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:

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
Cases (N)
Deaths (N)
Fatality rates (%)
All pts with Acute HAV
115,551
381
0.3
Acute HAV plus Chronic HBV
231 27
11.7
Acute HAV plus CLD
2,311
107
4.6
Acute HAV, but no liver dz
113,009
247
0.2
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: Keefe EB. Viral Hepatitis : 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);
Missed opportunities for Vaccination

9. Hepatitis B

10. Epidemiology of hepatitis B
Virus identified in 1966
Worldwide health problem
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
Risk of chronic infection
Slide 67
Risk of chronic infection
The risk of progression to chronic HBV infection is inversely proportional to the age at infection. Up to 50 to 90% of neonates and infants born to HBeAg positive mothers become HBV carriers, as compared to 20 to 30% among children infected between the age of 1-5 years, and less than 5% among immunocompetent adults.
McMahon BJ, Alward WL, Hall DB, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985;151:
Tassopoulos NC, Papaevangelou GJ, Sjogren MH, et al. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology 1987;92:
Chang MH, et al. Natural history of hepatitis B virus infection in children. J Gastroenterol Hepatol 2000;15 Suppl:E16-9.

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:

16. Estimated Incidence of Acute Hepatitis B United States, 1978-199580
Safer Injection Practices 70
Infant
immunization 60 50
Cases/100,000 40
Vaccine
licensed
HBsAg screening
of pregnant women 30 20
Adolescent immunization 10 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95
Source: CDC

17. Infectious Disease Burden among Released Inmates, United States, 199635
12,000
34,000 TB
29-32
million
4.5 million
HCV
12-15
155,000
million
HBV (chronic)
13-19
98 –145,000
750,000
HIV 17
39,000
229,000
AIDS
% of Total Infected Population
Infected Inmates Released
Infected US Population
Infection/ Disease
Good afternoon-
Review CDC’s progress in implementation of programs to prevent hepatitis C
Integration into CDC’s existing public health programs
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
Homeless , % ,000
Hospitalized , % ,000
Military 1,900, % ,000
Nursing Home 1,700, % ,000
Additional Infected Persons ,000
(800,000 – 1,200,000)
Total ~ 5 million
U.S. Census Bureau of Justice, Center for Medicare, Medicaid Services

23. Hepatitis C: A Global Health Problem
Key Point: According to CDC estimates, approximately 3-4 million people in the US are currently infected with the hepatitis C virus (see map). There are, however, a few distinct geographic regions where infection is especially common. In Egypt, for example, HCV infection occurs in 10% to 30% of the general population. Likewise, the prevalence of infection is greater than 10% in certain parts of Asia and high rates of infection have been found in certain geographic regions of Japan, Taiwan, and Italy. As noted below, however, there are a number of countries where data are not available.1
Reference:
1. 1. World Health Organization. Wkly Epidemiol Rec. 2000;75:17-28.
3. Edlin, et al. Five Million Infected with the Hepatitis C Virus: A Corrected Estimate. Presented at AASLD, Oral presentation 44.
4. Fontanet, A. Annual Report of Emerging Diseases for Year Accessed 03/13/06 at
Region
Total population (millions)
HCV prevalence (rate %)
Infected populations (millions)
No. countries where data not available
Africa
602
5.3
31.9 12
Americas
785
1.7
13.1 7
E Mediterranean
466
4.6
21.3
Europe
858
1.03
8.9 19
SE Asia
1500
2.15
32.3 3
W Pacific
1600
3.9
62.2 11
Total
5811
3.1
169.7 57

24. Prevalence of HCV in Select Populations
Key Point: The prevalence of individual populations in the United States is presented above.
References
1. Centers for Disease Control. Prevention and control of infections with hepatitis viruses in correctional settings: recommendations and reports. Morb Mortal Wkly Rep. 2003;52(RR-1):1-33.
2. Edlin B. Prevention and treatment of hepatitis C in injection drug users. Hepatology. 2002;36(5 suppl 1):S210-S219.
3. National Household Survey on Drug Abuse. The NHSDA report: injection drug use. March 14, 2003.
4. Poles M et al. Hepatitis C virus/human immunodeficiency virus coinfection: clinical management issues. Clin Infect Dis. 2000;31:
5. Labreque S. In: Hepatitis C Choices
6. Alter M et al. The prevalence of hepatitis C virus infection in the United States, 1988 through N Engl J Med. 1999;341:
7. Nyamathi A et al. Risk factors for hepatitis C virus infection among homeless adults. J Gen Intern Med. 2002;17(2):
8. Bräu N et al. Prevalence of hepatitis C and coinfection with HIV among United States veterans in the New York City metropolitan area. Am J Gastroenterol. 2002;97:
9. Jonas M. Children with hepatitis C. Hepatology. 2002;36(5 suppl 1):S173-S178.

25. Prevalence of HCV in Select Populations
IVDU %
Alcoholics 11%
Incarcerated %
Homeless 22%
Veterans %
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. Symptoms of Advanced Liver Disease
Changes in mental status
Anorexia
Jaundice
Weight loss
Muscle wasting
Decreased libido
Abdominal distention
Leg swelling
SOB
Hematemesis
Abdominal pain
Diarrhea
N/V

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

29. Natural History of HCV Infection
Key Point: The outcomes of HCV infection and estimates of their frequency are shown in the slide. The majority of patients with acute infection develop chronic hepatitis; however, the severity of chronic liver disease can vary. The most important sequelae of chronic HCV infection include progressive liver fibrosis leading to cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC).
References
1. Hoofnagle J. Hepatitis C: the clinical spectrum of disease. Hepatology. 1997;26(suppl 1):15S-20S.
2. National Institutes of Health. NIH consensus statement on management of hepatitis C: NIH Consens State Sci Statements. 2002;19(3):1-46.

