A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice.
ABSTRACT A single nucleotide polymorphism (SNP) upstream of the IL28B gene has been associated with response of patients with chronic hepatitis C to therapy with pegylated interferon and ribavirin and also with spontaneous clearance of acute hepatitis C in a heterogeneous population. We analyzed the association between IL28B and the clinical presentation of acute hepatitis C virus (HCV) infection in a homogeneous population.
We analyzed the SNP rs12979860 in 190 women from the German anti-D cohort (infected with HCV genotype 1b via contaminated rhesus prophylaxis) and its association with spontaneous clearance. Clinical data were available in 136 women with acute infection who were also evaluated for IL28B genotype. Based on results of a TaqMan polymerase chain reaction assay, the rs12979860 SNP genotypes studied were C/C, C/T, or T/T.
Spontaneous clearance was more common in patients with the C/C genotype (43/67; 64%) compared with C/T (22/90; 24%) or T/T (2/33; 6%) (P < .001). Jaundice during acute infection was more common among patients with C/C genotype (32.7%) than non-C/C patients (with C/T or T/T) (16.1%; P = .032). In C/C patients, jaundice during acute infection was not associated with an increased chance of spontaneous clearance (56.3%) compared with those without jaundice (60.6%). In contrast, in non-C/C patients, jaundice was associated with a higher likelihood of spontaneous clearance (42.9%) compared with those without jaundice (13.7%).
The SNP rs12979860 upstream of IL28B is associated with spontaneous clearance of HCV. Women with the C/T or T/T genotype who did not develop jaundice had a lower chance of spontaneous clearance of HCV infection.
- SourceAvailable from: Jason Grebely
[Show abstract] [Hide abstract]
- " level [ Liu et al . , 2012 ] , early viral load decline [ Thomson et al . , 2011 ] , and HCV genotype [ Grebely et al . , 2014 ] ) , demographic features ( age [ Zhang et al . , 2006 ; Garten et al . , 2008 ] , gender [ Micallef et al . , 2006 ; Page et al . , 2009 ; Grebely et al . , 2014 ] ) , and host genetic ( IFNL3 [ Grebely et al . , 2010 ; Tillmann et al . , 2010 ; Grebely et al . , 2014 ] , IFNL4 [ Prokunina - Olsson et al . , 2013 ] , HLA DQB1 Ã 03 : 01 [ Duggal et al . , 2013 ] ) and biomarkers ( IP - 10 [ Grebely et al . , 2013a ] ) , as all these factors have been associated with spontaneous clearance . This study has some limitations . Most of the individuals with detectable HCV RNA at enr"
ABSTRACT: Understanding viral dynamics during acute hepatitis C virus (HCV) infection can provide important insights into immunopathogenesis and guide early treatment. The aim of this study was to investigate the dynamics of HCV RNA and alanine transaminase (ALT) levels during recent HCV infection in the Australian Trial in Acute Hepatitis C (ATAHC). ATAHC was a prospective study of the natural history of recently acquired HCV infection. Longitudinal HCV RNA and ALT levels were compared among individuals with persistent infection and spontaneous clearance. Among those with HCV persistence (n = 104) and HCV clearance (n = 30), median HCV RNA (5.2 vs. 4.1 log IU/ml, respectively) and ALT levels (779 vs. 1,765 IU/L, respectively) were high during month two following infection, and then declined during months three and four in both groups. Among those with HCV persistence, median HCV RNA was 2.9 log IU/ml during months four, increased to 5.5 log IU/ml during month five, and remained subsequently relatively stable. Among those with HCV clearance, median HCV RNA was undetectable by month five. Median HCV RNA levels were comparable between individuals with HCV persistence and HCV clearance during month three following infection (3.2 vs. 3.5 log IU/ml, respectively; P = 0.935), but markedly different during month five (5.5 vs. 1.0 log IU/ml, respectively; P < 0.001). In conclusion, dynamics of HCV RNA levels in those with HCV clearance and HCV persistence diverged between months three and five following infection, with the latter time-point being potentially useful for commencing early treatment. J. Med. Virol. © 2014 Wiley Periodicals, Inc.Journal of Medical Virology 10/2014; 86(10). DOI:10.1002/jmv.24010 · 2.22 Impact Factor
[Show abstract] [Hide abstract]
