Experimental model of hepatic fibrosis following repeated periportal necrosis induced by allylalcohol

Background/Aims: In most patients with chronic viral hepatitis the predomin ant lobular location of hepatic necrosis and fibrosis is the periportal zon e. We established a new simple model of hepatic fibrosis in rats by repetit ive periportal necrosis with allylalcohol. Methods: Of 40 male adult rats, 30 were injected with 0.62 mmol/kg of allylalcohol intraperitoneally twice a week, the remaining 10 with normal saline as controls. Ten rats were kill ed at each of 4, 8, and 16 weeks later. The extent of fibrosis was evaluate d according to the portal-portal extent. Transforming growth factor (TGF) b eta 1 mRNA in liver tissues was detected by reverse transcriptase polymeras e chain reaction, and its levels were determined by the endpoint titers of serial two-fold dilutions of cDNA. Results: After 4 weeks, periportal fibro sis was produced in only 6 out of 10 rats, and was mild in extent. However, after 8 weeks, 8 out of 9 survivors showed moderate to severe fibrosis, wh ich corresponded to a score of 7 or more. The extent of fibrosis correlated significantly with the amount of collagen and TGF beta 1 mRNA expression i n liver tissues. The collagen content and expression of TGF beta 1 mRNA wer e also upregulated significantly in liver tissues with a fibrosis score of 7 or more. Conclusions: Hepatic fibrosis can be sufficiently induced by rep etitive intraperitoneal injection of 0.62 mmol/kg of allylalcohol twice a w eek for 8 weeks. This simple model of hepatic fibrosis, in which TGF beta 1 is overexpressed at the transcriptional level, may be useful in the study of patients who have predominantly periportal necrosis and fibrosis.