Hepatitis C Epidemiology: 2015 Update

Hepatitis C Epidemiology: 2015 Update Vincent Lo Re, MD, MSCE Assistant Professor of Medicine and Epidemiology Division of Infectious Diseases Center for Clinical Epidemiology and Biostatistics University of Pennsylvania

Learning Objectives Upon completion of this presentation, learners should be better able to: Review prevalence, risk factors of HCV infection Determine who should be screened for HCV Appreciate impact of HIV suppression on liver outcomes Identify cofactors of HCV liver disease progression Recognize the beneficial effects of HCV eradication

Faculty and Planning Committee Disclosures Please consult your program book. Off-Label Disclosure There will be no off-label/investigational uses discussed in this presentation.

Outline Prevalence, risk factors of HCV infection HCV screening, diagnosis Natural history of HCV and impact of HIV Role of cofactors on liver outcomes in HIV Beneficial effects of HCV treatment

Worldwide Prevalence of HCV Estimated 170 million (3%) infected with HCV infection worldwide 5 million HIV/HCV-coinfected 62 M 4.4 M 9 M 32 M 21 M 32 M 10 M 600 K Hanafiah KM. Hepatology 2013;57:1333-42.

Estimated Prevalence (%) U.S. Prevalence of HCV Infection 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 National Health and Nutrition Examination Survey, 2003 2010 1.3% 3.6 (3.0-4.2) Anti-HCV 1.0% 2.7 (2.2-3.2) HCV RNA Estimated Persons Infected, million (95% CI) 5 8% with chronic HCV have HIV coinfection Chronic HCV more likely: Male Aged 40-59 years Born 1945-1965 Non-Hispanic black Less than high school Denniston MM. Ann Intern Med 2014;160:293-300.

HCV Genotypes: Worldwide Distribution HCV genotype 1 is most common genotype worldwide Non-genotype 1 comprises sizable number of HCV cases Messina JP. Hepatology 2015;61:77-87.

HCV Genotypes: U.S. Distribution General Population 1 NHANES (n=250) 1 73.7% HIV/HCV Coinfection 2 AACTG Cross-Sectional Analysis (n=66) 1 83.3% 3 7.4% 2 14.9% 3 9.1% 2 6.0% 6 3.1% 4 0.9% 1 Alter MJ. N Engl J Med. 1999;341:556-562. 2 Sherman KE. Clin Infect Dis. 2002;34:831-837. 4 1.6%

HCV Transmission Risk Factors Transfusion (before 7/92), 10% Other,* 5% Unknown, 10% Sexual, 15% Injection Drug Use, 60% Serodiscordant heterosexual couples, <1% * Health-care work; tattoos intranasal drugs; perinatal CDC. http://www.cdc.gov/hepatitis/hcv/index.htm HIV / HCV+ mother child, 2-5% HIV+/HCV+ mother child, 19%

Anti-HCV+, % Prevalence of HCV Infection in HIV, 100 85.1% 90 80 70 60 50 40 30 20 10 0 Injection Drug Use 14.3% Heterosexual Contact Sulkowski MS. Ann Intern Med 2003;138:197-207. By Risk Factor 9.8% 45.1% MSM Entire Cohort 1,955 HIV+ patients cared for at Johns Hopkins HIV Clinic

Increasing Incidence of Acute HCV Among HIV-Infected MSM Clusters of acute HCV in HIV+ MSM reported Ulcerative infections more common in incident cases Linkages made to: High-risk sexual behaviors (e.g., fisting, trauma) Recreational non-injection drug use Gilleece et al. JAIDS 2005; 40:41 46. Gotz et al. AIDS 2005; 19:969 974. Luetkemeyer A. JAIDS 2006; 41:31 36. Fierer DJ. J Infect Dis 2008; 198:683 686.

Treatment Cascade for Chronic HCV 50% of HCV+ Individuals are Unaware of Their HCV Status Yehia BR. PLoS One 2014;160:293-300.

50% of HCV+ Are Unaware of HCV Status Patient Barriers Reluctance to discuss HCV risk factors Clinician Barriers Providers unaware of or reluctant to ask about HCV risk factors Systemic Barriers Stigmatization of HCV in health system, community Institute of Medicine. Hepatitis and Liver Cancer. 2010.

Who Should Be Screened for HCV? All persons born 1945-1965 Persons at increased risk: History of injection drug use Received clotting factors made before 1987 Received blood transfusions/organs before July 1992 Hemodialysis Children born to mothers with HCV Known exposure to HCV Unexplained ALT levels HIV Screen HIV+ patients for HCV: At least once Annually, if IDU or MSM Smith BD. MMWR 2012;61(RR-4):1-32; Moyer VA. Ann Intern Med 2013;159:349-57.

How to Screen for HCV Infection? Anti-HCV antibody If positive HCV RNA testing to determine if viremic HCV RNA testing Anti-HCV positive Anti-HCV negative, but suspect acute HCV Anti-HCV negative, but severely immunocompromised Ghany MG. Hepatology 2009; 49:1335-74.

