Hepatocellular Carcinoma (HCC): Burden of Disease

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1 Hepatocellular Carcinoma (HCC): Burden of Disease Blaire E Burman, MD VM Hepatology

2 Hepatocellular Carcinoma (HCC) Primary HCCs most often arise in the setting of chronic inflammation, liver damage, and regenerative changes - Predisposition of the proliferating cell to a variety of genetic changes at the genomic and transcriptional levels HCC is a complex disease associated with many risk factors and cofactors Tumors may present as a single mass lesion or as diffuse growth - May be difficult to differentiate from surrounding cirrhotic tissue and regenerating nodules Tumors progress with local expansion, intrahepatic spread, and/or distant metastases Discovered via screening of high risk patients, as an incidental finding on imaging, or when symptomatic due to size or location Fattovich et al, Gastro 2004; El-Serag et al, NEJM 2011

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4 Hepatocellular Carcinoma 80-90% of HCCs arise in the setting of cirrhosis Chronic HBV and/or HCV underlie 80% of HCCs worldwide; lower proportion in the US Alcoholic liver disease and non-alcoholic steatohepatitis (NASH) contribute to many cases 5 30% of patients with cirrhosis will develop HCC during their lifetime HCC is the leading cause of death in cirrhosis Non-cirrhotic HCC most commonly attributable to: Chronic HBV infection Fibrolamellar HCCs Malignant transformation of adenomas Other poorly understood pathways El-Serag et al, NEJM 2011; Fattovich et al, Gastro 2004

5 Global Burden of HCC 5 th most common cancer globally High mortality: 2 nd or 3 rd leading cause of cancer death Significant regional variation in incidence rates Greatest burden of HCC in low resource regions of the developing world (85%) >80% of incident cases in sub-saharan Africa and Eastern Asia Incidence patterns reflect variation in risk factors for HCC - Countries with the highest burden of HBV and HCV infections have the highest incidence of HCC - NASH-related HCC rising in developed countries GLOBOCAN (WHO) 2012; MMWR (CDC) 2010; El-Serag et al, Gastro 2012

6 Age-standardized incidence rates of liver cancer in males per 100,000 population. IARC: International Agency for Research on Cancer

7 Burden of HCC in the United States HCC incidence has tripled over 30 years from 1975 to 2005, from 1.6 to 4.9 cases per 100,000 Largest proportional increases among US-born Hispanics and blacks; lowest increases among Asians Age distribution shifted to younger adults years Strong south to north gradient in HCC incidence and mortality Increases in US HCC incidence between 1975 and 2005 Age-standardized incidence per 100, Annual % Change Overall % Men % Women % Projected 36,000 new HCC cases in the US in 2015, and nearly 25,000 HCC deaths Venook et al, Oncologist 2010; Altekruse et al J Clin Oncol, 2009; Ramirez et al Plos One, 2012

8 Health Disparities in HCC In the US, HCC disproportionately and increasingly affects disadvantaged populations Highest rates among racial/ethnic minorities HCC cases are clustered in areas of low SES high poverty, high unemployment, low education Ethnic minorities also have worse survival Disparities in HCC prevention (ie: vaccination, treatment) Disparities in early detection (ie: surveillance) Disparities in HCC treatment rates Why are rates of HCC rising in the US? American Cancer Society: Cancer Facts and Figures 2015; Singal et al Am J Med 2014; Artinyan et al Cancer 2010

9 Hepatitis C (HCV) and HCC Chronic HCV = leading cause of HCC in Western world Among HCC cases in the US, 50-60% attributable to HCV, 10-15% to HBV, and 30-35% unrelated to viral hep HCV confers a fold increase in relative risk o Higher risk for GT 1b and 3, longer duration of high viremia Once HCV-related cirrhosis is established, HCC develops at an annual rate of 1-4% Factors that predispose HCV-infected patients to HCC: concomitant heavy alcohol use, obesity, diabetes, increasing age, HBV co-infection El-Serag et al, Gastro 2002; El-Serag et al, NEJM 2011; Altenkruse et al, Am J Gastro 2014

10 HCV and HCC HCV-related HCC has become the fastest-rising cause of cancer-related death in the US 130% increase in such cases between 2000 and 2009 Related to increased proportion of HCV-infected persons with longer duration of HCV disease and now cirrhosis Rising rates of obesity and diabetes among HCV-infected population Temporal trends of HCC risk factors in the US: greatest proportional increase in HCC cases related to HCV Projections indicate that without effective diagnosis and treatment, HCV-related HCC incidence will continue to rise Overall burden of HCV-related deaths rising and expected to peak in Altekruse et al, J Clin Onc 2009; El-Serag et al, Gastro 2012; Rein et al, Dig Liver Dis 2001

11 HCV Treatment and HCC Risk What is the role of HCV therapy in primary prevention of HCC? Of recurrent disease? For those with cirrhosis, HCV eradication lowers but does not eliminate the risk of incident HCC. Critical to continue surveillance post-cure In older studies, the risk of HCC was reduced by 57-75% for those treated with interferon-based therapy who achieved SVR Ability of oral direct acting antivirals to prevent HCC unstudied Recent breakthroughs in HCV therapy may change the trajectory of HCC in the US ONLY if an increasing number of patients are diagnosed and treated Singal et al, CGH 2010; DiBisceglie et al, NEJM 2008.

12 HCC Outcomes and Survival 2 nd or 3 rd leading cause of cancer mortality worldwide* HCC accounts for 9.1% of all cancer deaths Overall 5-year survival remains a dismal 12% with available therapy Yet 5-year survival rates approach 70% with surgical resection, ablation, or transplant for early stage disease Early diagnosis is crucial in order to provide effective treatment GLOBOCAN (WHO) 2012; SEER Database (NCI) 2010

13 HCC Outcomes and Survival With aggressive screening, the rate of resectable HCC diagnosed in high-risk patients reaches 30-50% Nearly twice the rate of unscreened populations In practice, HCC screening and surveillance is inadequate and inconsistently applied Even with ideal imaging every 6 months, up to 1/3 of HCCs are detected beyond Milan (transplant) criteria Half of these cancers are considered biologically aggressive (diffusely infiltrative, vascular infiltration, high AFP levels) Llovet et al, 2004 Liver Transplantation; Del Poggio et al, CGH 2014

14 Emerging Trends in HCC Incidence and Mortality SEER data used to examine temporal trends in HCC incidence, incidence-based mortality, and survival, (>63,000 cases) Found a deceleration of HCC incidence around 2006 HCC incidence is still rising in the US, yet this rise has slowed significantly Since 2009, for the first time in 4 decades, there was no increase in US incidence or IB-mortality Prediction that HCC incidence rates may stabilize and potentially decrease over next 3-5 years Major improvements in HCC mortality are achievable with improved application of early detection and utilization of curative therapies Njei et al. Emerging Trends in Hepatocellular Carcinoma. Hepatology, 2015

15 HCC Management Forner et al. Hepatocellular carcinoma, The Lancet, 2012.

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