C型肝炎相關之腎病變

10449 92

C

C ( extrahepatic manifestations )

( membranoproliferative glomerulonephritis ) C ( membranous nephropathy )

( focal segmental glomerulosclerosis )

C ( immunosuppressive therapy )

( plasma-exchange )

C ( Hepatitis C virus )

( Membranoproliferative glomerulonephritis ) ( Membranous nephropathy )

( Focal segmental glomerulosclerosis )

( mem- b r a n o u s g l o m e r u l o n e p h r i t i s )

80%~100% B

30%~45%

( SLE )

90% B

B

B C

1993 Johnson RJ

8 C

( m e m b r a n o p r o l i f e r a t i v e glomerulonephritis )

C

C 36%-40%

( extrahepatic manifesta- tions ) porphyria cutanea tarda

( sicca syndrome )

4%

2 0 % C

7

C

C

;

C

C 1993 Johnson RJ

8 C

3

C

5 6 % C

( cryoglobulinemia )

( idiopathic )

( c o m p l e m e n t ) rheumatoid factor

( immune complex )

( purpura ) ( arthralgia ) ( neuropathy )

( weakness )

( nephrotic syndrome )

porphyria cutanea tarda

6, 8

( membranous nephropathy )

C C

2.7%

rheumatoid factor

( focal segmental glo- merulosclerosis, FSGS ) HIV

Sabry A C

24%

Stehman-Breen C 12

6 C

C

IgA nephropathy fibrillary glomerulonephritis immunotactoid

glomerulopathy

C R N A

9.5kb

C E1 E2 P7 NS2 NS3 NS4AB

NS5AB C

RNA RNA ( negative strand RNA )

R N A C

13,14

C

8

C

( mesangial ) ( toll-like receptor 3, TLR3 )

15

C

( hypocomplementemia ) cryoglobulinemia rheumatoid factor

C G F R

16

Okada K

( indirect immunofluorescence ) C ( HCV core protein )

C

7 , 1 8

hepatitis C virus RNA hepatitis C virus RNA

C

19

C

( Symptomatic therapy )

( angiotensin convert- ing enzyme inhibitors, ACEI )

C ( HCV anti-viral thera- py )

C C

1994 Misiani R ( Interferon alfa-2a )

C

Johnson RJ

C ( Intron-A ) 3

5.8 4.1 g/day 2.0 2.6 g/day 14 11 HCV RNA

22

Ribavirin H u SL

Ribavirin C

23

Ribavirin 200 mg 400 mg

6 0 0 m g

Protein/Creatinine 6 0.5

Ribavirin ( conventional -INF ) 3

MU 3 ( pegylated -INF )

1.5 g/kg/week Ribavirin 600-1000 mg/d ( 10-15 mmol )

24 67%

flu-like syndrome

Ribavirin

10 g/dL Ribavirin

( erythropoietin )

750/mm

80,000/mm

8 g/dL 500/mm

25,000/mm

( immunosuppressive therapy) ( plasma-exchange )

Cyclophosphamide B-lymphocyte cryoglobulins

( steroid pulse therapy )

20

cryoglobulinemia

cryoglobulin

Cyclophosphamide C C

( remission )

27

ALT 5X ( bilirubin

2g/dL ) C

C

C

C

( pegylated -interferon ) C

1 9 8 4 B

1 5 B

9.8% 1999 0.7% B

2 8

C

2 9

C D - 2 0 (Anti-CD20 monoclonal antibody therapy Rituximab) B-lymphocyte

C ,

30

C NS3-4A protease inhibitors ( BILN 2061 ) NS5B polymerase inhibitors

C

31, 32

1.Brady HR, O'Meara YM, Brenner BM. Glomerular disease. In:

Kasper DL, Braunwald E, Fauci AS, et al, eds Harrison's Principles of Internal Medicine. 16th ed. New York: McGraw- Hill; 2005; 1692-3.

2.Hsu HC, Lin GH, Chang MH, Chen CH. Association of hepati- tis B surface (HBs) antigenemia and membranous nephropathy in children in Taiwan. Clin Nephrol 1983; 20: 121-9.

3.Johnson RJ, Gretch DR, Yamabe H, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection.

N Engl J Med 1993; 328: 465-70.

4.Cacoub P, Renou C, Rosenthal E, et al. Extrahepatic manifesta- tions associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. Medicine 2000; 79: 47-56.

5.Ali A, Zein NN. Hepatitis C infection: a systemic disease with extrahepatic manifestations. Cleve Clin J Med 2005; 72: 1005- 16.

6.Sterling RK, Bralow S. Extrahepatic manifestations of hepatitis C virus. Curr Gastroenterol Rep 2006; 8: 53-9.

7.Sabry A, E-Agroudy A, Sheashaa H, et al. HCV associated glomerulopathy in Egyptian patients: clinicopathological anal- ysis. Virology 2005; 334: 10-6.

