HCV viraemia is more important than genotype as a predictor of response to interferon in Sicily (southern Italy).
OBJECTIVE
To investigate host- and virus-related factors predictive of early and sustained alanine aminotransferase normalization after interferon therapy for HCV-related chronic liver disease, in an area where genotype 1 is highly prevalent.


METHODS
We studied 100 patients with HCV-RNA positive chronic liver disease (73 chronic hepatitis and 27 cirrhosis) undergoing alpha-interferon treatment. Thirty-four patients had an early response but relapsed, 15 patients remained into sustained response for at least 12 months after therapy, and 51 patients did not respond. Serum HCV-RNA levels were assessed by bDNA (Chiron), and genotype by LiPA (Innogenetics) and by sequencing of the 5' non-coding region.


RESULTS
Mean pre-treatment HCV-RNA level (x 10(3) genome equivalents/ml +/- SD) was lower in sustained responders (3854 +/- 7142) than in relapsers (9587 +/- 10163) or in non-responders (5709 +/- 6618). HCV subtype 1b was highly prevalent (82%), while types 1a, 2a, 3 and 4 were rare (about 5% each). However, the prevalence of 1b was much lower (31%) under 40 years of age. The prevalence of subtype 1b among sustained responders (74%) was similar to that observed among relapsers (82%) or non-responders (84%), but some nucleotide substitutions in the putative RNA loop of the 5' non-coding region were seen only among relapsers or non-responders. Multiple logistic regression model showed that early response to interferon was predicted by absence of cirrhosis and a pre-treatment HCV-RNA level below 350. Sustained response to interferon was predicted by pre-treatment HCV-RNA level below 350 and a low fibrosis score.


CONCLUSIONS
Among patients with hepatitis C from an area where subtype 1b is highly prevalent, absence of cirrhosis and low pre-treatment serum HCV-RNA level are the most important predictors of response to IFN. Some nucleotide substitutions found in the 5' non-coding region of subtype 1b are associated with non-response or relapse.
Magrin
S
S
Istituto di Medicina Generale e Pneumologia, University of Palermo, Italy.
Craxi
A
A
Fabiano
C
C
Marino
L
L
Fiorentino
G
G
Lo Iacono
O
O
Volpes
R
R
Di Marco
V
V
Almasio
P
P
Vaccaro
A
A
Urdea
M S
MS
Wilber
J C
JC
Bonura
C
C
Gianguzza
F
F
Capursi
V
V
Filiberti
S
S
Stuyver
L
L
Pagliaro
L
L
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D015995:Prevalence; D012802:Sicily / Q000453:epidemiology; D016896:Treatment Outcome; D014766:Viremia / Q000473:pathology / Q000821:virology*
D000998:Antiviral Agents; D016898:Interferon-alpha; D000410:Alanine Transaminase