il6 gene allelespecific cebpbinding activity affects the development of hbv infection through modulation of th17treg balance interleukin6 il6 has an important role in the pathogenesis of chronic viral hepatitis and related liver diseases although host genetics associated with the response to antiviral treatment have been reported little is known about the relationship between il6 genetic polymorphisms and the outcome of hepatitis b virus hbv infection in this study we determined the genotype distribution of rs1800796 polymorphism in healthy controls and cases including chronic hbv chb hepatitis c virus and hiv infection the rs1800796 was found to be associated with clinical outcome of chb in experimental and validation cohort the rs1800796c allele has twofold higher promoter activity than g allele consistently cd14 monocytes from subjects carrying the rs1800796c allele produced more il6 in response to in vitro hbv core antigen stimulation than those carrying g allele moreover chb patients carrying rs1800796c allele have significantly higher thelper 17 th17 and regulatory t cell treg ratio finally a transcription factor cebp binds in higher affinity to rs1800796c allele than to g allele these results suggest that genetic predisposition to higher il6 production is associated with increased risk to hbv infection and hepatic inflammation which might be due to cebpmediated regulatory effect on th17 and treg responses appropriate manipulation of il6 expression might be used to prevent and treat hbv infection