Stop HCC THE CASE FOR HEPATITIS C SCREENING OF BABY BOOMERS TO PREVENT LIVER FAILURE AND CANCER

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1 Stop HCC THE CASE FOR HEPATITIS C SCREENING OF BABY BOOMERS TO PREVENT LIVER FAILURE AND CANCER BARBARA J TURNER, MD, MSED J a m e s D a n d O n a I D y e P r o f e s s o r o f M e d i c i n e D i r e c t o r, R e s e a r c h t o A d v a n c e C o m m u n i t y H e a l t h ( R e A C H ) C e n t e r U n i v e r s i t y o f T e x a s H e a l t h S c i e n c e C e n t e r S a n A n t o n i o

2 You will learn answers to: What is hepatitis C and what does it do? Who is at risk for HCV infection? How do you diagnose persons with HCV infection? How do you conduct HCV screening and linkage to care? How to evaluate, manage, and cure chronic HCV?

3 What is Hepatitis C? TO UNDERSTAND HEPATITIS C (HCV), WE NEED TO LOOK CLOSER AT THE LIVER

4 The liver: Makes chemicals that your body needs to stay healthy Removes waste and harmful substances from your blood Protects against infection Builds and makes proteins and sugars Stores vitamins, sugars, fats and other nutrients Releases chemicals and nutrients in the body when needed.

5 Hepatitis C infection: Most common blood-born, contagious infection in US caused by a virus Often few or no symptoms for years Acute: short term illness but in 60-85% can lead to Chronic: long-term, potentially deadly disease of the liver and may lead to: Fibrosis (inflammation) Cirrhosis (scarring and liver failure) Liver cancer (HCC)

6 Effects of chronic HCV on the liver Fibrosis Cirrhosis Hepatocellular Carcinoma (with cirrhosis) Fibrosis 1 Chronic HCV infection can lead to the development of fibrous scar tissue within the liver HCC 3 Cancer of the liver can develop after years of chronic HCV infection Cirrhosis 1,2 Over time, fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure Chronic liver disease includes fibrosis, cirrhosis, and hepatic decompensation; HCC=hepatocellular carcinoma. 1. Highleyman L. Hepatitis C Support Project. Accessed August 18, 2011; 2. Bataller R et al. J Clin Invest. 2005;115: ; 2. Medline Plus. Accessed August 28, 2012; 3. Centers for Disease Control and Prevention. Accessed May 8, 2012.

7 Time from HCV infection until serious complications End Stage Liver Disease About 30 years Normal Liver Fibrosis Cirrhosis HCC Stable Disease Cure reduces but does not eliminate the risk of liver failure and hepatocellular carcinoma (HCC)

8 Liver Failure Significant cause of morbidity and mortality high demand for health care services About 50% of all U.S. liver transplantations result from liver damage from HCV infection at a cost of >$100,000 Although most persons with HCV will not need a transplant, even a few are very expensive

9 HCV and HBV: dominant causes of hepatocellular carcinoma in the US 33% (N=691) 15% 5% 47% HCV Both HBV Neither Calle EE. N Engl J Med Apr 24;348(17):

10 Hepatocellular Carcinoma (HCC) Most common type of liver cancer Chronic HCV increases the risk Treated with surgery, medications or liver transplant But poor prognosis so want to prevent development Obesity

11 Consequence: Hepatitis C Kills 1999 to 2007: HCV-associated mortality increased 50% 2013: 19,368 HCV-related deaths* 73% in persons aged Median age of death was 57 (or about 20 years less than average life expectancy) *These represent a fraction of deaths attributable in whole or in part to chronic hepatitis C Ward. Clin Liver Dis 2013;17:1-11

12 Who is at increased risk for HCV infection? WHY TARGET BABY BOOMERS? WHO ELSE TO TARGET?

13 HCV Statistics Nationally HCV infection is the most common blood borne infection An estimated 3.7 to 5 million persons have HCV In 1980s, yearly incidence of HCV infection around 230,000 cases per year but by 2001 declined to 25,000 cases Cirrhosis develops in 10% - 20% of persons with chronic HCV after 20 to 30 years. Chou R. Screening for Hepatitis C Virus Infection: Systematic Evidence Review No. 24.

