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To determine whether the presence of hepatitis C virus (HCV) viremia correlates with the severity of liver disease in anti-HCV-positive apparently healthy blood donors, we studied 98 blood donors found positive for anti-HCV using enzyme-linked immunosorbent assay (ELISA). Each subject underwent a liver biopsy, a test for HCV RNA in the serum by polymerase chain reaction (PCR), and a panel of liver injury tests. As a result, 97% of the anti-HCV-positive blood donors had some type of histological abnormality:22 (22%) had minimal changes, 1 (1%) had chronic lobular hepatitis, 40 (41%) had chronic persistent hepatitis (CPH), and 32 (33%) had chronic active hepatitis (CAH). Only 3 subjects had a normal liver histology. HCV RNA was detectable in the serum in 65% of the anti-HCV-positive donors. HCV RNA in serum was detectable in none of the donors with a normal liver histology, in 36% (confidence interval [CI], 17% to 59%) of those with minimal changes, in 70% (CI, 53% to 83%) of those with CPH, and in 87% (CI, 71% to 96%) of those with CAH (P = .00001). HCV RNA was detectable in 75% of the donors with elevated (> 45 U/L) alanine transaminase (ALT) values and in 59% of those with normal ALT levels (P = not significant). The incidence of chronic hepatitis was higher in HCV RNA-positive than in HCV RNA-negative donors (88% vs. 50%; P = .00005).(ABSTRACT TRUNCATED AT 250 WORDS)