Chronic hepatitis C: the viral load per liver cell before treatment as a new marker to predict long-term response to IFN-alpha therapy.
OBJECTIVE
So far, there are no reliable parameters that can predict the long-term sustained response to treatment with interferon-alpha in patients with chronic hepatitis C. In this study, we have developed a semi-quantitative method to determine the viral load per liver cell and have correlated this factor with the outcome of hepatitis C patients treated with interferon-alpha.


METHODS
Hepatitis C virus RNA levels were measured in serum, peripheral blood mononuclear cells and liver cells of randomly chosen hepatitis C patients before treatment with interferon-alpha (n=37). The number of cells present in the liver biopsies was determined by a polymerase chain reaction-based quantitation of the housekeeping gene beta-globin. The patients were divided into a responder ("R", n=15, 41%) and a non-responder ("NR", n=22, 59%) group, as defined by normal liver enzymes and negative hepatitis C virus-polymerase chain reaction 6 months after treatment.


RESULTS
Long-term sustained responders had a significantly lower viral load per liver cell (median: 5 vs. 650 copies/1000 liver cells, p-value: 0.0001), lower age (median: 32 vs. 54 years, p-value: 0.006) and lower percentage of geno- or serotype 1 (46% vs. 91%). Regarding viral load in serum and peripheral blood mononuclear cells, alanine aminotransferase levels, gamma-globulin levels and histological changes, no statistically significant differences were observed.


CONCLUSIONS
In chronic hepatitis C infection, a high viral load per liver cell represents a new marker to predict long-term response to therapy with IFN-alpha.
Schlaak
J F
JF
First Department of Medicine, University of Mainz, Germany.
Trippler
M
M
Ernst
I
I
Meyer zum Büschenfelde
K H
KH
Gerken
G
G
D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000628:therapy / Q000821:virology*; D006521:Hepatitis, Chronic / Q000628:therapy / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008099:Liver / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D012703:Serotyping; D016896:Treatment Outcome; D019562:Viral Load
D016898:Interferon-alpha; D012367:RNA, Viral