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

Background Interferon lambda 3 (IFN-lambda 3) 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-lambda 3. 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-lambda 3 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-lambda 3 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.