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

31. Natural History of HCV Cirrhosis
HCV-infected cirrhotic patients present a complex set of concerns and potential clinical outcomes. This slide illustrates the probability of survival in 384 patients with HCV-related compensated cirrhosis who participated in a 10-year longitudinal European study reported by Fattovich et al. The first curve represents the probability of survival after diagnosis in all patients with compensated cirrhosis. Five-year probability rate was 91%. The second curve represents the probability of survival after the appearance of the first major complication of disease in 65 patients who developed decompensated cirrhosis. The 5-year probability rate was 50%.
Reference
1. Fattovich G et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology. 1997;112:

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:

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

38. Reference
1. Davis G et al. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl. 2003;9(4):

39. Goals of Therapy
Clinically relevant goals for treatment of HCV are classified as primary or secondary. The primary goal is the eradication of the virus as evidenced by negative HCV RNA. The secondary goals include the histologic improvement of hepatic inflammation and fibrosis as evidenced by delayed fibrosis and progression to cirrhosis and prevention of hepatic decompensation and HCC.
Reference:
1. Lindsay K et al. Introduction to Therapy of Hepatitis C.Hepatology.2002;36(5) (Suppl.1):S

40. Predictors of Virologic Response
Efficacy of therapy is dependent on viral factors and host factors. Genotype and viral load have shown to impact the sustained virologic response of pegylated interferons. Host factors including age, cirrhosis, race, gender, and weight have also been shown to be predictors of response.
Reference:
1. Ferenci P. Predictors of response to therapy for chronic hepatitis C. Semin Liver Dis. 2004;24(suppl 2):25-31

41. Genotype Distribution in the US showing that the majority of patients have the difficult to treat Genotype 1
Reference:
Alter M et al. The Prevalence of Hepatitis C Infection in the United States 1998 through New England Journal Of Medicine. 1999;341(8):
Blatt L et al. Assessment of hepatitis c virus RNA and genotype from 6807 patients with chronic hepatitis c in the United States. Journal of Viral Hepatology. 2000;7:

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. Peg Interferon Ribavirin
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

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. Evaluated and treated (13.8%)
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:

51. Reasons for exclusion of patients from HCV antiviral therapy
Psychiatric disease 35 (21)%
Undecided (17)
Active alcohol abuse 23 (14)
Refused (10)
Multiple reasons 17 (10)
Medical comorbidity 11 (6)
Normal LFTs 8 (5)
Medication noncompliance 8 (5)
Active drug abuse 6 (3)
Treated outside VA 6 (3)
HCV RNA negative 6 (3)
Am J Gastroenterology 2002;97:

52. Psychiatric disorders among veterans with hepatitis C infection El-Serag HB, Kunik M, Richardson P, Rabeneck L. Gastroenterology 2002;123:
N=33,824 hospitalized HCV+ veterans identified
Psychiatric and substance-use disorders identified from computerized records.
Random non-HCV+ controls identified from hospitalized patients

53. Psychiatric disorders among veterans with Hepatitis C infection
86.4% of 33,824 pts had at least one past or present psychiatric, drug- or alcohol-related disorder recorded
Active disorders: 31%
HCV+ cases more likely than controls to have depression, PTSD, anxiety, alcohol and drug-use disorders.

54. What Happens if Treatment Doesn’t Work?
Remember, most treatment for Hepatitis C doesn’t actually work! Help your patients have realistic expectations without encouraging a defeatist attitude.
Patients are followed in clinic to monitor for HCC and liver decompensation (which occurs in 20% of patients with Hepatitis C.)
Liver transplantation is a consideration

55. Liver Transplant stats:
Liver transplant numbers: 81,634 done
Currently 16,961 waiting
05: 6443
06: 6650

56. Location of VA Transplant Centers
Kidney
Iowa City, IA
Nashville, TN
Pittsburgh, PA
Portland, OR
Liver
Nashville, TN *
Richmond, VA *
Heart
Cleveland, OH * +
Madison, WI *
Nashville, TN * +
Richmond, VA
Salt Lake City, UT *
Palo Alto, CA *
Lung
Richmond, VA +
Bone Marrow
Nashville, TN
San Antonio, TX
Seattle, WA
* Sharing Agreement Sites + Temporarily Inactive

57. Transplants – All VATCs

58. Liver Transplantation
6 months free from:
Tobacco, alcohol and all illicit substances with documented attendance at AA or in similar program
Patients do not have to be off Methadone.
Need complete psychological, social and dental evaluations plus a myriad of laboratory and radiological testing.
Must have support person able to attend all liver transplant evaluations, provide transportation, attend surgery, out of town, evaluations and commit to indefinite post-operative care.
Specific criteria for patients being referred for transplantation secondary to HCC – lesion size and number and evidence of metastasis determine eligibility.

59. Projecting future complications of chronic HCV in United States
Complications will increase over the next 20 years
Liver Transplantation 2003; 9:

60. Burden of Disease
Hepatocellular Carcinoma (Liver cancer) is the most common primary hepatic malignancy
The vast majority of patients with Hepatocellular Carcinoma (HCC) have underlying Cirrhosis
Risk of HCC in patients with HCV is 17 times higher than HCV negative controls
We also know that among patients with cirrhosis secondary to HCV, the risk of HCC development is 17X higher.

61. Take Home Points Screen for Hepatitis A, B, C
Immunize against Hepatitis A and B as appropriate
Patient Education
Refer quickly for Hepatitis B and C positivity
Screen all positive Hepatitis B and C patients for HCC

63. Thanks!
Questions?
Contact Information:
Kimberly Moore, MSN, CRNP, LNC
Cincinnati VA Medical Center
Department of Digestive Diseases and Hepatology
(513)