Response to retreatment with interferon-alpha plus ribavirin in chronic hepatitis C patients is independent of the NS5A gene nucleotide sequence

OBJECTIVE: Interferon-alpha plus ribavirin is an effective treatment for ch ronic hepatitis C patients. We evaluated whether the response to this combi ned therapy correlated with the presence of mutations in a region of 372 nu cleotides within the NS5A gene. METHODS: Sixty-two patients, 42 nonresponders and 20 relapsers to a previou s course of interferon-alpha, received 3 million units thrice weekly of int erferon-alpha-2b and 1-1.2 g daily of ribavirin for 12 months. Basal bioche mical and virological (HCV RNA and genotype) parameters were determined. Cl inical examinations were carried out at 1, 2, 3, 6, and 12 months. In addit ion, nucleotide sequencing of the NS5A gene was determined for viral sample s obtained from 38 of these patients at the baseline of the combined therap y, as well as in 15 of them before initiating the previous course of interf eron as monotherapy. RESULTS: On finishing the 12 months, 36 patients (58.1%) had normal aminotr ansferases and 25 (40.3%) cleared viremia. Nucleotide sequencing indicated the same level of genetic variability within the group of responder and non responder patients all along the 124 amino acid residues of the NS5A gene s tudied. Neither the type of amino acid substitution nor the number of them was significantly different in one group relative to the other. CONCLUSIONS: Therapy with interferon-alpha-2b plus ribavirin was well toler ated, achieving an end-of-treatment response in 25 (40.3%) patients. Respon se did not correlate with the presence of mutations in the NS5A gene analyz ed, including the interferon sensitivity determining region (ISDR) and its flanking sequences. (Am J Gastroenterol 1999;94:2487-2495. (C) 1999 by Am. Coll. of Gastroenterology).