Complete eradication of hepatitis C virus after interferon treatment for chronic hepatitis C.
BACKGROUND
Alpha-interferon therapy can lead to a persistent biochemical response, but discordant opinions have been expressed on the definition of sustained response and on the real possibility of complete eradication of hepatitis C virus (HCV).


OBJECTIVE
To define the clinical, virological and histologic profiles of the patients with sustained response.


METHODS
Twenty-eight patients with three different biochemical and virological patterns of response to interferon therapy (16 sustained responders, 6 responders with relapse and 6 non responders) were studied for a follow-up period of 36 months.


METHODS
HCV-RNA sequences were investigated in serum, peripheral blood mononuclear cells and in liver tissue by means of reverse transcriptase-polymerase chain reaction, targeted to the 5' non coding region. Viral load in serum was quantified by branched-DNA signal amplification. HCV genotypes were evaluated using a line probe assay.


RESULTS
All sustained responders showed persistent normal ALT values and loss of serum HCV-RNA during the treatment and in the entire follow-up period. The HCV clearance was also demonstrated in peripheral blood mononuclear cells and in liver tissue. Pre-treatment HCV-RNA quantitation showed that sustained responders had a significantly lower viral load compared to relapsers and non responders (p = 0.005). HCV genotyping showed that patients infected by genotypes 2a, 3a were more likely to achieve a sustained response. Interestingly, a prolonged response was also observed in the only three patients with pre-treatment detectable viral load infected by genotype 3a and in patients with genotype 1b and low viraemia levels. To assess the histologic outcome following HCV eradication, all sustained responders underwent a second liver biopsy in the follow-up period (6-18 months). Periportal necrosis and portal inflammation were significantly improved.


CONCLUSIONS
Our results suggest that persistent loss of HCV-RNA in serum, peripheral blood mononuclear cells and liver as well as histologic improvement are consistent with the complete HCV eradication even from intracellular compartments and from potential extra-hepatic sites of viral persistence. Moreover, pre-treatment viral load, HCV infecting genotypes and histologic features may influence the clinical outcome of hepatitis C and the response to interferon therapy.
De Mitri
M S
MS
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, Italy.
Morsica
G
G
Chen
C H
CH
Mele
L
L
Baccarini
P
P
Chianese
R
R
Piccinini
A
A
Lazzarin
A
A
Pisi
E
E
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D018709:Statistics, Nonparametric; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D007372:Interferons