title: Discordance between serum alanine aminotransferase (ALT) and virologic response to IFN-alpha2b in chronic hepatitis C patients with high and low pretreatment serum hepatitis C virus RNA titers.
abstract: Although serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA concentrations are primary markers used to assess the clinical benefit of interferon (IFN) therapy in patients with chronic HCV infection, discrepancies between these two variables exist. In this study, 103 patients with chronic hepatitis C were treated with 3 MIU IFN-alpha2b three times weekly for 24 weeks, followed by 24 weeks of observation. ALT and virologic responses were compared in patients with high pretreatment HCV RNA titers (defined as pretreatment HCV RNA concentrations at or above the 75th percentile of the distribution or >5,000,000 copies/ml) and low pretreatment HCV RNA titers (defined as pretreatment concentrations below the 75th percentile or < or =5,000,000 copies/ml). Analysis of the virologic response for the high-titer and low-titer groups demonstrated a significantly greater HCV RNA sustained response in the low-titer group (21%) compared with the high-titer group (7%) (p < 0.05). In contrast, the ALT sustained response was not significantly different between the low-titer group (21%) and the high-titer group (18%). Analysis of the correspondence between biochemical and virologic responses showed that only 38% of patients with high pretreatment HCV RNA titers had both a sustained ALT response and a sustained loss of HCV RNA compared with 75% of patients with low pretreatment HCV RNA titers. The level of agreement between the ALT and HCV RNA responses was greater for the low-titer group compared with the high-titer group (kappa = .6848 and kappa = .4966, respectively). Our results indicate that chronic HCV patients with high pretreatment HCV RNA titers showed greater discordance between sustained ALT and HCV RNA responses compared with patients with low pretreatment HCV RNA titers and that measurement of HCV RNA should be included in the assessment of response to IFN therapy in chronic hepatitis C patients.
authors.affiliation: National Genetics Institute, Culver City, CA 90230, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Blatt
authors.forename: M J
authors.initials: MJ
authors.lastname: Tong
authors.forename: J G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: J
authors.initials: J
authors.lastname: Russell
authors.forename: P
authors.initials: P
authors.lastname: Schmid
authors.forename: A
authors.initials: A
authors.lastname: Conrad
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D011994:Recombinant Proteins; D017186:Titrimetry; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase