Significance of metallothionein expression in liver disease

Abstract

Hepatic metallothionein (MT) expression, with various isoforms, and varying cellular localizations is a useful marker for clinico-pathogenesis of liver diseases. In acute liver toxicity caused by cadmium, carbon tetrachloride, or acetaminophen, MT plays a protective role, via the scavenging of radical species. In chronic hepatitis C patients, hepatic MT levels appear to be a biological factor associated with the severity of HCV infection, and are associated with a better response to IFN therapy. Transgenic mice that express HBsAg in the liver show hepatocellular damage, inflammation, regeneration, hyperplasia, and, eventually, neoplasia. The MT isoform, MT-1 help mitigate HBV-induced hepatitis. Analysis of MT gene expression in the livers of chronic hepatitis B patients is useful for understanding the features of distinct liver diseases and for judging disease progression. A profound down-regulation of isoform MT-1G in hepatocellular carcinoma was observed in 63% of tumors relative to the adjacent nonmalignant liver. MT has been implicated in the control of p53 folding with zinc exchange. Therefore, it appears MT may play a role in the pathogenesis of hepatocellular carcinoma. Overall MT is linked to a variety of liver diseases.