INTERFERON ACCUMULATION IN CIRRHOTIC RAT-LIVER

In patients with chronic hepatitis C, the therapeutic effect of interf eron (IFN) is influenced by the progression of liver disease. In a pre vious study, we showed that 2',5'-oligoadenylate synthetase activity i n the liner homogenate was significantly lower in cirrhotic rats than in controls after injection of murine IFN. To determine the reason for this decrease, we injected IFN into rats with thioacetamide-induced c irrhosis and used microautoradiography with human lymphoblastoid inter feron ([I-125]LyIFN). Accumulation of [I-125]LyIFN in cirrhotic rat li vers was approximately half of that in control rats (2880 +/- 900 vs 5 770 +/- 600 mm(2), P < 0.01). In the cirrhotic rat livers there were f ew grains on the hepatocytes, but many on collagen fibres. These resul ts suggest that binding of IFN to its hepatocyte receptors is hindered in the presence of cirrhosis, The decreased amount of IFN reaching he patocytes may contribute to the poor responses to IFN seen in patients with cirrhosis.