IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study

Abstract

Background and purposeContradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients.MethodsA total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records.Results2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G)1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection.ConclusionThis large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle East.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3663-6) contains supplementary material, which is available to authorized users.

An in vitro diagnostic certified point of care single nucleotide test for IL28B polymorphisms

“…In countries where healthcare budgets do not currently support these treatments it remains an open question as to whether clinicians will continue to use interferon-based treatments where IL28B testing could play an important role. Additionally, IL28B polymorphisms have been reported to be predictive for transition to cirrhosis [ 21 ], fibrosis [ 22 ], hepatocellular carcinoma [ 23 ],[ 24 ], and potentially to influence clinical responses in HBV infection [ 25 ], HAV infection [ 26 ] and glucose metabolism in type 2 diabetes [ 27 ]. Furthermore due to the distinct global distribution of IL28B alleles, and the fact that IL28B has the highest reported diversity of all interferon subtypes having undergone positive selection in European and African populations [ 28 ], it seems likely that IL28B polymorphisms are important determinants in other pathological situations.…”

Real life rates of sustained virological response (SVR) and predictors of relapse following DAA treatment in genotype 3 (GT3) patients with advanced fibrosis/cirrhosis

“…IL28BCC and PNPLA3GG genetic polymorphisms are considered predictors either of treatment response or progression of steatosis. In more detail, rs12979860 IL28BCC polymorphism has been associated with both, higher responses to IFN-based therapies and advanced disease in chronic HCV infection [ 8 , 9 ]. PNPLA3 encoding hydrolase against triglycerides and retinyl esters in hepatic stellate cells is associated with genetic variability.…”

Association of interferon lambda-4 rs12979860 polymorphism with hepatocellular carcinoma in patients with chronic hepatitis C infection

“…A large international study involving 2916 patients, mostly the European Caucasian population, revealed that the increased number of the T allele was significantly associated with the prevalence of cirrhosis/transition to cirrhosis in patients infected with HCV genotype 1. This association was evident in Caucasian European patients but not in Asian, Latin American, or Middle Eastern patients infected with HCV genotype 1[ 26 ].…”