On the Rise: Liver Cancer in Iowa Donald J. Hillebrand, MD. GI-Hepatology, Transplant Hepatology Medical Director, UnityPoint Health Center for Liver Disease 2017 Iowa Cancer Summit October 19-2017

On the Rise: Liver Cancer in Iowa Increasing incidence of liver cancer (HCC) in US/Iowa Driving forces behind the increasing incidence of HCC Strategies to prevent liver cancer Public health professionals Health care providers Strategies to detect early liver cancer

On the Rise: Liver Cancer in Iowa Increasing incidence of liver cancer (HCC) in US/Iowa Driving forces behind the increasing incidence of HCC Strategies to prevent liver cancer Public health professionals Health care providers Strategies to detect early liver cancer

Liver Cancer in Iowa Ranks 13th as leading cause of cancer deaths in Iowa Incidence and Mortality increasing in Iowa as throughout US Incidence has roughly tripled over the past 35 years 1975-79 incidence of 2 cases per 100,000 2010-14 incidence of 6 cases per 100,000

Bucking the Trend Increasing incidence and mortality Burden of various cancers in Iowa over time. Blue columns represent new cases diagnosed in Iowa each year (incidence) and red columns represent cancer deaths in Iowa each year (mortality).

Top 10 Types of Cancer in Iowa Estimated for 2017 13th leading cause of cancer deaths in Iowans among men and women combined 2nd leading cause of cancer deaths worldwide

US Liver Cancer Trend Increased incidence/mortality

US Liver Cancer Trend Increased incidence/mortality State Health Registry of Iowa Cancer in Iowa 2017

Liver Cancer Burden Iowa comparison

Clearly Targeted Males and Baby Boomers

Iowa Liver Cancer impact Greater toll among Black, Asian, Pacific Islanders

On the Rise: Liver Cancer in Iowa Increasing incidence of liver cancer (HCC) in US/Iowa Driving forces behind the increasing incidence of HCC Strategies to prevent liver cancer Public health professionals Health care providers Strategies to detect early liver cancer

US Liver Cancer Driving Forces Chronic Hepatitis C 50-60% Chronic Hepatitis B 10-15% Alcoholic Liver Disease 20-25% Metabolic Syndrome 20-30% Obesity Diabetes NAFLD (Non-Alcoholic Fatty Liver Disease) Hepatology. 2014 November ; 60(5): 1767–1775.

US Liver Cancer Driving Forces PAF (population attributable fraction) Accounts for both an estimate of relative risk as well as prevalence of a given risk factor in the population Hepatology. 2014 November ; 60(5): 1767–1775.

US Liver Cancer Trend Number of HCV driven HCC projected to peak in 2019 A recent mathematical model based on the prevalence and natural history of HCV in the U.S. general population of HCV-infected individuals estimated that the number of HCC cases increased from 37,697 between 1990 and 1999 to 86,765 (+130%) between 2000 and 2009, with a projected increase to 130,366 (+50%) cases between 2010 and 2019. NASH-related cirrhosis HCC increasing Hepatology. 2014 November ; 60(5): 1767–1775.

On the Rise: Liver Cancer in Iowa Increasing incidence of liver cancer (HCC) in US/Iowa Driving forces behind the increasing incidence of HCC Strategies to prevent liver cancer Public health professionals Health care providers Strategies to detect early liver cancer

Strategies to Prevent Liver Cancer Public Health Professionals Institute HCV screening per CDC recommendations CDC Recommendation: Adults Born from 1945-1965 (Baby Boomers) get Tested for Hepatitis C In addition to testing adults of all ages at risk for hepatitis C virus infection, CDC recommends: All adults born during 1945–1965 receive one-time testing for the hepatitis C virus (HCV). Testing should begin with anti-HCV. If the anti-HCV test is positive, or reactive, then a nucleic acid test (NAT) should follow. All persons identified with current HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services.

Strategies to Prevent Liver Cancer Public Health Professionals Key Facts about People Born 1945-1965 (Baby Boomers) and Hepatitis C Of the estimated 3.2 million people chronically infected with hepatitis C in the U.S., approximately 75% were born during 1945-1965. National prevalence data show that people born during these years are five times more likely than other adults to be infected with HCV. Hepatitis C is a leading cause of liver cancer and the leading cause of liver transplants; people born during 1945-1965 account for 73% of all hepatitis C- associated mortality.

Strategies to Prevent Liver Cancer Public Health Professionals Rationale for Recommendation High prevalence of hepatitis C in people born during 1945–1965, with 75% of people with hepatitis C born during these years. There is increasing HCV-associated morbidity and mortality, as annual HCV-associated mortality in the US increased more than 50% from 1999 to 2007. People born 1945-1965 with hepatitis C face increasing hepatitis C-associated morbidity and mortality. A high proportion of people with hepatitis C do not know that they are infected (estimates range from 45%-85%).

Strategies to Prevent Liver Cancer Public Health Professionals Testing based solely on elevated ALT levels is estimated to miss 50% of chronic infections. For those who are chronically infected, clinical preventive services including regular medical monitoring, hepatitis A and B vaccination, and behavior changes like alcohol reduction/cessation and achieving and maintaining a healthy BMI can improve health outcomes for people with hepatitis C. New therapies, including interferon-free regimens, can halt disease progression cure most infected with hepatitis C. One-time testing of those born 1945-1965 is estimated to identify 800,000 infections and, with linkage to care and treatment, avert more than 120,000 HCV-related deaths.  This strategy is estimated to save $1.5-$7.1 billion in liver disease-related costs.

Strategies to Prevent Liver Cancer Public Health Professionals Testing persons at high risk for infection, educating patients, and administering effective therapies for treating HBV and HCV is therefore an important component of prevention against HCC. Nearly 40-70% of individuals with HCV unaware Davis et al., assuming an SVR rate of ~80%, antiviral treatment will decrease cases of cirrhosis by a mere 5% in 2020. However, extending the treatment of half of infected persons would reduce HCC by 30.2%; treatment of all infected individuals would reduce the risk by 60.4% after just 10 years. Thus, a reduction in the incidence of HCC may not be achieved unless an increasing number of patients are diagnosed and treated.

Strategies to Prevent Liver Cancer Public Health Professionals Promote access to DAA (direct-activing antivirals) IA Medicaid currently has arbitrary restrictions limiting access Stage 3-4 fibrosis requirement Currently limits patients without advanced fibrosis to “inexpensive” 8-week treatments with drugs carrying > 98% cure rates for HCV ledipasvir/sofosbuvir glecaprevir and pibrentasvir

Effect of Cure SVR-12 (Sustained Virological Response - 12 weeks) Decreased liver inflammation and fibrosis Resolution of early cirrhosis in many patients Decreased development of primary liver cancer Decreased development of liver failure and liver related mortality Decreased need for liver transplantation Decreased all-cause mortality From the patient's perspective there is improvement in health related quality of life (HRQOL) and an increase in quality adjusted life years (QALYs)

Effect of Cure Extrahepatic Manifestations Ther Adv Infect Dis (2016) 3(1) 3_14. DOI: 10.1177/2049936115585942

Strategies to Prevent Liver Cancer Public Health Professionals In the US, injection drug use (IDU) is the primary risk factor for HCV infection and accounts for 68% of all new HCV infections. Roughly 32% of people who inject drugs become infected with HCV within the first year of injecting, and 53% become infected within five years (Hagan et al., 2008). Increases in HCV infection related to IDU among people 30 years of age and younger is a trend that has been reported by CDC in many areas of the country. Much of this increase in injection drug use among youth is related to increases in use of prescription opioids and heroin. In Iowa, rates of heroin and opioid-related overdoses have increased greatly over the last 10 years. ED visits related to opioid overdoses have increased by roughly 253% ED visits from heroin increased by 2,500% from 2003 through 2014 for individuals under 35 years of age (IDPH, 2016).

Strategies to Prevent Liver Cancer Public Health Professionals The whole number values in each county represent the counts of Iowans living with HCV who were 30 years of age or younger and residing in the county at time of diagnosis. The bottom values represent the rate of HCV per 100,000 population.

Strategies to Prevent Liver Cancer Public Health Professionals Addressing the increasing incidence of IDU-related HCV under age 30 years Opiate addiction treatment Needle exchange programs HCV screening HCV treatment Nearly all would be non-cirrhotic and most treatment-naive

Strategies to Prevent Liver Cancer Health care Providers Alcohol abuse screening Counseling regarding appropriate body weight goals Management of NAFLD/NASH HCV screening Risk factor guided Baby Boomers Linkage to care of any HCV+ patients Appropriate use of the curative HCV treatments HBV screening based on risk factors

On the Rise: Liver Cancer in Iowa Increasing incidence of liver cancer (HCC) in US/Iowa Driving forces behind the increasing incidence of HCC Strategies to prevent liver cancer Public health professionals Health care providers Strategies to detect early liver cancer

Late in the Game Majority Diagnosed with Regional/Distant Disease

Regional/Distant Disease Long term survival poor

Strategies to detect early liver cancer Public health professionals Education PSA similar to breast cancer (mammogram), cervical cancer (PAPs, HPV vaccination), colon cancer (colonoscopy), etc. Educate those with risk factors for or known liver disease that they should be undergoing surveillance* Promotion/Expectation of surveillance as Standard of Care

Strategies to detect early liver cancer Health care Providers AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update Jordi Bruix and Morris Sherman Recommendation 1. Patients at high risk for developing HCC should be entered into surveillance programs (Level I). The at-risk groups for whom surveillance is recommended are identified in Table 3.

Strategies to detect early liver cancer Health care Providers Imaging Criteria for diagnosis of HCC EASL and AASLD Criteria Nodules > 2 cm demonstrating early arterial enhancement and rapid venous/late phase wash out on CT/MRI in a cirrhotic liver

Strategies to detect early liver cancer Health care Providers High-Risk Group Cirrhosis represents a key risk factor for the development of HCC. The prevalence of cirrhosis among patients with HCC has been estimated to be 85%-95%7, and the HCC incidence rate among patients with cirrhosis has been shown to be 2%-4% per year. Therefore, patients with cirrhosis constitute a high-risk group for efforts at prevention and early detection. The fact that patients with HCC have underlying liver disease significantly impacts the management and therapeutic options.

Strategies to detect early liver cancer Health care Providers The AASLD recommends surveillance of adults with cirrhosis because it improves overall survival. Quality/Certainty of Evidence: Moderate Strength of Recommendation: Strong The AASLD suggests surveillance using ultrasound (US), with or without alpha fetoprotein (AFP), every 6 months. Quality/Certainty of Evidence: Low Strength of Recommendation: Conditional

Strategies to detect early liver cancer Health care Providers

Strategies to detect early liver cancer Health care Providers Small HCC’s such as those that can be detected by surveillance can be cured with an appreciable frequency. Early Detection, Curative Treatment, and Survival Rates for Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis: A Meta-analysis Amit G. Singal et al Published: 2014 https://doi.org/10.1371/journal.pmed.1001624 HCC surveillance was associated with improved early stage detection (odds ratio [OR] 2.08, 95% CI 1.80–2.37) and curative treatment rates (OR 2.24, 95% CI 1.99–2.52). HCC surveillance was associated with significantly prolonged survival (OR 1.90, 95% CI 1.67–2.17), which remained significant in the subset of studies adjusting for lead-time bias. Conclusions: HCC surveillance is associated with significant improvements in early tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis.

Education Top 5 Ways to Prevent Liver Cancer Ways to improve general health and decrease liver cancer: 1. Don’t smoke cigarettes 2. Reduce your alcohol intake 3. HBV vaccination 4. Practice safe sex 5. Do not share needles

Education Top 10 Ways to Prevent Liver Cancer? Ways to improve general health and decrease liver cancer: Weak evidence 6. Treat any disease that increases liver cancer 7. Exercise and maintain an appropriate weight 8. Limit exposure to cancer causing chemicals 9. Statins 10. Coffee … and to live healthier

On the Rise: Liver Cancer in Iowa Increasing incidence of liver cancer (HCC) in US/Iowa Driving forces behind the increasing incidence of HCC Strategies to prevent liver cancer Public health professionals Health care providers Strategies to detect early liver cancer 2017 Iowa Cancer Summit The End: Thank You for Your Attention!