Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model / Potencial terapêutico de células-tronco e melatonina na redução da fibrose hepática induzida por CCl4 no modelo de ratos experimentais

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Caracterización clínico-epidemiológica de los pacientes sometidos a trasplante hepático por cirrosis alcohólica en el Hospital Pablo Tobón Uribe de Medellín entre 2004 y 2015 / Clinical-epidemiological characterization of patients undergoing liver transplantation for alcoholic cirrhosis at the Pablo Tobón Uribe Hospital in Medellín between 2004 and 2015

Introducción. El alcohol ha sido asociado con más de 60 enfermedades diferentes y es el tercer factor de riesgo más común relacionado con muerte y discapacidad en el mundo. La enfermedad alcohólica hepática (EAH) es la causa más común de enfermedad hepática terminal (EHT) en los países occidentales. El objetivo de este estudio fue caracterizar la población adulta sometida a trasplante ortotópico hepático (TOH) indicado por EHT secundaria a EAH, en el Hospital Pablo Tobón Uribe (HPTU) de Medellín entre 2004 y 2015. Metodología. Estudio observacional retrospectivo. Se revisaron las historias clínicas electrónicas de todos los pacientes trasplantados en el HPTU entre los años 2004 y 2015, sometidos a TOH indicado por EHT secundaria a EAH. Se registraron las características demográficas, comorbilidades médicas y psiquiátricas, complicaciones tempranas y tardías, recaída en el consumo de alcohol posterior al TOH, supervivencia y causa de la muerte. Resultados. Se encontraron 59 pacientes trasplantados por cirrosis de origen alcohólico. El 91,5 % fueron de sexo masculino, el 82,6 % (38/46) tuvo un período abstinencia previo al TOH mayor o igual a 6 meses, y solamente el 10,2 % (6/59) de los pacientes estuvieron vinculados a un programa de adicciones. Se encontró comorbilidad psiquiátrica en el 30 % (18/59) con predomino de depresión. Se identificó recaída pesada en el consumo de alcohol postrasplante en 6 pacientes, este subgrupo se caracterizó por una alta mortalidad (66 %), pobre adherencia a la terapia inmunosupresora y alta frecuencia de depresión (83 %). En general, la cohorte tuvo una supervivencia a 5 y 10 años de 60,8 % y 28,1 %, respectivamente. Conclusiones. Las características epidemiológicas de la población son compartidas con reportes previos en relación al predominio de sexo masculino y adultos en la sexta década de la vida. La recaída en el consumo pesado de alcohol no es la regla, sin embargo, se encuentra asociada con abandono del tratamiento inmunosupresor y muerte. En comparación con reportes de otros países, nuestras tasas de complicaciones y mortalidad a 5 años son superiores.

Introduction. Alcohol has been associated with more than 60 different diseases and is the third most common risk factor related to death and disability throughout the world. Alcoholic liver disease is the most common cause of end-stage liver disease in Western countries. The main objective of this study was to characterize adult patients with orthotopic liver transplant due to alcoholic cirrhosis at the Pablo Tobón Uribe Hospital in Medellín between 2004 to 2015. Methodology. Observational retrospective study. We reviewed clinical records of all patients with orthotopic liver transplant due to alcoholic cirrhosis at the HPTU between 2004 and 2015, and retrieved demographic data, comorbidities, complications, consumption relapse and survival. Results. We analyzed 59 patients, 91.5% were male, 82.6% had an abstinence period previous to liver transplant equal or greater to six months, 10.2% were part of an addiction program, and 30% had psychiatric morbidities, mainly depression. We identified 6 patients with heavy alcoholic relapse after transplantation, this subgroup was characterized by a high mortality (66%), poor adherence to immunosuppressive therapy and high rates of depression (83%). In general, this cohort had a 5- and 10-year survival of 60.8% and 20.1%, respectively. Conclusions. The epidemiological characteristics of the population are shared with previous reports regarding the predominance of males and adults in the sixth decade of life. Relapse into heavy alcohol consumption is not the rule, however, it is associated with discontinuation of immunosuppressive treatment and death. In comparison with other reports, we have higher complications and mortality rates at 5 five years.

Frecuencia de síndrome hepatopulmonar en pacientes pediátricos trasplantados en un hospital de alta complejidad en Medellín, Colombia / Frequency of hepato-pulmonary syndrome in pediatric transplanted patients in a high complexity hospital in Medellín, Colombia

Introducción. El síndrome hepatopulmonar (SHP) es una complicación grave en los pacientes con enfermedad hepática crónica y/o hipertensión portal. La frecuencia descrita en adultos es entre 4 % y 47 %. En pediatría, los reportes también son muy variables y van desde el 3 % hasta el 40 %, desconociendo la real incidencia de este. El objetivo de esta descripción es conocer la frecuencia del SHP en pacientes pediátricos en un hospital de alta complejidad, por medio de una búsqueda activa del SHP en los estudios pretrasplante hepático hallados en las historias clínicas. Metodolo-gía. Estudio retrospectivo de 5 años, en un hospital de alta complejidad en Colombia, en menores de 15 años con un primer trasplante hepático. Resultados. Se contó con la información de 24 pacientes, se analizaron variables demográficas y se confirmó el SHP en 18 pacientes (75 %), encontrando una gravedad leve o moderada en el 33 % y 44 %, respectivamente, siendo en este grupo la cirrosis con complicaciones por hipertensión portal la indicación más frecuente para el trasplante, y como etiología de base, la atresia de vías biliares en un 61 %. Conclusión. El SHP en nuestra población se encontró con una alta frecuencia de presentación, por encima de lo reportado en la literatura, llevando a recomendar una búsqueda activa, con el objetivo de brindar un manejo integral y oportuno.

Introduction. Hepatopulmonary syndrome (HPS) is a serious complication in patients with chronic liver disease and/or portal hypertension. The frequency described in adults is between 4% and 47%. In pediatrics, reports are also highly variable and range from 3% to 40%, with the real incidence not clear yet. The objective of this study is to know the frequency of HPS in our population through an active search for HPS in pre-liver transplant studies in clinical records. Methodology. This is a 5-year retrospective study, in a reference hospital in Colombia, that included children under 15 years of age with a first liver transplant. Results. In 24 patients, the information was available, demographic variables were analyzed, and HPS was confirmed in 18 patients (75%), finding mild and moderate severity in 33% and 44%, respectively. In this group, cirrhosis with complications due to portal hyper-tension was the most frequent indication for transplantation and biliary atresia was the main etiology in 61%. Conclusion. HPS in our population was found with a high frequency, higher than is described in the literature, leading to the recommendation of an active search, with the aim of providing com-prehensive and timely management.

