title: Enhancing effect of the liver extract and flavin adenin dinucleotide mixture on anti-viral efficacy of interferon in patients with chronic hepatitis C.
abstract: A combined preparation of liver extract and flavin adenin dinucleotide (FAD) (Adelavin) has been widely used in patients with chronic liver diseases in Japan. One milliliter of this agent contains 15 microliters of phenol-soluble phase of liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using this preparation in the elimination of hepatitis C virus (HCV) from patients with chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days before 6 million units of IFN-alpha was intramuscularly injected once. Before and 48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS activities, and HCV RNA levels. The 2'5-AS activities were significantly increased by IFN after the intravenous injection of this preparation (p < 0.01), while an injection of IFN alone of this dose did not change its activities (n = 10). HCV RNA levels were significantly decreased by IFN only after the administration of the preparation (intramuscular, p < 0.01; intravenous, p < 0.01). The effect of intravenous injection of this preparation was also elicited in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These results suggest that this preparation may enhance the 2'5-AS production by IFN as a result of the increase in mitochondrial adenosin triphosphate production and may be a potent agent to enhance the anti-viral efficacy of IFN in patients with CH-C.
authors.affiliation: Department of Internal Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Ebinuma
authors.forename: S
authors.initials: S
authors.lastname: Tada
authors.forename: S
authors.initials: S
authors.lastname: Tsunematsu
authors.forename: K
authors.initials: K
authors.lastname: Atsukawa
authors.forename: T
authors.initials: T
authors.lastname: Masuda
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002908:Chronic Disease; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000627:therapeutic use*; D006526:Hepatitis C / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008110:Liver Extracts / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D004338:Drug Combinations; D008110:Liver Extracts; C102331:Adelavin 9; D005182:Flavin-Adenine Dinucleotide; D007372:Interferons