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Chronic HCV: a Global Health Problem

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Chronic HCV: a Global Health Problem Evolving Role of Current & Emerging Therapies in the Management of Hepatitis C (HCV) David H. Winston, MD, FACP, AGAF Section Head, Gastroenterology & Hepatology CIGNA HealthCare of Arizona, Sun City SUN CITY 1 2 HYBRID Objectives • Learn the current and future treatment strategies for HCV • Understand the epidemiology and natural history of HCV • Learn how to diagnose and screen for HCV 3 Hepatitis C Virus (HCV) • Single-stranded RNA virus • Only member of genus Hepacivirus in the Flaviviridae family • Humans are the only known natural host • Unlike the DNA viruses HIV and HBV CURE of HCV infection is possible Hepatitis C Differs from HIV and HBV: HCV can be Cured! HBV HIV HCV Host cell Viral RNA cccDNA Proviral DNA Host DNA Nucleus TREATMENTTREATMENT TREATMENT Long-term Long-term Viral Eradication = Cure suppression of viral suppression of viral replication replication2,3 1. Pawlotsky JM. J Hepatol 2006;44:S10-S13; 2. Siliciano JD, Siliciano RF. J Antimicrob Chemother 2004;54:6-9; 3. Lucas GM. J Antimicrob Chemother 2005;55:413-416 4 EPIDEMIOLOGY OF HCV Chronic HCV: A Global Health Problem FAR EAST ASIA 60 M WEST EUROPE U.S.A. 9 M EAST 3.2 M MEDITERRANEAN 20M SOUTH EAST ASIA 30 M AFRICA 32 M SOUTH AMERICA 10 M AUSTRALIA 0.2 M Weekly Epidemiological Record. N° 49, 10 December 1999, WHO 5 HCV Genotypes 6 HCV genotypes that differ from each other by 31-34% in their nucleotide sequences 1, 2, 3 1, 2, 3 1,2,3 6 4 1,3 4 1, 2, 3 1,2,3 5 Simmonds P. Curr Stud Hematol Blood Transfus. 1998;62:38-63. Genotype and Viral Load in U.S. Patients Genotype 4,5,6 HVL 2.7% Genotype 2,3 LVL Genotype 4,5,6 7.3% LVL 1.3% Genotype 2,3 HVL 14.7% Genotype 1 HVL Genotype 1 LVL 49.5% 24.5% HIGH VIRAL LOAD:>800,000 IU/ML Alter et al. N Engl J Med 1999;341;556-562. LOW VIRAL LOAD:<800,000 IU/ML Blatt et al. J Viral Hepatitis 2000;7(3):196-202. 6 Current Prevalence of HCV • 200 million persons have been infected with HCV worldwide (anti-HCV positive)1 • 170 million have chronic disease worldwide (HCV RNA positive)1 • 3.5 million Americans have been infected with HCV (anti-HCV positive)2 –True prevalence at least 5.2 million3 • 2.7 million Americans have chronic disease (HCV RNA positive)2 1. Edlin BR. Hepatology 2005:42(suppl 1):213A. 2. Denniston MM et al. Ann Intern Med 2014;160:293-300 3. Chak E, Talai AH, Sherman KE, Schiff ER, Saab S. Liver International 2011; 31:1090-1101 Chronic HCV Infection in the US • Chronic HCV cases not included in NHANES estimate: – Homeless – Incarcerated – Veterans – Active military – Healthcare workers – Nursing home residents – Chronic hemodialysis – Hemophiliacs Chak E, Talai AH, Sherman KE, Schiff ER, Saab S. Liver International 2011; 31:1090-1101 7 Prevalence of HCV in the U.S. (NHANES 2001-2010) Overall prevalence: 1% (2.7 million), 81% were born between 1945 and 1965 (Baby Boomers) 3 2.7 2.5 2.2 2 1.5 1.3 1.0 1.0 1 0.5 Anti-HCV Positive Anti-HCV Positive % 0 White Black Hispanic Male Female Denniston MM, et al. Ann Internal Med 2014;160(5):293-300. Chronic HCV in U.S. (3.2M) Undiagnosed ~2.4M (75%) Diagnosed .8M (25%) 59% of diagnosed HCV 41% of diagnosed HCV patients UNTREATED ~590K patients TREATED ~410K (18% of all HCV) (13% of all HCV) ALF @ www.liverfoundation.org/education/info/hepatitisc. Accessed April 8, 2014 CDC Hepatitis C fact sheet. @ www.cdc.gov. Accessed April 8, 2014 IOM. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, DC. 2010 8 Natural History of HCV: A Chronic Progressive Liver Disease HCV Natural Disease Progression Anti-HCV (+) Virus Cleared Cirrhosis HCV-RNA (-) •Connective tissues destroying hepatocytes 15% -25% (<6 months) •Generally irreversible 1%-4% 20-30% per year (20-30 years) Acute Chronic Fibrosis HCV HCV 75%-85% 60%-70% (>6 months) Anti-HCV (+) Hepatocellular HCV-RNA (+) Carcinoma (HCC) Chen SL and Morgan TR. Int. J. Med. Sci. 2006. 3:47-52. 9 HCV Disease Progression Stage 0 Stage 1 Stage 2 No Fibrosis Portal Fibrosis Periportal Fibrosis Few No Septa Septa Stage 4 Stage 3 Cirrhosis Bridging Fibrosis Many Sepa Razavi H, et al. Hepatology. 