Utilidad del sistema de recirculación de adsorbentes moleculares en la falla hepática: "diálisis hepática" / Usefulness of the molecular adsorbent recirculating system in liver failure: "liver dialysis"

INTRODUCCIÓN. La falla hepática ya sea aguda o crónica reagudizada representa un reto para el clínico ya que sus complicaciones conllevan una gran mortalidad, esto se ve aún más complicado ya que las opciones terapéuticas son limitadas, incluso muchas veces no se puede acceder a un programa de trasplante hepático oportuno que mejore la sobrevida de estos pacientes, es así que se ha desarrollado un sistema de "diálisis" hepática conocido como sistema de recirculación de adsorbentes moleculares el cual hace un efecto de detoxificación para eliminar sustancias que generan una noxa en el cuerpo humano. OBJETIVO. Entender la utilidad del sistema recirculante molecular adsorbente en la falla hepática, conocer sus indicaciones y complicaciones. METODOLOGÍA. Se realizó una revisión de la literatura con un enfoque descriptivo, retrospectivo cualitativo no experimental, de documentos que tratan sobre la utilización del sistema MARS para tratar la falla hepática, con evidencia desde el año 2004 hasta el 2021. La revisión bibliográfica se llevó a cabo en bases de datos como Pubmed, Embase, BVS, Google Scholar y Elsevier. RESULTADOS. Se identificaron 30 artículos que cumplieron criterios de inclusión de un grupo original de 343 artículos revisados. Se ha determinado que la evidencia sobre este sistema está compuesta sobre todo por reportes de caso y son pocos los ensayos controlados aleatorizados que empleen su uso, sin embargo, se ha podido determinar que este sistema es un puente al trasplante renal mientras se estabiliza al paciente en la Unidad de Cuidados Intensivos, disminuye los marcadores de falla hepática. CONCLUSIÓN. En Latinoamérica su uso es casi nulo de ahí la necesidad de entender el mecanismo de este novedoso sistema.

INTRODUCTION. Hepatic failure, whether acute or chronic, represents a challenge for the clinician since its complications entail a great mortality, this is even more complicated since the therapeutic options are limited, even many times it is not possible to access a timely liver transplant program to improve the survival of these patients, Thus, a hepatic "dialysis" system known as molecular adsorbent recirculation system has been developed, which has a detoxification effect to eliminate substances that generate a noxa in the human body. OBJECTIVE. To understand the usefulness of the molecular adsorbent recirculating system in liver failure, to know its indications and complications. METHODOLOGY. A literature review was performed with a descriptive, retrospective qualitative non-experimental qualitative approach, of papers dealing with the use of the MARS system to treat liver failure, with evidence from 2004 to 2021. The literature review was conducted in databases such as Pubmed, Embase, BVS, Google Scholar and Elsevier. RESULTS. Thirty articles were identified that met inclusion criteria from an original group of 343 articles reviewed. It has been determined that the evidence on this system is mainly composed of case reports and there are few randomized controlled trials that employ its use, however, it has been determined that this system is a bridge to renal transplantation while the patient is stabilized in the Intensive Care Unit, decreasing the markers of liver failure. CONCLUSIONS. In Latin America its use is almost null, hence the need to understand the mechanism of this novel system.

Nonalcoholic steatohepatitis: An emerging cause of cirrhosis in Colombia / La esteatohepatitis no alcohólica: una causa emergente de cirrosis en Colombia

Abstract Introduction: Cirrhosis of the liver is a significant cause of morbidity and mortality in Latin America; the increased prevalence of metabolic syndrome in our population could be changing the epidemiological profile of patients with advanced chronic liver disease. Aim: To characterize a group of patients with cirrhosis of the liver at an outpatient hepatology care center in Cartagena de Indias, Colombia, and determine the contribution of nonalcoholic steatohepatitis (NASH) as an etiological factor in this population. Materials and methods: Retrospective, cross-sectional, analytical study. All patients who attended the hepatology follow-up with a diagnosis of cirrhosis of the liver were in the six-monthly follow-up protocol that included screening for hepatocellular carcinoma (HCC) and esophageal varices. Results: 346 patients were included, most were women (54.3 %). The first and second causes of cirrhosis were cryptogenic (35 %) and NASH (30.9 %), respectively, followed by viral hepatitis (17 %) and autoimmune diseases (9 %). Of these patients, 87.4 % were within categories A and B of the Child-Turcotte-Pugh score, and only 12.5 % (33 patients) were in stage C. Also, 60 % had at least one clinical decompensation, 38 % a history of variceal hemorrhage, and 4 % a diagnosis of HCC; 80.6 % of patients with NASH cirrhosis had diabetes, and 46.7 % were overweight. Conclusion: NASH cirrhosis is an emerging cause of advanced chronic liver disease in Colombia.

Resumen Introducción: la cirrosis hepática es una importante causa de morbimortalidad en América Latina; el incremento de la prevalencia del síndrome metabólico en nuestra población podría estar cambiando el perfil epidemiológico de los pacientes con enfermedad hepática crónica avanzada. Objetivos: caracterizar un grupo de pacientes con cirrosis hepática y determinar la contribución de la esteatohepatitis no alcohólica (NASH) como factor etiológico de esta población en la ciudad de Cartagena de Indias, Colombia, en un centro de atención ambulatoria de hepatología. Métodos: estudio retrospectivo, transversal, analítico. Se incluyeron todos los pacientes que acudieron al seguimiento de hepatología con diagnóstico de cirrosis hepática que se encontraban en el protocolo de seguimiento semestral que incluía el cribado de hepatocarcinoma y várices esofágicas. Resultados: se incluyeron 346 pacientes. La mayoría fueron mujeres (54,3 %). La primera y segunda causa de cirrosis fue la criptogénica (35 %) y la NASH (30,9 %), respectivamente; seguidas de las hepatitis virales (17 %) y enfermedades autoinmunes (9 %). De estos pacientes, el 87,4 % se encontraba dentro de las categorías A y B de la escala pronóstica de Child-Turcotte-Pugh, y solo el 12,5 % (33 pacientes) en estadio C. El 60 % había presentado al menos una descompensación clínica, 38 % tenía antecedentes de hemorragia por várices y 4 %, diagnóstico de hepatocarcinoma. El 80,6 % de los pacientes con cirrosis NASH era diabético y el 46,7 % tenía exceso de peso. Conclusión: La cirrosis NASH es una causa emergente de enfermedad hepática crónica avanzada en Colombia.