8.Meyers CM, Seeff LB, Stehman-Breen CO, et al. Hepatitis C and renal disease: an update. Am J Kidney Dis 2003; 42: 631- 57.

9.Arase Y, Ikeda K, Murashima N, et al. Glomerulonephritis in au- topsy cases with hepatitis C virus infection. Intern Med 1998;

37: 836-40.

10.Stehman-Breen C, Alpers CE, Couser WG, et al. Hepatitis C virus associated membranous glomerulonephritis. Clin Nephrol 1995; 44: 141-7.

11.di Belgiojoso GB, Ferrario F, Landriani N. Virus-related glomerular diseases: histological and clinical aspects. J Nephrol 2002; 15: 469-79.

12.Stehman-Breen C, Alpers CE, Fleet WP, et al. Focal segmental glomerular sclerosis among patients infected with hepatitis C virus. Nephron 1999; 81: 37-40.

13. ABCDE 2006; 33: 523-32

14. B C

2006; 33: 438-52

15.Wornle M, Schmid H, Banas B, et al. Novel role of toll-like re- ceptor 3 in hepatitis C-associated glomerulonephritis. Am J Pathol 2006; 168: 370-85.

16.Tsui JI, Vittinghoff E, Shlipak MG, O'Hare AM. Relationship between hepatitis C and chronic kidney disease: results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol 2006; 17: 1168-74.

17.Okada K, Takishita Y, Shimomura H, et al. Detection of hepati- tis C virus core protein in the glomeruli of patients with mem- branous glomerulonephritis. Clin Nephrol 1996; 45: 71-6.

18.Sabry AA, Sobh MA, Irving WL, et al. A comprehensive study of the association between hepatitis C virus and glomerulopa- thy. Nephrol Dial Transplant 2002; 17: 239-45.

19.Yamabe H, Nakamura N, Nakamura M, et al. Hepatitis C virus- associated glomerulonephritis without hepatitis C virus in the blood. Am J Kidney Dis 2005; 46: e65-9.

20.Kamar N, Rostaing L, Alric L. Treatment of hepatitis C-virus- related glomerulonephritis. Kidney Int 2006; 69: 436-9.

21.Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a thera- py in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994; 330: 751-6.

22.Johnson RJ, Gretch DR, Couser WG, et al. Hepatitis C virus-as- sociated glomerulonephritis. Effect of alpha-interferon therapy.

Kidney Int 1994; 46: 1700-4.

23.Hu SL, Jaber BL. Ribavirin monotherapy for hepatitis C virus- associated membranous nephropathy. Clin Nephrol 2005; 63:

41-5.

24.Sherman M, Cohen L, Cooper MA, et al. Clinical recommen- dations for the use of recombinant human erythropoietin in pa- tients with hepatitis C virus being treated with ribavirin. Can J Gastroenterol. 2006; 20: 479-85.

25.Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, ma- nagement, and treatment of hepatitis C. Hepatology 2004; 39:

1147-71.

26.Sulkowski M. Management of the hematologic complications of hepatitis C therapy. Clin Liver Dis 2005; 9: 601-16.

27.Kurihara I, Saito T, Nakayama K, et al. A case of hepatitis C virus associated membranous glomerulonephritis ameliorated by corticosteroid therapy. Nippon Jinzo Gakkai Shi 1998; 40:

290-4.

28.Ni YH, Chang MH, Huang LM, et al. Hepatitis B virus infec- tion in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 2001; 135:

796-800.

29.Houghton M, Abrignani S. Prospects for a vaccine against the hepatitis C virus. Nature 2005; 436: 961-6.

30.Roccatello D, Baldovino S, Rossi D, et al. Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobuli- naemic glomerulonephritis. Nephrol Dial Transplant 2004; 19:

3054-61.

31.De Francesco R, Migliaccio G. Challenges and successes in de- veloping new therapies for hepatitis C. Nature 2005; 43: 953- 60.

32.Pawlotsky J. Therapy of hepatitis C: from empiricism to eradi-

cation. Hepatology 2006; 43: S207-20.

Chen-Wang Chang, Cheng-Hsin Chu, Wen-Hsiung Chang, and Yi-Chou Chen

The hepatitis C virus general encroaches upon the liver and causing the liver pathological change. Liver cirrhosis and even hepatocelluar carcinoma can be seen in patient with HCV infection. Except of liver, HCV can involve other organ and causing many extrahepatic manifestations, nephropathy is one of the most important ex- trahepatic manifestations that maybe neglected. Most of the HCV-related nephropathy is membranoproliferative glomerulonephritis, and membranous nephropathy, focal segmental glomerulosclerosis are also reported previ- ously. Except of symptoms control, anti-HCV therapy, immunosuppressive therapy and plasma-exchange can be used for treatment of HCV related nephropathy. ( J Intern Med Taiwan 2006; 17: 259-263 )

Division of Gastroenterology,

Division of Nephrology, Department of Internal Medicine,

Mackay Memorial Hospital, Taipei, Taiwan