14 Total No. Infected (millions) HCV is nearly 4 times as prevalent as HIV and HBV 4 Prevalence of Chronic Viral Infections 2.7 to 3.9 Million 1 75% Unaware of Infection 3 Undiagnosed Million 1 21% Unaware of Infection ~800,000 to 1.4 Million 1 65% Unaware of Infection Diagnosed 1 0 HIV HBV HCV HBV=hepatitis B virus; HCV=hepatitis C virus; HIV=human immunodeficiency virus. 1. Institute of Medicine. Washington, DC: The National Academies Press; Chak E, et al. Liver Int. 2011;31(8):

15 How is HCV spread? Source: CDC and Prevention

16 Prevalence of HCV by birth year NHANES, 2002

17 Age of HCV-infected population by year and risk of advanced liver disease/hcc Thomas D. Nature Medicine 2013:19,

18 USPSTF Guidelines One time screening of all baby boomers (born 1945 through 1965) for HCV infection (USPSTF Rating: Class I, Level B) Enzyme immunoassay (EIA) is the initial screening test for anti-hcv antibodies. Followed by Polymerase Chain Reaction (PCR) for the virus

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20 Guidelines: Other risk groups Unexplained chronic liver disease or high ALT Injection-drug use (even once) or intranasal drug abuse Ever in jail Long-term hemodialysis (ever) Transfusions or organ transplants: before July 1992 or clotting factor given before 1987, HCV+ transfusion Tattoo in an unregulated setting Children born to HCV-infected women Healthcare/public safety workers exposed to HCV+ blood HIV infection Born in a high risk country

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22 Percent 8 HCV Antibody Prevalence and Patient Characteristics NHW NHB MA < HS > HS > 2 times 1-2 times Below Race/Ethnicity Education Poverty threshold income NHW: Non-white Hispanic NHB: Non-Hispanic Black MA: Mexican American HS: High School Ditah et al. J Hepatol. 2014;60:691-8.

23 Percent HCV Antibody Prevalence by Patient Characteristics, cont Mean N alcoholic drinks/d N of lifetime sexual partners Lifetime drug use

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25 How about Texas? WHAT REGIONS HAVE MORE HCV? WHAT ABOUT LIVER CANCER IN TX?

26 Chronic HCV in Texas In 2000, nearly 400,000 Texans (1.79%) were estimated to be chronically HCV+ Yalamanchili K. Proc (Bayl Univ Med Cent) Jan; 18(1): 3 6.

27 Incidence rate per 100,000 Racial-ethnic incidence for HCC in U.S. and Latinos in S. Texas White Black Asian S. Texas Latinos El-Serag HB et al, Ann Intern Med 2003 Ramirez AG, PLoS One. 2014; 9(6): e Year * Per 100,

28 What about diagnosing HCV infection? TWO IMPORTANT TESTS: ANTI-HCV ANTIBODY AND HCV RNA BABY BOOMER SCREENING PROGRAMS HERE IN TX

29 Testing for HCV infection HCV antibody (anti-hcv) Positive: shows that the individual has been infected at some point with HCV Negative If exposure to HCV within the past 6 months in an individual suspected of having liver disease, retest Test for HCV RNA if positive for anti-hcv To determine if still infected Test for HCV RNA if patient is immunocompromised (may not have anti-hcv).

30 Screening Tests for HCV Infection

31 Our HCV Program Project funded by the CDC to implement HCV screening for all never-screened baby boomers admitted to University Hospital in San Antonio Two 1115 Medicaid Waiver projects to implement preventive, HCV screening and linkage to care of baby boomers within in 5 Bexar county primary care practices and 2 primary care practices in the Rio Grande Valley Cancer prevention grant to implement HCV testing in 12 South Texas and 10 Dallas primary care practices

