Non-alcoholic fatty liver disease in patients with diabetes mellitus

Abstract

Non-alcoholic fatty liver disease (NAFLD), including the disease stages steatosis and non-alcoholic steatohepatitis, is the most common cause of chronic liver disease worldwide and linked to the epidemic of diabetes mellitus and obesity. It is characterized by a high cardiovascular and liver-related mortality and expected to be the leading cause for liver transplantation in the near future. This review summarizes recent progress made in our understanding of the disease pathogenesis and the clinical management of patients with NAFLD. Strategies to manage diabetes mellitus will be evaluated in terms of their effectiveness in treating patients with NAFLD and novel pharmacological targets capable to treat diabetes mellitus and NAFLD will be highlighted.

Keywords::

• diabetes mellitus
• insulin resistance
• insulin sensitizer
• intestinal microbiota
• lifestyle
• lipotoxicity
• NAFLD
• NASH
• nuclear receptor agonist
• vitamin E

Financial & competing interests disclosure

M Fuchs has received consulting fees from Intercept Pharmaceuticals in 2014. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Due to the epidemic of diabetes and obesity, the worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) is on the rise not only in adults, but also children, even in developing countries.

• Disease pathogenesis is multifactorial and not entirely understood, but lifestyle, intestinal microbiota and adipose tissue play a key role.

• Diagnosis of NAFLD can be made non-invasively, whereas the assessment of disease severity may still require a liver biopsy for some time.

• First-line treatment of NAFLD includes lifestyle modifications and aggressive management of diabetes mellitus and obesity.

• Numerous pharmacologic agents have been explored in the treatment of NAFLD, but there is a paucity of data regarding efficacy and safety when used for an extended period of time.

• So far, no treatment approach has been shown to improve cardiovascular disease that represents the most common cause of death in NAFLD.

• Novel treatment approaches targeting multiple events in disease pathogenesis (e.g., nuclear receptor agonists) are being explored and are showing promising results.

• There is a great need for accurate and non-invasive disease staging that will aid in monitoring treatment and identifying patients at high risk to develop liver cirrhosis.