EARLIER LOSS OF HEPATITIS-C VIRUS-RNA IN INTERFERON THERAPY CAN PREDICT A LONG-TERM RESPONSE IN CHRONIC HEPATITIS-C

To distinguish responders from non-responders early in interferon IFN) treatment would be beneficial in patients with chronic hepatitis C. T hose patients unlikely to respond would be spared the cost and hazard of prolonged treatment. Forty-three chronic hepatitis C patients who h ad received IFN-alpha therapy (6-9 MU; six times weekly for 2 weeks fo llowed by thrice weekly for 22 additional weeks) were randomly enrolle d into the present study Serially obtained sera were retrospectively t ested for HCV-RNA by reverse transcription-polymerase chain reaction ( AmplicorTM HCV) with a low limit detection of approximately 10(2)copie s/mL. Genotypes were determined by type-specific primers. Sixteen subj ects were defined as sustained responders (SR), who showed sustained l oss of viraemia with normalized alanine aminotransferase values for at least 6 months of follow-up after completion of therapy. The other 27 subjects were non-responders (NR), whose viraemia persisted during fo llow-up. Pretreatment serum HCV-RNA levels (P < 0.0001) and the genoty pe (P < 0.01) were significant predictors for sustained response to IF N therapy. Hepatitis C virus RNA was detectable in only one (6%) SR an d in 23 (85%) NR at the second week of therapy (P < 0.0001) and was de tected in none of the SR subjects and in 18 (67%) NR at the fourth wee k of therapy (P < 0.0001). Pretreatment viral load tvas correlated wit h the time until loss of viraemia. Multivariate analysis revealed that loss of viraemia at the second week of therapy was the strongest pred ictor for a long-term response, followed by the initial viral load and loss of viraemia at the fourth week of therapy. These findings sugges t that it is possible to predict a long-term response to IFN as early as at the second and fourth weeks after the start of therapy by identi fying the presence or absence of HCV-RNA with a sensitive assay.