The Effect Of Interferon-Alpha Plus Ribavirin On Hepatic Fibrosis In Patients With Chronic Hepatitis C

OBJECTIVE: The main pathogenic mechanism of the progress of chronic viral hepatitis into cirrhosis is represented by fibrogenesis. Hepatic fibrosis is a reversible wound healing response characterized by accumulation of extracellular matrix (ECM), which follows chronic but not self-limited liver disease. The hepatic stellate cells (HSC) play a central role based on their ability to undergo activation following liver injury. Tissue inhibitors of metalloproteinases (TIMPs) may play a major role. The aim of this study was to investigate the effect of interferon-alpha plus ribavirin on liver TIMP-1,alpha-smooth muscle actin(α-SMA) and liver histology in patients with chronic hepatitis C. We assessed the difference between patients with sustained viral response and non-sustained viral response. We also explored the correlation of the changes between TIMP-1 ,α-SMA and liver histology scores,HCVRNA and ALT.METHODS A total of 23 patients were included in this study. All patients had received a 48-week interferon-alpha-2b plus ribavirin and had successively undergone follow-up for 24 weeks. In each patient, paired liver biopsies had been performed: 1 week before treatment and 2 week after the end of treatment. The patients were divided into two groups according to the viral response at 24 weeks after treatment: sustained viral response (SVR) group and non-sustained response(NSVR) group. After hematoxylin-eosin(HE) and Gormori dye, pathologic grading,staging,fibrosis scores and necroinflammation scores of semi-quantitative scoring system (SSS) were evaluated. α-SMA and TIMP-1 in liver tissue wereexamined by immunohistochemical techniques and BI-2000 image analysis system.RESULTS Overall, liver a-SMA, T1MP-1, fibrosis scores andnecroinflammation scores after treatment were significantly lower than those before treatment (PO.05). The parameters between SVR patients and NSVR patients were all compatible at baseline (P>0.05). Post-treatment liver a-SMA . TIMP-K fibrosis scores and necroinflammation scores were significantly lower than pretreatment scores (PO.05) in SVR patients. But it was not the case in NSVR patients (P>0.05). There was statistical difference in the changes of a-SMA and TIMP-1 between SVR and NSVR patients (PO.05).In SVR patients, the changes of both a-SMA and TIMP-1 were significantly correlated with those of necroinflammation scores, fibrosis scores and stage (correlation coefficient: 0.559, 0.949, 0.703 (a-SMA) and 0.718, 0.816, 0.539 (TIMP-1), PO.05) ; there was no correlation between the changes of both a-SMA and TIMP-1 and HCVRNA, grade and ALT(P >0.05).In NSVR patients, the changes of both a-SMA and TIMP-1 had a significantly positive correlation with those of fibrosis scores and stage (correlation coefficient : 0.876, 0.780 (a-SMA) and 0.772, 0.676 (TIMP-1), P O.05); and they were not significantly correlated with the changes of necroinflammation, HCVRNA, grade and ALT (P >0.05).CONCLUSION Overall, liver a-SMA and TIMP-1 after treatment are significantly lower than those before treatment. In SVR group, liver a-SMA and TIMP-1 after treatment are significantly lower than those before treatment. In NSVR group, both a-SMA and TIMP-1 in liver afer treatment decrease in some degree compared with those before treatment, but the changes have no statistical significance. The changes of a-SMA and TIMP-1 are significantly different in different response groups. In all patients (SVR or NSVR group), the changes of both a-SMA and TIMP-1 in liver are significantly correlated with fibrosis scores and stage, and they are not correlated with HCVRNA, grade and ALT. In SVR patients, they also correlate with necroinflammation, but it is not the case in NSVR group.