Current Concepts in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Nahum Méndez-Sánchez; Marco Arrese; Daniel Zamora-Valdés; Misael Uribe


Liver International. 2007;27(4):423-433. 

In This Article

Abstract and Introduction

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of chronic liver disease, representing the leading cause of hepatology referral in some centres. However, its pathophysiology is not completely understood. Insulin resistance is one of the major mechanisms involved in disease prevalence and progression. Owing to the lack of an effective pharmacological therapy, recommendations on treatment are scarce and are based mainly on lifestyle changes, including diet and exercise. A review of the current literature on pathogenesis of NAFLD is presented in this article.

Nonalcoholic fatty liver disease (NAFLD) has gained recognition worldwide as a common chronic liver disease and as a cofactor in other diseases.[1,2] The subclinical nature of the disease has lead to increased efforts to achieve its diagnosis and to prevent its potential progression to nonalcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma (see Figure 1).[3,4] The main issues in the diagnosis, follow-up and management of the disease remain the difficulties in developing a noninvasive diagnostic method and the understanding of its pathophysiology. Insulin resistance is a consistent finding in patients with NASH[5,6]; however, it is not clear why not all patients with insulin resistance develop NASH, and it has been proposed that specific hepatic alterations are responsible for the development of steatosis and its progression to steatohepatitis in insulin-resistant patients. The purpose of this paper is to describe the pathogenic mechanisms of the disease.

Natural history of nonalcoholic fatty liver disease. Obesity and insulin resistance are the major risk factors for nonalcoholic hepatic steatosis, which presents in 30-90% of this population. Around 10-20% of these patients are carriers of nonalcoholic steatohepatitis (NASH), which might progress to cirrhosis in 3-5% of the patients after 20 years. An yet unknown percentage of patients will develop hepatocellular carcinoma (HCC).


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