The role of genomic and antigenomic HCV-RNA strands as predictive factors of response to pegylated interferon plus ribavirin therapy.
BACKGROUND
Hepatitis C virus replicates by the synthesis of an antigenomic HCV-RNA. As the end point of anti-viral therapy is to decrease viral replication, the amount of antigenomic HCV-RNA could influence the response.


OBJECTIVE
To study if amounts of genomic and antigenomic HCV-RNA in the baseline liver biopsy are predictive factors of response to anti-viral therapy.


METHODS
Eighty-eight patients with chronic HCV infection (anti-HIV-negative) treated with pegyltaed-interferon-alpha2b plus ribavirin for 12 months were included. Intrahepatic genomic and antigenomic HCV-RNA concentrations were determined by real-time polymerase chain reaction and percentage of infected hepatocytes by in situ hybridization.


RESULTS
Of the 88 patients, 31% were responders while 69% were not. Median of antigenomic HCV-RNA in liver of responders and non-responders was 120 000 copies/microg RNA (range: 10,000-775,000) vs. 150,000 copies/microg RNA (range: 100-3,200,000; P = 0.38). Median of genomic HCV-RNA in liver of responders was 1,250,000 copies/microg RNA (range: 5000-9,000,000) and in non-responders 3,180,000 copies/microg RNA (range: 4600-18,000,000; P = 0.0191). Predictive factors of response in the logistic regression were: intrahepatic amount of genomic HCV-RNA, percentage of infected hepatocytes and previous therapy.


CONCLUSIONS
Response to 12 months of therapy with pegylated interferon-alpha2b plus ribavirin depends on the amount of genomic HCV-RNA in the pre-treatment liver biopsy.
López-Alcorocho
J M
JM
Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain.
Rodríguez-Iñigo
E
E
Castillo
I
I
Castellanos
M E
ME
Pardo
M
M
Bartolomé
J
J
Quiroga
J A
JA
Carreño
V
V
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D016679:Genome, Viral / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b