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Responder Interferon ? Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV-Hepatitis C Virus Coinfection.

ABSTRACT: Liver fibrosis progresses faster in individuals coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Interferon ?3 (IFN-?3) has both antiviral and proinflammatory properties. Genotypes at IFNL single-nucleotide proteins (SNPs; rs12979860CC and rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFN-? genotypes and significant liver fibrosis in HIV-HCV coinfection.From the prospective Canadian Co-infection Cohort (n = 1423), HCV RNA-positive participants in whom IFN-? genotypes were detected and who were free of fibrosis, end-stage liver disease, and chronic hepatitis B at baseline (n = 485) were included. Time to significant fibrosis (defined as an aspartate transaminase level to platelet count ratio index [APRI] of ?1.5) by IFN-? genotypes was analyzed using Cox proportional hazards, with adjustment for age, sex, ethnicity, alcohol use, CD4(+) T-cell count, HCV genotype, ?-glutamyl transferase level, and baseline APRI. Haplotype analysis was performed, with adjustment for ethnicity.A total of 125 participants developed fibrosis over 1595 person-years (7.84 cases/100 person-years; 95% confidence interval [CI], 6.58-9.34 cases/100 person-years). Each genotype was associated with an increased fibrosis risk, with adjusted hazard ratios of 1.37 (95% CI, .94-2.02) for rs12979860CC, 1.34 (95% CI, .91-1.97) for rs8103142TT, and 1.79 (95% CI, 1.24-2.57) for rs8099917TT. Haplotype TCT was also linked with a higher risk (hazard ratio, 1.14 [95% CI, .73-1.77]).IFN-? SNPs rs12979860, rs8099917, and rs81013142 were individually linked to higher rates of fibrosis in individuals with HIV-HCV coinfection. IFN-? genotypes may be useful to target HCV treatments to people who are at higher risk of liver disease.

SUBMITTER: Moqueet N

PROVIDER: S-EPMC4907413 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Responder Interferon λ Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV-Hepatitis C Virus Coinfection.

Moqueet Nasheed N Cooper Curtis C Gill John J Hull Mark M Platt Robert W RW Klein Marina B MB

The Journal of infectious diseases 20160316 1

<h4>Background</h4>Liver fibrosis progresses faster in individuals coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Interferon λ3 (IFN-λ3) has both antiviral and proinflammatory properties. Genotypes at IFNL single-nucleotide proteins (SNPs; rs12979860CC and rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFN-λ genotypes and significant liver fibrosis in HIV-HCV coinfection.<h4>Methods</h4>From the pr ...[more]

PMID: 26984148

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Project description:BACKGROUND:Higher levels of small low-density lipoprotein (LDL) and lower levels of high-density lipoprotein (HDL) subclasses have been associated with increased risk of cardiovascular disease. The extent to which HIV infection and HIV/hepatitis C virus (HCV) coinfection are associated with abnormalities of lipoprotein subclasses is unknown. METHODS:Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy in plasma samples from 569 HIV-infected and 5948 control participants in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM), Coronary Artery Risk Development in Young Adults (CARDIA), and Multi-Ethnic Study of Atherosclerosis (MESA) studies. Multivariable regression was used to estimate the association of HIV and HIV/HCV coinfection with lipoprotein measures with adjustment for demographics, lifestyle factors, and waist-to-hip ratio. RESULTS:Relative to controls, small LDL levels were higher in HIV-monoinfected persons (+381?nmol/l, P?<0.0001), with no increase seen in HIV/HCV coinfection (-16.6?nmol/l). Levels of large LDL levels were lower (-196?nmol/l, P?<0.0001) and small HDL were higher (+8.2??mol/l, P?<?0.0001) in HIV monoinfection with intermediate values seen in HIV/HCV coinfection. Large HDL levels were higher in HIV/HCV-coinfected persons relative to controls (+1.70??mol/l, P?<0.0001), whereas little difference was seen in HIV-monoinfected persons (+0.33, P?=?0.075). Within HIV-infected participants, HCV was associated independently with lower levels of small LDL (-329?nmol/l, P?<0.0001) and small HDL (-4.6??mol/l, P?<0.0001), even after adjusting for demographic and traditional cardiovascular risk factors. CONCLUSION:HIV-monoinfected participants had worse levels of atherogenic LDL lipoprotein subclasses compared with controls. HIV/HCV coinfection attenuates these changes, perhaps by altering hepatic factors affecting lipoprotein production and/or metabolism. The effect of HIV/HCV coinfection on atherosclerosis and the clinical consequences of low small subclasses remain to be determined.

Dataset Information

Responder Interferon ? Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV-Hepatitis C Virus Coinfection.

Publications

Responder Interferon λ Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV-Hepatitis C Virus Coinfection.

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