HCV: Racial Disparities Charles D. Howell, M.D., A.G.A.F Professor of Medicine University of Maryland School of Medicine Baltimore, MD
Charles Howell Disclosures Research Grants Boehringer Ingelheim, Inc. Bristol Myer Squibb, Inc. Gilead Sciences, Inc. Advisory Boards Genentech, Inc. Janssen, Inc. Vertex, Inc.
Hepatitis C Virus (HCV) in US 4 million infected with HCV (NHANES 1999-2002) 3 million with chronic HCV (viremia) Most common blood-borne viral infection Leading cause for cirrhosis & primary hepatocellular carcinoma (HCC) Indication for ~50% of liver transplants Armstrong GL et al. Ann Intern Med. 2006;144(10):705-714.
Factors Associated with Fibrosis in HCV Age at infection Duration of infection Metabolic factors (steatosis, obesity, diabetes) Compromised immune system Genetic factors HIV co-infection HBV co-infection Heavy alcohol use Normal liver Cirrhosis Poynard T, et al. Lancet.1997;349:825-832. Monto A, et al. Hepatology. 2002;36:729-736. Marcolongo M, et al. Hepatology. 2009;50:1038-1044. Cecil Medicine 23 rd edition. Saunders Elsevier, Philadelphia, PA 2008.
HCV Genotypes in US Germer JJ, et al. J Clin Microbiol. 2011 May 25. [Epub ahead of print]
NHANES III Demographic Characteristics of Persons Infected with HCV Genotypes 1, 2, and 3 Genotype 1 Genotype 2/3 % Overall White Black Hispanic Nainan OV et al. Hepatology 2005:42(suppl 1):660A.
Greater HCV Burden in African Americans (AA) HCV twice as prevalent in AA vs. Caucasian (CA) or White (3.0% vs. 1.5%) Race and Ethnicity (NHANES 1999-2002): 2.6 million CA (65%) 920,000 AA infected with HCV (23%) 260,00 Mexican Americans (6.5%) AA: 12-13% of US pop. & 23% of HCV cases 9% of AA 40-49 years old infected compared to 3.8% of CA Estimate 1-2 million AA infected (higher incarceration and homeless rates) Armstrong GL et al. Ann Intern Med. 2006;144(10):705-714.
Trends in HCC Incidence in US NCI SEER Data 14 Per 100,000 Population 12 10 8 6 4 2 0 1992-93 1994-96 1997-99 2000-2002 2003-2005 Total African American.Asian/Pacific Isl Hispanic American Indian/Alaska Native White American Altekreuse, et al. J. Clin. Oncol. 27 (9):1485, 2009
Annual Hepatitis C Mortality Rates: Race/Ethnicity Wise M, et al. Hepatology. 2008;47:1128 1135.
Mortality Rate from HCV Exceeds that of HIV 15,106 12,734 1815 Ly et al. AIM 156:271-278, 2012
HCV-related Deaths in 2007 73.4% Age 45-59 45-54 39% 55-64 34% 70% Males [OR 2.4 95% CI (2.3-2.4)] 18% Non-Hispanic Black [OR 1.9 (1.8-2.0)] 15% Hispanic [OR 3.4 (3.2-3.50] 2.9% HIV Co-infection [OR 5.8 (5.3-6.4)] 3.6% HBV Co-infection [OR 70.3 (63.5-77)] 57.2% Chronic Liver Disease [OR 57 (55-59)] 19.4% Alcohol-related condition [OR 13 (12.8-14)] Ly et al. AIM 156:271-278, 2012
Aging of HCV-Infected Persons in the US: Disease Progression Davis G, et al. Gastroenterology. 2010;138:513-521.
Projected Prevalence of Chronic HCV, Cirrhosis, and Complications Projected Number of Patients With Decompensated Cirrhosis and Hepatocellular Carcinoma 160,000 Number of Cases 140,000 120,000 100,000 80,000 60,000 40,000 Decompensated Cirrhosis Hepatocellular Carcinoma (HCC) 20,000 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 Year Davis GL, et al. Gastroenterology. 2010;138(2):513-521 e516.
HCV Cured by Treatment: Sustained Virological Response (SVR) Tantamount to cure; HCV RNA remains negative in 99% Associated with improvement in liver histology (inflammation, fibrosis) Less frequent liver-related complications Reduced risk of liver decompensation Reduced risk of hepatocellular carcinoma Reduced liver-related mortality Pearlman B, Traub N. Clin Infect Dis. 2011;52:889-900.
Milestones in Therapy of HCV: Overall SVR Rates Average SVR Rates from Clinical Trials 1991 1999 2002 2010 79%* 68%* 54-56% 34% 42% 39% 42-46% 6% 16% Peg-IFN/ RBV 12m T12/ PR24/48 *Data from genotype 1 patients Adapted from Strader DB, et al. Hepatology. 2004;39(4):1147-1171. Hezode C, et al. N Engl J Med. 2009; 360(18):1839-1850. Kwo P, et al. Presented at: EASL; April 23, 2009; Copenhagen, Denmark. Abstract 4. Kwo PY, et al. Lancet. 2010;376(9742):705-716. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416; Poordad F, et al. N Engl J Med. 2011;364(13):1195-1206. Telaprevir prescribing information at http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf. Accessed September 12, 2012.
Screening and Diagnosis
Prevalence of Chronic Hepatitis C Infection In the US, 2.7 3.9 million people are living with chronic HCV infection; 75% are unaware they are infected Centers for Disease Control and Prevention. Hepatitis C FAQs for Health Professionals. Available at: http://www.cdc.gov/hepatitis/hcv/hcvfaq.htm. Accessed January 6, 2011. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C; 2010.
Secondary Prevention of HCV: Risk-based Screening (1998) Goal: diagnosis before advanced fibrosis/cirrhosis when treatment more effective and beneficial Screen at risk groups for anti-hcv Abnormal ALT History of past or current Injection Drug Use Chronic hemodialysis Recipients of clotting factors before 1987 Recipients of transfusion or organ transplant prior to July 1992 Needle stick or mucosal exposure to HCV+ blood Children of HCV+ mothers Sexual partners of HCV+ (AASLD) Enzyme Immunoassay (EIA) 3.0: sensitivity 97-99% & positive predictive value 98-99% in high prevalence groups MMWR 47 (RR-19), October 16, 1998. Armstrong GL et al. Ann Intern Med. 2006;144(10):705-714.
New 2012 Recommendations Individuals Who Should Be Screened for HCV Baby Boomers Born from 1945 1965 Adults born during 1945 1965 should receive one-time testing for HCV without prior ascertainment of HCV risk As of 2012, this includes all individuals between 47 and 67 years of age! Division of Viral Hepatitis, National Center for H. I. V. Aids Viral Hepatitis S. T. D. T. B. Prevention. MMWR Recomm Rep. 2012;61(RR-4):1-32.
Three-fourths Chronic HCV in the US Were Born Between 1945 and 1965 1,600,000 Estimated Prevalence by Age Group Individuals (n) 1,400,000 1,200,000 1,000,000 800,000 600,000 400,000 200,000 0 <1920 1920-1929 1930-1939 1940-1949 1950-1959 1960-1969 Birth Year Group 1970-1979 1980-1989 1990+ Pyenson B, et al. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. New York, NY: Milliman, Inc; 2009.
New 2012 Recommendations Individuals Who Should Be Screened for HCV IDU Clotting factors made before 1987 Received blood/organs before July 1992 Hemodialysis Elevated alanine aminotransferase [ALT] levels HIV Testing also should be performed based on the need for exposure management, including: Health care, emergency, and public safety workers after needlestick/mucosal exposure to HCV-positive blood Children born to HCV-positive women Division of Viral Hepatitis, National Center for H. I. V. Aids Viral Hepatitis S. T. D. T. B. Prevention. MMWR Recomm Rep. 2012;61(RR-4):1-32.
New 2012 Recommendations Reduce Alcohol Use in Patients with HCV All persons with identified HCV infection should receive brief alcohol screening, brief counseling if positive, followed by referral to appropriate care and treatment services Screening tools: National Institute on Alcohol Abuse and Alcoholism WHO NIAAA. Helping Patients who Drink Too Much. http://pubs.niaaa.nih.gov/publications/practitioner/cliniciansguide2005/clinicians _guide.htm Management of Substance Abuse. World Health Organization: http://www.who.int/substance_abuse/activities/sbi/en/index.html. Babor TF, Higging JC. In: Brief Intervention for Hazardous and Harmful Drinking: A Manual for Use in Primary Care. World Health Organization; 2001. http://whqlibdoc.who.int/hq/2001/who_msd_msb_01.6b.pdf. National Center for H. I. V. Aids Viral Hepatitis S. T. D.T. B. Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32. http://www.cdc.gov/mmwr/pdf/rr/rr6104.pdf.
