Immunotolerance in liver transplantation: a primer for the clinician.

The use of immunosuppressive medications for solid organ transplantation is associated with cardiovascular, metabolic, and oncologic complications. On the other hand, the development of graft rejection is associated with increased mortality and graft dysfunction. Liver transplant recipients can withdraw from immunosuppression without developing graft injury while preserving an adequate antimicrobial response - a characteristic known as immunotolerance. Immunotolerance can be spontaneously or pharmacologically achieved. Contrary to the classic dogma, clinical studies have elucidated low rates of true spontaneous immunotolerance (no serologic or histological markers of immune injury) among liver transplant recipients. However, clinical, serologic, and tissue biomarkers can aid in selecting patients in whom immunosuppression can be safely withdrawn. For those who failed an immunosuppression withdrawal trial or are at high risk of rejection, pharmacological interventions for immunotolerance induction are under development. In this review, we provide an overview of the mechanisms of immunotolerance, the clinical studies investigating predictors and biomarkers of spontaneous immunotolerance, as well as the potential pharmacological interventions for inducing it.

Trasplante hepático en hepatitis alcohólica aguda: ¿debemos decir que no?

Alcohol liver disease is one of the main indications for liver transplantation (LT). Currently, an abstinence period <6 months is required to include a patient with alcohol liver disease on the waiting list, a period that has not been shown to reduce the risk of relapse. Alcoholic hepatitis is characterized by hepatic decompensation secondary to recent, excessive consumption of alcohol, and LT may be the option in a well-selected group of patients who do not respond to medical treatment, but due to established sobriety intervals are excluded, this requires a change in the criteria established by the committees. We propose an evaluation algorithm to consider alcoholic hepatitis unresponsive to medical treatment for LT.

La enfermedad hepática por alcohol es una de las principales indicaciones de trasplante hepático (TH). Actualmente se requiere un período de abstinencia > 6 meses para incluir a un paciente con enfermedad hepática por alcohol en lista de espera de TH, periodo que no ha demostrado disminuir el riesgo de recaída. La hepatitis aguda por alcohol se caracteriza por una descompensación hepática secundaria a un consumo de alcohol excesivo reciente, y el TH puede ser la única opción en un grupo bien seleccionado de pacientes que no responden al tratamiento médico, pero debido a los intervalos de sobriedad establecidos son excluidos, y esto requiere un cambio en los criterios establecidos por los comités. Proponemos un algoritmo de evaluación para considerar para TH la hepatitis aguda por alcohol no respondedora a tratamiento médico.

Position statement on the use of albumin in liver cirrhosis.

Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.

Bone Disease and Liver Transplantation: A Review.

Liver transplantation is currently the most effective and almost routine treatment for chronic and acute liver diseases. The survival of transplanted patients has increased exponentially, which has led to more knowledge of the long-term complications secondary to the underlying pathology or the various treatments that must be followed. Bone metabolic disease is a chronic complication of liver transplantation that inhibits quality of life. The factors that contribute to the development of bone disease are different according to the various etiologies of liver damage. All patients should be examined for osteoporosis risk factors because the incidence of new fractures in transplant patients is higher during the first year after transplantation, reflecting the greater bone loss during this time. This article outlines a proposal for a treatment algorithm; we propose that pharmacologic therapy in patients post liver transplant should first consider the diagnosis of osteoporosis by bone mineral density, the patient's personal and family history of spine and femoral neck fractures, and the use glucocorticoids (dose and time) until a tool is available that allows the best estimation of the fracture risk in this population of patients.

Renal and brain failure predict mortality of patients with acute-on-chronic liver failure admitted to the intensive care unit.

