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La enfermedad hepática no alcohólica se ha convertido en una afección de gran prevalencia y en una de las principales causas de cirrosis hepática en los países desarrollados. El aumento de la incidencia de esta enfermedad se produce de forma paralela al incremento de las tasas de obesidad y diabetes mellitus tipo 2. En la etiopatogenia de estas 3 enfermedades tienen un papel central la resistencia a la insulina y la inflamación.
La resistencia a la insulina produce el aumento de la lipólisis del tejido adiposo, lo cual libera una gran cantidad de ácidos grasos libres (AGL) que se acumulan en el hígado y generan la esteatosis hepática. El acúmulo de AGL interfiere a su vez en la resistencia hepática a la insulina y genera alteraciones en el metabolismo de la glucosa.
En parte de los sujetos con esteatosis, el exceso de AGL, sumado a un aumento de las citocinas proinflamatorias y un descenso de las antiinflamatorias, genera estrés oxidativo. El resultado del aumento del estrés oxidativo es el incremento del daño tisular que induce a la progresión hacia la esteatohepatitis no alcohólica. A su vez, en un porcentaje de los pacientes, la esteatohepatitis puede evolucionar a cirrosis.
Desde el punto de vista terapéutico, se están evaluando diferentes tratamientos basados en la disminución de la resistencia a la insulina, que ya en estudios controlados han logrado disminuir el grado de infiltración grasa en el hígado y en algunos casos revertir el daño histológico.
Palabras clave:
Esteatohepatitis
Inflamación
Resistencia a la insulina
Ácidos grasos libres
Nonalcoholic liver disease has become highly prevalent and is one of the main causes of liver cirrhosis in developed countries. The increase in the incidence of this disease has been produced in parallel with the increase in the rates of obesity and type 2 diabetes mellitus. Insulin resistance and inflammation play a central role in the etiopathogenesis of these three disorders.
Insulin resistance increases adipose tissue lipolysis, which releases a large quantity of free fatty acids (FFA). These are accumulated in the liver, leading to hepatic steatosis. The accumulation of FFA in turn is involved in insulin resistance in the liver and generates alterations in glucose metabolism.
In some patients with steatosis, the excess FFA, together with an increase in proinflammatory cytokines and a decrease in antiinflammatory cytokines, generate oxidative stress. This increases tissue damage, inducing progression to nonalcoholic steatohepatitis. In some patients, steatohepatitis can progress to cirrhosis.
From the therapeutic point of view, several treatments based on reduction of insulin resistance are being evaluated. In controlled studies these treatments have reduced the degree of fatty infiltration in the liver and in some patients have reversed histological damage.
Key words:
Steatohepatitis
Inflammation
Insulin resistance
Free fatty acids
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