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Challenges of Treatment of Hepatitis C in the Incarcerated US Population USPHS Scientific and Training Symposium June 23, 2011 Dr William Resto-Rivera MD, USPHS Kiesha Resto Pharm D, USPHS Objectives #1) Compare Hepatitis C Virus (HCV) infections in prison population versus the regular population. #2) Analyze the challenges of identifying and treating prison population. #3) Review common & rare side effects that are related to Hepatitis C therapy. #4) Discuss challenges in treating patients with co-morbid conditions. #5) Review recent FDA approved medications for HCV. US Hepatitis Statistics 1.3% • US population infected Hepatitis C Virus (HCV) • People infected with HCV will pass through US prison system every year 29-43% • US Prison population infected with 16-40% HCV Reference #4 Population • Baby boomers account for 2 out of 3 cases of HCV patients. • Peak prevalence men born in early 1950’s • HCV is over-represented in African Americans. Reference #5 Every 100 people infected with HCV 75-85 develop chronic infection 5-20 develop cirrhosis 60-70 develop chronic liver disease 1-5 die from cirrhosis or liver cancer Center of Disease Control & National Institutes of Health Convention January 2003 identified 5 optimal approaches to Screening & treating HCV in US prisons • #1 Testing of HCV in Prisons would identify many Infected Americans • #2 Prison Substance Abuse programs would decrease HCV infections & future prisons cost • #3 Patients can be Selected using Published Guidelines • #4 Prisons Treatment Reflects Community Standards and Require Sufficient Medical Workforce • #5 Collaboration Between Correctional & Public Health Systems is Needed Reference #14 Factors for Treatment • Screening • Screening and Diagnosis of Hepatitis C individuals. • Screening for candidates for treatment • Safety , Efficacy & Cost • Monitoring Laboratories and ADR • Patient Tolerate treatment • Viral Response to treatment • EVR/SVR • Source of funding Hepatitis C Not a Routine Universal Screening Routine screening based on 4 criteria: • • • • Amenable to treatment Interfere with activities of daily living Progress without treatment during time of incarceration Risk of transmission Reference # 14 To Screen or to Not Screen Rhode Island State Corrections Screened all incoming inmate • 4263 Males – 23% + HCV • 499 Females – 40% HCV Out of inmates who tested + HCV 66% did not report high risk behaviors Reference #16 Wisconsin State Corrections 91% HCV infected inmates identified through testing 27% of population with risk factor IVDA Indiana State Corrections Universal testing found 13% of population HCV (+) Reference #14 USA and territories Incarcerated population 2008 Total Federal & State Prisons Territorial Prisons Local Jails 2,424,279 1,518,559 13,576 785,556 ICE Facilities 9,957 Military Facilities 1,651 Jails in Indian Country 2,135 Juvenile Facilities 92,845 Reference #3 Break down of 2,424,279 16-40% 1 to 3 % • US prison population infected with HCV 387,884 -- 969,711 • Progress to end stage liver disease 3,878 -- 29,091 Summary of Assumptions of Paid Cost per Patient Per Month (PPPM) as of 2008 Reference #22 Medicare Disease States Commercial Age<65 Age >65 $525 more than avg $460 more then avg $370 more than avg $772 more then avg $611 more than avg $13,900 $7,100 $7,100 $12,700 $4,200 $4,200 $5,500 $2,400 $2,400 $4,900 $2,100 $2,100 $38,900 $24,700 $24,700 $5,600 $3,800 $3,800 $3,900 $2,200 $2,200 $174 more than avg Chronic HCV Infection (without Cirrhosis) Compensated Cirrhosis without Complication Decompensated Cirrhosis 6 months 0- Decompensated Cirrhosis months +6 Hepatocellular Carcinoma months Hepatocellular Carcinoma months Liver Transplant 6 months Liver Transplant 18 months Liver Transplant 18 months 0-6 +6 06+ Missed Opportunity Benefits for treatment during Incarceration •Lower cost in long run for HCV treatment •Stable living environment •Accessible medical care •High Risk Population •Direct Observed Medication •Abstinence from Substance abuse •Coordination between Rehabilitation programs and treatment Hepatitis C • • Multiple Genotypes • 1 Most common (US) Approx. 80% • 2/3 US Approx 20% • 4 Egypt RNA Virus • Family Flavovirus ( Denque, yellow fever) US Hepatitis C Statistics • Genotype 1 40-50% Successful SVR at 12 months • Genotype 2/3 70-80% Successful SVR at 12 months Contraindications to Ribavirin 1. Thalassemias (sickle cell anemia) or other hemoglobinopathy. 2. Significant cardiac disease (arrhythmias, angina, CABG, MI) in the past 12 months. 3. Renal dialysis or creatinine clearance < 50 mL/min. 4. 5. Hypersensitivity to ribavirin Pregnancy Reference #1 Ribavirin Side Effects Black Box Warnings: • Hemolytic Anemia Warning (primarily in the first two weeks of therapy) • Pregnancy Warning. Negative pregnancy test is required pre-therapy & at every evaluation • Respiratory Warning for patients requiring assisted ventilation Reference #1 Contraindication Peg-Interferon • Serious concurrent medical diseases; severe hypertension, heart failure, coronary heart disease, COPD , autoimmune disorders, uncontrolled endocrine disorder • Decompensate cirrhosis, History of solid organ transplant • Platelet count <75,000/mm3 or ANC <1,500 cells/mm3 • Ongoing injection drug use or alcohol use • Severe uncontrolled psychiatric disease Reference #1 Carswell 20072010 Statistical Data: Annals Internal Medicine 2004 (6) Statistical Data: Hematology 2002 (7) 26% 55% 64% 63% 25% 63% 21% 32% 42% 35% 43% 63% 48% 64% Mood Changes 42% 26% 35% Gastro-intestinal 21% 20% Adverse Event Headache Pruritis Decrease Appetitie Nausea / vomiting Fatigue Anemia Neutropenia Thrombocyto 42% 22% 21% 20% 21% 4% Reference # 6 & #7 Management of Side Effects • Headaches/ Body aches • • Tylenol • FLUIDS, FLUIDS, FLUIDS • NSAIDS!!!??? Nausea & Vomiting • Promethazine Hemoglobin adjustment 10-11 g/dl 8.5-10 g/dl <8.5 g/dl If no or minimal symptoms, then no dose modification If symptomatic, decrease ribavirin by 200 mg/day Peginterferon alfa 2b ( Peg-Intron) Reduce 25-50% Ribavirin ↓ to 600 mg daily (200 mg AM & 400mg PM) Peginterferon alfa 2b (Peg-Intron) Discontinue until resolved. Ribavirin Discontinue until resolved. If hemoglobin is <12g/dL for over 4 weeks at the reduced/adjusted dose then discontinue ribavirin Reference #1 Absolute Neutrophil Count (ANC) Adjustment <750 Peginterferon alfa 2b (Peg-Intron) Reduce to a 25% -50% dose <500 Peginterferon & Ribavirin Discontinue both until resolved Granulocyte Colony Stimulating Factor (G-CSF): If the patient is responding to treatment and neutropenia persists despite reduced peginterferon dose, consider G-CSFDosage: Filgrastim 300 microgram subcu. daily. Goal: ANC >1500 Reference #1 Platelet Adjustment <50,000 Peginterferon alfa 2b (Peg-Intron) <30,000 Discontinue until resolved. Ribavirin If on Peg-Intron, then discontinue ribavirin. Peginterferon Discontinue until resolved. Ribavirin Discontinue until resolved. Reference #1 Serious Adverse Reaction • Auto immune • Arrhythmias • Depression / Psychosis • CHF • Permanent thyroid dysfunction Patients with Comorbid conditions • Pre-exiting Cardiac Condition • Renal Disease • Autoimmune Disease • Depression Case Studies Digest of Liver Disease 2011 Nephrology, Dialysis, Transplant 2003 Journal of Rheumatology 1996 • Tx 23 pre-existing heart disease patients with INF & Ribavirin • 52% reached SVR, 39% relapse, 9% non responders • EKG & Echo show no signs of progression of preexiting heart disease • Tx 7 patients with vasculititis and GN successfully with INF & Ribavirin • 19 patient referred from PCP for polyarthritis, polyarthralgia, or positive rheumatoid factors where found to have hepatitis Reference # 8-#10 New Treatment Options Boceprevir ( Victrelis) • • • • FDA approved May 13, 2011 Hepatitis C Genotype 1 Naïve & Relapse patients 800 mg tablets x 44 weeks after 4 week lead in Telaprevir (Incivek) • • • • FDA approved May 23, 2011 Hepatitis Genotype 1 Naïve and Relapse patient 750 mg tablets TID for first 12 weeks of therapy Telaprevir (Incivek) • Naive & Relapser (1088) • Treatment 75% SVR • Control 45% SVR ADVANCE • Naïve ( 704) • Treatment 80% SVR • Control 50% SVR • No benefit extending tx • 92% SVR @ 24wks • 88% SVR @ 48wks ILLUMINATE • Relapsers (650) • Treatment 56% SVR • Control 22% SVR REALIZE Reference #20 Boceprevir (Victrelis) SPRINT-2 RESPOND2 • Treatment Naïve (1,097) • Treatment Group 69% SVR Control Group 40% SVR • African American Treatment 69%SVR Control 40% SVR • Non-Responders and Relapsers (403) • Treatment Group 66% SVR Control Group 21% SVR Reference #21 Adverse Effects Boceprevir (Victrelis) • Fatigue, Headache, Nausea, Dysgeusia • Anemia (3% require discontinuation of therapy) Telaprevir (Incivek) • Fatigue, Headache, Nausea, Pruritis • Anemia & Rash ( 0.6-1.1% require discontinuation of therapy) Summary • Prison are an ideal setting to treat a large population of HCV (+) people. • Screening for HCV need to be examined cost/benefit per institution. • Treating patient while incarcerated can be a cost saving to society • HCV treatment is associated with multiple side effects that need an educated multidiscipline approach to manage Summary • Guidelines are established for screening and to help guide management of adverse events. • Patient with co-morbidies are an increase challenge to treat but can be treated safely and effectively with proper monitoring. • New Antiviral medications just approved will improve overall outcomes in the future. References 1. Federal Bureau of Prisons Clinical Guideline Prevention of Hepatitis C and Cirrhosis June 2009 2. Raison. Depression During Pegylated Interferon-Alpha Plus Ribavirin Therapy: Prevalence and Prediction. J Clin Psychiatry. 2005 January ; 66(1): 41–48. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615913/pdf/nihms3152.pdf ( Accessed 4/11) 3. http://en.wikipedia.org/wiki/Incarceration_in_the_United_States (Accessed 9/24/10) 4. Jennifer A. Tan, Tom A. Joseph, Sammy Saab, Treating hepatitis C in the prison population is cost-saving ,Hematology . 2008; 48: 1387-1395 5. Suzanne M. Kirchhoff, Economic Impacts of Prison Growth, Congressional Research Service, April 13, 2010. http://assets.opencrs.com/rpts/R41177_20100413.pdf (Accessed 9/24/10 ) 6. Hadziyannis, S. Peginterferon-2a and Ribaviriin Combination Therapy in Chronic Hepaitits C. Annals of Internal Medicine. 2004 ;140: 346-357 7. Fried, M. Side Effects of Therapy of Hepaptitis C and Their Management. Hepatology. 2002: 36. References 8. Bruchfeld, A. Lindahl, K. Interferon and Ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrology Dialysis Transplantation, 2002;18, 1573-1580. http://ndt.oxfordjournals.org/content/18/8/1573.short ( Accessed 4/2011) 9. EL-Atrebi, K. El-Bassyouni, H. Management of rare side effects of peginterferon and ribavirin therapy during hepatitis C treatment: a case report. Case Journal 2009:2 : 7429 10. Lovy M.R, Starkemaum G. Hepatitis C Infection Presenting with Rheumatic Manifestations: Mimic of Rheumatoid. Journal of Rheumatology 1996; 23;979-983 11. Center of Disease Control Morbidity and Mortality Weekly Report. Prevention and Control of Infections with Hepatitis Viruses in Correctional Settings. January 24, 2003 / Vol. 52 / No. RR-1 12. Durante-Mangoni E, Iossa D. Safey and efficacy of peginterferon alpha plus ribavirin in patients with chronic hepatitis C and coexisting heart disease. Dig Liver Dis 2011 [ pub ahead of print]. 13. Ghany M, Strader B. Diagnosis, Management, and Treatment of Hepatitis C: An Update. HEPATOLOGY 2009; 49: 1335-74 References 14. Spaulding A, Weinbaum C. A Framework for Management of Hepatitis C in Prisons. Annals of Internal Medicine 2006; 144: 762-769 15. 15. Kim R. The Burden of Hepatitis C in the United States. Hepatology 2002;36:S30-S34 16. Macalino G. A Missed Opportunity: Hepatitis C Screening of Prisoners. AM J Public Health. 2005;95: 1739-1740 17. Sutton A, Edmund J. Estamating the cost-effectiveness of detecting cases of chronic hepatitis C infection on reception into prison. BMC Public Health 2006;6;170 18. Mc Hutchinson J, Brunce B. Chronic Hepatitis C: An Age Wave of Disease Burden. Am J Manag Care 2005;11:S286-S295 19. Wong J, McQuillan G. Estimating Future Hepatitis C Morbidity Mortality, and Cost in the United States. Am J Public Health. 2000;90:1562-1569 20. http://www.hivandhepatitis.com/hep_c/news/2011/0524_2011_a.html ( Accessed 6/2/11) References • 22. B. Pyenson. Consequences of Hepatitis C virus (HCV): Cost of a Baby Boomer Epidemic of Liver Disease. Vertex Pharmaceuticals Incorporations. Miliman, Inc. May 2009. QUESTIONS ??