Perfil epidemiológico de pacientes intoxicados con acetaminofén con intenciones suicidas / Epidemiological profile of patients intoxicated with acetaminophen for suicidal purposes / Perfil epidemiológico de pacientes intoxicados com acetaminofen (Paracetamol) com intenções suicidas

Objetivo: este estudio busca describir los individuos evaluados por sobredosis de acetaminofén entre 2019 y 2020 en un centro de referencia de trasplante hepático en Colombia. Metodología: estudio derivado del análisis secundario de historias clínicas entre el 1.º de enero de 2019 y el 31 de diciembre de 2020. Los criterios de inclusión abarcan individuos con ingestión aguda y voluntaria de dosis tóxicas de acetaminofén (>4 g/día). Resultados: sesenta y tres casos, 68% mujeres, 67% menores de 18 años y 54% estudiantes. Reportó historia personal de enfermedad psiquiátrica el 60% y el 35% al menos un intento de suicidio previo. La mediana de dosis de acetaminofén fue 15g, 46% refirieron co-ingesta de otras sustancias y 13% estaba bajo efecto de sustancias psicoactivas. El 57% tenía la intención clara de suicidarse, así como 81% vomitó antes de acudir al servicio de urgencias, 22% recibió medidas de descontaminación y 10% no recibió N - acetilcisteína. Quince individuos desarrollaron lesión hepática aguda, nueve con criterios de severidad. Conclusiones: la población era predominantemente joven, la historia de enfermedad psiquiátrica fue muy prevalente y la mayoría refirieron un evento vital que explicara el comportamiento impulsivo de consumo. Ninguno desarrolló criterios para trasplante hepático, lo cual podría explicarse por la edad de los individuos, los episodios de vómito temprano, y la ausencia de enfermedad hepática crónica o de consumo de sustancias hepatotóxicas.

Objective: this study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Colombia. Methodology: study derived from a secondary analysis of the clinical records between January 1st, 2019, to December 31st, 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). Results: sixty-three cases, 68% women, 67% <18-year-old, and 54% students. 60% had personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g, 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. Fifteen individuals developed an acute liver injury, nine with severity criteria. Conclusions: the population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred a vital event that explains the impulsive behavior in acetaminophen consumption. None developed criteria for liver transplantation, and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.

Objetivo:este estudo busca descrever os indivíduos avaliados por sobredose de acetaminofen entre 2019 e 2020 num centro de referência de transplante hepático na Colômbia. Metodologia: estudo derivado da análise secundário de histórias clínicas entre o dia 1.º de janeiro de 2019 e 31 de dezembro de 2020. Os critérios de inclusão abrangem indivíduos com ingestão aguda e voluntária de dose tóxicas de acetaminofen (>4 g/dia).Resultados:sessenta e três casos, 68% mulheres, 67% menores de 18 anos e 54% estudantes. Reportou história pessoal de doença psiquiátrica, 60% e 35% pelo menos uma tentativa de suicídio prévio. A média de dose de acetaminofen foi de 15g, 46% referiram com ingestão de outras sustâncias e 13% estava sob efeito de sustâncias psicoativas. 57% tinham a intenção clara de suicidar-se, assim como 81% vomitou antes de acudir ao serviço de urgências, 22% receberam medidas de descontaminação e 10% não recebeu N - acetilcisteína. Quinze indivíduos desenvolveram lesão hepática aguda, nove com critérios de severidade. Conclusões: a população era predominantemente jovem, a história de doençapsiquiátrica foi muito prevalente e a maioria referiram um evento vital que explicasse o comportamento impulsivo de consumo. Nenhum desenvolveu critérios para transplantehepático, o qual se poderia explicar pela idade dos indivíduos, os episódios de vómito precoce, e a ausência de doença hepática crónica ou de consumo de sustâncias hepatotóxicas.

Survival in Patients with Cirrhosis According to Etiology. Retrospective Cohort / Sobrevida en pacientes con cirrosis de acuerdo con su etiología. Cohorte retrospectiva

Abstract Introduction: Cirrhosis is the final stage of chronically progressive liver diseases of various etiologies. It is a common disease, with a variable prevalence in each country. Its peak incidence occurs between 40 and 50 years of age, predominantly in men. Aims: To compare a cohort of patients diagnosed with cirrhosis, evaluate their complications and survival according to etiology, describe clinical and laboratory aspects, and determine the role of a fatty liver. Materials and methods: A retrospective cohort study was carried out with patients who held a specialized hepatology consultation in the center of liver and digestive diseases (CEHYD) in Bogotá, Colombia, between January 2010 and June 2019. Results: We reviewed a total of 1,200 medical records (56.8 % women). There were no statistically significant differences in median survival between groups by etiology, sex, presence or absence of complications, or Child. We noted that the older the age at the diagnosis of cirrhosis, the higher the risk of death; HR 1.04 (95 % CI 1.02-1.075). For each month that follow-up increases, the risk of death decreases by 90 %; HR 0.1 (95 % CI 0.03-0.29). For each month that the follow-up of complications increases, the risk of death is reduced by 2 %; HR 0.98 (95 % CI 0.97-0.99). Conclusions: Survival by etiology was similar in the different groups. Nonalcoholic steatohepatitis (NASH) was the leading cause of cirrhosis in this cohort. Efforts should focus on its diagnosis and management in the early stages.

