SAITOH, Y., MIURA, M., NIITSUMA, H., NUMATA, N., OHORI, H., ISHII, M. and TOYOTA, T. Changes of Serum Hepatitis C Virus Levels in Patients with Chronic Hepatitis C Treated with Two Courses of Interferon Administration. Tohoku J. Exp. Med., 1994, 173 (4), 361-369-To assess the efficacy of repeated interferon (IFN) administration in patients with chronic hepatitis C unresponsive to initial therapy, serum hepatitis C virus (HCV)-RNA levels were measured in 12 patients who had failed prior IFN therapy. Serum HCV-RNA was assayed by measuring DNA complementary to HCV-RNA using a quantitative reverse transcription-polymerase chain reaction assay. The mean total dose of IFN was 227.8 megaunits for first treatment and 270.7 mega-units for second treatment. Five responders with a normal alanine aminotransferase (ALT) concentration (less than 40IU/liter) at the end of the first treatment also had a normal ALT concentration at the end of the second treatment. By contrast, all nonresponders with an elevated ALT concentration during the first treatment likewise had an elevated ALT concentration at the end of the second treatment. HCV-RNA levels before the first treatment varied from 10⁶ to 10⁸ copies/μl. The serum HCV-RNA levels fell in 9 out of 10 patients after the first treatment and in 11 out of 12 patients after the second treatment. One patient had unchanged normal serum ALT levels after two courses of IFN treatment. These results suggested that the outcome of a second course of IFN treatment was similar biochemically and virologically to a first course, and that patients who did not respond initially seldom respond to additional IFN therapy. Therefore, readministration of IFN should be restricted to patients who respond biochemically and virologically to initial treatment. The optimal second dose shall be determined with further studies.