The Degree of TGF-beta1 and alpha-SMA Expression in Liver Tissues with its Prognostic Value for the Therapeutic Efficacy of Interferon in Chronic Hepatitis B / 대한간학회지

ABSTRACT

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of alpha-interferon (IFN) on liver histology as well as on activation of hepatic stellate cell ( HSC) and trans for ming growth fact or beta-1 (TGF beta-1) expression. We had also investigated the clinical usefulness of TGFbeta-1 and alpha-smooth muscle actin (alpha-SMA) expression in liver tissue for predicting a response to alpha-IFN therapy in chronic hepat it is B. METHODS: We studied the expression of TGFbeta-1 and alpha-SMA in liver biopsys pecimens from 51 chronic hepatitis B pat ients. Using immunohistochemical staining and a semiquant it ative scoring met hod, we also evaluated TGF-beta1 and alpha-SMA expression in liver stellate cells before and after alpha-IFN therapy in liver tissue from rebiopsys pecimen of the 12 chronic hepatitis B pat ients. Recombinant IFN alpha-2b (Intron A) in doses of 6 MU/ d was given to patients intramus cularly three times per week for 6 months (total doses , 432 MU). The patients were divided into two groups according to serum alanine aminotransferase levels as well as HBV- DNA and HBeAg s eroconversion stat e. Histological grading and staging scores were according to modified Histological Activity Index (HAI) grading systems of Ishak (1995). RESULTS: The index of portal inflammation and total scores of HAI grading significantly decreased in biopsies after alpha-IFN treatment, but the scores of fibrosis staging showed no significant change in biopsies after IFN treatment. A significant decrease in alpha-SMA expression, especially in periportal area, was found, but the change of TGFbeta-1 expression was not significant. The immunoreactivity of alpha-SMA was significantly lower in responders than in non-responders, whereas the diffference of immunoreactivity of TGF-beta1 between these two groups was not found. CONCLUSIONS: These findings suggest that alpha-IFN therapy may reduce the necroinflammatory activity in liver tissues of chronic B viral hepatitis and that the degree of alpha-SMA expression before treatment may be employed as a pottent predicting indicator for the therapeutic efficacy of IFN-alpha.