title: A liver slice culture-based ex vivo assay to predict the outcome of antiviral therapy for chronic hepatitis C.
abstract: A liver slice culture-based, ex vivo drug suppression assay was developed as a pre-therapeutic predictor for the outcome of antiviral therapy. To investigate its clinical application, 106 consecutive patients with chronic hepatitis C virus (HCV) infection were evaluated. Ex vivo drug suppression assay was performed before administrating a standard course of peginterferon plus ribavirin combination therapy. Stepwise logistic regression model was used to estimate sustained virological response (SVR) on the presence of various clinicopathological parameters. Suppression of HCV replication in the ex vivo assay was present in 32 patients, 29 (90.6%) of whom achieved SVR. Stepwise logistic regression analysis indicated that the presence of interferon suppression effect in the ex vivo assay (odds ratio [OR], 5.552; 95% confidence interval [CI], 1.114-27.673; P = 0.036), genotype 1 (OR; 0.045, 95% CI, 0.008-0.259; P = 0.001), HCV-RNA level (OR, 0.739; 95% CI, 0.617-0.885; P = 0.001), the presence of fatty metamorphosis (OR, 0.205; 95% CI, 0.053-0.793; P = 0.022), and albumin (OR, 9.687; 95% CI, 2.237-41.940; P = 0.002) were independent determinants of SVR. Categorical analysis revealed that 17 of 17 (100%) patients with genotype non-1 and positive ex vivo suppression test achieved SVR, while 20 of 40 (50%) with genotype 1 and negative ex vivo suppression test achieved SVR. In conclusion, the ex vivo drug suppression assay may serve as an independent pre-therapeutic predictor for the SVR in interferon-based antiviral therapy.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: M-L
authors.initials: ML
authors.lastname: Chang
authors.forename: K-F
authors.initials: KF
authors.lastname: Sung
authors.forename: I-S
authors.initials: IS
authors.lastname: Sheen
authors.forename: S-M
authors.initials: SM
authors.lastname: Lin
authors.forename: C-T
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000418:Albumins / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques / Q000379:methods; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D012367:RNA, Viral