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 chronic hepatitis C patients. We evaluated whether the response to this combined therapy correlated with the presence of mutations in a region of 372 nucleotides within the NS5A gene.


METHODS
Sixty-two patients, 42 nonresponders and 20 relapsers to a previous course of interferon-alpha, received 3 million units thrice weekly of interferon-alpha-2b and 1-1.2 g daily of ribavirin for 12 months. Basal biochemical and virological (HCV RNA and genotype) parameters were determined. Clinical examinations were carried out at 1, 2, 3, 6, and 12 months. In addition, nucleotide sequencing of the NS5A gene was determined for viral samples obtained from 38 of these patients at the baseline of the combined therapy, as well as in 15 of them before initiating the previous course of interferon as monotherapy.


RESULTS
On finishing the 12 months, 36 patients (58.1%) had normal aminotransferases and 25 (40.3%) cleared viremia. Nucleotide sequencing indicated the same level of genetic variability within the group of responder and nonresponder patients all along the 124 amino acid residues of the NS5A gene studied. 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 tolerated, achieving an end-of-treatment response in 25 (40.3%) patients. Response did not correlate with the presence of mutations in the NS5A gene analyzed, including the interferon sensitivity determining region (ISDR) and its flanking sequences.
Ibarrola
N
N
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, Spain.
Moreno-Monteagudo
J A
JA
Sáiz
M
M
García-Monzón
C
C
Sobrino
F
F
García-Buey
L
L
Lo Iacono
O
O
Moreno-Otero
R
R
Martínez-Salas
E
E
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000235:genetics*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; D012254:Ribavirin; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase