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There is a recognized clinical need for an effective treatment of nonalcoholic fatty liver disease (NAFLD); current approaches remain suboptimal and no drug has so far been approved by International Agencies.
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Several factors complicate the development of novel pharmacotherapies, particularly the imprecision of surrogate markers, making histologic assessment compulsory.
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Incretin mimetics, farnesoid x-receptor blockers, peroxisome proliferator activated receptor α/δ agonists, and lysyl
The Role of Medications for the Management of Patients with NAFLD
Section snippets
Key points
Insulin sensitizers
As insulin resistance is the basis for liver fat accumulation, insulin sensitizers probably remain the best pharmacologic option for NAFLD treatment.
Lipid-lowering drugs, antioxidant and hepatoprotective agents
Several studies confirm a link between altered hepatocyte cholesterol metabolism and hepatic-free cholesterol accumulation and NAFLD development and progression. Dietary lipid intake is also an important cofactor in NAFLD development and progression,23 as in some genetic variants linked with lipid metabolism, like the patatin-like phospholipase domain-containing protein 3,24 supporting the concept that drugs used for lipid control may be an effective treatment of NAFLD.25 Reducing lipid levels
Ursodeoxycholic Acid (UDCA)
The rationale for using UDCA (a tertiary bile acid) as a broad hepatoprotective agent is based on a large body of preclinical data55 and on controlled trials (Box 3). The histologic efficacy remains controversial but there is strong evidence of biochemical effectiveness (on ALT), arguing in favor of a broader hepatoprotective effect of UDCA.
Between 1994 and 2008, 4 studies on UDCA treatment were published on NASH. At doses of 12 to 15 mg/kg/d UDCA monotherapy did not produce any significant
New areas of research
Several new areas of research are being exploited or old areas are receiving new interest and developments, to provide more effective and safer drugs for NAFLD treatment (Box 4).
Summary
There is a definite clinical need for an effective treatment of NAFLD, but current approaches remain suboptimal. Several factors will complicate the development of novel pharmacotherapies, including: (1) the multifactorial pathogenesis of NAFLD, (2) the heterogeneity of the patient population, (3) the imprecision of current disease staging techniques, (4) ill-validated surrogate markers, making histologic assessment compulsory, (5) the slowly progressive nature of NASH and the tendency of a
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Cited by (26)
NASH: A glance at the landscape of pharmacological treatment
2016, Annals of HepatologyCitation Excerpt :Despite intensive research and numerous trials, as of today there are no approved treatments for NAFLD/NASH. The most favorable results have been obtained with the use of pioglitazone and/or vitamin E, whereas the effectiveness of other compounds, namely high-dose urso-deoxycholic acid, has never been systematically proven.13 In addition, there are no data on the long-term safety of these compounds.13
Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?
2016, Diabetes and MetabolismCitation Excerpt :limited treatment duration (maximum, 2 years). Nonetheless, a significant benefit of both weight loss and drug treatment on liver histology has been reported in recent reviews [60,61], but only a few data are available on the risk of progression to diabetes. Considering that overweight/obesity and insulin resistance are a hallmark of NAFLD, there is no surprise that weight loss may considerably affect diabetes risk.
EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
2016, Journal of HepatologyNonalcoholic Fatty Liver Disease Review: Diagnosis, Treatment, and Outcomes
2015, Clinical Gastroenterology and HepatologyCitation Excerpt :A proactive treatment approach is prudent in patients with biopsy-proven NASH because of the risk of progressive histologic damage. Several promising pharmacologic agents need to be further studied in patients with NASH.1,56–58 The most fundamental step in the management of NAFLD is treating the risk factors that are commonly associated with metabolic syndrome through lifestyle modifications, which may serve as both primary and secondary prevention for NAFLD.57,59,60
Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial
2015, Digestive and Liver DiseaseCitation Excerpt :However, more than 50% of patients fail to achieve their target weight loss [3]. Given the poor compliance with lifestyle modifications, the increased risk for CVD, and the strong association with metabolic syndrome (MS) in NAFLD patients, medications such as insulin sensitizers, lipid-lowering drugs, omega-3 polyunsaturated fatty acids, and vitamins have become important options for the treatment of NAFLD and may influence both NAFLD and its related cardiac and arrhythmic complications [5,6]. Resveratrol is a natural polyphenol found in grapes, peanuts, berries, and red wine.
The Mexican consensus on nonalcoholic fatty liver disease
2019, Revista de Gastroenterologia de Mexico
Funding Sources: Prof Marchesini: Funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. HEALTH-F2-2009-241762 for the project FLIP.
Conflict of Interests: Prof Marchesini: Advisory board Sanofi; Speaker’s fee from Merck-Sharp and Dome, Lilly, NOVO Nordisk, Boehringer Ingelheim, Sanofi. Dr Mazzella, Dr Ricciardi, Dr Mazzotti: No conflict of interest.