Hepatitis C Virus



Hepatitis C Virus


Anthony Chang, MD





Key Facts


Terminology



  • Hepatitis C virus (HCV)


  • Wide spectrum of immune complex-mediated glomerular injuries in association with HCV infection


Clinical Issues



  • Over 200 million people worldwide are infected


  • Infected children have high rate of spontaneous resolution


  • 17-55% of HCV-infected patients progress to cirrhosis


  • 2-23% develop HCC


Microscopic Pathology



  • Spectrum of glomerular injury



    • Membranoproliferative glomerulonephritis (MPGN)


    • Cryoglobulinemic GN


    • Membranous glomerulonephritis (MGN)


    • Fibrillary GN


    • Immunotactoid glomerulopathy


    • IgA nephropathy


Top Differential Diagnoses



  • HCV-associated focal segmental glomerulosclerosis


  • Hepatitis B virus-associated immune complex disease


  • Lupus nephritis


  • HIV-associated immune complex disease


Diagnostic Checklist



  • No pathognomonic features for HCV infection


  • Coinfection with HIV is common







Periodic acid-Schiff reveals increased cellularity that highlights the lobularity of the glomerular tufts, which is characteristic of a membranoproliferative injury pattern.






Many double contours of the GBMs image are noted in this patient with cryoglobulins (not shown) and hepatitis C infection.


TERMINOLOGY


Abbreviations



  • Hepatitis C virus (HCV)


Definitions



  • Wide spectrum of immune complex-mediated glomerular injuries in association with HCV infection


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • HCV



    • RNA virus: Single-stranded, positive sense


    • Infects hepatocytes and B lymphocytes


    • Blood-to-blood with rare sexual transmission


  • Unknown pathogenic mechanism of kidney diseases



    • Possible contributing factors include



      • Circulating immune complexes of HCV antigen and antibodies


      • Cryoglobulins


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Over 200 million people worldwide are infected


  • Age



    • Infected children have high rate of spontaneous resolution


  • Gender



    • Young females may spontaneously resolve and are less likely than males to develop cirrhosis or hepatocellular carcinoma (HCC)


Presentation



  • Proteinuria


  • Hematuria


Laboratory Tests



  • Serologic test



    • HCV antibodies


  • PCR



    • HCV viral load


  • HCV genotyping


Natural History



  • 17-55% of HCV-infected patients progress to cirrhosis


  • 2-23% develop HCC


Treatment



  • Drugs



    • Ribavirin


    • Pegylated interferon-α


  • Kidney &/or liver transplantation


Prognosis



  • HCV genotype 2A and 3A have high cure rates


MICROSCOPIC PATHOLOGY


Histologic Features



  • Membranoproliferative glomerulonephritis (MPGN)



    • Accentuation of glomerular tuft/lobules


    • Duplication of glomerular basement membranes or “tram track”


  • Cryoglobulinemic GN



    • Endocapillary hypercellularity


    • “Wire loop” or hyaline “thrombi” deposits



      • PAS positive


  • Membranous glomerulonephritis (MGN)



    • Thickened glomerular basement membranes with subepithelial “spike” formation


  • Fibrillary GN



    • Mesangial expansion


  • Immunotactoid glomerulopathy



    • Mesangial expansion


  • IgA nephropathy



    • Variable mesangial hypercellularity



ANCILLARY TESTS


Immunofluorescence



  • MPGN



    • IgG and C3 granular staining of glomerular capillary walls and mesangial regions


  • Cryoglobulinemic GN



    • IgG &/or IgM staining along glomerular capillaries and mesangial areas


    • Polyclonal or rare monoclonal light chain staining


  • MGN



    • IgG granular staining of the capillary walls and some mesangial areas


  • Fibrillary GN



    • IgG granular staining of capillary walls and mesangial areas


    • Polyclonal staining for kappa and lambda light chains


  • Immunotactoid glomerulopathy



    • IgG granular staining of mesangial areas and capillary walls


    • Monoclonal light chain staining is typical


  • IgA nephropathy



    • IgA granular mesangial staining with variable involvement of capillary walls


Electron Microscopy



  • MPGN



    • Subendothelial & mesangial electron-dense deposits


    • Duplication of GBM


  • Cryoglobulinemic GN



    • Subendothelial & mesangial electron-dense deposits


    • Substructural organization of deposits may be present


  • MGN



    • Subepithelial & mesangial electron-dense deposits


  • Fibrillary GN



    • Randomly arranged fibrils ˜ 20 nm in diameter


  • Immunotactoid glomerulopathy



    • Microtubules with hollow centers arranged in parallel arrays measuring > 30 nm in diameter


  • IgA nephropathy



    • Mesangial electron-dense deposits with variable subendothelial or subepithelial involvement


DIFFERENTIAL DIAGNOSIS


HCV-associated Focal Segmental Glomerulosclerosis



  • Segmental sclerosis of glomeruli


  • Absence of immune complex deposition


Hepatitis B Virus-associated Immune Complex Disease



  • Pathologically identical to HCV-associated immune complex disease


Lupus Nephritis

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Hepatitis C Virus

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