<i><scp>IL</scp>28<scp>B</scp></i> genotype is not useful for predicting treatment outcome in <scp>A</scp>sian chronic hepatitis <scp>B</scp> patients treated with pegylated interferon‐α

Holmes, Jacinta A; Nguyen, Thang; Ratnam, Dilip; Heerasing, Neel; Tehan, Jane V.; Bonanzinga, Sara; Dev, Anouk; Bell, Sally; Pianko, Stephen; Chen, Robert; Visvanathan, Kumar; Hammond, R.; Iser, David; Rusli, Ferry; Sievert, William; Desmond, Paul; Bowden, D. Scott; Thompson, Alexander

doi:10.1111/jgh.12110

Cited by 41 publications

(16 citation statements)

References 32 publications

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“…Other previous studies tried to determine whether having favourable IL28B genotype markers is associated with a better response to interferon therapy in HBeAg-negative adult patients, but the results were inconclusive. Some reports have suggested that the presence of favourable IL28B genotypes is associated with a better response to treatment[31,37], while others have indicated that there is no association between IL28B SNPs and the response to treatment with interferon[26,38]. In the present study, we demonstrated a statistically significant relationship between the rs12979860 marker and the response to treatment with interferon in patients with CHB.…”

Section: Discussionsupporting

confidence: 55%

“…To evaluate the therapeutic effects, we assessed virological, serological and biochemical responses by analysing HBV DNA levels, HBsAg status and ALT activity before, during and 24 wk after the end of therapy. A limit of 2000 IU HBV DNA/mL, which has been used in the literature, was adopted in the virological response analysis[26]. In our study, we determined the impact of genetic markers on the efficacy of therapy by comparing patients in terms of achieving a defined therapeutic response.…”

Section: Methodsmentioning

confidence: 99%

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Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Domagalski¹,

Pawłowska²,

Zaleśna³

et al. 2016

WJG

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AIMTo investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODSWe enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.RESULTSThe PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed.CONCLUSIONIL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.

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Section: Discussionsupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Domagalski¹,

Pawłowska²,

Zaleśna³

et al. 2016

WJG

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“…Holmes et al . retrospectively analysed the role of IFN‐λ3 rs12979860 in 96 Australian patients (62% HBeAg‐positive) treated with 48 weeks of PegIFN and followed up for 39 months . The majority of the patients (84%) carried CC genotype, whereas 15% and 1% carried CT and TT genotype, respectively, with similar frequency of CC genotype according to HBeAg status (85% and 83%).…”

Section: Host Genetics and Response To Ifn Therapymentioning

confidence: 99%

Systematic review with meta‐analysis: do interferon lambda 3 polymorphisms predict the outcome of interferon‐therapy in hepatitis B infection?

Galmozzi

Viganò

Lampertico

2014

Aliment Pharmacol Ther

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Summary Background Interferon lambda 3 (IFN‐λ3) polymorphisms are the strongest genetic predictor of outcome of hepatitis C virus infection and of response to Pegylated interferon (PegIFN)‐based therapy. Whether this holds true for hepatitis B virus (HBV) infection is matter of controversy. Aim To review the association between host genomics and spontaneous or interferon‐induced clearance of HBV with specific reference to the recently identified interleukin 28B gene now renamed IFN‐λ3. Methods A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and abstracts using free text words and combinations of the following terms ‘IL28B’, ‘IFN lambda’, ‘genomics’, ‘hepatitis B virus’, ‘interferon’ ‘GWAS’, ‘treatment’, ‘SNPs’, ‘HLA’, ‘polymorphisms’. Results Genome‐wide association studies convincingly demonstrated an association between SNPs in the HLA locus and spontaneous resolution of HBV infection in subgroups of Asian patients, yet no information is available for Caucasians. The preliminary observations of an association between IFN‐λ3 SNP and virological and serological responses to IFN in both HBeAg‐positive and ‐negative patients could not be replicated by subsequent studies. Yet, majority of studies performed so far suffer several limitations in terms of sample size, selection of the patients, endpoints of therapy, treatment strategies and duration of follow‐up. Conclusions While host genetics is associated with an increased likelihood of spontaneous clearance of HBV among genotype B/C patients, the relationship between IFN‐λ3 polymorphisms and response to IFN has not been confirmed. Further studies in large cohorts of homogeneous patients are required, before this genetic test can be recommended in clinical practice.

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“…A report published by Holmes et al (2013) showed that IL28B genotype (rs12979860) is not a useful predicting marker for treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α. The study includes very small number of patients as well control subjects.…”

Section: Dear Editormentioning

confidence: 99%

IL-28B Genetic Analysis And HBV Disease Association Studies With Small Number Study Subjects; Should We Rely On Results?

Afzal

2017

Journal of Gastroenterology and Hepatology Research

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Hepatitis B Virus (HBV) is one of the leading cause of cirrhosis and hepatocellular carcinoma worldwide. The virus has 10 different genotypes and has a specific geographic distribution for each genotype. Viral genotypes and certain mutations in the viral genome are associated with differential clinical features and therapeutic response. It is also evident that during HBV infection certain host genetic factors play major role in determining the outcome of infection and also impact the outcomes of antiviral therapy. IL28B plays an important role in the outcome of HBV infection and it could inhibit the viral replication. There are some functional genetic variants in IL28B gene which regulate the expression of IL28B. These genetic variants played significant role in predicting

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IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon‐α

Abstract: In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.

Cited by 41 publications

References 32 publications

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Systematic review with meta‐analysis: do interferon lambda 3 polymorphisms predict the outcome of interferon‐therapy in hepatitis B infection?

IL-28B Genetic Analysis And HBV Disease Association Studies With Small Number Study Subjects; Should We Rely On Results?

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