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Hepatology
Novel host genetic variations associated with spontaneous clearance of a single-source outbreak of HCV1b infections
  1. Hong You1,
  2. Sandu Liu2,
  3. Yong Xie3,
  4. Rui Cong1,
  5. Yameng Sun1,
  6. Jingjing Ren4,
  7. Kangfei Wei4,
  8. Xin Jin4,
  9. Yujian Shi4,
  10. Haiying Zhang5,
  11. Jie Li6,
  12. Lai Wei5,
  13. Hui Zhuang6,
  14. Mingliang Cheng7,
  15. Jidong Jia1
  1. 1Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, China
  2. 2Department of Infectious Diseases, Qiannan People's Hospital, Guizhou, China
  3. 3Department of Infectious Diseases, Pingtang People's Hospital, Guizhou, China
  4. 4Beijing Genomic Institute, Shenzhen, Guangdong, China
  5. 5Hepatology Institute, Peking University People's Hospital, Beijing, China
  6. 6Department of Microbiology, Peking University Health Science Center, Beijing, China
  7. 7Department of Infectious Diseases, Guiyang Medical College, Guizhou, China
  1. Correspondence to Dr Mingliang Cheng; chengml@21cn.com, Dr Jidong Jia; jia_jd{at}ccmu.edu.cn

Abstract

Background and aims A total of 105 patients were identified as accidentally infected with hepatitis C virus genotype 1b (HCV1b) through blood transfusion from a single blood donor. This group provides a unique patient population to study host factors involved in the spontaneous clearance of HCV and disease progression.

Methods Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance.

Results Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9–12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10−5).

Conclusions Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance.

  • HCV
  • GENETICS
  • CHRONIC HEPATITIS

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjgast-2014-000010

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