title: Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C.
abstract: Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon-based therapy. We aimed to investigate long-term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty-three patients had TF, and 62 patients were treatment-naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥ 2 stage increase in fibrosis during follow-up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma-glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01-1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81-19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon-based CHC treatment may lead to accelerated FPR in the long-term compared with the natural course.
authors.affiliation: Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Baran
authors.forename: M
authors.initials: M
authors.lastname: Gulluoglu
authors.forename: O M
authors.initials: OM
authors.lastname: Soyer
authors.forename: A C
authors.initials: AC
authors.lastname: Ormeci
authors.forename: S
authors.initials: S
authors.lastname: Gokturk
authors.forename: S
authors.initials: S
authors.lastname: Evirgen
authors.forename: S
authors.initials: S
authors.lastname: Yesil
authors.forename: F
authors.initials: F
authors.lastname: Akyuz
authors.forename: C
authors.initials: C
authors.lastname: Karaca
authors.forename: K
authors.initials: K
authors.lastname: Demir
authors.forename: S
authors.initials: S
authors.lastname: Kaymakoglu
authors.forename: F
authors.initials: F
authors.lastname: Besisik
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000998:Antiviral Agents; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase
keywords: fibrosis progression; gamma-glutamyl transferase; hepatitis C; nonresponder; treatment failure