Barriers to Healthcare: Access Access (e.g., insurance status, ability to pay for healthcare) most important predictor of the quality of healthcare across racial and ethnic groups (IOM: Unequal Treatment) Black Americans twice as likely to have no private health insurance Latina American 3 times less likely to have private health insurance Affordable Care Act 2010 access for 60% (~30 million) of uninsured
Barriers to Healthcare: Patient & Provider Knowledge AA, older age, and < high school education less knowledgeable about HCV Low rate of HCV risk factor documented in primary care clinics IDU-12% Blood transfusion before 92-2% Minorities with a HCV risk factor less likely to receive testing (23% vs 35%, P = 0.004) Dig Dis Sci (2011) 56:213 219; World J Gastroenterol (2007) 21; 13(7): 1074-1078.
Disparities in HCV Treatment: Pegnterferon & Ribavirin AA & Hispanics less likely to be treatment candidate according to clinicians AA and Hispanics receive fewer interferon prescriptions for HCV AA more likely to decline treatment (did not explain the disparity) Provider & facility factors have larger effect on variability in treatment than patient factors Gut 56:385, 2007; AP&T 24: 585, 2006; Am J Gastro 100: 1772, 2005; Am J Gastro 100:2186, 2005; HEPATOLOGY 46: 1741, 2007
HCV Screening in Minorities Outcomes and impact of new HCV screening on future liver-related morbidity and mortality need to be closely monitored Less access to health care and other barriers to risk-based screening and treatment Identify and distribute best practices Broad community-based screening; not limited to physician offices Referral to care and treatment
Treatment Considerations
2 Protease Inhibitors (PIs) Approved for HCV Genotype 1 Protease Inhibitor Additional Regimen Components Boceprevir 800 mg TID (q7- PEG-IFN alfa + 9hrs) 1,2 weight-based RBV Telaprevir 750 mg TID PEG-IFN alfa + (q7-9hrs) 2,3 weight-based RBV Considerations Naïve to previous therapy Previous treatment failure Compensated cirrhosis Response-guided therapy (RGT) Naïve to previous therapy Previous treatment failure Compensated cirrhosis RGT For patients with genotype 2/3 infection, HCV therapy with PEG-IFN/RBV remains the standard of care (SVRs-75-82%) 1. Boceprevir prescribing information at http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf. Accessed September 12, 2012. 2. Ghany MG, et al. Hepatology. 2011;54(4):1433-1444. 3. Telaprevir prescribing information at http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/201917lbl.pdf. Accessed September 12, 2012.
Boceprevir: Treatment Naïve Patients SVR and Race P < 0.0001 P < 0.0001 P < 0.004 P < 0.044 n = 311 n = 316 n = 311 n = 52 n = 52 n = 55 Non-Black/African-American Black/African American BOC: boceprevir 800 mg q8h; PR: PegIFN -2b 1.5 µg/kg/wk + weight-based RBV 600-1400 mg/day RGT: boceprevir response-guided therapy FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202258lbl.pdf. Accessed June 2011.
Telaprevir: Treatment Naïve Patients SVR Rates by Race or Ethnicity 258/325 229/315 153/318 16/26 24/40 8/28 27/35 30/44 15/38 TVR: Telaprevir 750 mg q8h; PR: PegIFN -2a 180 µg/wk + weight-based RBV 1000-1200 mg/day; Pbo: placebo FDA Antiviral Drugs Advisory Committee. http://www.fda.gov/advisorycommittees/committeesmeetingmaterials/drugs/antiviraldrugsadvisorycommittee/uc m247236.htm. Accessed June 2011.
HCV Genome & Gene Products: Potential Targets for Direct Acting Antiviral Agents (Present & Future) TenCate V, et al. Hepat Med. 2010;2:125-145. Protease Inhibitors: boceprevir; telaprevir
The Future: Various Paradigms Being Developed Simultaneously Interferon-free regimens PR + single DAA PIs Nucleoside analogs NS5A Inhibitors Quad PR + DAA-1 + DAA-2 DAA = direct-acting antiviral. 33
Under-representation in HCV Clinical Trials Few minorities enrolled in clinical trials 1989-2002; 2004-2006: 3 clinical trials of peginterferon & ribavirin for HCV genotype 1 in AA 2009: 1st clinical trial of peginterferon & ribavirin for HCV genotype 1 in Latino Whites AA and Latinos poorly represented in direct acting antiviral clinical trials Increased participation in clinical trials necessary improve efficacy of therapy in AA evidence-based management