Chronic hepatitis C virus patients with breakthroughs during interferon treatment can successfully be retreated with consensus interferon

Patients with chronic hepatitis C who have not had a sustained hepatitis C virus (HCV)-RNA response or serum alanine transaminase (ALT) response to a 6-month course of interferon (IFN) may respond to higher dose retreatment w ith consensus interferon (CIFN), Some nonresponders to initial IFN treatmen t have a transient response defined as undetectable HCV RNA or normalizatio n of ALT during treatment, but subsequently have a "breakthrough" while sti ll on treatment. The aim of this study was to determine if nonresponders wh o had breakthroughs responded differently to CIFN retreatment than nonrespo nders without breakthroughs using data from a large, multicenter trial. ALT and HCV RNA were monitored frequently during initial IFN therapy (either 9 meg CIFN or 3 MU IFN-alpha 2b 3 times per week). HCV-RNA breakthroughs wer e observed in 86 of 467 (18%) of all treated patients, and ALT breakthrough s were observed in 90 of 467 (19%) of all treated patients. There was no as sociation between breakthroughs and the presence of either binding or neutr alizing anti-IFN antibodies. When the patients who were nonresponders to in itial IFN treatment were retreated with CIFN (15 mcg) for 12 months, 27% of those with viral breakthroughs had a sustained viral response compared wit h 8% in prior nonresponders without breakthroughs (P =.102). Sustained ALT responses were observed in 39% with breakthroughs compared with 10% in thos e without breakthroughs (P =.014). The data suggest that prior nonresponder s with breakthroughs have a greater chance of responding to retreatment tha n do nonresponders without breakthroughs. However, most breakthrough patien ts would be missed unless repeated HCV-RNA testing were conducted during th erapy.