Hepatitis C virus-associated tubulointerstitial injury

Am J Kidney Dis. 2003 Apr;41(4):767-75. doi: 10.1016/s0272-6386(03)00024-6.


Background: Tubulointerstitial damage is recognized as a determinant of the prognosis of kidney disease. Various types of viral infection have been reported to induce tubulointerstitial lesions; however, that caused by hepatitis C virus (HCV) remains unclear, although glomerular lesions caused by this viral infection have been well documented.

Methods: To identify any association, we retrospectively investigated 320 patients who underwent renal biopsy and did not have extrarenal diseases causing tubulointerstitial nephritis.

Results: Of these patients, 13 patients had HCV infection and 307 patients did not. In a case-control study, HCV infection showed a significant association with the prevalence of tubulointerstitial injury. To offset the secondary tubulointerstitial change caused by advanced glomerulopathy, we performed a glomerular stage-matched comparison of patients with membranous nephropathy (MN). Nine patients with MN among the 13 HCV-infected patients and 18 HCV-negative patients with electron microscopic glomerular stage-matched MN were randomly selected from the overall pool of patients. Comparing areas of interstitial fibrosis and inflammatory cell infiltration, both were greater in HCV-infected than HCV-negative patients. In biopsy tissues from HCV-infected patients, positive signal for HCV was observed in the perinuclear area of tubular epithelial cells and infiltrating cells on immunohistochemistry and in situ hybridization. By a strand-specific reverse-transcription polymerase chain reaction for HCV, both genomic- and replicative-strand RNA were detected in renal tissues.

Conclusion: These results suggest that HCV infection is a potent pathogenic factor of tubulointerstitial injury.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Case-Control Studies
  • Female
  • Glomerulonephritis / epidemiology
  • Glomerulonephritis / pathology
  • Glomerulonephritis, Membranous / epidemiology
  • Glomerulonephritis, Membranous / pathology
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepacivirus / isolation & purification
  • Hepatitis C / complications*
  • Hepatitis C / epidemiology
  • Hepatitis C / virology
  • Hepatitis C Antibodies / blood
  • Hepatitis C Antigens / analysis
  • Humans
  • Japan / epidemiology
  • Kidney Glomerulus / pathology
  • Male
  • Middle Aged
  • Nephritis, Interstitial / epidemiology
  • Nephritis, Interstitial / etiology*
  • Nephritis, Interstitial / pathology
  • Nephritis, Interstitial / virology
  • Prevalence
  • RNA, Viral / analysis
  • Retrospective Studies


  • Hepatitis C Antibodies
  • Hepatitis C Antigens
  • RNA, Viral