Hepatitis A, B and C: An overview with special considerations for our Veteran population

1. Hepatitis A, B and C:An overview with special considerations for our Veteran population • Kimberly Moore, MSN, CRNP, LNC • Cincinnati VA Medical Center • Department of Digestive Diseases and Hepatology

2. Hepatitis A • Identified 1973 • 75,000 cases/yr in U.S. • Self limiting disease in most • Severe disease in: • Adults > 40 years • Patients with Chronic Liver Disease (CLD) are at risk of Fulminate Hepatic Failure (FHF) in 40% of cases Gitlin et al, AJG, 1998

3. Hepatitis A • Modes of transmission • Oral fecal route • Ingestion of contaminated food/water • Close person to person contact

4. Outcome of HAV Super-infection in Patients with Chronic Viral Hepatitis Vento et al. NEJM 1998:338: 286-290

5. Hepatitis A • Carries a high risk of liver failure and mortality in patients with CLD • Vento et al reported: • 41% of patients with Hep B or C developed liver failure • Bini et al reported: • 33% fatality rate in HCV patients with superimposed HAV infection Bini et al, Hepatology 2005 Vento et al, NEJM 1998

6. Estimated risk of death from acute HAV, US, 1983-1988 Calculated from an estimated .2% HbsAG carrier rate in the US, and 2% prevalence of CLD in the US. Hadler et al. Viral Hepatitis and Liver Disease. Baltimore. Williams and Wilkins: 1991: 14-20. Keefe EB. Viral Hepatitis 1999: 5:77-88

7. Hepatitis A-prevention • HAV vaccine-indication: • Chronic liver disease • IV drug users • Men who have sex with men • Travelers to endemic areas • Kitchen workers, employees of day care centers, healthcare personnel

8. Susceptibility to Hepatitis A in Patients with CLD due to HCV: Shim et al. (2005) Hepatology. 42 (3); 688-695 Missed opportunities for Vaccination

9. Hepatitis B

10. Epidemiology of hepatitis B • Virus identified in 1966 • Worldwide health problem • 350-400 million carriers worldwide • 250,000 deaths annually • Vaccine available 1982 • >1 million die annually of HBV related CLD

11. Transmission of HBV • Perinatal • IVDA • Sexual • Hemodialysis • Close person to person contacts • Infected blood • children in hyperendemic areas

12. Risk of chronic infection HBV - Epidemiology

14. Incidence of Cirrhosis in HBV/HCV Co-infection vs. HCV alone Fuiano B et al. Ital J Gastroent 1992: 24:409-11

15. Risk of HCC with HBV/HCV Co-infection in Cirrhotic Patients Koff RS J Clin Gastro 2001:33:20-26 Benvegnu L et. Al. Cancer 1994:74:2442-48

16. Estimated Incidence of Acute Hepatitis BUnited States, 1978-1995 80 Safer Injection Practices 70 Infant immunization 60 50 Cases/100,000 40 Vaccine licensed HBsAg screening of pregnant women 30 20 Adolescent immunization 10 0 78 79 81 82 83 84 85 87 88 89 90 91 92 93 94 95 80 86 Source: CDC

17. Infection/ Disease Infected US Population Infected Inmates Released % of Total Infected Population AIDS 229,000 39,000 17 HIV 750,000 98 –145,000 13-19 HBV (chronic) 1.0-1.25 million 155,000 12-15 HCV 4.5 million 1.3-1.4 million 29-32 TB 34,000 12,000 35 Infectious Disease Burden among Released Inmates, United States, 1996 Source: NCCHC, Hammet, Greifinger et.al. unpublished data

18. Review of Hepatitis A, B, C serological testing • HBsAg - exposure • HBsAb - marker for immunity • HAV Ab total – marker for immunity • HCVAb -exposure • HCV PCR –gold standard to diagnose HCV

19. Hepatitis B Treatment • Treatment is generally advised for patients with active disease • Lamivudine, Entecavir, Adefovir, Pegylated Interferon, combination therapy • Hepatocellular Carcinoma screen is recommended

20. Healthy people 2010 goals: • Identify individuals with Hepatitis C • Education • Vaccinated against Hep A/B • Evaluate for liver disease and treat • Immunize against Hepatitis B • Immunize high risk groups, including illicit drug users, against Hepatitis A

21. Facts about Hepatitis C Virus(HCV) • 5.0 million Americans Infected • Non-A Non-B hepatitis recognized in the 1970’s • HCV genome isolated 1989 • HCVRNA mutates rapidly • No vaccine available • 6 different genotypes

22. HCV Epidemiology: Corrected estimate Edlin BR, et al Hepatology 2005;42:213A Estimated 3.9 million who have been infected (NHANES) Number HCV Ab # Infected Incarcerated 1,200,000 35% 426,000 Homeless 800,000 43% 344,000 Hospitalized 895,000 16% 132,000 Military 1,900,000 0.5% 9,000 Nursing Home 1,700,000 4.2% 79,000 Additional Infected Persons 991,000 (800,000 – 1,200,000) Total ~ 5 million U.S. Census Bureau of Justice, Center for Medicare, Medicaid Services

