<i><scp>IFNL</scp>4</i> rs368234815 and rs117648444 variants predict off‐treatment <scp>HB</scp>sAg seroclearance in <scp>IFN</scp>‐treated <scp>HB</scp>eAg‐negative chronic hepatitis B patients

Galmozzi, E.; Facchetti, F.; Grossi, G.; Loglio, Alessandro; Viganò, Mauro; Lunghi, G.; Colombo, Massimo; Lampertico, Pietro

doi:10.1111/liv.13526

Cited by 10 publications

(7 citation statements)

References 37 publications

(95 reference statements)

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“…Because only the rs368234815-dG allele provides functional significance to rs117648444, this marker should not be tested alone. The combination of rs368234815 and rs117648444 improved and explained the association with viral clearance and expression of interferon-stimulated genes, providing support for the primary causal role of IFN-λ4 and its variants in these associations (Galmozzi and Aghemo 2014; Terczynska-Dyla and others 2014; Bhushan and others 2017; Bhushan and Chinnaswamy 2018; Galmozzi and others 2018).…”

Section: Introductionmentioning

confidence: 85%

Genetics of the Human Interferon Lambda Region

Prokunina‐Olsson

2019

Journal of Interferon & Cytokine Research

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Humans are polymorphic in their ability to produce type-III interferons. Most individuals of African ancestry are genetically capable of generating all 4 type-III interferons (IFN-λ1, 2, 3, and 4), whereas the majority of individuals of European and Asian ancestry lack IFN-λ4 and thus can generate only IFN-λ1, 2, and 3. All 4 type-III IFNs are encoded by genes located within a ∼55 kb genomic region on human chromosome 19. Although IFN-λ4 appears to be important in animals, genetic alterations acquired in the Hominidae lineage, and particularly in humans, resulted in the elimination of IFN-λ4 or restriction of its activity, suggesting that IFN-λ4 function might be detrimental to human health. Genetic variants within the IFNL region, including those controlling production and activity of IFN-λ4, have been strongly associated with clearance of hepatitis C virus (HCV) infection. There is growing evidence for association of the same genetic variants with a multitude of other disease conditions. This article reviews the genetic landscape of the human IFNL genetic locus, with an emphasis on the genetic control of IFN-λ4 production and activity, and its association with viral clearance.

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Section: Introductionmentioning

confidence: 85%

Genetics of the Human Interferon Lambda Region

Prokunina‐Olsson

2019

Journal of Interferon & Cytokine Research

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“…IFNλ4 rs368234815 and rs117648444 variants were reported to strongly predict HBsAg clearance in 126 HBeAg-negative patients treated with IFN and followed up for a median of 11 years. 11 This study reported that the 15-year cumulative probability of HBsAg loss in the 62 carriers of the rs368234815 TT/TT genotype, which abolishes IFNλ4 protein production and in the 19 patients carrying the rs117648444 T allele, which produces an impaired IFNλ4-S70 protein, was significantly higher than in the 45 subjects who encoded only the fully functional IFNλ4-P70 (42% vs 11%, P = .003).…”

Section: Key Pointsmentioning

confidence: 80%

“…However, the preliminary observations of an association between favorable IFNλ4 polymorphisms and increased chances of a sustained virological and serological response in both HBeAg‐positive and ‐negative patients were not confirmed in subsequent studies . Recently, IFNλ4 rs368234815 and rs117648444 variants were reported to strongly predict HBsAg clearance in 126 HBeAg‐negative patients treated with IFN and followed up for a median of 11 years . This study reported that the 15‐year cumulative probability of HBsAg loss in the 62 carriers of the rs368234815 TT/TT genotype, which abolishes IFNλ4 protein production and in the 19 patients carrying the rs117648444 T allele, which produces an impaired IFNλ4‐S70 protein, was significantly higher than in the 45 subjects who encoded only the fully functional IFNλ4‐P70 (42% vs 11%, P = .003).…”

Section: Peg‐ifn In Nuc‐naïve Patientsmentioning

confidence: 94%

Treatment of hepatitis B: Is there still a role for interferon?

Viganò

Grossi

Loglio

et al. 2018

Liver International

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The goal of antiviral therapy in patients with chronic hepatitis B (CHB)is to improve quality of life and survival by preventing the progression of liver disease and early liver-related deaths. This can be achieved by sustained or maintained suppression of hepatitis B virus (HBV) replication either by pegylated interferon (Peg-IFN) or with nucleot(s) ide analogues (NUCs), i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and recently approved tenofovir alafenamide (TAF).

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“…However, a three-way interaction was identified between IFNL4/HLA-DQ and HBV infection with a multifactor dimensionality reduction test ( Fan et al, 2016 ). Two SNPs and in the IFNL4 gene, which was also analyzed in this study, could predict IFN treatment response in HBeAg-negative HBV patients ( Galmozzi et al, 2018 ). Similar to our results, SNPs in the IFNL4 gene could not influence the reaction of Thai HBV patients to PEG-IFN ( Limothai et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China

Zheng

Shen

Xia

et al. 2022

PeerJ

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Hepatitis B virus (HBV) infection causes Hepatitis B, which is one of the most common causes of hepatocellular carcinoma (HCC). The single nucleotide polymorphisms (SNPs) of the host immune genes could impact HBV infection, viral clearance, and treatment effect. However, the contradictory roles of several studies suggest further analysis of various populations. The whole blood and biochemical indexes of 448 HBV patients and matched controls were collected from the Yunnan population to investigate the genetic roles of IFNL4 and the downstream genes (MxA and MxB). The genotypes, alleles, and haplotypes frequencies of the seven SNPs (rs11322783, rs117648444, rs2071430, rs17000900, rs9982944, rs408825, and rs2838029) from the HBV patients and controls were analyzed. However, no association was identified between the SNPs and HBV infection. Then, biochemical index levels were evaluated among the HBV patients with different genotypes of the seven SNPs. The results indicated that the liver function index levels (including alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), and albumin (ALB)) were influenced by the genotypes of the SNPs in HBV patients. Moreover, when the HBV patients were divided into HBsAg-positive and -negative groups, the association between the SNP genotypes and the biochemical indexes still existed. In addition, although the genetic polymorphisms in the IFNL4, MxA, and MxB genes were not significantly associated with HBV infection in the Yunnan population, these genes could indirectly influence disease progression by associating with the biochemical index levels of Yunnan HBV patients.

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

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

Cited by 10 publications

References 37 publications

Genetics of the Human Interferon Lambda Region

Genetics of the Human Interferon Lambda Region

Treatment of hepatitis B: Is there still a role for interferon?

Genetic polymorphisms in the IFNL4, MxA, and MxB genes were associated with biochemical index of chronic HBV patients from Yunnan, China

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