Search

Background Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D’Amico might provide new insights on timing for antiviral therapy. Methods We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n = 575) or cirrhosis (n = 2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. Results The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. Conclusion Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3–5) who are at greatest risk and have the most to gain from therapy. [ABSTRACT FROM AUTHOR]

Background & Aims In patients with chronic HCV-1 infection, recent evidences indicate that determination of a dinucleotide polymorphism (ss469415590, ΔG/ TT) of a new gene, designated IFN λ-4, might be more accurate than the 12979860 CC type of the IL28B locus in predicting sustained virological response ( SVR) following peg-interferon and ribavirin. In addition, combined genotyping of different SNPs of the IL28B locus was shown to help dissect patients most prone to SVR among those with rs12979860 CT. We examined whether single or combined genotyping of two IL28B SNPs, rs12979860 and rs8099917, and ss469415590 variation might improve the prediction of SVR. Results In the study cohort of 539 patients, 38% had SVR. The SNPs 12979860 CC, rs8099917 TT, and rs469415590 TT/ TT correlated significantly with SVR (68%, 50%, and 67%). Carriers of either the triplotype rs12979860 CC_ss469415590 TT/ TT_rs8099917 TT or the diplotype rs12979860 CC_ss469415590 TT/ TT had the highest SVR rate (72%). In carriers of the rs12979860 T allele, neither the rs8099917 nor the ss469415590 improved the response prediction. After pooling this finding with data from previous studies, in rs12979860 T heterozygous individuals the co-presence of the rs8099917 TT SNP was associated with improved response prediction. Conclusion In HCV-1 patients, the rs12979860 polymorphism appeared as the hit SNP better predicting response following peg-interferon and ribavirin treatment. Additional ss469415590 or rs8099917 genotyping had no added benefit for response prediction. In the subset of carriers of the rs12979860 T allele, genotyping of the rs8099917 SNP was unhelpful in the present investigation, but may inform clinical prediction of treatment response when our data were pooled with previous investigations. [ABSTRACT FROM AUTHOR]

Background & Aims: The pool of HCV genotype 1 patients likely to be cured by peg-interferon and ribavirin remains to be quantified. Methods: In 1045 patients treated with peg-interferon and ribavirin, two therapeutic strategies were confronted: the first one evaluated only baseline variables associated with sustained virological response (SVR), and the second one included the rapid virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was the threshold to retain a strategy as clinically relevant. Results: Overall, 414 patients (39.6%) attained SVR. In the first strategy, the hierarchy of features independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637–7.101), low (<400,000IU) viremia (OR 2.907; CI 2.111–4.004), F0–F2 fibrosis (OR 1.631; CI 1.122–2.372) and type 2 diabetes (OR 0.528; CI 0.286–0.972). In the alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274–9.208), IL28B CC genotype (OR 3.306; CI 2.301–4.751), low viremia (OR 2.175; CI 1.542–3.070), and F0–F2 fibrosis (OR 1.506; CI 1.012–2.242). Combining the favorable baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66 patients (6.3%, overall) with all predictors could be anticipated to reach the >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR patients, the likelihood of SVR was 61.8% in those with unfavorable predictors, 80% in the presence of a single predictor, and 100% when both predictors were present. By using this model, 200 patients (19.1%) were predicted to have an 80% chance of being cured with dual therapy. Conclusions: A consistent subset of naïve HCV-1 patients, identified by some baseline characteristics and RVR, may benefit from dual treatment with peg-interferon and ribavirin. [Copyright &y& Elsevier]