HEPATITIS C BASICS ILAN S. WEISBERG, MD DIRECTOR HEPATOLOGY LENOX HILL HOSPITAL JUNE 20, 2015
Overview Understand the GLOBAL and US burden of chronic HCV infec<on Review the natural history of HCV infec<on Realize current HCV screening guidelines Recognize the impact that disease eradica<on has on the natural history of HCV related complica<ons
GLOBAL PREVALENCE OF HCV >2.9% 2.0%- 2.9% 1.0%- 1.9% <1.0% No data available Perz JF, et al. 42nd Annual Mee<ng of IDSA; Boston, MA; Sept 30- Oct 3, 2004. Data source: World Health Organiza<on.
Hepa<<s C Genome Heterogeneity 7 distinct genotypes 30% difference at nucleotide level 25% - 30% difference at amino acid level Long-standing viral diversity Simmonds P. Curr Stud Hematol Blood Transfus. 1998;62:49-50.
USA Genotype Distribu<on Genotypes 4,5,6 3% Genotypes 2 and 3 22% Genotype 1 75% Hoofnagle JH. Hepatology 2002;36:S21- S29. McHutchison JG, et al. N Engl J Med 2009;361:580-93.
USA: BURDEN OF DISEASE 180 million people infected worldwide 4-5 million (2%) in the USA Primary indica<on for liver transplant Leading cause of liver related death 7 to 13 thousand deaths annually Extrahepa<c manifesta<ons less well recognized: NHL, MCL 4-5 million 75% Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C; 2010."
HCV Is Leading Cause of Liver Transplants in the US Primary cause of disease among adults on the liver transplant wait list, 2011 Primary cause of disease among adult liver transplant recipients, 2011 Acute hepatic necrosis HBV Malignancy 2.6% 2.8% All others 26.4% 6.0% Cholestatic disease 9.0% HCV 30.1% Alcoholic liver disease 23.2% Metabolic liver disease Acute hepatic necrosis Cholestatic disease 2.5% 4.0% All others 22.3% 9.1% Alcoholic liver disease 17.6% HCV 23.5% Malignancy 20.9% Available at: hcp://srtr.transplant.hrsa.gov/annual_reports/2011/pdf/03_%20liver_12.pdf.
CumulaRve Mortality (%) 35 30 25 20 15 10 5 HCV Viremia Was Associated With Increased Mortality in a Prospec<ve Taiwanese Cohort Study AnR- HCV+, HCV RNA detectable AnR- HCV+, HCV RNA undetectable AnR- HCV All Causes (n=2394) 12 30.1%* 10 12.8% 12.4% 0 0 2 4 6 8 10 12 14 16 18 20 8 6 4 2 Liver Cancer (n=115) 10.4%* 1.6% 0.3% 0 0 2 4 6 8 10 12 14 16 18 20 20 18 16 14 12 10 8 6 4 2 ExtrahepaRc Diseases (n=2199) 19.8%* 12.2% 11.0% 0 0 2 4 6 8 10 12 14 16 18 20 Follow- Up (Years) Follow- Up (Years) Follow- Up (Years) REVEAL HCV: Risk Evalua<on of Viral Load Eleva<on and Associated Liver Disease/Cancer (1991-2008). An<- HCV seronega<ve (n=18,541); an<- HCV seroposi<ve (n=1095; detectable HCV RNA: 69.4%). Average follow- up: 16.2 years. Among extrahepa<c causes of death, 68.5% and 69.3% were noncancer deaths for HCV seronega<ve and seroposi<ve, respec<vely. *P<.001 for comparison among all 3 groups and P<.001 for HCV RNA detectable vs undetectable. Lee M- H, et al. J Infect Dis. 2012;206:469-477.