25. Prevalence of HCV in Select Populations • IVDU 80 - 90% • Alcoholics 11% • Incarcerated 16 - 41% • Homeless 22% • Veterans 6 - 8% • US population 1.8%

26. Symptoms of HCV • Lack of energy, • Weakness • General malaise • RUQ dull pain • Nausea • Arthralgias/myalgias • Extrahepatic manifestations of hcv

27. Changes in mental status Anorexia Jaundice Weight loss Muscle wasting Decreased libido Abdominal distention Leg swelling SOB Hematemesis Abdominal pain Diarrhea N/V Symptoms of Advanced Liver Disease

28. Factors associated with Disease Progression • Alcohol consumption • Disease acquisition at >40 years • Male gender • Coinfection with HIV or HBV • Immunosuppression

30. HCV disease progression • Cirrhosis • Decompensated cirrhosis • Ascites, SBP, bleeding varices, encephalopathy • HCC • Liver transplant • Death

32. Hepatitis C Care within the VA Health Care System Burden of HCV in US veterans “The prevalence or Hepatitis C (5.4%) in United States Veterans exceeds the estimate from the general population by more than 2 – fold” Hepatology 2005; 41:88-96 Mil Med 2002; 167: 756 - 759

33. HCV screening: VA guidelines • Vietnam-era veteran • Blood transfusion before 1992 • Past or present IV drug use • Blood exposure of skin or mucous membranes • H/o multiple sexual partners • History of intranasal cocaine use

34. HCV screening guidelines (cont) • History of hemodialysis • Tattoo or repeated body piercing • Unexplained liver disease • Unexplained/abnormal ALT • Intemperate or immoderate use of alcohol

35. Available testing for HCV • ELISA tests for AB to HCV (HCV Ab) • Recombinant immunoblot assay (RIBA) • HCV PCR testing • Genotyping

36. Laboratory Testing for Hepatitis C • HCV antibody • Once positive, will always be positive, even if treated and cleared. Please DO NOT keep ordering this test. • If antibody positive but no viral load (negative HCV bDNA and TMA,) either patient experienced spontaneous clearance (7% occurrence rate) or the original antibody was falsely positive. Confirm with HCV RIBA (if returns positive, patient had and cleared the virus; if returns negative, antibody was falsely positive • HCV bDNA and TMA • This is the “viral load” or amount of virus in the blood – this is what treatment attempts to clear.

37. Patient Education and Counseling • Protection of others from transmission • Protect liver from further harm • Discussion of prognosis • Discussion of treatment options

42. Treatment of Hepatitis C • Liver biopsy usually required prior to treatment for patients with genotype 1. • Weekly Interferon injections • Twice daily Ribavirin pills (dose based on weight) • Treatment duration is 6 months for genotype 2 and 3; 12 months for genotype 1. • HCV bDNA and TMA is rechecked after tx for 3 months to see if meds are working to clear the virus (need a 2 log drop in the bDNA to show tx effectiveness.)

43. Treatment of Hepatitis C (cont’d) • 35% treatment success rate (sustained viral response or SVR) for African Americans with genotype 1 • 45% treatment success rate (SVR) for Caucasians with genotype 1 • Near 70% SVR for genotypes 2 and 3 • Females do better than males; younger patients do better than older patients (in terms of tolerance and clearance)

44. Criteria: Consideration for Treatment • Preferably no ongoing alcohol or illicit drug use • Psychiatric diseases must be managed and fairly well controlled • Normal or abnormal transaminases • No active medical problems with expected mortality

45. blocks virus into cells inhibits intracellular replication stimulates bodies immune system renally cleared antifibrotic action Synergistic with Interferon Induces defective replication of HCV RNA Better tolerated than Interferon Not effective monotherapy Peg Interferon Ribavirin

46. Side effects: Peg Interferons • Flu like symptoms • Fatigue • Depression/mood lability/insomnia • Anorexia • Injection site reactions • Can stimulate Autoimmune disease • Skin problems • Visual changes • Lab alterations

47. Side effects: Ribavirin • Teratogenicity • Hemolytic anemia • MI with anemia • SOB, pulmonary infiltrates or pneumonitis • Skin rash

48. Hepatitis C Treatment – Adverse Events • Dose discontinuations common • Most common reasons sited for dose discontinuation: • Psychiatric (increase in depression, anxiety, anger, nightmares, hallucinations/delusions, decrease in impulse control) • Systemic (fatigue, headache, arthralgias, arthritis, skin rash) • Gastrointestinal adverse events (nausea, anorexia) • Cytopenias • Thyroid Dysfunction • Liver failure • Your clients on treatment WILL experience potentially severe side effects – expect it!

49. Barriers to HCV Antiviral Therapy

50. Show rates and Treatment Eligibility in Consecutive Veterans referred to HCV clinic (N=557) Evaluated and treated (13.8%) Evaluated and not treated (29.6%) No show for HCV clinic (56.6%) Cawthorne et al, Am J Gastroenterol 2002;97:149-155