A Polymorphism Near IL28B Is Associated With Spontaneous Clearance of Acute Hepatitis C Virus and Jaundice
Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA. Gastroenterology
(Impact Factor: 16.72).
11/2010; 139(5):1586-92, 1592.e1. DOI: 10.1053/j.gastro.2010.07.005
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.
Available from: Jason Grebely
- " 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"
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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.
Available from: PubMed Central
- "IFNλ includes IFNλ 1, 2 and 3, also known as IL29, IL28A, and IL28B.43 Several studies24,44–48 have shown that single nucleotide polymorphisms (SNPs) in the IL28B region may play a critical role in determining the outcome of acute infection (clearance versus persistence). A strong association has been found between polymorphisms in or near IL28B, the pathogenesis of HCV, and outcome of acute HCV infection. "
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ABSTRACT: Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon-alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies.
Available from: Manfred Wiese
- "A large HCV genotype 1b single source outbreak after immunization of about 3000 women with virus contaminated anti-D immunoglobulin occurred in East Germany in 1978–1979 . Samples from this anti-D cohort were collected since 2008 by members of the East German HCV study group . The HCV RNA–positive samples from 91 of these patients were randomly selected  and included in this study. "
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ABSTRACT: No information is available on the possible influence of the genetic heterogeneity of major hepatitis C virus (HCV) cell receptors on selection of virus variants.
Anti-D globulin preparations contaminated with the HCV strain AD78 caused hepatitis C infection in more than 3000 women in East Germany in 1978. Analysis of the core to NS2 gene sequences of this strain in several globulin batches revealed the presence of three closely related but distinct virus variants of the same strain. Apparently even distribution of these three virus variants was observed in 91 patients infected with the AD78 strain. None of these patients was infected with more than one virus variant, suggesting a selection mechanism of a particular virus variant in each patient. To verify the hypothesis that heterogeneity of HCV cell receptors might influence the virus variant selection, single-nucleotide polymorphisms (SNPs) in low-density lipoprotein receptor (LDLR), occludin (OCLN), and scavenger receptor B1 (SCARB1) genes in AD patients were analyzed. No evident correlation between receptor polymorphisms and presence of a particular virus variant was noted.
SNPs of HCV cell entry receptors have no influence on virus selection in patients infected with an inoculum containing different virus variants.
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