Significance of liver negative-strand HCV RNA quantitation in chronic hepatitis C

Background/Aims Liver negative-strand hepatitis C virus (HCV) RNA is the most direct indicator of active viral replication but has only been examined in a few semiquantitative studies. Methods Positive- and negative-strand HCV RNA in the right (R) and left (L) liver lobes was quantified by rTth-based strand-specific real-time polymerase chain reaction for 48 chronic hepatitis C patients. Results Close correlations between lobes were seen for positive- and negative-strand amounts (r=0.950; P<0.001 and r=0.920; P<0.001, respectively). The ratio of negative to positive strands (median, 0.14 for R and 0.13 for L) varied by 2 log directly in relation to HCV replication assessed by liver negative strands but had no relation to liver positive strands and circulating HCV. Only negative-strand quantitation was inversely correlated with age (r=−0.322; P=0.026 for R and r=−0.340; P=0.018 for L), while liver tissues with hepatitis B virus DNA contained larger amounts of each strand. In 27 patients treated with enhanced interferon monotherapy, the amounts of liver negative strands (<4 log copies/100 ng RNA) were the only independent predictor of a sustained virologic response. Conclusions Negative-strand quantitation is uniform in the liver and bears distinct relevance to the disease.