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

<div><p>Background & aims</p><p>It has yet to be firmly established whether host <i>IFNL3</i> (<i>IL28B</i>) genotype influences interferon responsiveness in patients with chronic hepatitis B. We investigated associations between single-nucleotide polymorphisms (SNPs) in the <i>IFNL3</i> region and response to peginterferon alfa-2a in 701 patients enrolled in three large, randomized, international studies.</p><p>Methods</p><p>Responses were defined as hepatitis B surface antigen (HBsAg) loss and/or hepatitis B e antigen (HBeAg) seroconversion plus hepatitis B virus (HBV) DNA <2000 IU/ml in HBeAg-positive patients, and HBsAg loss and/or HBV DNA <2000 IU/ml in HBeAg-negative patients (24 weeks after end of treatment). Associations between treatment response and the number of copies of the poor-response allele at three SNPs (rs8099917, rs12980275, rs12979860) were explored with logistic regression models in Asian and white patients.</p><p>Results</p><p>The HBeAg-positive and -negative populations comprised 465 (92% Asian, 50% HBV genotype C) and 236 (79% Asian, 41% HBV genotype C) patients, respectively, and had respective response rates of 26% and 47%. The <i>IFNL3</i> genotype was strongly associated with ethnicity. There was no association between <i>IFNL3</i> genotype and treatment response in HBeAg-positive or -negative patients. Independent predictors of treatment response were: sex, HBV DNA level and alanine aminotransferase level in HBeAg-positive Asian patients; age in HBeAg-negative Asian patients; and HBV DNA in HBeAg-negative white patients.</p><p>Conclusions</p><p>This is the largest analysis to date of associations between <i>IFNL3</i> genotype and peginterferon response in patients with chronic hepatitis B. The data suggest that <i>IFNL3</i> polymorphism is not a major determinant of the response to peginterferon alfa-2a in either HBeAg-positive or HBeAg-negative patients.</p></div

Rates of HBeAg seroconversion in HBeAg-positive patients according to genotype at rs12980275, rs12979860, and rs8099917.

<p>Some patients did not have data available for all genotypes, and percentages are calculated on the basis of the number of patients with data.</p

Response rates according to host <i>IFNL3</i> genotype.

<p>Response rates according to genotype at rs12980275, rs12979860, and rs8099917 in HBeAg-positive Asian (A) and white (B) patients, and in HBeAg-negative Asian (C) and white (D) patients. Some patients did not have data available for all genotypes, and response rates are calculated on the basis of the number of patients with data.</p

Demographic and clinical characteristics of patients Included in the analyses.

<p>Demographic and clinical characteristics of patients Included in the analyses.</p

Associations between baseline covariates and treatment outcome in univariate logistic regression analyses.

<p>Associations are shown for HBeAg-positive Asian (A) and white (B) patients, and in HBeAg-negative Asian (C) and white (D) patients. ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus. After adjusting for significant baseline covariates, there were no statistically significant associations between <i>IFNL3</i> genotypes and response in the final logistic regression models (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199198#pone.0199198.g003" target="_blank">Fig 3</a>).</p

Associations between baseline covariates and treatment outcome in multivariate logistic regression analyses.

<p>Associations are shown for HBeAg-positive (A) and HBeAg-negative (B) patients. ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus.</p