sis. Also, the activity of fetal P3 and P4 promoters was Increased prevalence of hepatitis C virus (HCV) infechigher in the nontumorous than in the tumorous area tion has been found in patients with hepatocellular carof the liver of HCC patients. The expression of IGF-II cinoma (HCC). The expression of insulinlike growth factranscripts was correlated with the rate of cell mitotic tor II (IGF-II) has been linked to hepatocarcinogenesis activity by measuring the expression of the proliferating in the experimental animal and in humans. Since reacticell nuclear antigen (PCNA) gene. PCNA messenger RNA vation of fetal IGF-II transcripts has been observed in (mRNA) levels progressively increased from normals to human HCC, we have analyzed the levels of adult P1 CAH and to cirrhotic patients, and persisted at a high and fetal P3 and P4 IGF-II promoter-derived transcripts level in the tumorous and in the nontumorous area of in the liver of patients with HCV-related chronic active HCC subjects, thus showing that the increase of IGF-II hepatitis (CAH), cirrhosis, and HCC by means of a semitranscripts in CAH and cirrhosis is accompanied by an quantitative reverse-transcription polymerase chain reactivation of cell mitosis in these samples. These data action (RT-PCR) assay. Transcripts derived from adult suggest that the activation of IGF-II gene expression P1 promoter were increasingly expressed from normals from adult and fetal promoters may play a role in premato patients with CAH and cirrhosis, but were undetectlignant proliferation observed in HCV-related chronic able in the tumorous area of 5 of 7 HCC patients and liver disease. (HEPATOLOGY 1996;23:1304-1312.) present at low levels in the nontumorous area of all HCC patients. Transcripts derived from fetal P3 promoter were not detectable in normal subjects, while they were
Hepatitis C virus (HCV) is a positive-stranded RNA expressed abundantly in most CAH and all cirrhotic pavirus that plays a major role in the development of tients. Transcripts from fetal P4 promoter were detected chronic liver disease (CLD). 1,2 Acute posttransfusion at high levels in 3 of 9 CAH patients and in the majority hepatitis due to HCV is followed by chronic hepatitis of cirrhotic patients. Increased expression of fetal proin more than 50% of cases, 3,4 and 20% to 50% of these moter-derived transcripts was also found in the liver of patients eventually progress to cirrhosis. 3, Mounting HCC patients, although levels were lower than in cirrhoevidence suggests that HCV infection may play a role in the development of hepatocellular carcinoma (HCC) in cirrhotic patients. [6] Chronic injury of liver cells and Abbreviations: HCV, hepatitis C virus; CLD, chronic liver disease; HCC, the associated inflammatory and regenerative rehepatocellular carcinoma; IGF-II, insulinlike growth factor II; IGF-IR, insusponse that occurs in CLD are known to represent a linlike growth factor type I receptor; RT-PCR, reverse-transcription polymerase chain reaction; CAH, chronic active hepatitis; PCNA, proliferating cell preneoplastic process that may evolve toward malignuclear antigen; PCR, polymerase chain reaction; mRNA, messenger RNA; nancy. 8-10 However, the mechanisms responsible for the GAPDH, glyceraldehyde-3-phosphate dehydrogenase.