Hepatocellular carcinoma Mary Ann Y. Huang, M.D., M.S., FAASLD Transplant hepatologist Peak Gastroenterology Associates Porter Adventist Hospital Denver, Colorado
Background - Worldwide Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver Worldwide, it is the 5 th most common cancer in men and 7 th most common in women Third leading cause of cancer related mortality in the world (500,000 people affected) Viral hepatitis (both hepatitis B and C) account for the majority of HCC cases 80-90% cases occur in the setting of cirrhosis
Background United States Median survival time approximately 11 months Overall 5 year survival < 12% Fastest rising cause of cancer related death in the US Population-based data showed HCC incidence has doubled 1.4 per 100,000 in 1975-77 4.8 per 100,000 in 2005-07 3 fold increase in both genders from 1975-2007
Rising incidence Approximately half of the increases in HCC cases are attributed to the aging hepatitis C patients Prevalence of cirrhosis and decompensated liver disease doubled from 1996-2006 Prevalence of HCC increased 10 fold from 1996-2006 Incidence has slowed down annually between 2010-12 (0.7% annually) Increase in subgroups, such as white men aged 55-64 years Rates in Hispanics now exceed Asians Geographic variation exists with the highest rate now in Texas
Gastroenterology 2017 152, 812-820.e5DOI: (10.1053/j.gastro.2016.11.020) Copyright 2017 AGA Institute Terms and Conditions
Hepatitis B Etiologies of liver disease Leading risk factor for HCC globally 90% of patients have cirrhosis Accounts for 50% of cases found worldwide HCC can develop in the absence of cirrhosis Accounts for 10-15% of HCC cases in the US Family history of HCC Typically non-white (African American, Asian)
Hepatitis C Etiologies of liver disease Leading risk factor for HCC in the US Annual risk is 1-4% in patients with HCV Baby boomers (patients born between 1945-1965) Achieving a sustained virologic response (SVR), or cure, is associated with lower incidence of HCC 0.9% with SVR vs 3% without SVR
Etiologies of liver disease Non-alcoholic fatty liver disease Currently leading cause of chronic liver disease in the US Almost all patients have features of metabolic syndrome Insulin resistance Visceral obesity SEER-Medicare database show a statistically significant association between metabolic syndrome and HCC
HCC in Non-alcoholic fatty liver disease Appears to be associated with NASH cirrhosis Elevated risk which is approximately 1% yearly Lower than hepatitis C cirrhosis In patients with NAFLD or NASH in clinic based cohort study Absolute risk of HCC between 0-6% in 20 year follow up Population-based cohort studies of patients with NAFLD/NASH 0.3% over 6 years in one study No HCC in another study
Treatments Anti-viral treatments reduce risk of HCC Hepatitis B Patients treated up to 5 years saw a reduction in development of HCC from 7.4% to 3.9% Hepatitis C Multiple studies show that achieving a sustained viral response (ie cure from hepatitis C) reduces risk of HCC in patients with and without cirrhosis
Treatments Surgical options Often limited due to underlying cirrhosis Ablative therapy Radiofrequency ablation Microwave ablation Cryoablation Intra-arterial therapy Transarterial chemoembolization Y-90 Oral chemotherapeutic agents
Liver transplant Most curative treatment for HCC in select patients HCC was a contraindication for transplant until 1996 when Milan criteria were introduced 5 year survival < 35% before 1996 5 year survival > 70% after 1996 Criteria 1 lesion 5 cm 3 lesions with no one > 3 cm No vascular invasion No metastasis
Outcomes HCC accounts for > 20% of all liver transplants in US (<5% before 2002) Transplant outcomes in HCC patients within criteria are excellent (81% survival at 5 years) Prognostic markers are available to predict risk of recurrent tumor Down staging of large tumors, if successful, lead to equivalent survival as patients within Milan criteria Discrepancy between number of patients on the waitlist and number of transplants performed
Summary Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer deaths in the United States Appears to be related to aging patients with hepatitis C Limited treatment options are available although treatment of underlying viral hepatitis reduces patients risk of HCC Liver transplant is the most curative treatment in patients with cancer burden within the Milan criteria