Resumen Introducción: la cirrosis es el estadio final de enfermedades hepáticas crónicamente progresivas de diferentes etiologías. Es una enfermedad frecuente, con una prevalencia variable en cada país. Su pico de incidencia se presenta entre los 40 y 50 años, predominantemente en hombres. Objetivos: comparar una cohorte de pacientes con diagnóstico de cirrosis, evaluar sus complicaciones y sobrevida de acuerdo con su etiología, describir los aspectos clínicos y de laboratorio, y determinar el papel del hígado graso. Materiales y métodos: se realizó un estudio de cohorte retrospectiva, en donde se incluyeron pacientes que asistieron a consulta especializada de hepatología en el centro de enfermedades hepáticas y digestivas (CEHYD), en la ciudad de Bogotá, durante enero de 2010 y junio de 2019. Resultados: se revisaron un total de 1200 historias clínicas (56,8 % mujeres). No se evidenció diferencias estadísticamente significativas en las medianas de sobrevida entre los grupos por etiologías, sexo, presencia o no de complicaciones, o Child. Se evidenció que entre mayor edad en el diagnóstico de cirrosis, el riesgo de muerte es mayor; HR 1,04 (IC 95 % 1,02-1,075). Por cada mes que aumenta el seguimiento se reduce el riesgo de muerte en 90 %; HR 0,1 (IC 95 % 0,03-0,29). Por cada mes que aumenta el seguimiento de las complicaciones se reduce el riesgo de muerte en 2 %; HR 0,98 (IC 95 % 0,97-0,99). Conclusiones: La sobrevida por etiología fue similar en los diferentes grupos. La esteatohepatitis no alcohólica (NASH) fue la principal causa de cirrosis en esta cohorte. Se deben orientar esfuerzos a su diagnóstico y manejo en fases tempranas.

Enfermedad hepatobiliar asociada a COVID-19 / Hepatobiliary disease associated with COVID-19

La enfermedad COVID-19, causada por el coronavirus tipo 2 (SARS-CoV-2), ha tenido un gran impacto en la salud a nivel mundial. A pesar de considerarse una enfermedad principalmente respiratoria, el virus SARS-CoV-2 también es responsable de otro tipo de manifestaciones extrapulmonares, como son las enfermedades hepatobiliares. En esta revisión se describen los posibles mecanismos de patogénesis implicados en la lesión hepática causada por el SARS-CoV-2. Adicionalmente, se analiza la relación entre COVID-19 y la enfermedad hepática crónica, las implicaciones que tiene en el carcinoma hepatocelular y en el trasplante hepático, así como las recomendaciones para la vacunación contra el SARS-CoV-2 en los pacientes afectados por enfermedad hepática. Por último, se proponen algunas estrategias para superar el reto al que se enfrenta el médico en el manejo delos pacientes con enfermedades hepatobiliares y COVID-19.

COVID-19, caused by the type 2 coronavirus (SARS-CoV-2), has had a major impact on health worldwide. Despite being mainly a respiratory disease, the SARS-CoV-2 virus is also responsible for other types of extrapulmonary manifestations, such as hepatobiliary diseases. This review describes the possible mechanisms of pathogenesis involved in liver injury caused by SARS-CoV-2, the relationship between COVID-19 and chronic liver disease, the effects that it has on hepatocellular carcinoma and liver transplantation, as well as the recommendations for vaccination against SARS-CoV-2 in patients affected by liver disease. Finally, some strategies are suggested to overcome the challenge faced by the clinician in the management of patients with hepatobiliary disease and COVID-19.

Respiratory muscle strength and exercise capacity of children and adolescents with chronic liver diseases / Força muscular respiratória e capacidade de exercício de crianças e adolescentes com hepatopatias crônicas

Introdution: Chronic liver diseases are characterized by inflammatory and fibrotic lesions of the liver that cause systemic complications. These complications can negatively interfere with the respiratory muscle strength and exercise capacity of developing children and adolescents. Objectives: to compare respiratory muscle strength and exercise capacity in children and adolescents with chronic hepatopathy, using predicted values from healthy individuals of the same age. Methodology: a cross-sectional study was performed. Children and adolescents from 6 to 16 years old with chronic hepatopathies were included. For the evaluation of respiratory muscle strength, the maximal respiratory pressures were measured through manovacuometry. A six-minute walk test was used to assess exercise capacity. The Wilcoxon test was used to verify the difference between the evaluated and predicted values of the distance traveled. Results: In total, 40 subjects were analyzed; 57.5% of the subjects were female, and the subjects had a mean age of 11.68±2.82 years. In the comparison between the measured and predicted maximal respiratory pressures, a median (IQR) difference of -21,47 (33-95) cmH2O (p< 0.001) was found for the maximal inspiratory pressure, and a mean difference of 30.68±17,16 cmH2O (p< 0.001) was found for the maximal expiratory pressure. Regarding exercise capacity, the measured average distance traveled was 346.46±49.21 m, which was 185.54±63,90 m (p< 0.001) less than the predicted value. Conclusion: Children and adolescents with chronic liver disease have reduced respiratory muscle function and exercise capacity.

Introdução: as doenças hepáticas crônicas são caracterizadas por lesões inflamatórias e fibróticas do fígado que causam complicações sistêmicas. Essas complicações podem interferir negativamente na força muscular respiratória e na capacidade de exercício de crianças e adolescentes em desenvolvimento. Objetivo: comparar a força muscular respiratória e a capacidade de exercício em crianças e adolescentes com hepatopatia crônica, utilizando valores preditos de indivíduos saudáveis da mesma idade. Metodologia: trata-se de um estudo transversal. Foram incluídas crianças e adolescentes de 6 a 16 anos com hepatopatias crônicas. Para a avaliação da força muscular respiratória, as pressões respiratórias máximas foram medidas por meio da manovacuometria. Teste de caminhada de seis minutos foi usado para avaliar a capacidade de exercício. O teste de Wilcoxon foi utilizado para verificar a diferença entre os valores avaliados e previstos da distância percorrida. Resultados: no total, 40 sujeitos foram analisados; 57,5% dos sujeitos eram do sexo feminino, idade média de 11,68±2,82 anos. Na comparação entre as pressões respiratórias máximas medidas e previstas, foi encontrada diferença mediana (IQ) de -21,47 (33-95) cmH2O (p<0,001) para a pressão inspiratória máxima e diferença média de 30,68±17,16 cmH2O (p<0,001) para a pressão expiratória máxima. Em relação à capacidade de exercício, a distância média percorrida foi 346,46±49,21 m, média 185,54±63,90 m (p<0,001) inferior ao valor previsto. Conclusão: crianças e adolescentes com doença hepática crônica apresentam redução da função muscular respiratória e da capacidade de exercício.