- "While there are known host factors that can determine the infection outcome of an HCV infection (Ge et al. 2009; Thomas et al. 2009; Rauch et al. 2010; Tillmann et al. 2010), there currently exists very little information on how virus genetics affect the infection outcome. Using a phylogenetic method combined with data from an Australian prisoner cohort, we showed that diversity in the virus genotype could partly explain diversity in the infection out- come. "
ABSTRACT: Infection by hepatitis C virus (HCV) leads to one of two outcomes; either the infection resolves within approximately 6 months or the virus can persist indefinitely. Host genetics are known to affect the likelihood of clearance or persistence. By contrast, the importance of the virus genotype in determining infection outcome is unknown, as quantifying this effect traditionally requires well-characterized transmission networks, which are rare. Extending phylogenetic approaches previously developed to estimate the virus control over set-point viral load in HIV-1 infections, we simulate inheritance of a binary trait along a phylogenetic tree, use this data to quantify how infection outcomes cluster and ascertain the effect of virus genotype on these. We apply our method to the Hepatitis C Incidence and Transmission Study in prisons (HITS-p) data set from Australia, as this cohort prospectively identified incident cases including viraemic subjects who ultimately clear the virus, thus providing us with a unique collection of sequences from clearing infections. We detect significant correlations between infection outcome and virus distance in the phylogeny for viruses of Genotype 1, with estimates lying at around 67%. No statistically significant estimates were obtained for viruses of Genotype 3a.Evolutionary Applications 03/2014; 7(5). DOI:10.1111/eva.12151 · 4.57 Impact Factor
[Show abstract] [Hide abstract]
- ". Previously published studies have demonstrated a role of the IL-28B rs12979860 polymorphism in predicting both spontaneous and treatment-induced HCV clearance [Ge et al., 2009; Thomas et al., 2009; McCarthy et al., 2010; Montes-Cano et al., 2010; Thompson et al., 2010; Tillmann et al., 2010]. However, it is conceivable that the factors related to natural or pharmacologically induced HCV clearance, such as serum cholesterol [Ramcharran et al., 2010] and the IL-28B rs12979860 polymorphism [McCarthy et al., 2010; Tillmann et al., 2010], could also be involved in the natural course of chronic HCV infection, at least in patients with persistently normal or near-normal levels of transaminases in whom no other strong predictors of fibrosis progression have been identified. In fact, IL-28B seems to play a central role in the immune response to viral infections [Ank et al., 2006a]; in particular, in a differentiated murine hepatocyte cell, line IFN-l inhibits HBV replication with kinetics and efficiency similar to those of Type I IFNs [Robek et al., 2005]. "
ABSTRACT: The interleukin 28B (IL-28B) rs12979860 C/T polymorphism is a predictor of spontaneous and treatment-induced hepatitis C virus (HCV) clearance. The C/C genotype is associated with higher serum cholesterol, predictor of a favorable outcome in chronic hepatitis C. Whether IL-28B polymorphism and serum cholesterol play a role in modulating the history of mild hepatitis C is unknown. To clarify this issue, 93 untreated patients infected with HCV with normal or near-normal transaminases and an initial Ishak staging score ≤1 were investigated retrospectively in the longitudinal study (median histological follow-up of 10 years). An additional confirmatory cohort of 143 patients with chronic HCV infection and abnormal levels of transaminases was evaluated in the cross-sectional study. In the longitudinal study, at the end of follow-up, Ishak staging scores progressed more frequently among carriers of a T/* allele who had a baseline serum cholesterol ≤175 mg/dl than in remaining patients: 6/36 (change ≤0), 15/45 (change 1-2), 6/12 (change ≥3), improvement chi-square P < 0.02, OR 3.1, 95% C.I. 1.3-7.7. In the cross-sectional study, the frequency of patients carrying the T/T genotype or serum cholesterol values ≤175 mg/dl increased starting from those with a staging score ≤2 (36/76, 47.4%), to those with a staging score of 3-4 (26/41, 63.4%) and to those with a staging score of 5-6 (20/26, 76.9%, P < 0.01 for linear trend). In conclusion, the interaction between IL-28B rs12979860 T/T genotype and low serum cholesterol concentration is an independent predictor of a worse disease course among patients infected with HCV with normal or near-normal transaminases.Journal of Medical Virology 05/2012; 84(5):747-55. DOI:10.1002/jmv.23259 · 2.22 Impact Factor