Higher Cancer Rates in HCV Patients: Real-World Evidence from a Large Health Maintenance Organization Cancer diagnosis rate is higher for HCV pa<ents vs. non- HCV pa<ents, even when excluding liver cancer (p<0.001) Univariate analysis shows that cancer rates were significantly higher for liver cancer, non- Hodgkin lymphomas, and total cancer sites Cancer rates are higher in HCV parents; these results suggest another possible manifestaron of HCV ALL SITES (W/O HCC) ALL SITES (W/ HCC) PROSTATE RENAL LUNG HEAD / NECK NON-HODGKIN LYMPHOMA CRUDE HCV vs. NON- HCV CANCER RATES MYELOMA PANCREAS LIVER COLON / RECTUM STOMACH ESOPHAGUS * * * * * * * * * * * * ** 0.1 1 10 100 RATE RATIO (95% CI): HCV vs. NON-HCV *p<0.001; **p<0.005 Nyberg AH, EASL, 2015, O058
NATURAL HISTORY OF HCV INFECTION Acute Infec<on Chronic HCV Asymptoma<c Infec<on 20-30 years Cirrhosis HCC ESLD
GROWING BURDEN OF HCV MORBIDITY AND MORTALITY Na<onal mul<ple cause mortality data from 1999-2007 HCV related deaths have overtaken HIV HCV related deaths increased to >15,000 73% of deaths occurred in persons age 45-65 Mortality Rate per 100,000 Persons Ly KN et al. 2012. Annals of Internal Medicine
FORECASTING THE MORBIDITY AND MORTALITY OF HCV IN THE USA Rein et al. Journal of Diges<ve and Liver Disease. 2010
HCV Disease Burden in the U.S. q 1.76 million will develop cirrhosis q 418,000 will develop liver cancer, and q 1,071,000 will die from complications of hepatitis C infection or 1/3 of all persons currently infected Rein, DB, Wittenborn, JS, Weinbaum, CM, et al. Journal of Digestive Liver Diseases 2010.
Increasing Health Care Costs Associated With Progressive Liver Disease in the Aging HCV- Infected Popula<on Prevalence (95% CI) Health Care Cost (95% CI) While the prevalence of HCV infec<on is declining from its peak, the incidence of advanced liver disease and associated health care costs con<nue to rise Modeling does not take into account any impact of birth cohort screening A system dynamic modeling framework was used to quantify the HCV-infected population, the disease progression, and the associated cost from 1950-2030. CI=confidence interval. Razavi H, et al. Hepatology. 2013. Epub ahead of print.
Predictions for 2010-2019 193,000 HCV deaths 720,700 million years of advanced liver disease 1.83 million years of life lost $11 billion in direct medical care costs $21.3 and $54 billion societal costs from premature disability and mortality Wong Am J Pub Health 2000
HCV- Infected Persons in the US: Es<mated Rates of Detec<on, Referral to Care and Cure CDC & USPSTF recommend 1-time testing of baby boomers (born 1945-1965) 3500 3000 X1000 persons 2500 2000 1500 1000 500 50% 32-38% 20-23% 7-11% 5-6% 0 Infected Diagnosed Referred HCV RNA Treated Cure to care test Holmberg S, N Engl J Med 2013; 368: 1859
RISK BASED SCREENING FOR HCV The op<mal approach to detec<ng HCV infec<on is to screen persons for a history of risk of exposure and test selected individuals who have an iden<fiable risk factor AASLD 2009 Injec<on drug use Blood Transfusion Prior to 1992 Hemophiliacs receiving blood products before 1987 Unexplained eleva<on in ALT Hemodialysis HIV Children of HCV Mothers Sexual Partners of HCV
CDC Has Revised Screening Recommenda<ons for HCV
New York State Law Goes into Effect January 1, 2014 HepaRRs C Virus TesRng (Chapter 425 of the Laws of 2013) This new law requires a hepa<<s C virus screening test to be offered to all pa<ents born between 1945 and 1965 who are receiving health services as a hospital inpa<ent or receiving primary care services and applies to physician, physician assistant, or nurse prac<<oner. The law further requires that the health care provider refer a pa<ent who receives a posi<ve screening test to another provider to receive confirmatory tes<ng and follow- up care.
Rising incidence of HCV in non- urban individuals < 30 years of age MMWR May 2015 surveillance data 2006-2012 364% increase in acute HCV in persons < 25 from 4 Appalachian states (KY, TN, WV, VA) Primarily non- hispanic white individuals from non- urban communi<es Associated with increased injec<on of prescrip<on opioid analgesics Similar findings reported in analagous popula<ons in Upstate NY Zibbel et al. MMWR May 2015 Aibbel et al. Am J Pub Health. 2014
EVOLUTION OF HCV THERAPY 2015 > 95% SVR RATE (%) 1986 6% 1986 16% 1998 34% 2002 44% 2011 ~70%
IMPACT OF SVR ON NATURAL HISTORY OF HCV INFECTION NonResponders SVR Decompensa<on 13% 1.3% Liver Transplanta<on 11% 0.7% Hepatocellular Carcinoma 9.1% 1.4% Liver Related Death 6.8% 0.7% Everson et al. HALT- C Study Group. 2009 Lok et al. HALT- C Study Group. 2009.
SVR Associated with a Reduc<on in All- Cause Mortality SVR Backus L, Boothroyd D, Phillips B, et al. Clin Gastro Hepatol 2011.
Conclusions Global and US burden of HCV is rising as the infected popula<on ages Tremendous toll an<cipated for both individuals living with HCV and health care delivery systems To change the disease, efforts to improve screening must be coupled with increased access to highly ac<ve an<viral medica<ons
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