Management of Patients With Nonalcoholic Fatty Liver Disease

Abstract and Introduction

Abstract

Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH) are the most common causes of chronic liver disease in industrialized countries. NAFLD has also been strongly associated with type II diabetes and cardiovascular diseases. This study was a multipurposed review, which included discussion of recent studies investigating the cellular and genetic basis of these diseases, the pathogenesis of NAFLD and the current treatment and management of nonalcoholic steatohepatitis. Currently, maintaining a healthy weight through dietary changes and exercise, the use of insulin-modulating pharmacologic agents for diabetes control and the use of lipid-lowering, anti-oxidants have been the most widely recommended treatments. Inclusion of pathogenic mechanisms in treatment design will allow future therapies to target-specific pathways involved in NAFLD pathogenesis.

Introduction

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common form of chronic liver disease in the Western world and is increasing in importance in other parts of the world.^[1] The term NAFLD at the histological level comprises a spectrum of liver damage including in its common form, or simple steatosis, as well as nonalcoholic steatohepatitis (NASH), a potentially progressive form of NAFLD defined by the presence steatosis as well as hepatocyte ballooning, inflammation and variable degrees of fibrosis. Importantly, the presence of obesity at least doubles the prevalence of NASH and its progression to cirrhosis, liver failure and hepatocellular carcinoma.^[2] In this regard, it is important to note that NASH can complicate and accelerate other liver disease progression including chronic hepatitis C and B infection.

Although NAFLD patients lack a history of excessive alcohol intake^[3,4] there is abnormal fat accumulation in the liver. This increase in the fat accumulation creates a focus of abnormalities in target organ sensitivity to insulin, that is, insulin resistance (IR).^[5–9] In addition to IR, type 2 diabetes, visceral obesity and metabolic syndrome are all linked to NAFLD. In fact, NAFLD appears to be the hepatic manifestation of metabolic syndrome.^[10,11]

On the other hand, it should also be remembered that NAFLD is independently associated with an increased risk of diabetes mellitus (T2DM) (twofold increase) and cardiovascular disease (CVD) (1.4- to 2-fold increase).^[12] Furthermore, CVD is the most common cause of death among NAFLD patients.^[13] Although the association of cardiovascular mortality with NAFLD has been shown, the nature and strength of this association remain controversial.^[14,15] Adams et al.^[16] have shown that CVD accounts for about 25% of deaths in NAFLD patients versus 13% death from liver disease.

This review will focus on the current status of NAFLD with particular emphasis on the recent recommendations regarding the management of NAFLD and associated metabolic conditions.