Chronic hepatitis C: the viral load per liver cell before treatment as a new marker to predict long-term response to IFN-α therapy

Background/Aims: So far, there are no reliable parameters that can predict the long-term sustained response to treatment with interferon-α 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-α. 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-α (n=37). The number of cells present in the liver biopsies was determined by a polymerase chain reaction-based quantitation of the housekeeping gene β-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, γ-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-α.