Epidemiological trend of hepatitis C-related liver events in Spain (2000-2015): A nationwide population-based study.

Analysis the epidemiological trends of hospital admissions, intra-hospital deaths, and costs related to chronic hepatitis C (CHC) taking into account four major clinical stages [compensated cirrhosis (CC), end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), and liver transplantation (LT)] in Spain. Retrospective study in patients with chronic hepatitis C and a hospital admission in the Spanish Minimum Basic Data Set from 2000 to 2015. Outcome variables were admission, death, length of hospital stay and costs. A total of 868,523 hospital admissions with CHC (25.5% CC, 25.3% ESLD, 8.6% HCC, and 2.5% LT) were identified. Overall rates of admission and mortality increased from 2000-2003 to 2004-2007, but after 2008, these rates stabilized and/or decreased. An upward trend was found for hospitalization percentage in CC (from 22.3% to 30%; p < 0.001), ESLD (from 23.9% to 27.1%; p < 0.001), HCC (from 7.4% to 11%; p < 0.001), and LT (from 0.07% to 0.10%; p = 0.003). An upward trend was also found for case fatality rate, except in ESLD (p = 0.944). Gender and age influenced the evolution of hospitalization rates and mortality differently. The length of hospital stay showed a significant downward trend in all strata analyzed (p < 0.001). Cost per patient had a significant upward trend (p < 0.001), except in LT, and a decrease from 2008-2011 to 2012-2015 in CC (p = 0.025), HCC (p < 0.001), and LT (p = 0.050) was found. The initial upward trend of the disease burden in CHC has changed from 2000 to 2015 in Spain, improving in many parameters after 2004-2007, particularly in the 2012-2015 calendar period.This work has been supported by grantsfrom “Instituto de Salud Carlos III” (PI15CIII/00031, PI18CIII/00047). The study was also funded by the RD16CIII/0002/0002 project as part of the Plan Nacional R + D + I and cofoundedby ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional(FEDER).S

Nanotechnology: A reality for diagnosis of HCV infectious disease.

Hepatitis C virus (HCV) is the primary etiologic agent of liver cirrhosis or hepatocellular carcinoma. HCV elevated infection rates are mostly due to the lack of an accurate and accessible screening and diagnosis, especially in low- and middle-income countries. Conventional HCV diagnostic algorithm consists of a serological test followed by a nucleic acid test. This sequence of tests is time consuming and not affordable for low-resource settings. Nanotechnology have introduced new promising tests for the diagnose of infectious diseases. Based on the employment of nanoparticles and other nanomaterials which lead to highly sensitive and specific nanoscale tests, most of them target pathogen genome. Implementation of nanoscale tests, which are affordable, portable and easy to use by non-specialized personal, would improve HCV diagnosis algorithm. In this review, we have summed up the current emerging nanotechnology tools, which will improve actual screening and treatment programs, and help to reach HCV elimination proposal.Financial support was provided by the Community of Madrid , call for grants for the completion of Industrial Ph.D. to VB and RM ( IND2017/BMD-7683 ).S

Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study

Relevant resistance-associated substitutions (RASs) to elbasvir, the new HCV NS5A inhibitor, may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are few data outside clinical trials evaluating their prevalence and impact of elbasvir/grazoprevir. A multicenter cross-sectional study of 617 HCV-GT1a-infected individuals attended in 84 Spanish hospitals from the 17 Autonomous Communities and two Autonomous cities was performed. HCV population sequencing was used to identify RASs to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-GT1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%; respectively). Only 3.4% of patients had viruses with RASs that confer reduced susceptibility to elbasvir by geno2pheno [HCV] that identified exclusively the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations considered as RASs to elbasvir. Lower prevalence of RASs to elbasvir in our HCV-GT1a-Spanish cohort was observed than reported previously in clinical trials. This information may be essential to guiding the implementation of elbasvir/grazoprevir in Spain, expected at the beginning of 2017 and the management of GT1a-infected patients.This work was supported by grants from ‘Instituto de Salud Carlos III’ (Ref. PI14CIII/00011 to SR, MPY 1039/14 and PI15CIII/00031 to VB). CP is supported by the Portuguese ‘Fundação para a Ciência e Tecnologia’ (FCT)(grant number SFRH/BPD/77448/2011, part of the EDCTP2 program supported by the European Union). VB is supported by the Miguel Servet program run by the ‘Fondo de Investigación Sanitaria’ (ISCIII) (grant number CP13/00098). MAJS is supported by ‘Instituto de Salud Carlos III’ (grant numbers CD13/00013).S

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm 3 , respectively. CD4+ T nadir cells was 305 cells/mm 3 . Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.Financial support was provided by the Instituto de Salud Carlos III to VB (PI15CIII/00031), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016–78480-R) and The SPANISH AIDS Research Network RD16CIII/0002/0001, RD16CIII/0002/0002 and RD16/0025/0013 - ISCIII – FEDER. MRLP is supported by ISCIII - Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) (PIE 13/00040 and RD12/0017/0017 RETIC de SIDA). C.P. is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/ BPD/77448/2011 is part of the EDCTP2 programme supported by the European Union). V.B., A.F.R. and N.R. are supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098, CP14/CIII/00010 and CP14/00198, respectively)

Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain.

Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5-15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.The Instituto de Salud Carlos III (ISCIII) provided financial support by the Grant (CP13/00098, PI15CIII/00031 and PI18CIII/00020 to VB). CP is financed by national funds via FCT through Norma Transitória—DL57/2016/CP1376/CT0004.S