studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 703A
multi-color flowcytometry we analyzed frequency and function
of Tregs and effector T cells before and at the end of treatment
(treatment week (TW) 12) from HCV-patients after succesful
HCV elimination with sofosbuvir (SOF) in combination with
IFN plus ribavirin (n=14) versus patients treated with SOF plus
daclatasvir (DCV) and simeprevir (SMV), respectively (n=14).
In addition, we measured serum levels of immunomodulatory
cytokines. Results: Unlike IFN-free therapy, treatment with SOF
plus IFN significantly increased numbers of peripheral Tregs
(% Foxp3 + CD25 + CD4 + T cells TW0 vs. TW12 (MW±SD):
5.5±2.0 vs. 7.2±2.4; p90%) of sustained
virological response at week 12 (SVR12) in patients with
HCV infection genotype 4 (Abergel et al. ILC 2015, J Hepatol
2015; 62 (Suppl 2):S219; Poordad et al. ILC 2015, J Hepatol
2015; 62 (Suppl 2):S261). In the former study, two of the three
patients with virological relapse had a genotype 4r subtype.
In the later, NS5A variants were found at baseline in 4 out of
13 patients with virologic failure and in 13 out of 13 patients
at failure. In addition, the number of pre-treatment baseline
RAPs (Resistance Associated Polymorphisms) was associated
with virological failure in a study conducted by Sarrazin et
al. (AASLD, Hepatology 2014; 60 (Suppl) 1128A). Aim: The
objective of this study was to assess the NS5A natural polymorphisms
of the genotype 4 subtypes in order to investigate
the potential role of subtypes and RAPs in treatment outcome
with regimens containing an NS5A inhibitor. Methods: We
collected from the NCBI, European, and Japanese HCV databases,
47 HCV NS5A Genotype 4 sequences and proceeded
to multiple Sequence Alignment using Clustal W2. We analyzed
16 subtype 4a, 7 subtype 4b, 3 subtype 4d, 2 subtype
4m, 3 subtype 4o and 16 subtype 4r (no 4c or 4f were available).
We assessed the prevalence by subtypes of the main
RAPs: L28M, L30R, L31M, P58T and Y93H. Results: Seventy
five percent of the 16 genotype 4r strains included 2 RAPs
(L30R and L31M), in comparison with the 16 genotype 4a
which had only one RAP in all of the strains included (L31M)
(p