C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low Sensitivity When Predicting Flow Crossmatch

The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n=26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80–259.56, P=0.004, and no DSA C1q+ Ab: OR 5, 1.27–19.68, P=0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06–1.49, P=0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85–100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3–100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity

Arcuate ligament compression as a cause of early-onset thrombosis of the hepatic artery after liver transplantation

Background. Early hepatic artery thrombosis (HAT) is a potentially lethal complication after orthotopic liver transplantation (OLT) requiring immediate intervention.Aim. To report an infrequent cause of HAT after OLT and by itself a controversial clinical entity, the median arcuate ligament celiac artery compression.Case report. A 59-year-old female with hepatitis C virus-induced cirrhosis, Child B, MELD 15, underwent cadaveric-donor OLT with complete vena cava exclusion. Type 1 hepatic artery anatomy was found both in the donor and the recipient, the gastroduodenal artery was ligated. During the first eight postoperative days, clinical and analytical evolution was satisfactory and Doppler ultrasound showed no abnormalities. On the ninth postoperative day, the patient developed hypovolemic shock due to bleeding at the hepatic artery anastomosis, surgical reconstruction was performed. Postoperative color Doppler showed absent hepatic artery flow and an angiography suggested celiac artery compression. The patient was explored again the same day, liberating the celiac artery from the median arcuate ligament and performing thrombectomy and reconstruction of the hepatic artery anastomosis. The patient made a satisfactory recovery and color Doppler showed adequate flow in the hepatic artery. She is alive, free of biliary complications and enjoying a good quality of life 12 months after transplantation.Conclusion. Median arcuate ligament celiac artery compression is an infrequent anatomical variant that should be intentionally evaluated in the recipient at the time of arterial reconstruction in OLT and specifically be considered in early HAT to allow recognition and effective correction

Peripheral Regulatory Cells Immunophenotyping in Kidney Transplant Recipients with Different Clinical Profiles: A Cross-Sectional Study

Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induces peripheral tolerance. These subpopulations also might participate in maintaining allograft immunological quiescence in kidney transplant recipients (KTRs) with an excellent long-term graft function under immunosuppression (ELTGF). The aim of the study was to characterize and to enumerate peripheral Tregs, Bregs, and DCregs in KTR with an ELTGF for more than 5 years after transplant. Fourteen KTR with an ELTGF, 9 KTR with chronic graft dysfunction (CGD), and 12 healthy donors (HDs) were included in the study. CD19+-expressing peripheral B lymphocytes were purified by positive selection. IL-10-producing B cells, CD4+/CD25hi, and CD8+/CD28− Tregs, as well as CCR6+/CD123+/IDO+ DCs, were quantitated by flow cytometry. IL-10-producing Bregs (immature/transitional, but not CD19+/CD38hi/CD24hi/CD27+B10 cells), CCR6+/CD123+/IDO+ DCs, and Tregs from ELTGF patients had similar or higher percentages versus HD (P<0.05). By contrast, number of Tregs, DCregs, and Bregs except for CD27+B10 cells from CGD patients had lower levels versus HD and ELTGF patients (P<0.05). The findings of this exploratory study might suggest that in ELTGF patients, peripheral tolerance mechanisms could be directly involved in the maintenance of a quiescent immunologic state and graft function stability

COVID-19 en receptores de trasplante: reporte multicéntrico de la experiencia mexicana

Antecedentes: Los receptores de trasplante de órgano sólido (RTOS) parecen estar en un riesgo particularmente alto de cuadros severos de infección por coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) debido al uso crónico de medicamentos inmunosupresores y sus comorbilidades. Reportamos la primera descripción del curso clínico y desenlaces a corto plazo de los receptores de trasplante con enfermedad por coronavirus 2019 (COVID-19) confirmada en México. El objetivo de este trabajo es evaluar el curso clínico de estos pacientes. Material y métodos: Evaluamos de manera retrospectiva los RTOS (riñón e hígado) mayores de 18 años de edad, con diagnóstico confirmado de infección por SARS-CoV-2 provenientes de cinco centros de tercer nivel en México. Resultados: Se incluyeron 45 receptores de trasplante renal con una edad de 43 (intervalo intercuartílico [IQR]: 25-70) años. El ingreso hospitalario se requirió en 37 (75.5%) pacientes, de los cuales ocho (16.3%) fueron hospitalizados en la unidad de terapia intensiva. Se documentó lesión renal aguda en 33 (67%) pacientes. El tiempo de hospitalización fue de 8 (IQR: 6-12) días. Seis pacientes fallecieron (12.2%). Adicionalmente, 10 receptores de trasplante hepático fueron incluidos. Durante su evolución, 5 / 10 requirieron ingreso hospitalario; no se presentaron fallecimientos en este grupo de pacientes. Conclusiones: Los receptores de trasplante mostraron una alta tasa de mortalidad y complicaciones por la infección por SARS-CoV-2. Son necesarios más estudios para identificar los factores pronósticos y modalidades de tratamiento eficaces

Direct-acting antivirals and Hepatocellular Carcinoma: No evidence of higher wait-list progression or posttransplant recurrence

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT

Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments