Presentation on theme: "Kimberly Moore, MSN, CRNP, LNC Cincinnati VA Medical Center"— Presentation transcript:
1 Hepatitis A, B and C: An overview with special considerations for our Veteran population Kimberly Moore, MSN, CRNP, LNCCincinnati VA Medical CenterDepartment of Digestive Diseases and Hepatology
2 Hepatitis A Identified 1973 75,000 cases/yr in U.S. Self limiting disease in mostSevere disease in:Adults > 40 yearsPatients with Chronic Liver Disease (CLD) are at risk of Fulminate Hepatic Failure (FHF) in 40% of casesGitlin et al, AJG, 1998
3 Hepatitis A Modes of transmission Oral fecal route Ingestion of contaminated food/waterClose person to person contact
4 Outcome of HAV Super-infection in Patients with Chronic Viral Hepatitis Vento et al. NEJM 1998:338:
5 Hepatitis ACarries a high risk of liver failure and mortality in patients with CLDVento et al reported:41% of patients with Hep B or C developed liver failureBini et al reported:33% fatality rate in HCV patients with superimposed HAV infectionBini et al, Hepatology 2005Vento 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 HAV115,5513810.3Acute HAV plus Chronic HBV2312711.7Acute HAV plus CLD2,3111074.6Acute HAV, but no liver dz113,0092470.2Calculated 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 diseaseIV drug usersMen who have sex with menTravelers to endemic areasKitchen 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
10 Epidemiology of hepatitis B Virus identified in 1966Worldwide health problemmillion carriers worldwide250,000 deaths annuallyVaccine available 1982>1 million die annually of HBV related CLD
11 Transmission of HBV Perinatal IVDA Sexual Hemodialysis Close person to person contactsInfected bloodchildren in hyperendemic areas
12 Risk of chronic infection HBV - EpidemiologyRisk of chronic infectionSlide 67Risk of chronic infectionThe 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 2001:33:20-26Benvegnu L et. Al. Cancer 1994:74:
16 Estimated Incidence of Acute Hepatitis B United States, 1978-1995 80Safer Injection Practices70Infantimmunization6050Cases/100,00040VaccinelicensedHBsAg screeningof pregnant women3020Adolescent immunization10787980818283848586878889909192939495Source: CDC
17 Infectious Disease Burden among Released Inmates, United States, 1996 3512,00034,000TB29-32million4.5 millionHCV12-15155,000millionHBV (chronic)13-1998 –145,000750,000HIV1739,000229,000AIDS% of Total Infected PopulationInfected Inmates ReleasedInfected US PopulationInfection/ DiseaseGood afternoon-Review CDC’s progress in implementation of programs to prevent hepatitis CIntegration into CDC’s existing public health programsSource: NCCHC, Hammet, Greifinger et.al. unpublished data
18 Review of Hepatitis A, B, C serological testing HBsAg - exposureHBsAb - marker for immunityHAV Ab total – marker for immunityHCVAb - exposureHCV PCR –gold standard to diagnose HCV
19 Hepatitis B TreatmentTreatment is generally advised for patients with active diseaseLamivudine, Entecavir, Adefovir, Pegylated Interferon, combination therapyHepatocellular Carcinoma screen is recommended
20 Healthy people 2010 goals: Identify individuals with Hepatitis C EducationVaccinated against Hep A/BEvaluate for liver disease and treatImmunize against Hepatitis BImmunize high risk groups, including illicit drug users, against Hepatitis A
21 Facts about Hepatitis C Virus(HCV) 5.0 million Americans InfectedNon-A Non-B hepatitis recognized in the 1970’sHCV genome isolated 1989HCVRNA mutates rapidlyNo vaccine available6 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 # InfectedIncarcerated 1,200, % ,000Homeless , % ,000Hospitalized , % ,000Military 1,900, % ,000Nursing Home 1,700, % ,000Additional Infected Persons ,000(800,000 – 1,200,000)Total ~ 5 millionU.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.1Reference: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 atRegionTotal population (millions)HCV prevalence (rate %)Infected populations (millions)No. countries where data not availableAfrica6025.331.912Americas7851.713.17E Mediterranean4664.621.3Europe8581.038.919SE Asia15002.1532.33W Pacific16003.962.211Total58113.1169.757
24 Prevalence of HCV in Select Populations Key Point: The prevalence of individual populations in the United States is presented above.References1. 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 Choices6. 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 NauseaArthralgias/myalgiasExtrahepatic manifestations of hcv
27 Symptoms of Advanced Liver Disease Changes in mental statusAnorexiaJaundiceWeight lossMuscle wastingDecreased libidoAbdominal distentionLeg swellingSOBHematemesisAbdominal painDiarrheaN/V
28 Factors associated with Disease Progression Alcohol consumptionDisease acquisition at >40 yearsMale genderCoinfection with HIV or HBVImmunosuppression
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).References1. 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.
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%.Reference1. 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 veteranBlood transfusion before 1992Past or present IV drug useBlood exposure of skin or mucous membranesH/o multiple sexual partnersHistory of intranasal cocaine use
34 HCV screening guidelines (cont) History of hemodialysisTattoo or repeated body piercingUnexplained liver diseaseUnexplained/abnormal ALTIntemperate or immoderate use of alcohol
35 Available testing for HCV ELISA tests for AB to HCV (HCV Ab)Recombinant immunoblot assay (RIBA)HCV PCR testingGenotyping
36 Laboratory Testing for Hepatitis C HCV antibodyOnce 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 positiveHCV bDNA and TMAThis 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 transmissionProtect liver from further harmDiscussion of prognosisDiscussion of treatment options
38 Reference1. Davis G et al. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl. 2003;9(4):
39 Goals of TherapyClinically 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 1Reference: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 injectionsTwice 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 145% treatment success rate (SVR) for Caucasians with genotype 1Near 70% SVR for genotypes 2 and 3Females 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 usePsychiatric diseases must be managed and fairly well controlledNormal or abnormal transaminasesNo active medical problems with expected mortality
45 Peg Interferon Ribavirin blocks virus into cellsinhibits intracellular replicationstimulates bodies immune systemrenally clearedantifibrotic actionSynergistic with InterferonInduces defective replication of HCV RNABetter tolerated than InterferonNot effective monotherapy
46 Side effects: Peg Interferons Flu like symptomsFatigueDepression/mood lability/insomniaAnorexiaInjection site reactionsCan stimulate Autoimmune diseaseSkin problemsVisual changesLab alterations
47 Side effects: Ribavirin TeratogenicityHemolytic anemiaMI with anemiaSOB, pulmonary infiltrates or pneumonitisSkin rash
48 Hepatitis C Treatment – Adverse Events Dose discontinuations commonMost 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)CytopeniasThyroid DysfunctionLiver failureYour clients on treatment WILL experience potentially severe side effects – expect it!
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 nottreated (29.6%)No show forHCV 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 identifiedPsychiatric 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 recordedActive 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
56 Location of VA Transplant Centers KidneyIowa City, IANashville, TNPittsburgh, PAPortland, ORLiverNashville, TN *Richmond, VA *HeartCleveland, OH * +Madison, WI *Nashville, TN * +Richmond, VASalt Lake City, UT *Palo Alto, CA *LungRichmond, VA +Bone MarrowNashville, TNSan Antonio, TXSeattle, WA* Sharing Agreement Sites + Temporarily Inactive
58 Liver Transplantation 6 months free from:Tobacco, alcohol and all illicit substances with documented attendance at AA or in similar programPatients 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 yearsLiver Transplantation 2003; 9:
60 Burden of DiseaseHepatocellular Carcinoma (Liver cancer) is the most common primary hepatic malignancyThe vast majority of patients with Hepatocellular Carcinoma (HCC) have underlying CirrhosisRisk of HCC in patients with HCV is 17 times higher than HCV negative controlsWe 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 appropriatePatient EducationRefer quickly for Hepatitis B and C positivityScreen all positive Hepatitis B and C patients for HCC