Antipyrine clearance and response to interferon treatment in patients with chronic active hepatitis C

Abstract

To determine whether hepatic metabolic function affects the response to interferon treatment, we measured antipyrine clearance (APC) in 85 patients with chronic active hepatitis C and compared the results with treatment outcome. Among 55 patients who responded to interferon by normalization of alanine transaminase (ALT), median APC before treatment was 0.47 (range, 0.12 to 0.98; normal range, 0.34 to 1.02 mL/min/kg body wt), a value that was significantly greater than in 30 nonresponders (0.23; 0.08 to 0.67 mL/min/kg body wt, P < .001). APC was closely associated with response to interferon. The response rate among cases with values >0.25 mLmin/kg body weight was 79%, the same as in cases without cirrhosis. Cases without cirrhosis and with APC of >0.25 mLmin/kg body weight had an 85% chance of responding to interferon; this was unlikely a simple reflection of histological activity, because the correlation with Scheuer score was poor in this subgroup (r = -.31, P < .05). A second, independent group of 43 patients was used to test the predictive value of APC (using 0.25 mLmin/kg body wt as a cut-off) for response to interferon treatment. In this group, APC correctly predicted positive response to interferon in 75% of cases. APC was also used to measure the effects of treatment on hepatic metabolic function. Regardless of outcome, there was no change in APC at the end of a 6 month course of interferon treatment. Six months later, however, improvement in APC (14%; P < .05) was evident among responders but not in those who had failed to respond to interferon. In patients who continued to have normal ALT (18 of 19 tested were also nonviremic), the improvement in APC was sustained for at least 24 months, whereas among relapsers (defined by ALT increase), APC eventually declined to be less than the pretreatment value at 24 months. It is concluded that pretreatment APC is a powerful positive predictor of responsiveness to interferon treatment in patients with chronic hepatitis C, indicating that good hepatic metabolic function may be important in determining the effectiveness of interferon treatment. Furthermore, changes in hepatic metabolic function after apparently successful treatment, at least as determined by APC, appear to be subtle, delayed in onset, and maintained only in those who remain in biochemical remission. Show more