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Hepatitis C

Hepatitis C. Cengiz Pata Gastroenterology Department, Yeditepe University. Hepatitis C Virus Infection Magnitude of the Problem. Nearly 4 million persons in United States infected Approximately 35,000 new cases yearly 85% of new cases become chronic Leading cause of Chronic liver disease

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Hepatitis C

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  1. Hepatitis C Cengiz Pata Gastroenterology Department, Yeditepe University

  2. Hepatitis C Virus InfectionMagnitude of the Problem • Nearly 4 million persons in United States infected • Approximately 35,000 new cases yearly • 85% of new cases become chronic • Leading cause of • Chronic liver disease • Cirrhosis • Liver cancer • Liver transplantation Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.

  3. Hepatitis C VirusFate of Acute Infection Spontaneous resolution 15% Chronic 85% Alter MJ, et al. N Eng J Med. 1999;341:556-562.

  4. Hepatitis C VirusResponse to Acute Infection 200 +/- + - HCV RNA 150 Resolution ALT (IU/l) 100 Chronic 50 0 0 6 12 18 24 Month Illustration by Mitchell L. Shiffman, MD.

  5. Hepatitis C Virus InfectionNatural History Acute HCV Resolved 15% (15%) Chronic HCV 85% (85%) Stable 80% (68%) Cirrhosis 20% (17%) Slowly progressive 75% (13%) HCC Liver failure 25% (4%) HCC, hepatocellular carcinoma

  6. Hepatitis C Virus InfectionPopulation at Risk • Transfusion of blood products before 1992 • Intravenous drug use • Nasal inhalation of cocaine • Chronic renal failure on dialysis • Incarceration • Occupational exposure to blood products • Transplantation of an organ/tissue graft from an HCV-positive donor • Body piercing and potentially tattoo Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.

  7. Hepatitis C Virus InfectionPrevalence 4.0 3.0 1.8% Anti-HCV Positive (%) 2.0 1.0 0 All W B H M F Sex Race B, Blacks; F, female; H, Hispanic; M, male; W, Whites. Alter MJ, et al. N Eng J Med. 1999;341:556-562.

  8. Hepatitis C Virus Infection Prevalence by Age 5.0 4.0 3.0 Anti-HCV Positive (%) 2.0 1.0 0 < 11 11-19 20-29 30-39 40-49 50-59 60-69 ≥ 70 Age Group Alter MJ, et al. N Eng J Med. 1999;341:556-562.

  9. Hepatitis C:Diagnosis and Management

  10. Management of Chronic HCVTests Utilized LFTs

  11. Viral HepatitisRole of Diagnostic Testing • Identify patients with viral hepatitis infection • Previous exposure to hepatitis virus • Active infection • Inactive infection • Resolved infection • Assess response to therapy • Prior to onset of treatment • During and following treatment

  12. HCV infects cell HCV proteins expressed on surface of hepatocytes Antibodies to HCV proteins produced by host HCV antibodies DO NOT convey immunity Hepatitis C VirusHost Production of HCV Antibodies Y Y Y Y Y Y Y Y Illustration by Mitchell L. Shiffman, MD.

  13. HCV Antibody TestingLimitations • False positives • Autoimmune disorders • Spontaneous resolution of viral infection • False negatives • Chronically immune suppressed • Transplant recipients • Chronic renal failure on dialysis • HIV positive

  14. Hepatitis C VirusGenotypes in the USA Type 2 17% Type 3 10% Type 1 72% All others 1% McHutchinson JG, et al. N Engl J Med. 1998;339:1485-1492.

  15. Hepatitis C Virus InfectionLiver Biopsy • Only test that can accurately assess • Severity of inflammation • Degree of fibrosis • Determines the following • Risk for developing cirrhosis in future • Need for therapy • Need for ongoing therapy when initial treatment has failed

  16. Assessment of Liver HistologyNoninvasive Serum Tests 1.0 1.0 0.8 0.8 0.6 0.6 ACTITEST FIBROTEST 0.4 0.4 0.2 0.2 0 0 0 1 2 3 4 0 1 2 3 Fibrosis Stage Activity Grade Poynard T, et al. Hepatology. 2003;38:481-492.

  17. Chronic HCV With Normal Serum ALTALT Patterns and Flares 120 Single elevations 100 Periodic elevations Always normal 80 60 ULN ALT (IU/l) 40 20 0 0 3 6 9 12 15 18 21 24 Month Illustration by Mitchell L. Shiffman, MD.

  18. Chronic HCV InfectionSymptoms Symptomatic 100 37% Cirrhosis 80 7% 60 Percentage of Patients 40 20 56% Asymptomatic 0 Fatigue Unpublished data from MCV Hepatitis Program, 1995.

  19. Chronic HCV InfectionProgression to Cirrhosis Proportion of Patients Developing Cirrhosis According to Initial Level of Fibrosis Approximate Percentage of Patients With Cirrhosis 100 80 Bridging 60 Portal 40 None 20 0 0 5 10 15 20 Time (Years) Yano M, et al. Hepatology. 1996;23:1334-1340.

  20. Hepatitis C Virus InfectionIdentification of Patients • Found to have elevated serum ALT during • Routine physical examination • Routine blood testing after starting certain medications • Test positive for anti-HCV during • Volunteer blood donation • Health or life insurance applications • Physician • Inquires about previous risk behaviors

  21. Hepatitis C:Extrahepatic Manifestations

  22. Chronic Hepatitis C VirusExtrahepatic Manifestations • Nonspecific antibodies • Essential mixed cryoglobulinemia • Glomerulonephritis • Porphyria cutanea tarda • Leukocytoclastic vasculitis • Mooren’s corneal ulcer • Non-Hodgkin’s lymphoma • Autoimmune thyroiditis • Diabetes mellitus • Sjögren’s syndrome

  23. Chronic Hepatitis C VirusAutoantibodies Pawlotsky JM, et al. Hepatology. 1994;19:841-848.

  24. CryoglobulinemiaClassification Cacoub P, et al. Curr Opin Rheumatol. 2002;14:29-35.

  25. Immune Manifestations of HCVPathogenesis Illustration by Mitchell L. Shiffman, MD

  26. Occurs in dependent areas Deposition of cryoglobulins in small capillaries Ulcerations may develop Pruritic HCV and CryoglobulinemiaDermatitis

  27. HCV and CryoglobulinemiaManifestations • Dermatitis (dependent areas) • Vasculitis • Myalgias (fibromyalgia?) • Arthralgias (RA and/or ANA positive) • Membranoproliferative glomerulonephritis • Neuropathy • Chronic fatigue syndrome (?)

  28. Hepatitis C:Treatment

  29. Treatment of Chronic HCVPeginterferon and Ribavirin 100 80 60 Sustained Virologic Response (%) PegIFN-2a/RBV 40 PegIFN-2b/RBV 20 0 1 2-3 Genotype Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.

  30. Treatment of Chronic HCVEffect on Development of HCC • Interferon treatment reduces the risk of developing hepatocellular carcinoma among patients with chronic HCV (P = .002) • Hepatocellular carcinoma incidence • Untreated controls: 38% (24%-58%) • Interferon-treated patients: 4% (1%-15%) • HCC risk ratio: 0.067 (0.009-0.530; P = .01) Nishiguchi S, et al. Lancet. 1995;346:1051-1055.

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