Responder Interferon Lambda genotypes are associated with higher risk of liver fibrosis in HIV-Hepatitis C Virus Co-infection.

2016 | J Infect Dis

Topic(s): Hepatitis |

Abstract:

BACKGROUND:

Liver fibrosis progresses faster in HIV-HCV co-infected individuals. Interferon Lambda 3 (IFNL3) protein has both antiviral and pro-inflammatory properties. Genotypes at IFNL SNPs (rs12979860CC, rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFNL genotypes and significant liver fibrosis in HIV-HCV co-infection.

METHODS:

From the prospective Canadian Co-infection Cohort (n=1423), HCV RNA-positive participants with IFNL genotypes, free of fibrosis, end-stage liver disease and chronic Hepatitis B at baseline (n=485) were included. Time to significant fibrosis (AST-to-platelet ratio index (APRI) ≥1.5) by IFNL genotypes was analyzed using Cox proportional hazards, adjusting for age, sex, ethnicity, alcohol use, CD4 count, HCV genotype, GGT and baseline APRI. Haplotype analysis was performed, adjusting for ethnicity.

RESULTS:

125 participants developed fibrosis over 1595 person-years (7.84/100 person-years, 95% CI: 6.58, 9.34). Each genotype increased fibrosis risk (aHR [95% CI]): rs12979860CC, 1.37 [0.94, 2.02]; rs8103142TT, 1.34 [0.91, 1.97]; rs8099917TT, 1.79 [1.24, 2.57]. Haplotype TCT was also linked with higher risk, 1.14 [0.73, 1.77].

CONCLUSIONS:

IFNL SNPs rs12979860, rs8099917 and rs81013142 were individually linked to higher rate of fibrosis in HIV-HCV co-infection. IFNL genotypes may be useful to target HCV treatments to those who are at higher risk of liver disease.

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Moqueet N

BC Centre for Excellence in HIV/AIDS

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Responder Interferon Lambda genotypes are associated with higher risk of liver fibrosis in HIV-Hepatitis C Virus Co-infection.

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