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J Korean Med Assoc > Volume 48(2); 2005 > Article
Park and Park: Pathogenesis and Management of Non-alcoholic Steatohepatitis


Non-alcoholic fatty liver disease (NAFLD) has been characterized by a wide spectrum of liver damage that spans from steatosis, non-alcoholic steatohepatitis (NASH), cryptogenic liver cirrhosis and even to hepatocellular carcinoma. During the last few years, investigation has focused on the group of NASH, a relatively aggressive form of liver disease. One of the main reasons for the explosion of information on NASH provided by clinical and basic science studies is that its risk factors, such as obesity, type II diabetes mellitus, and dyslipidemia, are those of the most prevalent morbidities in the general population. Recently, obesity and type II diabetes mellitus have reached epidemic proportions in Korea. The pathogenesis of NASH is multifactorial. Insulin resistance and increased fatty acid may be important factors in the accumulation of hepatocellular fat, whereas oxidant stress, lipid peroxidation, mitochondrial dysfunction, and adenosine triphosphate (ATP) depletion may be important causes of hepatocellular injury in the steatotic liver. Because not all steatotic livers progress to NASH, some other environmental factors or combined genetic factors are thought to be required for progression to NASH and fibrosis. Life style modification continues to be the cornerstone of therapy. Exercise and diet may be effective means of improving insulin sensitivity. Some insulin-sensitizing agents and antioxidants have shown to be promising. Despite recent gains in the understanding of this disease entity, a number of unresolved issues related to its natural history, pathogenesis and treatment remain to be elucidated.


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Figure 1
Figure 2
Fatty acids impair the tyrosine phosphorylation of IRS-1. Tyrosine phosphorylation of insulin receptor substrates is a general mechanism of insulin action. Deactivating insulin receptor substrates such as IRS-1, leading to insulin resistance.
Table 1

THR: thyroid hormone receptor

SSHR: sex steroid hormone receptor

MAP: mitogen-activated protein


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