Eq/mL, P Γ΅ .01). There was no difference in the pre-Hepatitis C virus (HCV) replicates at a low rate, treatment proportion of HCV RNA -positive hepatoand this makes its detection and intrahepatic localcytes among patients with different biochemical reization difficult. To evaluate the clinical implications sponses to IFN-a therapy. In the posttreatment and effect of interferon alfa (IFN-a) therapy on hesamples, HCV RNA was undetectable by IS-RT-PCR patic expression of HCV RNA, HCV RNA was detected in 16 of 24 patients (P Γ΅ .01), including all 4 patients by in situ reverse-transcription polymerase chain rewho had complete and sustained response (SR). We action (IS-RT-PCR) in formalin-fixed paraffin-emconclude that HCV RNA was detected by IS-RT-PCR bedded liver sections from 26 patients with chronic in 0 to 35% of hepatocytes in patients with chronic hepatitis C. Results were compared with RT-PCR of HCV infection, detection of HCV RNA in liver by IS-HCV RNA extracted from liver sections/tissue. RT-PCR was associated with higher viremia levels, Twenty-four paired post -IFN-a treatment biopsy and IFN-a therapy reduced hepatocytic expression specimens were also assessed. Using RT-PCR of the of HCV RNA. (HEPATOLOGY 1996;23:1318-1323.) extracted RNA as a positive standard and non-HCV liver sections as the negative standard, the sensitivity and specificity of IS-RT-PCR were 69% and 100%, Hepatitis C virus (HCV) has been shown to be the respectively. HCV RNA was detected in the cytoplasm major causative agent responsible for most cases of parof hepatocytes (median, 5% hepatocytes positive; enteral non-A, non-B hepatitis. 1 Because the replicarange, 0 to 35%) and very occasionally in infiltrating tion rate of HCV is low, the diagnosis of HCV infection mononuclear cells. There was no correlation between has to rely on either indirect serological tests for antihepatic expression of HCV RNA and the clinical, biobody to HCV (anti-HCV), or very sensitive direct assays chemical parameters, total and activity scores of hisfor the detection of HCV RNA, including reverse-trantology activity index. Presence of HCV RNA in liver as detected by IS-RT-PCR was associated with higher scription polymerase chain reaction (RT-PCR) and serum HCV RNA levels (4.9 1 10 6 vs. 0.4 1 10 6 genome branched DNA amplification assay.
2-4 The low level of HCV in liver is reflected by the low level of expression of HCV antigens as detected by immunohistochemis-Abbreviations: HCV, hepatitis C virus; RT-PCR, reverse-transcription polytry 5,6 and HCV RNA by in situ hybridization. 7-10 Remerase chain reaction; IS, in situ; IFN, interferon; HBV, hepatitis B virus; cently, in situ reverse-transcription polymerase chain ALT, alanine transaminase; SR, sustained response; CR, complete response; Rel, relapse; NR, no response.