Desenvolvimento neuropsicomotor em crianças e adolescentes com doenças hepáticas: revisão sistemática com meta-análise / Neuropsychomotor development in children and adolescents with liver diseases: systematic review with meta-analysis

ABSTRACT BACKGROUND: The nature of liver disease, the evolutionary course and duration of liver diseases, as well as the degree of severity and disability can trigger multiple outcomes with repercussions on neuromotor acquisition and development. OBJECTIVE: To systematically review and conduct a meta-analysis to evaluate the effects of liver disease on the neuropsychomotor development of children and adolescents with their native livers and those who underwent liver transplantation. METHODS: Observational studies published since the early 1980s until June 2019 were sought in the PubMed and Scopus databases. An α value of 0.05 was considered significant. The statistical heterogeneity of the treatment effect between the studies was assessed by the Cochran's Q test and the I2 inconsistency test, in which values above 25 and 50% were considered indicative of moderate and high heterogeneity, respectively. Analyses were performed with Review Manager 5.3. RESULTS: Twenty-five studies met the eligibility criteria, including 909 children and adolescents with liver disease. Meta-analyses showed deficits in total IQ -0.41 (95%CI: -0.51 to -0.32; N: 9,973), verbal IQ -0.38 (95%CI: -0.57 to -0.18; N: 10,284) and receptive language -0.85 (95%CI: -1.16 to -0.53; N: 921) in liver transplantation, and those with native livers who had symptoms early had total and verbal IQ scores (85±8.8; 86.3±10.6 respectively) lower than the scores of those with late manifestations (99.5±13.8; 96.2±9.2). Gross motor skill was reduced -46.29 (95%CI: -81.55 to -11.03; N: 3,746). CONCLUSION: Acute or chronic liver disease can cause declines in cognitive, motor and language functions. Although the scores improve after liver transplantation, children remain below average when compared to healthy children.

RESUMO CONTEXTO: A natureza da doença hepática, curso evolutivo e duração das hepatopatias, bem como grau de severidade e incapacidade podem desencadear desfechos múltiplos e com repercussões na aquisição e desenvolvimento neuromotores. OBJETIVO: Revisar sistematicamente e avaliar por meta-análise os efeitos da doença hepática sobre o desenvolvimento neuropsicomotor de crianças e adolescentes com seus fígados nativos e aquelas que realizaram transplante hepático. MÉTODOS: As buscas foram realizadas nas bases de dados PubMed e periódicos Scopus desde as primeiras publicações na década de 1980 até junho de 2019, de estudos observacionais. Um valor de 0,05 foi considerado significativo. A heterogeneidade estatística do efeito do tratamento entre os estudos foi avaliada pelo teste Q de Cochran e o teste de inconsistência I2, no qual valores acima de 25 e 50% foram considerados indicativos de heterogeneidade moderada e alta, respectivamente. As análises foram realizadas com o Review Manager 5.3. RESULTADOS Vinte e cinco estudos preencheram os critérios de elegibilidade, incluindo 909 crianças e adolescentes com doenças hepáticas. As meta-análises mostraram déficits QI total -0,41 (IC 95%: -0,51 até -0,32; N: 9.973), QI verbal -0,38 (IC 95%; -0,57 até -0,18; N: 10.284) e linguagem receptiva -0,85 IC 95%: -1,16 até -0,53; N: 921) nos transplantes hepáticos e as com fígados nativos que apresentaram sintomas precocemente tinham escores de QI total e verbal (85±8,8; 86,3±10,6 respectivamente) menores do que aquelas com manifestações tardias (99,5±13,8; 96,2±9,2). Habilidade motora grossa apresentou-se reduzida -46,29 (IC 95%: -81,55 até -11,03; N: 3.746). CONCLUSÃO: A doença hepática aguda ou crônica pode determinar declínios nas funções cognitivas, motoras e de linguagem. Muito embora, os escores melhorem após transplante hepático, as crianças continuam abaixo da média quando comparadas às crianças sadias.

Estudio descriptivo de pacientes con cirrosis hepática de etiología viral, en la provincia de Matanzas / Descriptive study of patients with viral-etiology liver cirrhosis in the province of Matanzas

RESUMEN Introducción: la cirrosis hepática de etiología viral representa un impactante problema de salud a nivel mundial, no solo por su elevada tasa de prevalencia, sino por los costos generados en la atención médica. Objetivos: determinar el comportamiento de los pacientes cirróticos, de etiología viral, en la provincia de Matanzas. Materiales y métodos: se realizó un estudio descriptivo-retrospectivo en 47 pacientes con cirrosis hepática de etiología viral, atendidos en el Servicio de Gastroenterología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, de enero de 2016 a enero de 2018. Los resultados de las variables analizadas se expusieron en tablas de doble entrada. Resultados: el 68,1 % de los pacientes correspondió a cirrosis por virus C. Predominaron los mayores de 50 años, con carga viral entre 4-6,9 log10, y atendidos en régimen ambulatorio. En el 57,4 % se detectaron signos endoscópicos de hipertensión portal, que se corroboraron en el doppler hepático. La ascitis asociada a diferentes sepsis fueron las complicaciones más registradas. El 55,4 % fue clasificado como Child-Pugh A, y el 76,6 % en etapa clínica compensada. Conclusiones: el diagnóstico y seguimiento de la cirrosis hepática viral sigue siendo un verdadero reto para la comunidad médica. De ahí los esfuerzos que han de realizarse para su control desde las fases compensadas, para retardar la aparición de complicaciones (AU).

ABSTRACT Introduction: viral etiology liver cirrhosis is an impacting health problem around the world, not only because of its high prevalence rate but also because of the costs generated by its medical care. Objective: to determine the behavior of the patients with viral etiology liver cirrhosis in the province of Matanzas. Materials and methods: a descriptive-retrospective study was carried out in 47 patients with viral etiology liver cirrhosis treated in the service of Gastroenterology of the Hospital "Comandante Faustino Perez" of Matanzas, from January 2016 to January 2018. The results of the analyzed variables were shown in double-entry tables. Results: 68.1% of the patients presented cirrhosis caused by C virus, Patients elder 50 years old predominated, with 4-6.9 log10, treated in ambulatory regimen. Endoscopic signs of portal hypertension were found in 57.4%. It was corroborated with liver Doppler. Ascites associated to different sepsis were the most frequently registered complications. 55.4% were classified as Child-Pugh A, and 76.6% were in compensated clinical stage. Conclusions: viral liver cirrhosis diagnosis and follow-up is still a true challenge for the medical community, and hence the efforts that should be made to control it from the compensated stages to delay the appearance of complications (AU).

