title: Viral kinetics during antiviral therapy in patients with chronic hepatitis C and persistently normal ALT levels.
abstract: The aim of the present study was to compare viral kinetics between patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels and those with elevated ALT levels. Kinetic parameters were derived from nonlinear, least square fitting of serum hepatitis C virus RNA quantifications collected from patients with chronic hepatitis C and persistently normal (n = 20) and elevated (n = 19) ALT levels before and during treatment with 180 mug pegylated interferon alpha-2a once weekly plus daily ribavirin. Patients with chronic hepatitis C and persistently normal ALT levels showed a trend to lower pretreatment infected cell loss (delta) (P = .13) but no differences in efficacy of blocking virus production (epsilon) and infected cell loss during treatment (mdelta) compared with patients with elevated ALT levels. Differences were significant for epsilon (P = .02) and delta (P = .04) when applying updated "healthy" levels for ALT (0.75 times and 0.63 times upper limit of normal for male and female patients, respectively). A significant reduction of the kinetic parameters epsilon, delta, and mdelta was observed in patients with elevated gamma-glutamyltranspeptidase (GGT) levels compared with patients with normal GGT levels (P = .02, P = .005, and P = .02, respectively). In conclusion, viral kinetics are similar in patients with chronic hepatitis C and persistently normal ALT levels and those with elevated ALT levels. However, in patients with elevated GGT levels, a major association with reduced efficacy of blocking virus production and lower infected cell loss was observed. These data show that virological response in patients with chronic hepatitis C is less associated with baseline ALT than with GGT levels.
authors.affiliation: Klinik für Innere Medizin II, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Florence
authors.initials: F
authors.lastname: Micol
authors.forename: Michael
authors.initials: M
authors.lastname: von Wagner
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a