Factors influencing the response to interferon therapy in chronic hepatitis C. Studies on viral genotype and induction of 2',5'-oligoadenylate synthetase in the liver and peripheral blood cells.
BACKGROUND
The mechanism behind the antiviral action of interferon (IFN) therapy in chronic hepatitis C virus (HCV) infection is not well understood, and, furthermore, few factors have been shown to be good predictors of a favourable response to IFN treatment in chronic HCV infection.


METHODS
Freshly explanted liver cells and peripheral blood mononuclear cells (PBMC) from 80 patients with chronic HCV infection were used to study the capacity of IFN to induce the enzyme 2',5'-oligoadenylate synthetase (2'5'-AS) in vitro. The HCV genotype was determined in 53 patients. The induction of 2'5'-AS was correlated to the results of IFN-alpha treatment in 36 patients.


RESULTS
Normalization of transaminases during IFN treatment was significantly associated with 2'5'-AS levels in liver cells cultured in the absence of IFN. A similar tendency, although not statistically significant, was found for IFN-induced levels of 2'5'-AS in liver cells. No such associations were found when PBMC were analysed. Six patients showed a sustained biochemical response. These six did not deviate significantly from the remaining patients with regard to base-line or IFN-induced levels of 2'5'-AS in liver cells or PBMC. Eradication of HCV RNA during IFN treatment did not correlate with 2'5'-AS levels in liver cells. Comparison of HCV genotype and clinical response showed that patients with genotype 3a had the most favourable outcome. No association was found between liver histology and treatment outcome.


CONCLUSIONS
These data imply that direct effects of IFN on liver cells are of importance for the response to IFN treatment.
Grandér
D
D
Dept. of Oncology, Radiumhemmet, Stockholm, Sweden.
Hultcrantz
R
R
Weiland
O
O
Xu
B
B
Sangfelt
O
O
Björklund
A C
AC
Befrits
R
R
Björkholm
M
M
Gruber
A
A
Kinnman
N
N
Reichard
O
O
Widell
A
A
Einhorn
S
S
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004790:Enzyme Induction; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000628:therapy*; D006521:Hepatitis, Chronic / Q000628:therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D011994:Recombinant Proteins
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase