The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.T he effect of the hepatitis C virus (HCV) genotype 1 subtype on the response to treatment can be dramatic for some direct antiviral agent (DAA)-containing regimens (1)(2)(3)(4)(5)(6)(7)(8)(9). This is the case for simeprevir, a DAA recently approved for clinical use, that in combination with pegylated interferon and ribavirin (peg-IFN/ RBV) has a lower sustained virological response (SVR) rate for subtype 1a than for 1b (2). Simeprevir plus peg-IFN/RBV treatment achieves rates of SVR similar to those for peg-IFN/RBV treatment in HCV-1a-infected patients who present the viral variation Q80K. This variation is frequent in the HCV-1a subtype, but it is not found in HCV-1b (2, 5). Similarly, daclatasvir plus peg-IFN/RBV treatment also achieves higher SVR rates among HCV1b-infected patients than among HCV-1a-infected individuals (4). For interferon-free regimens, DAA combinations such as asunaprevir plus daclatasvir may only be indicated for subtype 1b, because of high relapse rates observed among patients with subtype 1a (3, 4). Because of these, accurate subtyping of HCV genotype 1-infected patients is needed for those who are candidates for DAAs.Sequencing of specific HCV genome regions with subsequent phylogenetic analysis is considered the gold standard of HCV genotyping (10). However, it includes several complex techniques and is time consuming. For these reasons, LiPA 2.0 is currently one of the most widely used genotyping assays. However, several studies have reported HCV genotyping errors using this commercial method (11-13). Those studies were not designed to evaluate the frequency of HCV-1 subtyping misclassifications, and they included few HCV-1-infected patients. Therefore, due to the high prevalence of HCV-1 infections in western countries and the importance of correct subtyping in clinical decisions, the accuracy of this method for HCV-1 subtyping needs to be evaluated in larger samples. For these reasons, we aimed to evaluate the accuracy of LiPA 2.0 for classifying HCV-1 by subtypes.This study was performed according to the ethical guidelines of the 1975 Declaration of Helsinki, and it was approved by the ethics committee of the Hospital Universitario de Valme (Seville, Spain).The first 110 consecutive patients starting from October 2001, who received a course of peg-IFN/RBV treatment in our hospital and who were infected with HCV-1, according to the LiPA 2.0 determination, were selected. All of them were Caucasian with a median age (quartile 1 to quartile 3) of 42 years (range, 39 to 46 years). Among the patients, 82 (81%) were male, and 48 (47.5%) were infected with HIV.To determine the HCV-1 subtype, we analyzed...

The aim of this study was to analyze the impact of core variations on sustained virological response (SVR) to pegylated interferon plus ribavirin (PEG-IFN/RBV) and its association with predictive factors of response in Caucasian patients infected with genotype 1 hepatitis C virus (HCV-1). Full-length core sequences were analyzed in 100 Caucasian HCV-1-infected patients who received therapy with PEG-IFN/RBV. The associations between variations in the core protein and SVR, as well as with predictors of SVR, were analyzed. Variations at core 62, 70 and 110 were selected as candidates. There were almost no variations at these positions among patients harboring HCV-1a. However, they were identified in 10 (30.3 %), 21 (63.6 %) and 13 (39.4 %) subjects with HCV-1b, respectively. Among the HCV-1b patients, 39.1 % individuals carrying core R62 and 70 % subjects with core R62G showed SVR (p = 0.141), and 66.7 % of HCV-1b patients harboring core R70 and 38.1 % with core R70Q achieved SVR (p = 0.157), whereas the rate of SVR was 70 % for individuals with core T110 and 15.4 % for those with core T110N (p = 0.004). No statistical interaction between core variations and IL28B genotype was observed. Patients with R70 showed higher median (interquartile range) baseline plasma levels of low-density-lipoprotein cholesterol (LDL-C) than those with R70Q (96 [86-118] mg/dL vs. 76 [54-88] mg/dL, p = 0.014). We concluded that a substitution at core 110 is associated with a lower rate of SVR in Caucasian HCV-1b-infected patients receiving PEG-IFN/RBV. Furthermore, the variation at the core 70 position is related to plasma levels of LDL-C in these patients.