INTRODUCTION AND OBJECTIVES: Acute on Chronic Liver Failure (ACLF) is characterized by organ failure and high 28-day mortality. Identifying clinical predictors associated with early mortality could have implications for the treatment of patients with ACLF. PATIENTS AND METHODS: Patients diagnosed with chronic liver failure that developed ACLF based on the EASL-CLIF Consortium definition admitted to the Intensive care unit of a tertiary hospital between 2012-2018 were included. Bivariate and multivariate Cox regression analyses were performed to identify factors associated with mortality. RESULTS: 148 patients (55% female) were diagnosed with ACLF of which 55% (n = 82) had ACLF grade 3, 28% (n = 41) grade 2 and 17% (n = 25) grade 1. The median age was 54 years (41-63). Hepatitis C virus (HCV) was the most frequent etiology in 29.8% (n = 44) of the patients with bacterial infection being the most predominant precipitant factor in 58.1% (n = 86). Ninety-day global cumulative survival was only 18%. When divided by grade, mortality reached to 10% in ACLF 3. Moreover, in the multivariate Cox regression analysis, renal failure (HR 3.26, 95% CI (2.13-4.99), brain failure (HR 1.37, 95% CI 1.09-2.04) and male sex (HR 1.62, 95% CI 1.10-2.40) were independent predictors of 28- and 90-day mortality. CONCLUSIONS: ACLF is a frequent syndrome among chronic liver disease patients. Brain and renal failure are significantly associated with higher mortality and are independent predictors of 28 and 90-day mortality.

Increased incidence of and microbiologic changes in pyogenic liver abscesses in the Mexican population.

BACKGROUND: Pyogenic liver abscess (PLA) is a rare disease with an estimated incidence that varies widely across the globe, being as high as 115.4/100000 habitants in Taiwan and as low as 1.1-1.2/100000 habitants in Europe and Canada. Even though there are multiple microorganisms capable of producing an abscess in the liver, including Entamoeba histolytica, fungi, and viruses, most abscesses are derived from bacterial infections. The epidemiology of PLA in Mexico is currently unknown. AIM: To describe the clinical, demographic and microbiologic characteristics of PLA in Mexico. METHODS: This is a retrospective study carried out in two centers, and included patients seen between 2006 and 2018 with the diagnosis of pyogenic abscess. We collected demographic, clinical, and microbiological information, treatment, complications, and outcomes. A logistic regression analysis was used to determine the association between different variables and mortality rates. RESULTS: A total of 345 patients were included in this study. 233 (67.5%) had confirmed PLA, 133 (30%) patients had no positive culture and negative serology and 9 (2.5%) had mixed abscesses. The mean age was 50 years (ranging from 16-97 years) and 63% were female. 65% of the patients had positive cultures for Extended Spectrum Beta-Lactamases (ESBL)-Escherichia coli and Klebsiella pneumoniae. Cefotaxime was administered in 60% of cases. The most common sources of infection were ascending cholangitis and cholecystitis in 34 (10%) and 31 (9%), respectively. The median length of hospital stay was 14 d. 165 patients underwent percutaneous catheter drainage. The inpatient mortality rate was 63%. Immunocompromised state [OR 3.9, 95%CI: 1.42-10.46], ESBL- Escherichia coli [OR 6.7, 95%CI: 2.7-16.2] and Klebsiella pneumoniae [OR 4-8, 95%CI: 1.6-14.4] predicted inpatient mortality by multivariate analysis. CONCLUSION: The prevalence of PLA is increasing in Mexico and has a very high mortality rate. ESBL-Escherichia coli and Klebsiella pneumoniae are the most common microorganisms causing PLA and are independent predictors of inpatient mortality.

[Lactococcus garvieae endocarditis in a patient undergoing chronic hemodialysis. First case report in Chile and review of the literature]. / Endocarditis por Lactococcus garvieae en un paciente sometido a hemodialisis crónica. Primer caso reportado en Chile y revisión de la literatura.

Reports of Lactococcus garvieae infections in humans are scarce, and only one of them in a patient under-going hemodialysis. We report the first case of Lactococcus garvieae infection in Chile, presenting as an infective endocarditis, ultimately fatal, in a patient with uncomplicated colonic diverticulosis and end stage renal failure undergoing chronic hemodialysis. We review the published cases and discuss the diagnostic and therapeutic challenges associated with this new, increasingly diagnosed pathogen, capable of producing serious infections in susceptible patients.

