Premium
IFNL 4 rs368234815 and rs117648444 variants predict off‐treatment HB sAg seroclearance in IFN ‐treated HB eAg‐negative chronic hepatitis B patients
Author(s) -
Galmozzi Enrico,
Facchetti Floriana,
Grossi Glenda,
Loglio Alessandro,
Viganò Mauro,
Lunghi Giovanna,
Colombo Massimo,
Lampertico Pietro
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13526
Subject(s) - hbsag , medicine , nonsynonymous substitution , interferon , genotype , hbeag , immunology , gastroenterology , allele , hepatitis b virus , gene , virus , biology , genetics , genome
Abstract Background & Aim Robust baseline predictors of interferon ( IFN ) response in HB eAg‐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 ( IFNL 4 ) 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 IFNL 4 rs368234815 and rs117648444 polymorphisms predict IFN ‐induced HB sAg clearance in CHB patients. Methods We sequenced the IFNL 4 gene on genomic DNA collected from 126 HB eAg‐negative CHB patients treated with IFN and followed up for a median of 11 (1‐23) years. Results The 15‐year cumulative probability of HB sAg loss in the 62 carriers of the rs368234815 TT / TT genotype, which abolishes the IFN λ4 protein production, was comparable to that of 19 patients carrying the rs117648444 T allele predicted to produce an impaired IFN λ4‐S70 protein (39% vs 42%, P = .827). In contrast, these 81 patients, either not producing IFN λ4 or producing an impaired IFN λ4‐S70 protein, had a significantly higher 15‐year probability of HB sAg loss compared to the 45 subjects predicted to encode only the fully functional IFN λ4‐P70 (42% vs 11% P = .003). At multivariate analysis, combination of the rs368234815 and rs117648444 genotypes strongly predicted HB sAg 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 IFNL 4 rs368234815 and rs117648444 functional variants are worth to be investigated as pretreatment combined predictors of IFN response in HB eAg‐negative CHB patients.