Abordagem Terapêutica do Fígado Gordo Não Alcoólico

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterised by excessive hepatic fat accumulation, associated with increased insulin resistance, in the absence of other causes of chronic liver disease. Currently, it is one of the major causes of chronic liver disease worldwide, with global prevalence estimated to be 25%, including a rising incidence among the paediatric population. NAFLD includes two distinct clinic conditions: non-alcoholic fatty liver (NAFL), defined by the presence of steatosis in more than 5% of hepatocytes; and non-alcoholic steatohepatitis (NASH). Diagnosis of NASH requires a liver biopsy with signs of lobular inflammation and hepatocellular ballooning. NAFLD is strongly associated with increased risk of developing hepatic fibrosis, which might evolve to cirrhosis, hepatic failure or hepatocellular carcinoma. A vast number of factors are associated with the pathogenesis of NAFLD, including environmental, genetic and epigenetic factors and also other features as gut microbiota. Obesity, type 2 diabetes, arterial hypertension and dyslipidemia represent the most important risk factors for NAFLD. In fact, NAFLD can be interpreted as the liver manifestation of metabolic syndrome.Lifestyle modifications to reduce body weight, including diet and physical activity, remain the first line of treatment in NAFLD. However, drug therapy should be indicated for patients at a significant risk of developing severe hepatic comorbidities. Although guidelines suggest the use of certain drugs, there are still no approved pharmacological therapies for NAFLD. Several drugs with different targets and mechanisms are currently being investigated in clinical trials, including metabolic modifiers, drugs altering intestinal microbiota, and also antioxidant, anti-inflammatory and antifibrotic agents.Given the growing burden of NAFLD, its asymptomatic progression to cirrhosis and the difficulties in its management with lifestyle changes, new therapeutic targets should be further investigated. It is crucial to develop more experimental studies and clinical trials in order to establish the safety and efficacy of new potential drugs.