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Low Complement C4 Predicts Improvement of Kidney Function After Direct-Acting Antiviral Therapy for Hepatitis C Virus

Meghan E Sise1, Ian Strohbehn2, Donald Chute2

  • 1Division of Nephrology Department of Medicine Massachusetts General Hospital Boston MA.

Hepatology Communications
|August 9, 2020
PubMed

Insights

Direct-acting antiviral therapies (DAAs) can improve kidney function in patients with hepatitis C virus (HCV) and chronic kidney disease (CKD). Low complement component 4 (C4) levels before treatment may predict this improvement, suggesting C4 as a marker for kidney dysfunction.

Area of Science:

  • Nephrology
  • Hepatology
  • Immunology

Background:

  • Hepatitis C virus (HCV) infection is associated with chronic kidney disease (CKD).
  • Direct-acting antiviral therapies (DAAs) are effective for HCV, but their impact on HCV-mediated kidney dysfunction requires further understanding.
  • Proteinuria is a key indicator of kidney damage in CKD patients with HCV.

Purpose of the Study:

  • To identify baseline predictors of proteinuria improvement following DAA treatment in patients with HCV and proteinuric CKD.
  • To evaluate the role of complement system biomarkers, specifically C3 and C4, in predicting kidney function changes after DAAs.
  • To assess the association between baseline complement component 4 (C4) levels and estimated glomerular filtration rate (eGFR) changes post-DAA therapy.

Main Methods:

  • A single-arm, pilot clinical trial using ledipasvir/sofosbuvir for HCV genotypes 1 or 4 and proteinuric CKD.
  • Measurement of plasma complement biomarkers (C3, C4) and urinary kidney injury biomarkers at multiple time points.
  • A retrospective cohort study analyzing C4 levels and eGFR changes before and after DAAs in patients with CKD and HCV.

Main Results:

  • In the pilot trial, 80% of patients achieved sustained virologic response. Patients with low baseline C4 showed improved proteinuria and urinary biomarkers.
  • The retrospective study included 50 patients; 40% had low baseline C4.
  • Patients with low baseline C4 demonstrated a significant improvement in eGFR (+3.4 mL/min/1.73 m²) compared to those with normal C4 (-4.4 mL/min/1.73 m²; P=0.028).

Conclusions:

  • Low baseline C4 may serve as a predictive marker for kidney function improvement in patients with HCV-related CKD treated with DAAs.
  • DAA therapy can lead to significant improvements in kidney function for specific patient subgroups with HCV and CKD.
  • Complement component 4 warrants further investigation as a biomarker in HCV-associated kidney disease.

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