32 Results from inpatient program Unique admissions: 9,037 Mean age: 56.6 y (SD 6.5) Women 44.7% Self-identified Hispanic 59.1% Excluded HCV diagnosis: 993 (10.9%) Prior HCV test but no HCV diagnosis: 2,957 (32.7%) Other exclusions or refused : 505 (5.6%) Screened: 4,582 (50.7% or >95% of eligible patients)

33 Testing and Follow-up Care Tested for HCV Ab (n = 4582) HCV Ab Positive (n = 316, 6.9%) HCV RNA Tested (n = 287, 91%) HCV Ab Negative (n = 4266, 93.1%) HCV RNA Incomplete (n = 29, 9%) HCV RNA Positive (n = 175, 61.1%) HCV RNA Negative (n = 112, 38.9%) Counseled (n = 131, 93.6%) Follow-up Laboratory/Imaging (n = 125, 71.4%)

34 Key findings from our program Hispanics less likely to have HCV infection equally likely to have chronic HCV four times more likely than non-hispanic whites to have more advanced liver disease at diagnosis Overweight or obese persons were more likely to have advanced liver disease Heavy alcohol users (past or current) and uninsured persons more likely to have advanced disease

35 What to tell patients newly diagnosed with chronic HCV AVOID RISKS AVOID SPREADING THE DISEASE THERE IS HOPE NEW EFFECTIVE DRUGS

36 Patient Counseling Case manager and health care team should: Teach patients about what HCV is and how it affects the liver Teach about ways to keep from spreading to others Teach about ways to reduce damage to the liver Provide assistance with getting follow up primary care and HCV specialty care Overcome barriers to care: Insurance No primary care provider

37 Persons with chronic HCV should: Take care not to spread hepatitis C to family, friends, others: Avoid exposure to blood Razors, toothbrushes, or other personal care items Do not give blood, body organs, tissues or semen Avoid rough sex Limit or, better even cut out, alcohol Be vaccinated for hepatitis A and hepatitis B Let the doctor of HCV diagnosis to avoid dangerous drugs Even some herbal medicines and over-the-counter drugs are risky Get HCV treatment

38 Factors that can worsen HCV liver damage Alcohol consumption HIV Co-infection with hepatitis A or B Older age (>40 years) at infection Diet high cholesterol Obesity related fatty liver disease?

39 Co-factors that worsen liver disease in persons with chronic HCV infection Alcohol adds fuel to the fire Cirrhosis Heavy Drinker No Scarring 1 0 Light or Non-Drinker < Years of Hepatitis C Infection

40 HIV shortens time to cirrhosis

41 What about obesity?

42 What can obesity do to the liver?

43 Non-alcoholic liver disease adds to HCV damage

44 The Good News! NEW HIGHLY EFFECTIVE MEDICATIONS

45 Goal of Treatment CURE!

46 Direct Acting Antivirals Gane, E.J., et al. American Journal of Transplantation. 2014;14(5):

47 What treatment is available? Harvoni One pill once a day Viekira Pak Two tablets once a day and 1 tablet once a day Olysio & Sovaldi Two pills once daily Ribavirn & Sovaldi Three pills twice a day & One pill daily Daklinza & Sovaldi Two pills once daily

48 Weekly blister packs

49 Preparing for HCV therapy Screen HCV Ab Confirm Infection & Genotype Stage Fibrosis Treat? With What? Relevant History and Physical Assess Compliance HCV Evaluation and Staging -Treatment history (interferon therapy or DAA) -Genotype (1, 2, 3..) and subgenotype (1a vs 1b). -Imaging -Viral load (copies/ml) -Fibrosis score (i.e. Fib-4) -Drug-drug interactions (DDIs)

50 HCV Genotype 1a: Most common in US Genotype 1 Genotype 2 Genotype 3 Genotype 4,5,6 2/3 genotype 1a 1/3 genotype 1b

51 Effectiveness of HCV medications Rate of cure for each regimen varies depending on Genotype Presence of cirrhosis Prior treatment for HCV Most of these have >90% cure rate every 10 people who get treated, 9 will be cured

