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Detection of intrahepatic hepatitis C virus replication by strand-specific semi-quantitative RT-PCR: preliminary application to the liver transplantation model.

Negro F, Giostra E, Krawczynski K, Quadri R, Rubbia-Brandt L, Mentha G, Colucci G, Perrin L, Hadengue A

Division of Gastroenterology and Hepatology, University Hospital, Geneva, Switzerland. Francesco.Negro@hcuge.ch

BACKGROUND/AIMS:

Although the hepatitis C virus infection recurs in virtually all patients after liver transplantation, up to 50% of patients may not have histological recurrent hepatitis 1 year after liver transplantation. To study the relationship between hepatitis C virus infection and liver disease after liver transplantation, we compared the intrahepatic hepatitis C virus replication levels with the liver histopathology among liver transplant recipients.

METHODS:

The intrahepatic negative-strand HCV RNA (i.e. the putative hepatitis C virus replication intermediate RNA) was evaluated by a semi-quantitative, strand-specific reverse transcriptase-polymerase chain reaction in 44 liver specimens from 23 patients with hepatitis C virus reinfection after liver transplantation. Results were compared with the time from liver transplantation, presence, grading and staging of the recurrent hepatitis, amount of hepatitis C virus antigens in the liver and serum HCV RNA levels.

RESULTS:

Negative-strand HCV RNA was detected in 42 liver specimens as early as 7 days after liver transplantation. Its titers correlated 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 specimens with hepatitis (p=0.492), and were unrelated to the liver disease grading and staging scores. The intrahepatic hepatitis C virus replication could occasionally precede the recurrence of the hepatitis by several months.

CONCLUSIONS:

Molecular evidence has been obtained for intrahepatic hepatitis C virus replication occurring early after liver transplantation. The level of replication is not correlated with the development of recurrent hepatitis, suggesting that hepatitis C virus may replicate without inducing morphological evidence of liver damage.

PMID: 9696486, UI: 98359675

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