Natural History of HCV Infection Acute HCV 14-45% Spontaneous Clearance 55-86% Chronic HCV 20% in 20 yrs Hepatic Inflammation Hepatic Fibrosis Extrahepatic Complications Cirrhosis 2-4% per yr 2-5% per yr Hepatocellular Carcinoma Hepatic Decompensation Seeff LB. Hepatology 2002;36 (Suppl 1):S35-46.

Complications of Cirrhosis Ascites/Peritonitis Variceal Hemorrhage Hepatic Encephalopathy Hepatocellular Carcinoma

Mortality from Chronic HCV Mortality Rates of HBV, HCV, HIV: United States, 1999 2007 1 Predictions for HCV Mortality: United States 2 HIV Hepatitis C Hepatitis B 1 Ly KN. Ann Intern Med 2012;156;271-8. 2 Rein RB. Dig Liver Dis 2011;43:66-72.

HIV Adversely Affects Every Aspect of Natural History of HCV clearance of HCV HCV viral load vs. HCV risk of end-stage liver disease (ESLD) vs. HCV risk of hepatocellular carcinoma (HCC) vs. HIV Spontaneous Clearance Acute HCV HIV HCC + Chronic HCV + Cirrhosis + + ESLD Weber R. Arch Intern Med 2006;166;1632-41.

Liver Disease is a Major Cause 40% 35% 30% 25% 20% 15% 10% 5% 0% of Death in HIV+ Persons Chronic viral hepatitis AIDS Liver Cardiac Cancer Other Causes of death in 33,308 HIV+ adults followed from 1999-2008 in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Weber R. Arch Intern Med 2006;166;1632-41.

Risk of ESLD by ART Status and Time Since Initiation 10,090 HIV/HCV patients Veterans Aging Cohort Study (VACS), 1996-2010 ART initiation, ESLD events ascertained ART risk of ESLD Anderson JP. Clin Infect Dis 2014;58:719-27. ART Status No ART Adjusted HR of ESLD (95% CI) Ref. Initiated ART 0.72 (0.54 0.94) Time Since ART Initiation No ART Adjusted HR of ESLD (95% CI) Ref. <2 years 0.75 (0.56 1.01) 2-4 years 0.69 (0.46 1.03) >4 years 0.53 (0.34 0.83)

Liver Decompensation Rates are Higher in HIV/HCV vs. HCV Only Patients 4,280 ART-Treated HIV/HCV-Coinfected 6,079 HCV-Monoinfected Lo Re V. Ann Intern Med 2014;160;369-79. Veterans Aging Cohort Study (1997-2010)

Decompensation Rates are Reduced with HIV Suppression HCV-Monoinfected Lo Re V. Ann Intern Med 2014;160;369-79. Veterans Aging Cohort Study (1997-2010)

Natural History of HCV Infection Acute HCV 14-45% Spontaneous Clearance 55-86% Chronic HCV 20% in 20 yrs Hepatic Inflammation Hepatic Fibrosis Cofactors: Alcohol and hepatitis B may accelerate fibrosis Cirrhosis 2-4% per yr 2-5% per yr Hepatocellular Carcinoma Hepatic Decompensation Seeff LB. Hepatology 2002;36 (Suppl 1):S35-46.

Advanced Liver Fibrosis (FIB-4>3.25), By Level of Alcohol Use and HIV/HCV Prevalence of Advanced Fibrosis Odds Ratio of Advanced Fibrosis Lim JK. Clin Infect Dis 2014;58:1449-58.

Anti-HBV Therapy Reduces Risk of Decompensation in HIV/HBV/HCV Incidence Rate (events/1,000 person-years) HIV/HBV/HCV (n=149) 24.1 HIV/HCV (n=4,902) 10.8 Group Risk (95% CI) of Decompensation HIV/HBV/HCV with no anti-hbv therapy 2.48 (1.37 4.49) HIV/HBV/HCV on anti-hbv therapy 1.09 (0.40 2.97) Lo Re V. Clin Infect Dis 2014;59:1-16.

Liver-related mortality or liver transplantation, % All-cause mortality, % Sustained Virologic Response (SVR) Reduces Mortality in HCV SVR=HCV RNA 24 weeks (now 12 weeks) after stopping therapy 530 patients followed median 8.4 years after interferon treatment 30 Liver-Related Mortality or Liver Transplantation 30 All-Cause Mortality P<0.001 P<0.001 20 20 10 Without SVR 10 Without SVR With SVR 0 0 1 2 3 4 5 6 7 8 9 10 Time, y With SVR 0 0 1 2 3 4 5 6 7 8 9 10 Time, y Van der Meer AJ. JAMA 2012:308:2584-93.

Take-Home Points One-time HCV screening recommended for all adults born from 1945-1965 Suppression of HIV with ART ESLD May be no safe level of alcohol in HIV/HCV HBV therapy can ESLD in HIV/HBV/HCV Successful HCV therapy ESLD, mortality

How often should HCV screening be performed in an HIV-infected MSM? 1) Once 2) Every 6 months 3) Yearly 4) Every other year

Which of the following can reduce the risk of ESLD in HIV/HCV patients (choose all)? 1) Use of ART 2) Suppression of HIV on ART 3) Nonhazardous alcohol consumption 4) HBV treatment if HBV-coinfected

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