Genes and hepatitis C: susceptibility, fibrosis progression and response to treatment

Liver Int. 2011 Apr;31(4):443-60. doi: 10.1111/j.1478-3231.2011.02449.x. Epub 2011 Jan 30.

Abstract

Hepatitis C virus contact and infection show three different phenotypes: spontaneous viral clearance (SVC), chronic hepatitis C (CHC) and sustained virological response (SVR) following antiviral treatment. Many factors, including genetics, influence the evolution of these three phenotypes. We performed a literature search (PubMed) up to 31 January 2010 without language restriction to identify relevant studies on genes and hepatitis C. Additional studies were sought by reviewing the reference lists of the identified articles. Meta-analysis (using Meta-disk 1.4) was conducted to evaluate the association of single nucleotide polymorphism (SNP) in the IL28B region and SVR. The candidate gene approach showed strong relationships between human leucocyte antigen class II (DQB1(*) 0301 and DRB1(*) 1101) and SVC. A cirrhosis risk score involving 7 SNPs has been validated recently. The set of odds ratios of studies demonstrated an association between SNP (rs12987960/rs8099917) in the IL28B and SVR in CHC treated with peginterferon plus ribavirin (OR: 4.6; 95% CI: 2.9-7.3). The overall distribution of protective allele correlated with ethnic differences in SVR (Asians, Europeans, Hispanic and Afro-Americans) together with SVC, but not with fibrosis stage or viral load. These polymorphisms did not influence SVR in very-easy-to-treat patients such as genotype 2/3, rapid virological responders or patients with acute hepatitis C. While the genetic fingerprint for fibrosis progression remains elusive, IL28b polymorphism predicts SVC and SVR. However, nearly half of patients achieving SVR did not show favourable genotype. Further genetic signals are warranted to complete the puzzle of factors influencing hepatitis C.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Variation*
  • Genome-Wide Association Study
  • HLA Antigens / genetics
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / pathology*
  • Odds Ratio
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide / genetics
  • Recombinant Proteins
  • Ribavirin / therapeutic use

Substances

  • HLA Antigens
  • interferon-lambda, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b