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Background & Aims IL28B polymorphisms, jaundice, decline in HCV-RNA, IP-10, and gender have been proposed to be indicative of spontaneous clearance of acute hepatitis C virus infection. The aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development of viral persistence and need for early antiviral treatment. Methods 136 patients (74 male; 35±15years) were analyzed. From variables predictive of spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cut-offs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cut-offs were: (I) presence of IL28B C/C ( p =0.027), (II) age ( p =0.031; cut-off: 35years), (III) peak-bilirubin ( p =0.018; cut-off: 6mg/dl), (IV) HCV-RNA decline within 4weeks ( p 2.5log), (V) serum IP-10 ( p =0.003; cut-off: 546pg/ml), (VI) presence of CD4(+) Th1 cells ( p =0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA decline of ⩾1log 10 but 10 to 1 point, a decline of ⩾2.5log 10 to 2 points. Three scores were evaluated (Score 1: I–IV; Score 2: I–V; Score 3: I–VI). Results A cut-off of ⩾3 points out of 5 in Score 1 (AUROC: 0.82; DeLong 95% CI: 0.76–0.93) predicted spontaneous clearance with a sensitivity of 71% (95% CI: 0.53–0.86) and specificity of 87% (95% CI: 0.73–0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score 2 including IP-10 (AUROC: 0.93; DeLong 95% CI: 0.86–0.93) at a cut-off of ⩾4 were: sensitivity 81%, specificity 95% (PPV: 100%; NPV: 77%). A cut-off of ⩾5 in Score 3 (AUROC: 0.98; DeLong 95% CI: 0.95–1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV: 100%; NPV: 88%). Conclusions The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.

Methods: We studied 157 patients in accordance with the inclusion criteria, who underwent paired liver biopsies from 1994 to 2012. Ninety-three patients had treatment failure (TF) and 64 patients were treatment-naive (TN). Annual fibrosis progression rate (FPR) was calculated and significant fibrosis progression (SFP) was defined as ≥2 stage increase in fibrosis during follow-up. Because of the differences in baseline biochemical and histological features, multiple regression analyses with backward elimination were performed to find out independent predictors of SFP and FPR. Results: Demographic characteristics and duration between paired liver biopsies were similar in TF and TN-groups. Baseline ALT and GGT levels (82±48 vs. 45±20 and 60±45 vs. 36±27, respectively), baseline mean fibrosis stage (2.9±1.1 vs. 1.9±0.8) and histologic activity index (6.7±1.9 vs. 4.3±1.6) were higher in TF-group compared to TN-group (p < 0.001). According to regression analyses strongest independent predictor of fibrosis progression was GGT level (OR: 1.03, 95%CI 1.01–1.5, p < 0.001). Treatment experience (OR: 4.55, 95%CI 1.27–16.2, p = 0.02) and follow-up ALT levels (OR: 4.20, 95%CI 1.41–12.5, p = 0.01) also appeared independent predictors of FPR and SFP. Conclusion: Failed interferon-based treatment against CHC may lead to accelerated FPR in long-term compared to natural course.