Elsevier

Clinics in Liver Disease

Volume 18, Issue 1, February 2014, Pages 73-89
Clinics in Liver Disease

The Role of Medications for the Management of Patients with NAFLD

https://doi.org/10.1016/j.cld.2013.09.005Get rights and content

Section snippets

Key points

  • 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.

  • Several factors complicate the development of novel pharmacotherapies, particularly the imprecision of surrogate markers, making histologic assessment compulsory.

  • Incretin mimetics, farnesoid x-receptor blockers, peroxisome proliferator activated receptor α/δ agonists, and lysyl

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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    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.

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