Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n ‫؍‬ 47; 1a, n ‫؍‬ 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n ‫؍‬ 36) or nonresponders (NR; n ‫؍‬ 24). Additionally, the sequence of the PKR/eIF-2␣ phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of >4 mutations in the PKRBD region was associated with SVR (P ‫؍‬ 0.001) and early virologic responses (EVR; 12 weeks) (P ‫؍‬ 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P ‫؍‬ 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n ‫؍‬ 23) region was well conserved. The presence of >4 mutations in the PKRBD region (odds ratio [OR] ‫؍‬ 9.9; P ‫؍‬ 0.006) and an age of <40 years (OR ‫؍‬ 3.2; P ‫؍‬ 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P ‫؍‬ 0.05). The genetic variability in the PKRBD (>4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.

No abstract

In conclusion, the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon.

Background There is scarce evidence on fourth doses of SARS-CoV-2 vaccines in chronic kidney disease (CKD) patients. We have evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. Methods This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analyzed factors associated to persistent negative humoral response and to higher anti-Spike antibody titers as well as the efficacy of vaccination on COVID-19 severity. Results Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titers in HD (P = 0.001) and ND-CKD (P = 0.014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titers at 12 months were independently associated to repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titers and not being a KT. Breakthrough COVID-19 was registered in 137 (6%) patients, of whom 5% required admission. Admitted patients had prior titers below 620 UI/ml and median values were lower (P = 0.020) than in non-admitted patients. Conclusions A fourth vaccine dose increased anti-Spike antibody titers or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titers or KT recipients) derived the least benefit in terms of antibody titers. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titers.

No abstract