Disfunción renal en el paciente cirrótico / Renal dysfunction in the cirrhotic patient

La disfunción renal es una complicación común en pacientes con cirrosis avanzada y está asociadaa un incremento significativo en la mortalidad. Este deterioro de la función renal puede ser reversible en algunos casos, si se identifica y se trata su etiología. La lesión renal aguda (LRA) de origen prerrenal y la necrosis tubular aguda (NTA) son las entidades más frecuentes en pacientes con enfermedad hepática crónica y cirrosis, constituyendo un desafío en los escenarios clínicos actuales. La aparición de nuevos biomarcadores como la lipocalina asociada a la gelatinasa de neutrófilos (NGAL), puede ser un factor determinante para esclarecer el origen de estas dos entidades. En la actualidad, la clasificación de la enfermedad renal establece que un aumento en la creatinina sérica basal >0,3 mg/dL dentro de las primeras 48 horas, o un incremento mayor al 50% desde la línea de base, son suficientes para definir lesión renal aguda, por lo cual, cambios leves en la creatinina sérica en un periodo corto de tiempo, contribuyen a una identificación temprana y previenen desenlaces negativos. Esta revisión de tema abordará la lesión renal aguda en cirrosis desde la fisiopatología, la clasificación actual según guías internacionales, los avances en biomarcadores y las principales etiologías, finalizando con un abordaje general y estrategias de prevención.

Kidney dysfunction is a common complication in patients with advanced cirrhosis and is associated with a significant increase in mortality. This deterioration of kidney function may be reversible in some cases, if its etiology is identified and treated. Acute kidney injury (AKI) of prerenal origin and acute tubular necrosis (ATN) are the most frequent entities in patients with chronic liver disease and cirrhosis, constituting a challenge in current clinical scenarios. The emergence of new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), may be a determining factor in clarifying the origin of these two entities. Currently, the classification of renal disease establishes that an increase in basal serum creatinine >0,3 mg/dL within the first 48 hours, or an increase higher than 50% from the baseline, are enough to define acute kidney injury, therefore slight changes in serum creatinine in a short period of time contribute to an early identification and prevent negative outcomes. This literature review will address acute kidney injury in cirrhosis from its pathophysiology, current classification according to international guidelines, advances in biomarkers and the main etiologies associated with it, ending with a general approach and prevention strategies.

Colestasis inducida por anabólicos: reporte de caso y revisión de la literatura / Anabolic-induced cholestasis: case report and literature review

La función metabólica y de excreción está determinada principalmente por la actividad hepática, esto predispone al hígado a lesión inducida por toxicidad, en donde la disfunción es mediada directa o indirectamente por xenobióticos y/o sus metabolitos. La enfermedad hepática inducida por fármacos (DILI) es una condición poco frecuente, que se relaciona hasta con el 50% de las insuficiencias hepáticas agudas, y de ahí su importancia. La lesión directa puede estar dirigida a hepatocitos, conductos biliares y estructuras vasculares; no obstante, diferentes xenobióticos pueden interferir con el flujo de bilis mediante el bloqueo directo de proteínas de trasporte en los canalículos. Actualmente no existen marcadores absolutos para el diagnóstico de esta entidad y las manifestaciones clínicas pueden ser variables, desde el espectro de alteraciones bioquímicas en ausencia de síntomas, hasta insuficiencia hepática aguda y daño hepático crónico, por lo cual es principalmente un diagnóstico de exclusión basado en evidencia circunstancial. A partir de esta inferencia, se han desarrollado escalas y algoritmos para evaluar la probabilidad de lesión hepática inducida por medicamentos, tóxicos, herbales o suplementos. En la mayoría de los casos, es característico que la condición del paciente mejore cuando se elimina el fármaco responsable del daño. Aunque el patrón colestásico generalmente tiene mejores tasas de supervivencia en comparación con otros patrones, también se asocia con un alto riesgo de desarrollar enfermedad hepática crónica o ser el desencadenante de manifestaciones inmunológicas en el hígado. Se presenta el caso clínico de un paciente con patrón colestásico de DILI por uso de esteroides anabólicos.

Metabolic and excretory function is determined mainly by liver activity which can make this organ susceptible to toxic injury, where dysfunction is directly or indirectly mediated by xenobiotics and/ or their metabolites. Drug-induced liver disease (DILI) is a rare condition, which is associated with up to 50% of acute liver failure, and hence its importance. Direct injury can be directed to hepatocytes, bile ducts, and vascular structures, however, different xenobiotics can interfere with bile flow by directly blocking transport proteins in the canaliculi. Currently there are no definite markers for the diagnosis of this condition, and clinical manifestations can be variable, including biochemical changes in the absence of symptoms to acute liver failure and chronic liver damage, which makes it mainly an exclusion diagnosis based on clinical evidence. Scales and algorithms have been developed to assess the probability of drug, toxic, herbal, or supplement-induced liver injury. In most cases, the patient's condition typically improves when the drug responsible for the injury is removed. Although the cholestatic pattern generally has better survival rates compared to other patterns, it is also associated with a high risk of developing chronic liver disease or acting as a trigger for immune disorders in the liver. The clinical case of a patient with a cholestatic pattern of DILI due to the use of anabolic steroids is presented.

Aplicación de la escala de MELD en los pacientes del Programa de Trasplante Hepático / Application of the MELD scale in patients of the Liver Transplant Program

INTRODUCCIÓN. La escala Model for End-Stage Liver Desease se utiliza para conocer el estadio de la enfermedad hepática y para la asignación de órganos en los pacientes candidatos a trasplante. OBJETIVO. Validar la utilidad de la escala en pacientes adultos del Programa de Trasplante Hepático y su aplicación en la priorización de injertos para pacientes en lista de espera. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo. De una población de 103 Historias Clínicas, se tomó una muestra de 95 registros del Programa de Trasplante Hepático del Hospital de Especialidades Carlos Andrade Marín en el período mayo 2016 a marzo 2020. Criterios de inclusión: datos de pacientes con diagnóstico de enfermedad hepática terminal, de ambos sexos, con edades comprendidas entre 14 y 65 años. La información se tomó del sistema AS400 y se analizaron en el programa estadístico International Business Machines Statistical Package for the Social Sciences, versión 23.0 y el estimador Kaplan-Meier. RESULTADOS. La sobrevida en lista de espera fue del 86,3% (82; 95) y en el post trasplante del 72,5% (44; 62) a los 12 meses y 68,9% (42; 62) a los 46 meses de seguimiento. DISCUSIÓN. Esta escala se consideró para los pacientes graves, asignándoles un puntaje que les permitió tener la opción de recibir un trasplante en relación a otros pacientes. CONCLUSIÓN. Se validó la utilidad de la escala, no se encontró diferencia significativa, pero mantuvo el principio de prioridad para los pacientes con mayor severidad.

