Diagnosis of occult hepatitis C without the need for a liver biopsy

The diagnosis of occult hepatitis C virus (HCV) infection is based on the presence of HCV-RNA in the liver. This study aimed to evaluate the use of combining non-invasive assays to diagnose occult HCV. A total of 122 patients with occult HCV (HCV-RNA in the liver without detectable anti-HCV and serum HCV-RNA) and 45 patients with cryptogenic chronic hepatitis (without HCV-RNA in the liver and negative for anti-HCV and serum HCV-RNA) were included. HCV-RNA was tested in peripheral blood mononuclear cells (PBMCs) and in 2 ml of ultracentrifuged serum. Anti-core HCV was examined by a non-commercial enzyme-linked immunosorbent assay. All controls were negative for the three HCV markers studied. Among patients with occult HCV, 36% were anti-core HCV positive, 57% had serum HCV-RNA after ultracentrifugation, and 61% had HCV-RNA in PBMCs. Combining the results of the assays, 91% of the patients were positive for at least one marker. Intrahepatic HCV-RNA load was significantly higher in patients who were positive simultaneously for the three HCV markers than in patients who were negative for all markers (P = 0.006) and than in those with one or two HCV markers (P = 0.039). Replication of HCV in liver was detected more frequently in patients with three (93%, P = 0.002), two (82%, P = 0.001), and one HCV marker (73%, P = 0.011) than in those without markers (27%). In conclusion, testing for all these markers allows diagnosis of occult HCV without the need for a liver biopsy and these assays may help to elucidate the clinical significance of occult HCV infection.