The study by Horae et al. in patients who are anti-HCV - positive and HCV RNA serum - negative and have normal alanine aminotransferase levels suggests that some of these patients may have continued low-grade replicative HCV disease based on the presence of inflammatory infiltrates within the liver. Unfortunately, the authors did not use state-of-the-art technology to support their claims, such as determining hepatic RNA levels in liver tissue, using ultracentrifugation technology to increase the sensitivity of RNA detection in the serum, or employing situ hybridization to determine if hepatocytes were infected with the HCV virus. However, what is important in this group of patients is the long-term outcome. Will these patients progress histologically and will they have ongoing fibrosis and even possibly develop cirrhosis and hepatocellular cancer, or will these histologic findings regress with time and will the immune response eventually lead to complete eradication of the virus from the liver? Past experience in medicine indicates that there probably is a whole spectrum of responses. The authors already reported that 7.5% of the patients in this group had completely normal histology. In the past, the timeline with respect to eradication of HCV RNA from the serum following treatment with interferon has been studied extensively. A similar assessment and timeline of eradication of the virus from hepatic tissue have not been studied to date. The rarity of reactivation of HCV despite the use of immunosuppressive or cytolytic therapy, particularly in the transplant setting, suggests that viral replication is controlled in HCV antibody - positive, HCV RNA - negative individuals. In conclusion, long-term follow-up in this reported group of patients will be necessary to determine what the long-term impact of these clinical and histologic findings are. A repeat biopsy 3 to 5 years after the index biopsy would give important further information regarding the natural history in these patients.
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