Tissue quantitation of hepatitis C virus RNA with morphologic correlation in the diagnosis of recurrent hepatitis C virus in human liver transplants

Background: Histologic findings and liver enzymes in liver transplants are often non-diagnostic of recurrent hepatitis C virus (HCV) disease. In addit ion, the relationship between HCV replication and the presence of recurrent HCV hepatitis after liver transplantation remains unclear. We studied live r transplant recipients to determine if quantitation of HCV RNA in liver ti ssue by reverse transcriptase-polymerase chain reaction (RT-PCR) correlates with histopathologic disease and/or liver enzymes. Methods: Twenty-six pat ients who received liver transplants for HCV infection were evaluated. Four sequential biopsies were analyzed for each patient. HCV RNA was extracted and quantified using the Amplicor HCV Monitor Test. Histologic examination and RNA quantitation were blinded. All available liver enzymes on the day o f liver biopsy were analyzed. Results: HCV RNA quantity in liver tissue was significantly increased at the time of clinically-suspected recurrence (P <.0001). HCV RNA levels were highest in biopsies with lobular hepatitis and nonspecific inflammation, followed by biopsies with cytomegalovirus infect ion, chronic hepatitis, and acute cellular rejection. HCV RNA quantity had a significant correlation with increasing portal inflammation (P =.0002), d ecreasing amount of interface hepatitis (P =.0333), and presence of acidoph ilic bodies (P =.0316). Increasing HCV RNA levels significantly correlated with decreasing number of episodes of treated rejection. HCV RNA quantity d id not correlate with other histologic features or liver enzymes. Conclusio ns: HCV RNA levels are highest at the time of active hepatocellular destruc tion. Elevated HCV RNA indicates recurrence. HCV RNA quantitation may be a useful diagnostic test for determining recurrent disease and distinguishing it from other causes of inflammation, such as rejection.