57(6):2164-2170 Chronic HCV: Progression to Cirrhosis 15%-30% of patients Mild Moderate Severe Cirrhosis 50-65% of patients Decom. Cirrhosis 20%-30% of patients HCC 0 1020304050 Years Shiffman ML. Viral Hepatitis Rev. 1999;5:27-43 10 Factors Associated With Disease Progression • ETOH consumption: >30 g/day in males >20 g/day in females • Disease acquisition at > 40 years •Male • HIV or HBV co-infection • Hepatic Steatosis: obesity, metabolic syndrome Ishida et al. Clin Gastro and Hepatol 2008;6:69-75 Swain et al. EASL 2005. Patton et al. J Hepatol 2004;40:484-490. Poynard et al. Lancet 1997; 349: 825-832. Factors Associated With Disease Progression: ETOH • > 30 g/day in male: 2-3 drinks > 20 g/day in females: 2 drinks NIH Consensus Statement on Hepatitis C, 2002. 11 HCV and Alcohol 100 80 60 HCV 40 HCV + alcohol Cirrhosis (%) 20 0 10 20 30 40 Years Following Exposure Excessive alcohol intake characterized as > 20 g/day for women and > 30 g/day for men Wiley TE, et al. Hepatology. 1998:28:805-809. Factors Associated With Disease Progression: Age Patients infected with HCV when over 40 have a higher degree of fibrosis regardless of how long they have had the disease 12 HCV Fibrosis Progression: Effect of Age 4.0 3.0 Age at time of infection 2.0 > 40 years < 40 years 1.0 Fibrosis Score 0 < 10 11-20 21-30 31-40 > 40 Duration of Infection (Years) Poynard T, et al. Lancet. 1997;349:825-832. Factors Associated With Disease Progression: Obesity Obesity-related insulin resistance can lead to fatty liver and NASH and accelerate the development of fibrosis in HCV Clouston AD, Jonsson JR, Powell EE. Clin Liver Dis 2007;11:173-189. 13 Fibrosis Progression in HCV: Effect of Hepatic Steatosis 100 Steatosis: 80 <5% 5-10% 60 11-30% >30% 40 progression 20 % of patients with fibrosis withpatients of % 0 0 20406080100 Months Fartoux L et al. Hepatology. 2005;41:82-87. Factors Not Influencing Progression • Transaminase level (ALT) • Viral load • Mode of transmission • Genotype Swain et al. EASL 2005. Patton et al. J Hepatol 2004;40:484-490. Poynard T, et al. Lancet 1997;349:825-832. 14 Chronic HCV: The Epidemic has Just Begun At least 2.7 million persons are chronically infected with HCV Between 2010-2030 if NO treatment is provided 1,040,000 will have developed cirrhosis 254,664 will have developed HCC 537,928 will die Davis G, Alter MJ, El-Serag H, Poynard T, Jennings LW. Gastroenterology. 2010;138:513-521 Estimated Prevalence of Esee Chronic HCV and Cirrhosis Peak Prevalence ● Acute infections peaked between 1970 and 1990 The● The highest peak prevalence of chronic of HCV cirrhosis prevalence is projected was to2001 be ● The highest prevalence of cirrhosis is projected to be between 2010 and 2030 Davis G, Alter MJ, El-Serag H, Poynard T, Jennings LW. Gastroenterology. 2010;138:513-521 15 The Tsunami of HCV Cirrhosis Complications: Decompensation and HCC Hepatic decompensation • Ascites • Variceal bleed • Encephalopathy Davis G, Alter MJ, El-Serag H, Poynard T, Jennings LW. Gastroenterology. 2010;138:513-521 Diagnosis & Screening of HCV 16 Importance of Diagnosing HCV • The Primary Care Provider (PCP) has a unique window of opportunity to make a diagnosis of HCV and refer for treatment prior to the development of cirrhosis and its complications –Improved survival –Improve quality of life –Will reduce the economic burden of HCV and result in cost savings HCV Screening Is the First Step on the Road to a Cure Treatment Cure Counseling Evaluation Screening 17 HCV Patients Are Undiagnosed Because of Screening Barriers to Diagnosis Undiagnosed ~2.4M (75%) Diagnosed .8M (25%) 59% of diagnosed HCV 41% of diagnosed HCV patients UNTREATED ~590K patients TREATED ~410K (18% of all HCV) (13% of all HCV) ALF @ www.liverfoundation.org/education/info/hepatitisc. Accessed September 3, 2011 CDC Hepatitis C fact sheet. @ www.cdc.gov. Accessed September 3, 2011 IOM. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, DC. 2010 HCV Patients Are Undiagnosed Because of Screening Barriers to Diagnosis • Patient Barriers –Persons infected with HCV are usually asymptomatic and unaware of their infection –Persons infected with HCV are usually unaware of the risk factors for HCV IOM. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Washington, D.C. 2010 Centers for Disease Control and Prevention. MMWR. 1998;47(RR-19):1-39 18 I hope I don’t have Hepatitis C 19 The Lack of Symptoms in Chronic HCV Infection Symptomatic The most common symptom is fatigue 37% 100 Cirrhosis 80 80 7% 60 40 Patients (%) 20 0 56% Fatigue Asymptomatic Alter MJ, et al. N Engl J Med 1999;341(8):556-62 HCV Patients Are Undiagnosed Because of Screening Barriers to Diagnosis • Primary Care Provider Barriers1 – Routine HCV risk factor assessment not current PCP practice2 – Elevated LFTs, not risk factors, is current marker for PCPs ordering a liver panel3 • Normal ALT in males is up to 30 • Normal ALT in females is up to 19 1IOM.
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