52 Real world HCV cascade of care Yehia et al. PloS one, 2014

53 Monumental costs of HCV drugs Science 11 July 2014

54 Problem of the cost of drugs

55 So what s the problem?

56 Barriers persist even with effective new drugs Provider Barriers Not enough specialists to treat the ~2-3 million patients with chronic HCV in this country Specialists in academic medical centers not accessible to many marginalized populations HCV patients feel stigmatized by specialists that may not serve low income, minorities or drug users Patient Barriers Patients have poor knowledge or misinformation about HCV Difficulty accessing healthcare Competing priorities other diseases, family issues, no $ Low perceived health risks for a disease without symptoms

57 How do we connect patients to treatment? Insurance Medicaid may not approve treatment unless you have cirrhosis or HCC (too late?) Patient Assistance Program If NO insurance Requires application and proof that have no income

58 The Case of Mr. Bud Wiser Mr. W is a 54 y/o Hispanic male (born 1950) Receives his primary care at federally qualified health center Routine testing for HCV shows Anti-HCV+ Follow-up testing shows HCV RNA 2,500,000 Has distant history of blood transfusion before 1992 Drinks 4-6 beers per day Only symptom is fatigue that is limiting his ability to work as day laborer

59 What next? Physical exam Easiest and most cost effective first step in evaluating for cirrhosis HCV without cirrhosis has few exam findings Hepatomegaly suggests active inflammation; massive HM suggests cofactor such as alcohol Small liver suggests cirrhosis Splenomegaly suggests portal hypertension Mr Bud Wiser has no enlarged organs

60 Look for these physical exam findings Spider angiomata of chest/neck suggests portal hypertension, lower extremity edema Palmar erythema, gynecomastia suggests altered estrogen metabolism c/w cirrhosis (spiders) (icterus) (ascites and jaundice)

61 Laboratory tests for chronic HCV HCV genotype Hepatic function panel (total bilirubin, AST, ALT, Alk phos) CBC with platelets INR Albumin Creatinine HIV (1% of HCV pts will be HIV + but 40% of HIV pts will be HCV positive Imaging (ultrasound)

62 Mr Bud Wiser s test Lab AST 53, ALT 42, AP 136 ALB 3.1, T BILI 1.2, WBC 3.4, HGB 13.5, PLT 105,000 INR 2.0 HIV negative Ultrasound notes irregular liver border, mild splenomegaly and no masses Impression: cirrhosis

63 FIB-4 calculation Fibrosis-4 (FIB-4) Calculator The Fibrosis-4 score helps to estimate the amount of scarring in the liver. Enter the required values to calculate the FIB-4 value. Age (years) [54] x AST Level (U/L) [53] FIB-4 = Platelet Count (10 9 /L) [105] x ALT (U/L) [42] = 4.21 Interpretation: Using a lower cutoff value of 1.45, a FIB-4 score <1.45 had a negative predictive value of 90% for advanced fibrosis. In contrast, a FIB-4 >3.25 would have a 97% specificity and a positive predictive value of 65% for advanced fibrosis. Source: Sterling RK, Lissen E, Clumeck N, et. al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology 2006;43:

64 Child-Pugh score for cirrhosis Surgical risk for major abdominal surgery: Childs A = 10%; Childs B = 31%; Childs C = 82%

65 Cirrhosis, HCV and HCC Our patient is at high risk for developing hepatocellular carcinoma because he has BOTH cirrhosis and HCV Liver cancer is now among the top 10 cancers in Texas Early detection of HCV and treatment is key to survival because once HCC develops, the prognosis is poor. Refer all HCC for specialty care

66 Plans for Mr Bud Wiser Apply for Medicaid If rejected, can still apply for drug assistance program through companies that make anti-hcv drugs Counsel about his alcohol use!! Also review his diet obese or high cholesterol Avoid drugs metabolized in the liver Monitor every 6 months for risk of HCC (ultrasound)

67 Thousand of people also heading for disaster

68 What to do? Screen all baby boomers and at risk groups for HCV infection Diagnose chronic HCV infection and evaluate disease stage Counsel and link chronically infected to counseling and care Monitor patients with cirrhosis for HCC (even if cured of HCV still at risk for HCC)

69 Together we can STOP HCV and HCC

70 Thank You!