Semin Liver Dis 2007; 27(2): 173-193
DOI: 10.1055/s-2007-979470
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Cytokines and Chemokines in the Development of Steatohepatitis

Patricia F. Lalor1 , Jeff Faint1 , York Aarbodem1 , Stefan G. Hubscher1 , David H. Adams1
  • 1Liver Research Group, MRC Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham, United Kingdom
Further Information

Publication History

Publication Date:
22 May 2007 (online)


Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) share similar morphological characteristics despite the obvious etiological differences between the two conditions. In both conditions the first manifestation of injury is the accumulation of fat within hepatocytes (steatosis), and in a proportion of patients this is followed by the development of necroinflammatory activity that leads to cirrhosis. Steatosis alone is considered to be relatively innocuous and is usually reversible, and it is the development of liver cell ballooning and inflammation (steatohepatitis) that determines whether a patient progresses to irreversible liver damage and fibrosis. This has led to the two-hit theory in which the first hit is accumulation of fat in the liver and the second hit involves an inflammatory insult or challenge to the liver, for example, through oxidative stress or in response to pathogenic stimuli such as endotoxin. Although the nature of the hits remains poorly understood, it is clear that the critical event in progression is the development of inflammation, and the fact that it is impossible to distinguish alcoholic from nonalcoholic steatohepatitis on histological grounds suggests that common pathogenic mechanisms are involved. We focus on the role of cytokines and particularly chemokines in instigating and driving the inflammatory infiltrate in steatohepatitis. A better understanding of this process might allow therapeutic intervention to switch off the inflammatory response before irreversible damage occurs in both ALD and NAFLD.


David H Adams, M.D. 

The Liver Research Group, Institute for Biomedical Science, The University of Birmingham Medical School

Edgbaston, Birmingham B15 2TT, United Kingdom