Nonalcoholic Fatty Liver Disease: A Wide Spectrum Disease (original) (raw)
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Exploring lipid-related treatment options for the treatment of NASH
Current vascular pharmacology, 2012
The liver plays a major role in lipid metabolism, importing free fatty acids (FFA) and manufacturing, storing and exporting lipids: derangements in any of these processes can lead to non-alcoholic fatty liver disease (NAFLD) . NAFLD can be seen as the result of an imbalance between lipid availability and lipid disposal resulting in hepatic steatosis . NAFLD is considered by many as the hepatic manifestation of insulin resistance (IR) and is strongly associated with the metabolic syndrome . The rapid increase in obesity and diabetes mellitus (DM) during the last decade is associated with an increase in the prevalence of NAFLD, making it the most common cause of chronic liver disease in the Western countries with up to 30% of the population affected . Histological evaluation is the gold standard for precisely estimating the degree of liver damage caused by simple steatosis or by non-alcoholic steatohepatitis (NASH).
An Update on Management of Nonalcoholic Fatty Liver Disease & Nonalcoholic Steatohepapititis is the Time Ripe for Achieving Resolution of NAFLD & NASH Soon, 2021
We earlier reviewed how obesity has assumed an endemic/pandemic proportions that has resulted in escalating incidence and prevalence of associated escalating worldwide incidence of Metabolic Syndrome (MetS) with non alcoholic fatty liver disease (NAFLD), that is correlated with enhanced morbidity. Later we tried to detail how probiotics, L-Carnitine (LC), Nicotinamide Ribose (NR) Combination, along with Apical Sodium Dependent Bile Acids Transporter (ASBT) or Volixibat and Silybin, Vitamin D, Allyl Isothiocyanate (AITC), might aid in treating and understand the etiopathogenesis of NAFLD. The prevalence of NAFLD all over the world is approximately 25%, with that of non alcoholic steatohepapititis (NASH), varying from 1.5%=6.45%. Particularly NASH, specifically the ones associated with fibrosis possess a greater chance of generation of side effects that include progression to cirrhosis as well as liver-associated mortality. Despite an improvement was observed with vitamin E, Pioglitazone. liraglutide in histological appearance in liver randomized controlled clinical trials (RCT), at present no drugs exists that have received FDI approval for NASH. The aim of this review was to update the newer drugs getting evaluated, undergoing phase 2-3 trials. Currently there are Obeticholic acid, elafibranor, cenicriviroc, resmetriom, in addition to aramchol, that are the five agents that are getting analysed in big, histology dependent phase 3 trials. Hopefully within another 2-4 years, newer, efficacious drugs will be available for the therapy of NASH. Besides that a lot of phase 2 trials are continuing for different drugs. Further depending on outcomes of phase 2-3 trials, combination treatments are getting evaluated. For future therapeutic approaches would be made up of variations in NASH phenotypes, besides personalized approaches based on various NASH phenotypes in addition to response of every single patient. Further recently there were reports of utilization of curcumin with nonselective beta blocker for regression from cirrhosis (reviewed by us). Hopefully once there are approved therapies for NAFLD/NASH, we can work in that direction.
Non-alcoholic fatty liver disease: what has changed in the treatment since the beginning?
World journal of gastroenterology : WJG, 2014
Non-alcoholic fatty liver disease (NAFLD) is an umbrella term to describe the entire spectrum of this common liver disease. In patients with NAFLD, especially those with non-alcoholic steatohepatitis (NASH), most often have one or more components of the metabolic syndrome, but this is not universal. Although most patients with NAFLD share many clinical features, only a subset of patients develops significant liver inflammation and progressive fibrosis. On the other hand, not all patients with NASH exhibit insulin resistance. NASH can be seen in patients who are lean and have no identifiable risk factors. Many clinical studies have tried numerous drugs and alternative medicine, however, investigators have failed to identify a safe and effective therapy for patients with NASH. As summarized, the heterogeneity of pathogenic pathways in individual patients with NASH may warrant the development of an individualized treatment according to the underlying pathogenic pathway. The differentia...
Hepatology (Baltimore, Md.), 2017
NASH/NAFLD is rapidly becoming one of top causes of cirrhosis, hepatocellular carcinoma and indication for liver transplantation. Except for life style modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is hard to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD and has been shown to improve liver histology. In order to have approved regimens for treatment of NASH/NAFLD, a number of issues that must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with adva...