Endocarditis por Lactococcus garvieae en un paciente sometido a hemodialisis crónica. Primer caso reportado en Chile y revisión de la literatura / Lactococcus garvieae endocarditis in a patient undergoing chronic hemodialysis. First case report in Chile and review of the literature

Resumen Los casos reportados de infección por Lactococcus garvieae son escasos y sólo uno asociado a hemodiálisis. Comunicamos el caso de endocarditis infecciosa de curso fatal por L. garvieae en un paciente con una enfermedad renal crónica sometido a hemodiálisis y portador de diverticulosis colónica no complicada. Se realiza una revisión de los casos publicados y se discuten los actuales desafíos diagnósticos y terapéuticos de este patógeno, capaz de producir infecciones graves y potencialmente fatales en pacientes susceptibles. Este sería el segundo caso de infección asociada a hemodiálisis y el primero reportado en Chile.

Reports of Lactococcus garvieae infections in humans are scarce, and only one of them in a patient under-going hemodialysis. We report the first case of Lactococcus garvieae infection in Chile, presenting as an infective endocarditis, ultimately fatal, in a patient with uncomplicated colonic diverticulosis and end stage renal failure undergoing chronic hemodialysis. We review the published cases and discuss the diagnostic and therapeutic challenges associated with this new, increasingly diagnosed pathogen, capable of producing serious infections in susceptible patients.

La experiencia de "tocar fondo" en alcohólicos recuperados: Una aproximación fenomenológica / The Experience of "Hitting Rock Bottom" Among Recovering Alcoholics: A Phenomenological Approach

El objetivo del presente estudio es describir la experiencia de "tocar fondo" en alcohólicos recuperados, para lo cual se utilizó el método fenomenología) y se practicó una entrevista en profundidad a cinco hombres y tres mujeres seleccionados entre la comunidad de Alcohólicos Anónimos, por medio del procedimiento de máxima variación en los casos. Los hallazgos mostraron que en la experiencia de "tocar fondo", generada por una acumulación de sucesos críticos, el alcohólico toma conciencia de su ruina existencial, se pregunta por su propia vida, siente deseos de cambiar, detiene su camino hacia la autodestrucción, busca ayuda, experimenta sentimientos de esperanza y liberación, y comienza un proceso de transformación y renacimiento, por así decirlo, que lo conduce a una vida más plena y saludable. Dicho renacer culmina con el abandono de la bebida. Esta experiencia entraña un enorme sufrimiento, precede el proceso de recuperación del alcohólico y parece ser un eslabón ineluctable de dicho proceso, cuya gravedad podría reducirse al conocer las experiencias de tocar fondo de otros alcohólicos.

Availing of the phenomenological method, this study aims to describe the experience of "hitting bottom" among recovering alcoholics. In-depth interviews were conducted with five men and three women who belong to the Alcoholic Anonymous community. These individuals were selected through a maximum variation sampling procedure. The results demonstrate that, due to the accumulation of critical events, in "hitting bottom" an alcoholic becomes aware of his/her existential ruin, is questioned for his/her life, feels a desire to change course, desists from the road toward self-destruction, seeks help, experiences feelings of hope and liberation, and begins a process of rebirth and transformation that leads him/her to stop drinking and therefore to a healthier life. Such an experience involves enormous suffering, precedes the process of recovery from alcoholism whereto it seems to be necessary.

La prevención temprana de la violencia: una revisión de programas y modalidades de intervención / The early violence prevention: revision of programs and intervention modalities

Se presenta una revisión de modalidades de prevención temprana de la violencia realizadas a nivel internacional, las cuales han mostrado ser efectivas en la reducción de agresión en niños pre-escolares, y en algunos casos, en la prevención del comportamiento violento durante la adolescencia y la juventudSe presenta una revisión de modalidades de prevención temprana de la violencia realizadas a nivel internacional, las cuales han mostrado ser efectivas en la reducción de agresión en niños pre-escolares, y en algunos casos, en la prevención del comportamiento violento durante la adolescencia y la juventud