Successful HCV Therapy Reduces Liver Disease Severity and Inflammation Biomarkers in HIV/HCV-Coinfected Patients With Advanced Cirrhosis: A Cohort Study

Medrano, Luz María; Berenguer, Juan; Salgüero, Sergio; González-García, Juan; Díez, Cristina; Hontañón, Víctor; García-Broncano, Pilar; Ibáñez‐Samaniego, Luis; Bellón, José M.; Jiménez-Sousa, María Ángeles; Resino, Salvador

doi:10.3389/fmed.2021.615342

Cited by 15 publications

(11 citation statements)

References 49 publications

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“…Regarding HIV/HCV-coinfected patients, there are limited data on their status following DAA therapy. However, some of our findings are similar to those described in previous studies showing improved liver function ( 56 – 61 ) and a decrease in plasma chemokine levels (CXCL10, CCL2, and CXCL8) ( 45 , 62 – 66 ). Chemokines attract leucocytes to the liver, promoting cirrhosis and the appearance of LRE ( 67 ), and they are surrogate markers of liver inflammation ( 68 ).…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 92%

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

et al. 2021

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“…The introduction of both HAART for HIV-1 infection and DAAs against HCV has significantly improved the prognosis of HIV/HCV co-infected patients with ESLD [ 1 , 2 , 3 , 7 , 8 , 9 , 10 , 11 ]. However, reinfection of graft is practically inevitable in HCV positive transplanted patients and the presence of co-infection with HIV makes the evolution towards fibrosis more rapid [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…The introduction of direct-acting antiviral agents (DAAs) against HCV has significantly improved the prognosis of HCV/HIV co-infected patients undergoing liver transplantation for end stage liver disease (ESLD) [ 7 , 8 , 9 , 10 , 11 ]. However, recent studies have suggested that DAA-mediated HCV eradication could represent an impediment to HIV reservoir elimination in coinfected patients [ 4 , 12 ], and that DAA treatment does not completely normalize immune and liver functions as well as the risk of hepatocellular carcinoma development [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Reinfection of Transplanted Livers in HCV- and HCV/HIV-Infected Patients Is Characterized by a Different MicroRNA Expression Profile

Dalla

Bulfoni

Cesselli

et al. 2022

Cells

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Background: After liver transplantation, HCV/HIV co-infected patients present, compared to the HCV mono-infected ones, increased HCV viral load, rapid progression to liver fibrosis and higher mortality. Liver biopsies (LB), obtained routinely 6 months after transplantation, represent a unique model to assess the early events related to graft re-infection. Here, we used miRNA sequencing of LB obtained from both HCV-and HCV/HIV-infected recipients, to identify transcriptional profiles able to explain the more severe outcome of these latter. Methods: miRNAs of 3 healthy livers, 3 HCV-LB and 3 HCV/HIV-LB were sequenced by Illumina HiSeq2500 platform. The DIANA-miRPath v3.0 webserver and DIANA-microT-CDS algorithm (v5.0) were used to characterize the functions of differentially expressed (DE-) miRNAs, querying the KEGG and Gene Ontology-Biological Process databases. Results: LB obtained from infected patients were characterized, with respect to controls, by a miRNA profile related to viral infection, immune system signaling and DNA damage in HCV-induced carcinogenesis. Instead, HCV-LB and HCV/HIV-LB differed in the expression of miRNAs involved in immunological and apoptotic processes and in extracellular matrix remodeling. Conclusions: liver reinfection processes are associated with early miRNA changes. Further studies are necessary to establish their prognostic role and possible actionability.

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“…However, whether the improved clinical outcomes of DAA coincide with better immunological outcomes is still unclear. There is good evidence that SVR reduces the rate of progression to cirrhosis and lowers levels of soluble inflammatory biomarkers in cirrhotics [61], an indication that HCV clearance is directly responsible for improvement in both liver tissue integrity and hepatic immune homeostatic function, with far reaching effects on systemic immunity.…”

Section: Liver Cirrhosis Is Associated With Altered Immune Homeostasismentioning

confidence: 99%

Variable Normalization of Naïve CD4+ Lymphopenia and Markers of Monocyte and T Cell Activation over the Course of Direct-Acting Anti-Viral Treatment of Chronic Hepatitis C Virus Infection

Auma

Shive

Kostadinova³

et al. 2021

Viruses

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Chronic hepatitis C virus (HCV) infection is associated with naïve CD4+ T cell lymphopenia and long-standing/persistent elevation of cellular and soluble immune activation parameters, the latter heightened in the setting of HIV co-infection. The underlying mechanisms are not completely understood. However, we recently reported that accelerated peripheral cell death may contribute to naïve CD4+ T cell loss and that mechanistic relationships between monocyte activation, T cell activation, and soluble inflammatory mediators may also contribute. Chronic HCV infection can be cured by direct-acting anti-viral (DAA) therapy, and success is defined as sustained virological response (SVR, undetectable HCV RNA (ribonucleic acid) at 12 weeks after DAA treatment completion). However, there is no general consensus on the short-term and long-term immunological outcomes of DAA therapy. Here, we consolidate previous reports on the partial normalization of naïve CD4+ lymphopenia and T cell immune activation and the apparent irreversibility of monocyte activation following DAA therapy in HCV infected and HCV/HIV co-infected individuals. Further, advanced age and cirrhosis are associated with delayed or abrogation of immune reconstitution after DAA therapy, an indication that non-viral factors also likely contribute to host immune dysregulation in HCV infection.

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Successful HCV Therapy Reduces Liver Disease Severity and Inflammation Biomarkers in HIV/HCV-Coinfected Patients With Advanced Cirrhosis: A Cohort Study

Cited by 15 publications

References 49 publications

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

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

Reinfection of Transplanted Livers in HCV- and HCV/HIV-Infected Patients Is Characterized by a Different MicroRNA Expression Profile

Variable Normalization of Naïve CD4+ Lymphopenia and Markers of Monocyte and T Cell Activation over the Course of Direct-Acting Anti-Viral Treatment of Chronic Hepatitis C Virus Infection

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