1. This is the most comprehensive compilation of epidemiological information on Hepatitis C Graciously provided by the University Hepatitis Center (last updated 2008)

2. Hepatitis C Update 2008 Tanya Schreibman, MD University Hepatitis Center Bradenton, Fl

3. Hepatitis C Update 2008 Epidemiology Natural History and Clinical Presentation Diagnosis, Screening and Barriers Treatment Final Comments

4. Hepatitis C Update 2008: Epidemiology

6. 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  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.

7. True or False? You can only get hepatitis C by injecting drugs.

8. Answer: False It is true that you can get Hepatitis C by sharing needles or injecting drugs. However, this is not the only way that you can get Hepatitis C.

10. Hepatitis C Virus Infection Population 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.

13. HCV Sexual Transmission Unlikely in Heterosexual Monogamous Couples 895 monogamous heterosexual partners of HCV infected patients –Ten year prospective follow up study 3 HCV infections during followed up –None were sexually transmitted from partner –In one couple,partners were different genotypes –In two couples, partners had same genotypes but different strains

15. Hepatitis C Update 2008: Natural History and Clinical Presentation of Hepatitis C Infection

20. 4 Stages of Liver Damage Stage 1 (F1) Beginning of liver damage Damage has started with some slight scarring Stage 2 (F2) Moderate liver damage scarring advances in the liver & surrounding blood vessels

21. 4 Stages of Liver Damage Stage 3 (F3) Significant liver damage; the liver becomes fibrotic (scarred) and connects with other scarred areas. Stage 4 (F4) Final stage of liver damage, also called cirrhosis; the liver is severely damaged and no longer functions properly

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

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

26. True or False? You can get hepatitis C and not even feel sick?

27. Answer: True You can have Hepatitis C for many years and not even feel sick or have any symptoms. The only way for you to know if you have Hepatitis C is to test your blood.

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

37. Hepatitis C Update 2008: Screening and Diagnosis

42. Testing for Hepatitis C Virus Anti-HCV Antibodies ELISA screening test –Sensitivity: 97% –Detects circulating HCV antibodies False positive reactions may occur –Cross-reacting circulating antibodies Positive predictive value –95% with risk factors and elevated ALT –50% without risk factors and normal ALT Illustration by Mitchell L. Shiffman, MD.

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

47. Chronic HCV Infection Normal vs Elevated Serum ALT Normal ALTElevated ALT Portal 26% No fibrosis 23% Mild 39% Cirrhosis 6% Bridging 6% Portal 20% No fibrosis 16% Mild 33% Cirrhosis 18% Bridging 13% Shiffman ML, et al. J Infect Dis. 2000;182:1595-1601.

48. Hepatitis C Virus Infection Liver 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

50. Hepatitis C Update 2008: Treatment

52. True or False? HIV related disease is the number one cause of death in HIV patients co-infected with hepatitis C.

53. Answer: False Liver-related death is the number one cause of death in co-infected patients. That is why it is important to talk to your healthcare provider about treatment.

58. Current Treatment Recommendations Combination therapy for 6-12 months of pegylated interferon plus ribavirin is the standard of care Pegylated interferon (injection) helps fight the virus in two ways: –It helps healthy cells defend themselves against the virus –It strengthens the immune system, which helps to stop the virus from growing in number

59. Ribavirin Ribavirin is a pill, that when taken with pegylated interferon, helps the pegylated interferon do its job. It helps slow down the replication of hepatitis C. It is usually taken as long as you are taking pegylated interferon. Ribavirin cannot fight HCV on its own.

60. Treatment of Chronic HCV Peginterferon and Ribavirin 0 20 40 60 80 100 12-3 Genotype Sustained Virologic Response (%) PegIFN-2a/RBV PegIFN-2b/RBV Fried MW, et al. N Eng J Med. 2002;347:975-982. Manns MP, et al. Lancet 2001;358:958-965.

67. Protease Inhibitor: Telaprevir(VX-950) Courtesy of Dr. J-M Pawlotsky.

69. Hepatitis C Update 2008: Final Comments

73. Hepatitis C Virus Infection Prevalence by Age 0 1.0 2.0 3.0 4.0 5.0 < 1111-1920-2930-3940-4950-5960-69≥ 70 Age Group Anti-HCV Positive (%) Alter MJ, et al. N Eng J Med. 1999;341:556-562.

74. Armstrong GL, et al. Hepatology. 2000;31:777-782. Hepatitis C Virus Infection The Burden of Disease 0 1.0 2.0 3.0 1960198020002020 Year All patients Infection for > 20 years Anti-HCV Positive (%)

76. Chronic HCV Infection Progression to Cirrhosis 0 20 40 60 80 100 05101520 Time (Years) Bridging Portal None Approximate Percentage of Patients With Cirrhosis Yano M, et al. Hepatology. 1996;23:1334-1340. Proportion of Patients Developing Cirrhosis According to Initial Level of Fibrosis

78. Zein CO, et al. Am J Gastroenterol. 2005;100:48-55. Chronic HCV and Diabetes Mellitus Case Prevalence 179 chronic HCV pts Prevalence of diabetes mellitus and insulin resistance noted Compared with expected rate based on NHANES III study after adjusting for –Age, Sex, Race Prevalence of DM or insulin resistance higher in those with chronic HCV 0 4 8 12 16 20 FemalesMales Number of Cases Observed Expected

79. Zein CO, et al. Am J Gastroenterol. 2005;100:48-55. Chronic HCV and Diabetes Mellitus Relationship to Fibrosis Stage 0 10 20 30 40 01234 Histologic Stage Percentage of Patients

80. Fattovich G, et al. Gastroenterology. 1997;112:463-472. HCV in Patients With Cirrhosis Survival and Rate of Decompensation 0 20 40 60 80 100 Survival (%) Stable Decompensation 10-Year Cumulative Survival 0 10 20 30 40 50 0246810 Years Percentage of Patients Decompensation HCC Cumulative Probability

82. HCV RNA and Liver Histology Fibrosis Genotype No Fibrosis Portal Fibrosis Bridging Fibrosis Cirrhosis  Serum HCV RNA does not correlate with level of fibrosis 0 2 4 6 8 Log HCV RNA (copies/mL) 1 2 3 4 Ferreira-Gonzalez A, et al. Semin Liver Dis. 2004;24:9-18.