INTRODUCTION. The Model for End-Stage Liver Desease scale is used to determine the stage of liver disease and for organ allocation in transplant candidates. OBJECTIVE. To validate the usefulness of the scale in adult patients of the Liver Transplantation Program and its application in the prioritization of grafts for patients on the waiting list. MATERIALS AND METHODS. Observational, descriptive study. From a population of 103 Medical Records, a sample of 95 records was taken from the Liver Transplantation Program of the Carlos Andrade Marín Specialty Hospital in the period may 2016 to march 2020. Inclusion criteria: data from patients with a diagnosis of terminal liver disease, of both sexes, aged between 14 and 65 years. The information was taken from the AS400 system and analyzed using the International Business Machines Statistical Package for the Social Sciences, version 23.0 and the Kaplan-Meier estimator. RESULTS. Survival on the waiting list was 86,3% (82; 95) and post-transplant survival was 72,5% (44; 62) at 12 months and 68,9% (42; 62) at 46 months of follow up. DISCUSSION. This scale was considered for seriously ill patients, assigning them a score that allowed them to have the option of receiving a transplant in relation to other patients. CONCLUSIONS. The utility of the scale was validated, no significant difference was found, but it maintained the principle of priority for patients with greater severity.

Sarcopenia in children and adolescents with chronic liver disease / Sarcopenia em crianças e adolescentes com doença hepática crônica

Abstract Objective: To investigate the occurrence of sarcopenia in children and adolescents with chronic liver disease. Methods: A series of cases, with patients aged 6-19 years of both genders, who were treated in Liver Outpatient Clinics. Weight, height, muscle strength (assessed by manual grip strength), and muscle mass (estimated through dual-energy X-ray absorptiometry) were measured. Sarcopenia was diagnosed based on the simultaneous presence of muscle mass and muscle strength déficits, defined as the values below the mean for muscle mass and strength of the studied population, according to gender. A descriptive analysis (mean and standard deviation) was performed, and the difference of means was calculated by Student's t-test. Results: A total of 85 patients were studied, mostly females (64.7%), with a mean age of 11.7 (SD = 3.4) years. Sarcopenia was identified in 40% of the patients. Muscle strength déficit was found in 54.1% of the subjects, and 50.6% showed muscle mass déficit. The mean muscle mass for males was higher than that for females (6.07; SD = 1.22 kg/m2 vs. 5.42; SD = 1.10 kg/m2; p = 0.016). However, there was no significant difference in sex-related muscle strength (male = 0.85; SD = 0.52 kgf/kgm2 and female = 0.68; SD = 0.30 kgf/kgm2; p = 0.113). Conclusion: The research findings identified that sarcopenia is a condition found in pediatric patients treated at a public referral institution for chronic liver disease.

Resumo Objetivo: Investigar a ocorrência de sarcopenia em crianças e adolescentes com hepatopatias crônicas. Métodos: Série de casos, constituído por pacientes entre 6 e 19 anos, de ambos os sexos, acompanhados em ambulatórios de especialidade em hepatopatias. Foram feitas medidas de peso, altura, força muscular (avaliada pela força de preensão manual) e a massa muscular estimada a partir da absorciometria por dupla emissão de raios X. O diagnóstico de sarcopenia baseou-se na presença simultânea de déficit de massa muscular e de força muscular. Adotaram-se como déficit os valores abaixo da média para massa e força muscular da população estudada, segundo sexo. Realizou-se análise descritiva (média e desvio-padrão), bem como a diferença de médias com o teste do t de Student. Resultados: Foram estudados 85 pacientes, a maioria do sexo feminino (64,7%), com média de 11,7 (DP = 3,4) anos. A sarcopenia foi identificada em 40% dos pacientes, 54,1% apresentaram déficit de força muscular e 50,6% déficit de massa muscular. A média da massa muscular para o sexo masculino foi maior do que no feminino (6,07; DP = 1,22 kg/m2 vs 5,42; DP = 1,10 kg/m2; p = 0,016). No entanto, não houve diferença significante para força muscular com relação aos sexos (masculino = 0,85; DP = 0,52 kgf/kgm2 e feminino = 0,68; DP = 0,30 kgf/kgm2; p = 0,113). Conclusão: Os achados da pesquisa identificaram que a sarcopenia é uma condição presente em pacientes pediátricos atendidos em uma instituição pública de referência para doença hepática crônica.

Implicaciones de la microbiota intestinal en las enfermedades crónicas del hígado / Implications of the intestinal microbiota in the chronic liver diseases

RESUMEN La microbiota se refiere al conjunto de todos los de microorganismos que se localizan de manera normal en distintos sitios de los cuerpos de los seres vivos pluricelulares, tales como el cuerpo humano. Las modificaciones del eje intestino-hígado se ha convertido en la actualidad en un grave problema científico al haberse encontrado en diversas investigaciones, que esta microbiota está relacionada con el daño hepático con independencia de la causa de la lesión hepática. Se realizó una revisión sistemática sobre las implicaciones demamicrobiota intestinal en las enfermedades hepáticas. Se realizó una revisión de artículos científicos publicados entre 2012 y 2018 en diversas bases de datos en línea. Se presenta el conocimiento existente hasta el momento sobre la microbiota intestinal en pacientes portadores de enfermedades hepáticas, con hincapié en las hepatitis C y la cirrosis hepática. La composición de microbiota de intestino estuvo asociada con el perfil inflamatorio y marcadores de fibrosis hepática, las que mejoraron con el tratamiento de antivirales de acción directa aunque las medidas de permeabilidad intestinal e inflamación permanecían inalteradas. Se reporta mejoría de los pacientes portadores de hepatitis viral tipo C, con antivirales de acción directa la cual estuvo asociada con modificaciones de la microbiota intestinal, que se correlacionó con mejoría en la fibrosis e inflamación hepática, los avances en este campo abren nuevas perspectivas en la biomedicina (AU).

