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Role of complement component C4 in treatment response and disease progression in chronic hepatitis C patients

S J Chowdhury1,2, V K Karra1, R Bharali2

  • 1Department of Medicine, Maulana Azad Medical College, Delhi University, New Delhi, India.

Journal of Viral Hepatitis
|January 10, 2015
PubMed

Insights

Low C4 complement levels and a specific C4 gene variant (rs2857009 CC genotype) predict poor response to hepatitis C treatment. A new score combining C4 levels and protein can predict successful treatment outcomes.

Area of Science:

  • Immunology
  • Virology
  • Genetics

Background:

  • Hepatitis C virus (HCV) immune evasion mechanisms and treatment response remain unclear.
  • Previous studies link complement component 4 (C4) levels to HCV persistence and disease progression.

Purpose of the Study:

  • To investigate the relationship between serum C4 levels, its functional single nucleotide polymorphisms (SNPs), and treatment response in patients with chronic hepatitis C (CHC).

Main Methods:

  • Studied 84 CHC patients and 75 healthy controls.
  • Assessed C4 expression (mRNA and protein) using Real-time PCR and ELISA.
  • Genotyped functional C4 SNPs (rs2857009) using Amplification Refractory Mutation System-Polymerase Chain Reaction (AS-PCR).

Main Results:

  • Significantly lower baseline C4 levels in CHC patients compared to healthy controls (P < 0.001).
  • The rs2857009 CC genotype was associated with reduced C4 mRNA and protein expression.
  • Baseline C4 serum level and total protein were independent predictors of treatment response; a score of ≥ 0.542 predicted positive response.
  • Increased age, rs2857009 SNP, and HCV genotype correlated with disease progression.

Conclusions:

  • The rs2857009 CC genotype is linked to decreased C4 expression and potentially poorer treatment outcomes in CHC.
  • Serum C4 levels and total protein can serve as independent predictors for hepatitis C treatment response.
  • A novel predictive score incorporating these factors may aid in identifying patients likely to respond to treatment.

Keywords:
chronic hepatitis Ccomplement system component 4fibrosisrs2857009treatment response

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