IFNL4 rs368234815 and rs117648444 variants predict off-treatment HBsAg seroclearance in IFN-treated HBeAg-negative chronic hepatitis B patients

Enrico Galmozzi, Floriana Facchetti, Glenda Grossi, Alessandro Loglio, Mauro Viganò, Giovanna Lunghi, Massimo Colombo, Pietro Lampertico

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND & AIM: Robust baseline predictors of interferon (IFN) response in HBeAg-negative chronic hepatitis B (CHB) patients are not currently available. The recently described rs368234815 TT/ΔG dinucleotide and rs117648444 nonsynonymous P70S polymorphisms in IFN lambda 4 (IFNL4) gene, which are strongly associated with response to IFN in hepatitis C virus (HCV) infection, could be also useful in IFN-treated CHB patients. Here we assessed whether IFNL4 rs368234815 and rs117648444 polymorphisms predict IFN-induced HBsAg clearance in CHB patients.

METHODS: We sequenced the IFNL4 gene on genomic DNA collected from 126 HBeAg-negative CHB patients treated with IFN and followed up for a median of 11 (1-23) years.

RESULTS: The 15-year cumulative probability of HBsAg loss in the 62 carriers of the rs368234815 TT/TT genotype, which abolishes the IFNλ4 protein production, was comparable to that of 19 patients carrying the rs117648444 T allele predicted to produce an impaired IFNλ4-S70 protein (39% vs 42%, P  =  .827). In contrast, these 81 patients, either not producing IFNλ4 or producing an impaired IFNλ4-S70 protein, had a significantly higher 15-year probability of HBsAg loss compared to the 45 subjects predicted to encode only the fully functional IFNλ4-P70 (42% vs 11% P = .003). At multivariate analysis, combination of the rs368234815 and rs117648444 genotypes strongly predicted HBsAg clearance (HR 5.90, 95% CI 1.70-20.9, P = .006) together with pretreatment serum HBV DNA levels (HR 0.57, 95% CI 0.39-0.83, P = .003).

CONCLUSION: IFNL4 rs368234815 and rs117648444 functional variants are worth to be investigated as pretreatment combined predictors of IFN response in HBeAg-negative CHB patients.

Original languageEnglish
Pages (from-to)417-423
Number of pages7
JournalLiver International
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 2018

Keywords

  • Journal Article

Fingerprint Dive into the research topics of 'IFNL4 rs368234815 and rs117648444 variants predict off-treatment HBsAg seroclearance in IFN-treated HBeAg-negative chronic hepatitis B patients'. Together they form a unique fingerprint.

Cite this