SUMMARY Microbiota refers to the whole of microorganisms located in a normal way in different places of the bodies of pluricelular living beings, like the human body. The modifications of the axis intestine-liver have become a serious scientific problem, because in different researches researchers have found that this microbiota is related to hepatic damage depending on the cause of this hepatic lesion. To carry out a systematic review on the implication of intestinal macrobiota in liver diseases. The scientific articles published in the period 2012-2018 in different databases on line were reviewed. A total of 26 bibliographic sources were used, original articles and reviews. The authors present knowledge existent up to the moment on intestinal microbiota in patients who have liver diseases, making emphasis on hepatitis C and hepatic cirrhosis. The composition of the intestine microbiota was associated to an inflammatory and markers of hepatic fibrosis that improved with the treatment of direct action antivirals although the measures of intestinal permeability and inflammation remained inalterably. It is reported an improvement of patients carriers of viral hepatitis type C with the use direct action retrovirals, what was linked to modifications in the intestinal microbiota, and correlated to an improvement of fibrosis and liver inflammation; the advances obtained in this field open new perspectives in biomedicine (AU).

Recomendaciones para manejo de pacientes con enfermedad hepática crónica y trasplantados hepáticos durante pandemia por COVID-19 / Recommendations for the management of patients with chronic liver disease and liver transplanted recipients during the COVID-19 pandemic

The SARS-CoV-2 virus and the associated disease COVID-19 has quickly become a pandemic. People with underlying chronic diseases or in an immunosupressed state are at risk of having a worse outcome. Cirrhotic patients and liver transplant recipients are considered to be in this higher risk group due to their immunosuppressed state. The aim of this article is to present recommendations based on expert opinion regarding the management of patients with compensated and decompensated liver pathologies who take medication for their immunosuppressed state in medical check-ups and basic treatment management both of patients with and without the COVID-19 disease.

El virus SARS-CoV-2 asociado a la enfermedad COVID-19, se han instalado a nivel de pandemia mundial. Las personas portadoras de enfermedades crónicas o estados de inmunosupresión se encuentran en riesgo de desarrollar un curso más grave. Se considera que los pacientes con cirrosis hepática, patología autoinmune o trasplante hepático se encontrarían dentro de este grupo de mayor riesgo por su estado de inmunosupresión. Presentamos recomendaciones de manejo basadas en opinión de experto, en pacientes con patología hepática compensada y descompensada e inmunosuprimidos farmacológicos, en relación a controles médicos y manejo de terapia de base tanto en pacientes sin COVID-19 como en pacientes infectados.

Enfermedades hepáticas y su relación con hiperglicemia / The relationship between liver diseases and hyperglycemia

La Diabetes Mellitus tipo 2 (DM2) y las enfermedades crónicas del hígado(ECH), definida para esta revisión como cualquier alteración funcional o estructural de este órgano, desde inflamación hasta fibrosis, son patologías que frecuentemente se asocian, y su coexistencia se relaciona con peor pronóstico y mayores complicaciones de ambas entidades. El objetivo de este artículo es describir la relación entre hiperglicemia y enfermedades del hígado, sus procesos fisiopatológicos comunes y tratamiento, distinguiendo las patologías más relevantes, entre ellas la Diabetes Hepatogénica (DH), la enfermedad hepática por Virus Hepatitis C (VHC) y la Enfermedad Hepática Grasa No Alcohólica (EHGNA). La DH es aquella diagnosticada en pacientes con cirrosis asociada a insuficiencia hepática, sin antecedentes previos de alteración de la glicemia. En la actualidad el diagnóstico se realiza en etapas tardías de la enfermedad. El VHC tiene un efecto diabetogénico conocido. Algunas terapias antivirales usadas para VHC evidencian mejoría de las alteraciones metabólicas al lograr respuestas virológicas sostenidas. En DM2, la EHGNA es frecuente, con mayor incidencia de fibrosis, hepatocarcinoma (HCC) y riesgo cardiovascular (RCV). Es necesario realizar una pesquisa e intervención precoz de EHGNA a los pacientes con DM2. En el manejo de éstos, la baja de peso ha demostrado ser efectiva en el control glicémico y en la mejoría histológica. Dentro de las terapias antidiabéticas, además del uso de metformina, debería considerarse aquellas que han demostrado a la fecha beneficios en EHGNA, como son tiazolidinedionas (pioglitazona) y/o análogos de GLP-1 (liraglutide) y optimizar el control de otros factores de RCV.

Type 2 Diabetes Mellitus (DM2) and chronic liver diseases (CLD) defined in this revision as any functional or structural alteration in the organ, covering from inflammation to fibrosis, are pathologies that are frequently associated, and when found together are related to worse prognosis and higher complications in both conditions. The objective of this article is to describe the relationship between hyperglycemia and liver diseases, their common physio-pathological processes and treatments, identifying the most important pathologies, including Hepatogenic Diabetes (HD), Hepatitis C Virus (HCV) liver disease and Non-Alcoholic Fatty Liver Disease (NAFLD). Hepatogenic diabetes (HD) is diagnosed in patients with liver failure associated to cirrhosis with no previous record of impaired glycemia. Currently, diagnosis is made during the late stages of the disease. Hepatitis C virus (HCV) has a known diabetogenic effect. Some antiviral therapies used for HCV show improvement in metabolic alterations by achieving sustained virological responses. Non-alcoholic fatty liver disease (NAFLD) in DM2 patients is common, presenting higher risk for fibrosis, hepatocellular carcinoma (HCC) and increased cardiovascular risk (CVR). Early screening and interventions for NAFLD in DM patients are necessary. Weight loss has been shown to be effective in glycemic control and histological improvement. Anti-diabetic therapies, in addition to the use of metformin, should consider therapies that have shown benefits for managing NAFLD, such as thiazolidinedione (pioglitazones) and/or aGLP-1 (Liraglutide), and optimally controlling other cardiovascular risk (CVR) factors.