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Currently treatment options for Non-Alcoholic Steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease (NAFLD) and one of the commonest causes of cirrhosis worldwide, are mainly limited to promotion of life style changes in diet and exercise habits as well as to control of comorbidities such as type 2 diabetes mellitus and dyslipidemia. With regard to pharmacotherapy, the armamentarium to treat NASH is rather limited and currently only vitamin E and pioglitazone are recommended in selected patients although their longterm benefit has not been demonstrated and some caution has been recommended due to potentially unwanted side-effects of these drugs. Indeed, several additional agents are in the therapeutic pipeline and are currently being tested in controlled trials as can be checked in open databases such as ClinicalTrials.gov (https://clinicaltrials.gov). The therapeutic targets being tackled are diverse and derive from recent basic and clinical research that had identified factors involved in NASH pathogenesis and progression. Among these factors are insulin resistance (IR), adipokine/cytokine imbalance, excessive oxidative stress, dysregulation of both lipid and carbohydrate metabolism and ongoing fibrogenesis. Most of the above mentioned factors are directly or indirectly regulated by the farnesoid X receptor (FXR), a nuclear hormone receptor regulated by bile acids (BAs), thus rendering the agonism of this receptor a potentially useful pharmacological target to treat NASH. This contention had previous support from pre-clinical studies and the recent publication of the FLINT study, a multicenter, randomized and placebo controlled trial examining the effects of obeticholic acid (OA), a synthetic FXR agonist, in patients with steatohepatitis opens windows of hope about counting with effective drugs for treating NASH.

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2015-04-07   |   598 visitas   |   Evalua este artículo 0 valoraciones

Vol. 14 Núm.3. Mayo-Junio 2015 Pags. 430-432 Ann Hepatol 2015; 14(3)