No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B

Wei, Lai; Wedemeyer, Heiner; Liaw, Yun–Fan; Chan, Henry Lik‐Yuen; Piratvisuth, Teerha; Marcellin, Patrick; Jia, Jidong; Tan, Deming; Chow, Wan-Cheng; Brunetto, M.R.; Diago, M.; Gürel, Selım; Morozov, Viacheslav; He, Hua; Yunfen, Zhu; Wat, Cynthia; Surujbally, Bernadette; Thompson, Alexander

doi:10.1371/journal.pone.0199198

Cited by 7 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, a major scientific finding via GWAS was that variations in the IL28B gene are strongly associated with treatment outcome in patients with chronic hepatitis C . Although few studies proposed IL28B plays a similar role in CHB, and other studies show no association, these findings were not validated in the present study. Further, we did not identify SLC16AP as being associated with PEG‐IFN response, a result which is contrary to a previous report of an association with HBsAg clearance in a small cohort of patients treated with PEG‐IFN and adefovir .…”

Section: Discussioncontrasting

confidence: 56%

“…Very few GWAS have explored the impact of host genetic factors on treatment response in CHB patients. While variations in the IL28B gene have been shown to be strongly associated with spontaneous (as well as interferon‐induced) viral clearance in patients with chronic hepatitis C, the role for IL28B in the PEG‐IFN response in patients with CHB is unclear . Two studies have suggested that variations in the HLA‐DQA2 and SLC16A9 may be associated with PEG‐IFN response in CHB patients, although both studies were limited in size and the findings have not yet been validated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic variation in FCER1A predicts peginterferon alfa‐2a‐induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B

Wei

Pavlović

Bansal³

et al. 2019

Journal of Viral Hepatitis

Self Cite

View full text Add to dashboard Cite

In a multicentre, genome‐wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa‐2a for ≥ 24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post‐treatment, using serological and/or virological endpoints. Thirty‐six single‐marker analyses and a gene‐by‐gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome‐wide significance (P < 5 × 10−8) in single‐marker analyses, but suggestive associations (P < 1 × 10−5) were identified for 116 SNPs. In gene‐by‐gene analyses, one gene, FCER1A (rs7549785), reached genome‐wide significance (P = 2.65 × 10−8) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intragenic association was for rs7712322 (POLR3G, P = 7.21 × 10−7). POLR3G encodes the G subunit of the polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa‐2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted (clinicaltrials.gov number NCT01855997).

show abstract

Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Genetic variation in FCER1A predicts peginterferon alfa‐2a‐induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B

Wei

Pavlović

Bansal³

et al. 2019

Journal of Viral Hepatitis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Unlike HCV infection, the relevance of IL28B SNPs to the treatment efficacy of PEG-IFN in patients with HBV infection remains controversial [29,30], and no genetic factors have been confirmed to influence the effects of PEG-IFN therapy in HBV-infected Asian patients [3]. Our results may provide some new insights into factors predicting the effects of PEG-IFN therapy for HBV infection, although the precise mechanism remains to be clarified.…”

Section: Discussionmentioning

confidence: 82%

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients

Enomoto

Aizawa

Hasegawa

et al. 2020

IJMS

View full text Add to dashboard Cite

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0 × 10−4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

show abstract

“…After screening the titles and abstracts, 40 full-text articles were assessed for eligibility. Finally, 13 studies involving 2,510 patients were included in the meta-analysis (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)27). These included studies were published between 2011 and 2020, with sample sizes ranging from 52 to 701.…”

Section: Study Characteristicsmentioning

confidence: 99%

Interleukin-28B Polymorphisms Predict the Efficacy of Peginterferon Alpha in Patients With Chronic Hepatitis B: A Meta-Analysis

Ying

Gao

et al. 2021

Front. Med.

View full text Add to dashboard Cite

Background: Polyethylene glycol interferon alpha (PEG-IFN-α) is the most frequently used pharmacotherapeutic approach in patients infected with hepatitis B virus (HBV). Numerous studies have reported that interleukin-28B (IL-28B) genetic polymorphisms are related to the therapeutic efficacy of PEG-IFN-α, but the results are inconsistent. The present meta-analysis aimed to analyze the association between IL-28B genetic polymorphisms and the prognosis of patients with chronic hepatitis B (CHB) treated with PEG-IFN-α to inform clinical practice.Methods: PubMed, EBSCO, and Scopus databases were searched for relevant literature published before February 30, 2021. We calculated the crude odds ratios (ORs) with 95% confidence intervals (CIs) of the cited articles. A total of 2510 patients with CHB treated with PEG-IFN-α in 13 clinical cohort studies were analyzed.Results: The overall analysis demonstrated a potential association between IL-28B genetic polymorphisms and response to PEG-IFN-α; however, the association was not statistically significant. Furthermore, the subgroup analysis revealed that among patients with HBeAg-negative CHB, the rs12979860 CC genotype and rs8099917 TT genotype were associated with more significant treatment response to PEG-IFN-α (CC vs. non-CC: OR 2.78, 95% CI 1.00–7.76, I2 = 83%; TT vs. non-TT: OR 2.16, 95% CI 1.35–3.48, I2 = 0%). Among Asian patients with CHB, the rs12979860 CC genotype was associated with a more significant treatment response to PEG-IFN (CC vs. non-CC: OR 1.88, 95% CI 1.18–2.99, I2 = 0%).Conclusion: This meta-analysis revealed that the IL-28B rs12979860 CC genotype and rs8099917 TT genotype indicated a better treatment response than non-CC and non-TT genotypes for PEG-IFN-α in patients with CHB.

show abstract

No association between IFNL3 (IL28B) genotype and response to peginterferon alfa-2a in HBeAg-positive or -negative chronic hepatitis B

Cited by 7 publications

References 38 publications

Genetic variation in FCER1A predicts peginterferon alfa‐2a‐induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B

Genetic variation in FCER1A predicts peginterferon alfa‐2a‐induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients

Interleukin-28B Polymorphisms Predict the Efficacy of Peginterferon Alpha in Patients With Chronic Hepatitis B: A Meta-Analysis

Contact Info

Product

Resources

About