March 2009 and May 2013 (Period 2), and compared the results with a previously evaluated cohort (Period 1, between January 1990 and February 2009). RESULTS: During the analyzed period, 78 deceased donor transplants were performed. The frequency of DGF was 9%. Multivariate analysis showed that recipient older age (OR: 1.074419; 95% CI: 1.0009-1.155116; p = 0.05), transoperative amines administration (OR: 7.73; 95% CI: 1.037-57.6; p = 0.046), and hypotension during surgery in the recipient (OR: 11.6; 95% CI: 1.33-100.8; p = 0.026) were risk factors for DGF. CONCLUSION: The incidence of DGF has significantly decreased in the past five years when compared to the previous 20 years in our hospital.

[Indications for liver transplant]. / Indicaciones de trasplante hepático.

Liver transplantation (LT) is the treatment of choice in selected patients with end-stage liver disease and in some with acute liver failure, hepatocellular carcinoma (HCC) and other diseases with no synthetic liver failure. Currently, LT has an overall survival > 90 % at 1 year. Proper selection of LT candidates is important given the shortage in organ donation. The allocation and priorization of organs to patients with chronic liver failure (CLF) in waiting lists, is determined by the MELD priority score (Model of End Stage Liver Disease). Indications for LT in patients with CLF are the same regardless of the etiology (any type of hepatic decompensation or development of HCC). Priority MELD is a variant to this classification used only in special cases such as in those with stable hepatopathy but severe extra-hepatic features (e.g., HCC or hepato-pulmonary syndrome). The indication for LT in patients with acute liver failure (ALF) and acute failure associated to chronic liver failure (ACLF) are not fully established; there are prognostic factors that may guide the decision for urgent LT and some centers, like the King's College Hospital criteria in the UK. Currently, LT is a therapeutic modality in some primary liver tumors (HCC, cholangiocarcinoma) and neuroendocrine liver metastatic tumors. These protocols have provided significant opportunities for long-term survival (> 70% at 5 years). The high demand and shortage of organs have fostered the development of new strategies to benefit more patients, such as the use of extended criteria donors, or "domino" transplants. This review focuses on the most relevant data on the different indications of LT.

[Incidence of acute rejection in patients with renal graft dysfunction]. / [Incidencia de rechazo agudo en pacientes con disfunción del injerto renal].

INTRODUCTION: Acute rejection has been identified as the main cause of renal graft dysfunction during the first year after transplantation; it is associated with chronic structural and functional damage, which causes loss of graft and decrease in patient survival. MATERIAL AND METHODS: We performed a retrospective and descriptive research consisting in a review of the final reports of biopsies performed due to renal graft dysfunction during the postransplant period. Patients included were transplanted at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) from January 2007 to December 2011. RESULTS: A total number of 223 patients underwent renal transplantation during the period considered for this study purpose, 222 biopsies were performed due to renal graft dysfunction in 118 patients (52.9%). 74.5% of patients developed graft dysfunction in the first year after transplantation. The main histopathological findings reported were immunologic events in both living donor (LDRTR) and deceased donor renal transplant recipients (DDRTR), borderline changes were the most common diagnosis. The median time to detect immune events as cause of dysfunction was shorter for DDRTR and they tend to occur in the first 4 months after transplantation. CONCLUSION: We observed an incidence of 11.8% for acute rejection in the first year after transplantation for LDRTR and 17.4% for DDRTR. Further studies are needed to determine the causes of immunological events and their implications in the evolution of renal graft and patient's survival.