Polimorfismos en los genes de la enzima alcohol deshidrogenasa (ADH1) y la citocromo P450 2E1 (CYP2E1) en pacientes con cirrosis y carcinoma hepatocelular / Polymorphisms in alcohol dehydrogenase (ADH1) and cytochrome p450 2E1 (CYP2E1) genes in patients with cirrhosis and/or hepatocellular carcinoma

Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales. Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular. Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project. Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %). Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y la asociación con los polimorfismos.

Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.

Ventilatory support and hospital stay after liver transplant in cirrhotic patients with hepatopulmonary syndrome / Suporte ventilatório e tempo de hospitalização após transplante hepático em cirróticos com síndrome hepatopulmonar

ABSTRACT Objective To compare mechanical ventilation time, need for non-invasive ventilation, length of intensive care unit stay, and hospital stay after liver transplant in cirrhotic patients with and with no diagnosis of hepatopulmonary syndrome. Methods This was a prospective cohort study with a convenience sample of 178 patients (92 with hepatopulmonary syndrome) who were diagnosed as alcoholic or hepatitis C virus cirrhosis. The statistical analysis included Kolmogorov-Smirnov test and Students t test. Data were analyzed using SPSS version 16.0, and p values <0.05 were considered significant. Results Out of 178 patients, 90 underwent transplant (48 with no hepatopulmonary syndrome). The Group diagnosed with Hepatopulmonary Syndrome had longer mechanical ventilation time (19.5±4.3 hours versus 12.5±3.3 hours; p=0.02), an increased need for non-invasive ventilation (12 versus 2; p=0.01), longer intensive care unit stay (6.7±2.1 days versus 4.6±1.5 days; p=0.02) and longer hospital stay (24.1±4.3 days versus 20.2±3.9 days; p=0.01). Conclusion Cirrhotic patients Group diagnosed with Hepatopulmonary Syndrome had higher mechanical ventilation time, more need of non-invasive ventilation, as well as longer intensive care unit and hospital stay.

RESUMO Objetivo Comparar tempo de ventilação mecânica, necessidade de uso de ventilação não invasiva, tempo de permanência na unidade de terapia intensiva e tempo de hospitalização após transplante hepático em cirróticos com e sem diagnóstico de síndrome hepatopulmonar. Métodos Estudo de coorte prospectiva com amostra de conveniência composta por 178 pacientes (92 com síndrome hepatopulmonar) com diagnóstico de cirrose por álcool ou pelo vírus da hepatite C. A análise estatística foi realizada por meio do teste Kolmogorov-Smirnov e do teste t de Student. Os dados foram analisados pelo programa SPSS versão 16.0, e valores de p<0,05 foram considerados significantes. Resultados Dos 178 pacientes, 90 foram transplantados (48 sem síndrome hepatopulmonar). O Grupo com Síndrome Hepatopulmonar apresentou maior tempo de ventilação mecânica (19,5±4,3 horas versus 12,5±3,3 horas; p=0,02), maior necessidade de uso de ventilação não invasiva (12 versus 2; p=0,01), maior permanência na unidade de terapia intensiva (6,7±2,1 dias versus 4,6±1,5 dias; p=0,02) e maior tempo de hospitalização (24,1±4,3 dias versus 20,2±3,9 dias; p=0,01). Conclusão O Grupo com Síndrome Hepatopulmonar apresentou maiores tempo de ventilação mecânica, necessidade de uso de ventilação não invasiva, permanência na unidade de terapia intensiva e tempo de hospitalização.