Nonalcoholic Steatohepatitis

Elizabeth M. Brunt, M.D.

Disclosures

Semin Liver Dis. 2004;24(1) 

In This Article

Abstract and Introduction

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as a common liver disorder that represents the hepatic manifestation of the metabolic syndrome, a variably defined aggregate of disorders related to obesity, insulin resistance, type II diabetes, hypertension and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury that carries a risk for progressive fibrosis, cirrhosis, and end-stage liver disease. Hepatocellular carcinoma (HCC) is a documented complication in an as yet unknown percentage of cases of NASH cirrhosis. The diagnosis of nonalcoholic steatohepatitis requires histopathologic evaluation because the lesions of parenchymal injury and fibrosis cannot be detected by imaging studies or laboratory tests. This article will briefly discuss prevalence studies and the pathophysiology of NAFLD and focus on current discussions related to the specific lesions in the pathology of NASH, including the challenges of pediatric NASH and NASH-related cirrhosis.

The central role of insulin resistance in NASH has been confirmed in clinical correlation studies and animal models and in recent therapeutic intervention trials. Multifaceted functions of visceral adipose tissue and the polygenic and interrelated pathways that link obesity, insulin resistance, hepatic steatosis, and the subsequent progression to parenchymal necroinflammation and fibrosis continue to be elucidated. With all the progress that has occurred, it is interesting that liver biopsy evaluation has retained an essential role in the clinical diagnosis of NASH and is recognized as a significant component for analysis in the growing number of therapeutic trials. This article will focus on pathology while providing an overview of current advances in the field.

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