DETECTION OF INTRAHEPATIC HEPATITIS-C VIRUS-REPLICATION BY STRAND-SPECIFIC SEMIQUANTITATIVE RT-PCR - PRELIMINARY APPLICATION TO THE LIVER-TRANSPLANTATION MODEL

Background/Aims: Although the hepatitis C virus infection recurs in vi rtually all patients after liver transplantation, up to 50% of patient s may not have histological recurrent hepatitis 1 year after liver tra nsplantation. To study the relationship between hepatitis C virus infe ction and liver disease after liver transplantation, we compared the i ntrahepatic hepatitis C virus replication levels with the liver histop athology among liver transplant recipients. Methods: The intrahepatic negative-strand HCV RNA (i.e. the putative hepatitis C virus replicati on intermediate RNA) was evaluated by a semi-quantitative, strand-spec ific reverse transcriptase-polymerase chain reaction in 44 liver speci mens from 23 patients with hepatitis C virus reinfection after liver t ransplantation. Results were compared with the time from liver transpl antation, presence, grading and staging of the recurrent hepatitis, am ount of hepatitis C virus antigens in the liver and serum HCV RNA leve ls. Results: Negative-strand HCV RNA was detected in 42 liver specimen s as early as 7 days after liver transplantation. Its titers correlate d with the amount of intrahepatic hepatitis C virus antigens, but not with HCV RNA levels in serum. Levels of negative-strand HCV RNA in 19 specimens without hepatitis were comparable to those seen in 25 specim ens with hepatitis (p=0.492), and were unrelated to the liver disease grading and staging scores. The intrahepatic hepatitis C virus replica tion could occasionally precede the recurrence of the hepatitis by sev eral months. Conclusions: Molecular evidence has been obtained for int rahepatic hepatitis C virus replication occurring early after liver tr ansplantation. The level of replication is not correlated with the dev elopment of recurrent hepatitis, suggesting that hepatitis C virus may replicate without inducing morphological evidence of liver damage.