Gastroenterology

Gastroenterology

Volume 139, Issue 5, November 2010, Pages 1586-1592.e1
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
A Polymorphism Near IL28B Is Associated With Spontaneous Clearance of Acute Hepatitis C Virus and Jaundice

https://doi.org/10.1053/j.gastro.2010.07.005Get rights and content

Background & Aims

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.

Methods

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.

Results

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%).

Conclusions

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.

Section snippets

Study Population

Between 1978 and 1979, Rhesus factor–negative women were exposed to contaminated batches and anti-D prophylaxis in the former German Democratic Republic. At least 2867 women had documented exposure. A 25-year follow-up study evaluated liver-related outcome in a total of 1980 of the original 2867 women; of these 1980 women, only 48% developed chronic hepatitis, 52% had a self-limited infection, 7% had no acute hepatitis and no proof of infection, and 45% were identified as having self-limited

Patient Characteristics

The mean age at infection was 24.6 ± 4 years, with no significant difference among patients with C/C, C/T, or T/T genotypes, which was similar to the earlier reports on this cohort.15, 16 All were white female patients who were postpartum or who had undergone a therapeutic or spontaneous abortion and were from a limited geographic area with similar socioeconomic living conditions. No patients were or are currently known to be coinfected with human immunodeficiency virus or hepatitis B virus. No

Discussion

We describe a strikingly significant difference in spontaneous hepatitis C viral clearance rates in the women from the East German anti-D cohort associated with a recently described SNP in close association with the IL28B gene. This confirms and accentuates the findings of Thomas et al and Rauch et al because the association of IL28B with spontaneous clearance seemed more pronounced, although not statistically different, in our study compared with those described by Thomas et al and Rauch et al

Acknowledgments

The authors thank Karen Pieper and Dongliang Ge for their helpful statistical advice and discussion.

Members of the German anti-D Study Group include Rüdiger Behrens (Halle), Thomas Berg (Berlin, Leipzig), Silvio Frimmel (Rostock), Wolfgang Klemm (Cottbus), Micha Loebermann (Rostock), Edeltraud Meyer-Siegert (Berlin), Ute Oesen (Chemnitz), Norbert Steudel (Halle), Tatjana Walther (Chemnitz), Viola Weich (Berlin), Sven Wollschläger (Dresden), Alexander Zipprich (Halle), Michael Roggendorf

References (21)

There are more references available in the full text version of this article.

Cited by (293)

  • Hepatitis C: epidemiology, natural history, and diagnosis

    2023, Comprehensive Guide to Hepatitis Advances
  • Is the conquest of Hepatitis C imminent?

    2019, Expert Reviews in Molecular Medicine
View all citing articles on Scopus

Conflicts of interest The authors disclose the following: Drs Thompson, Shianna, McHutchison, and Goldstein are coinventors of a patent in relation to IL28B polymorphism and treatment response. The remaining authors disclose no conflicts.

Funding Supported by the German “Network of Competence for Hepatitis” (now Deutsche Leberstiftung; H.L.T., H.T., J.N., and U.S.), Wilhelm Sander Stiftung Project 2009.045.1 (J.T. and J.N.), the Duke Clinical Research Institute (H.L.T., A.J.T., K.P., and J.G.M.), and the Duke Institute for Genomic Science and Policy (K.V.S. and D.B.G.). A.J.T. also received funding support from the Richard B. Boebel Family Fund, the National Health and Medical Research Council of Australia, the Gastroenterological Society of Australia, and the Royal Australasian College of Physicians.

View full text