Spontaneous hepatitis C viral clearance and hepatitis C chronic infection are associated with distinct cytokine profiles in Mexican patients

Fierro, Nora A.; González-Aldaco, Karina; Torres-Valadez, Rafael; Trujillo-Trujillo, Maria E.; Román, Sonia; Trujillo-Ochoa, Jorge L; Panduro, Arturo

doi:10.1590/0074-02760140377

Cited by 16 publications

(6 citation statements)

References 18 publications

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“…In this setting, we have explored the lipid profile of SC and CHC patients, but similar to miRNA results, both profiles were similar with no statistically significant differences among them. Similar results were found in a small study on CHC and SC Mexican patients [40], where both groups showed similarities in lipid profile but differences in liver enzymes and cytokines. However, a lipidomic analysis on the serum of HCV-resistant cases showed clear differences from HCV antibody-positive individuals, even those who clear viremia either spontaneously or after antiviral therapy [41].…”

Section: Discussionsupporting

confidence: 89%

MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

Brochado-Kith

Sanz

Real

et al. 2019

JCM

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Factors involved in the spontaneous cleareance of a hepatitis C (HCV) infection are related to both HCV and the interaction with the host immune system, but little is known about the consequences after a spontaneous resolution. The main HCV extrahepatic reservoir is the peripheral blood mononuclear cells (PBMCs), and their transcriptional profile provides us information of innate and adaptive immune responses against an HCV infection. MicroRNAs regulate the innate and adaptive immune responses, and they are actively involved in the HCV cycle. High Throughput sequencing was used to analyze the miRNA profiles from PBMCs of HCV chronic naïve patients (CHC), individuals that spontaneously clarified HCV (SC), and healthy controls (HC). We did not find any differentially expressed miRNAs between SC and CHC. However, both groups showed similar expression differences (21 miRNAs) with respect to HC. This miRNA signature correctly classifies HCV-exposed (CHC and SC) vs. HC, with the has-miR-21-3p showing the best performance. The potentially targeted molecular pathways by these 21 miRNAs mainly belong to fatty acids pathways, although hippo signaling, extracellular matrix (ECM) interaction, proteoglycans-related, and steroid biosynthesis pathways were also altered. These miRNAs target host genes involved in an HCV infection. Thus, an HCV infection promotes molecular alterations in PBMCs that can be detected after an HCV spontaneous resolution, and the 21-miRNA signature is able to identify HCV-exposed patients (either CHC or SC).

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Section: Discussionsupporting

confidence: 89%

MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

Brochado-Kith

Sanz

Real

et al. 2019

JCM

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“…This could be the reason patients carrying the ∆G allele present greater liver damage. Furthermore, this hypothesis is consistent with recent findings that demonstrated that chronic HCV-infected patients express higher levels of interleukin-8 and RANTES in comparison with those who had SC [ 45 ]. Nonetheless, the impact of IL28B and IFNL4 polymorphisms on HCV-related disease progression is controversial [ 46 – 49 ].…”

Section: Discussionsupporting

confidence: 92%

Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

et al. 2016

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AimTo analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico.MethodsA total of 711 subjects from West Mexico (181 Amerindians and 530 Mestizos) were studied for the prevalence of IL28B (rs12979860C/T, rs8099917G/T) and IFNL4 (rs368234815∆G/TT) genotypes. A case-control study was performed in 234 treatment-naïve HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A real-time PCR assay was used for genotyping, and transitional elastography staged liver damage.ResultsSignificant Fst-values indicated differentiation between the studied populations. The frequencies of the protective C, T, TT alleles were significantly lower in the Amerindians than in Mestizos (p<0.05). The r2 measure of linkage disequilibrium was significant for all variants and the T/G/ΔG risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22–0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10–0.97, p = 0.04) in chronic patients. The Structure software analysis demonstrated no significant differences in ancestry among SC and chronic patients.ConclusionsWest Mexico´s population is genetically heterogeneous at the IL28B/IFNL4 polymorphisms. The T/G/ΔG high-risk haplotype predominated in Amerindians and the beneficial alternative haplotype in Mestizos. The C/T/TT haplotype was associated with SC and less liver damage in chronically infected Mestizo patients.

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“…Until this moment, evidences have suggested that the disrupted pattern of soluble inflammatory mediators induced by HCV infection remains even after viral clearance with DAA treatment, indicating that the inflammatory changes are not fully reversible upon viral clearance [ 11 ]. Increased levels of TGF- β and IL-15 were found in patients who spontaneously cleared HCV infection, while those patients with persistent infection presented elevated levels of CCL-5 and IL-8 [ 30 ]. Considering chemokine set, a decrease in CCL-2, CCL-4, and CXCL-10 levels were reported in HCV genotype 2- and 3-infected patients after antiviral treatment, with lower levels of CCL-4 at baseline associated to an early response to treatment [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C

Saraiva

Rosário

Medeiros

et al. 2018

Mediators of Inflammation

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This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1β, IL-15, IFN-γ, IL-4, IL-10, TGF-β, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-β and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

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Spontaneous hepatitis C viral clearance and hepatitis C chronic infection are associated with distinct cytokine profiles in Mexican patients

Cited by 16 publications

References 18 publications

MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

MicroRNA Profile of HCV Spontaneous Clarified Individuals, Denotes Previous HCV Infection

Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C

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