PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study.

Corrigendum to "PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study" [Biomed. Pharmacother. 159 (2023) 114220]. Biomed Pharmacother. 2023 Apr 27;114803. doi: 10.1016/j.biopha.2023.114803. PMID: 37120412.Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 and PI18CIII/00028 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, PI18CIII/00020 to AFR, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovación (AEI, PID2021-126781OB-I00 to AFR). The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (CB21/13/00044).S

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients

Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways ("cytokine-cytokine receptor interaction", "viral protein interaction with cytokine and cytokine receptor", "chemokine signaling pathway", and "hepatitis C"). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.This study was supported by grants from Instituto de Salud Carlos III (ISCII; grant numbers PI20/00474 and PI17/00657 to JB, PI20/00507 and PI17/00903 to JGG, PI18CIII/00020 to AF-R, PI18CIII/00028 to MA, and PI20CIII/00004 and PI17CIII/00003 to SR). AF-R and MA are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MAJS). The study was also funded by the RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002 projects as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Ref. INT16/00100. DS-C is a ‘Sara Borrell’ researcher from ISCIII (grant number CD20CIII/00001) and has also been supported through Fundación SEIMC-GESIDA by a fellowship award from Fundación ONCE ‘Oportunidad al Talento, 2019/20 and 2020/21’ co-financed by Fondo Social Europeo.S

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV‐coinfected and HCV‐monoinfected patients

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis. A cross-sectional study was carried out in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score). The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV- and HCV-infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7). Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 (MPY407/18) and PI18CIII/00028 (MPY385/18) to MAJS, PI14/01094 and PI17/00657 to JB, PI14/01581 and PI17/00903 to JGG, and PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11‐241). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT16/00100. CB and DR acknowledge funding from the Ministerio de Ciencia, Innovación y Universidades (RTI2018‐095166‐B‐I00).S

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients.

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis. A cross-sectional study was carried out in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score). The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV- and HCV-infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7). Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 (MPY407/18) and PI18CIII/00028 (MPY385/18) to MAJS, PI14/01094 and PI17/00657 to JB, PI14/01581 and PI17/00903 to JGG, and PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11‐241). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT16/00100. CB and DR acknowledge funding from the Ministerio de Ciencia, Innovación y Universidades (RTI2018‐095166‐B‐I00).S

Notes for genera – Ascomycota

Knowledge of the relationships and thus the classification of fungi, has developed rapidly with increasingly widespread use of molecular techniques, over the past 10--15 years, and continues to accelerate. Several genera have been found to be polyphyletic, and their generic concepts have subsequently been emended. New names have thus been introduced for species which are phylogenetically distinct from the type species of particular genera. The ending of the separate naming of morphs of the same species in 2011, has also caused changes in fungal generic names. In order to facilitate access to all important changes, it was desirable to compile these in a single document. The present article provides a list of generic names of Ascomycota (approximately 6500 accepted names published to the end of 2016), including those which are lichen-forming. Notes and summaries of the changes since the last edition of `Ainsworth Bisby's Dictionary of the Fungi' in 2008 are provided. The notes include the number of accepted species, classification, type species (with location of the type material), culture availability, life-styles, distribution, and selected publications that have appeared since 2008. This work is intended to provide the foundation for updating the ascomycete component of the ``Without prejudice list of generic names of Fungi'' published in 2013, which will be developed into a list of protected generic names. This will be subjected to the XIXth International Botanical Congress in Shenzhen in July 2017 agreeing to a modification in the rules relating to protected lists, and scrutiny by procedures determined by the Nomenclature Committee for Fungi (NCF). The previously invalidly published generic names Barriopsis, Collophora (as Collophorina), Cryomyces, Dematiopleospora, Heterospora (as Heterosporicola), Lithophila, Palmomyces (as Palmaria) and Saxomyces are validated, as are two previously invalid family names, Bartaliniaceae and Wiesneriomycetaceae. Four species of Lalaria, which were invalidly published are transferred to Taphrina and validated as new combinations. Catenomycopsis Tibell Constant. is reduced under Chaenothecopsis Vain., while Dichomera Cooke is reduced under Botryosphaeria Ces. De Not. (Art. 59)