Objective Prevention of Liver Cancer Smruti R. Mohanty, MD, MS Assistant Professor of Medicine Center for Liver Diseases Section of Gastroenterology University of Chicago September 6, 2006 Anatomy of Liver Liver cancer and its epidemiology? Various causes of liver cancer Clinical presentations of liver cancer Who is at risk for liver cancer? How do we screen for liver cancer? How do we make diagnosis of liver cancer? Outcomes of liver cancer What are the treatment options? Prevention of liver Cancer Anatomy of Liver Normal Liver 1
Normal Liver Cirrhosis Cirrhosis Cirrhosis 2
What is Liver Cancer? Definition of terms Liver cancer is a disease in which there are uncontrolled production of abnormal liver cells, which may spread inside or outside of the liver. AFP: It is protein produced by liver cancer cells and measured in the blood. It is a tumor marker for liver cancer Chronic liver disease: Any liver disease affect a person more than 6 months and cause ongoing liver damage. Liver function test: It indicative of how much liver has inflammation and damage. It measure blood thinner level (PT), protein of liver (albumin) etc. Liver Cancer Liver Cancer 3
Liver Cancer in CAT Scan Epidemiology of Liver Cancer The 5 th Most common cancer world wide Accounting 1 million cases in the world It causes approximately half millions deaths annually in the world Hepatitis B virus infection commonly seen as cause in Far East and Sub-Saharan Saharan Africa Hepatitis C virus is commonly associated with liver cancer in USA Spreading & Invasion of Liver Cancer Epidemiology of Liver Cancer Rising incidence over last decade in the world including developed countries 30% cases in USA are without any risk factors Alcohol, Diabetes, Obesity and smoking are implicated for liver cancer Recently, Fatty liver disease have been implicated for rising cases of liver cancer in US 4
Sex and Age Distribution of Liver Cancer Male are far more likely than female Disparity more in high incidence region Older patients with longstanding liver diseases Mean age at presentation between 50 and 60 years. Low mean age of presentation in Sub-Saharan Saharan Africa Mean age at diagnosis is 33 years. African American and Liver Cancer (HCC) Represents a 41% increase in mortality rate and a 46% increase in hospitalization 7 6 5 4 3 2 1 0 1.4 1976-1980 2.4 1991-1995 2.8 White Men 91-95 6.1 Black Men 91-95 Per 100,000 El-Sera HB et al. N Engl J Med 1999; 340:745-50 Ethnic and Racial Variations of Liver Cancer Marked variations in rate of liver cancer among various ethnic and races Asians >African American > Non-Hispanic White African American and Hispanics > whites > two fold in Mexican American compared to Whites Higher incidence in both Hispanic men and women Questions What are the causes of liver cancer? What are the warning signs? Who should be screened for liver cancer? Can we treat liver cancer? How can we prevent liver Cancer? 5
Causes of Liver Cancer Hepatitis B, C, & D virus Fatty Liver diseases (NASH) Hemochromatosis (Iron Overload) Diseases of bile ducts (PSC) Cirrhosis of Liver of any cause Family history of Liver cancer Hereditary Metabolic diseases (A1AT deficiency) Aflatoxin and Alcohol Others Diagnosis of Liver Cancer Ultra Sound of abdomen CT scan of abdomen MRI of abdomen Alfa Feto Protein (AFP) is a tumor marker, useful in the diagnosis AFP of 400 ng/ml is highly sensitive and specific How do the patients with liver cancer present to doctors? Abdominal pain, abdominal swelling and weight loss Blood in abdomen and low blood pressure Due to rupture of tumor into abdominal cavity High red blood cell count and low sugar Incidental findings or screening examination Enlarged and hard liver with irregular surface. Stages of Liver Cancer Staging: Whether cancer has spread within or outside the liver Information gathered from the staging process determine the stage of the disease Staging is important to plan for the treatment 6
Chance of recovery and Treatment Options The prognosis and treatment options depend on the following: The stage of the cancer How well the liver is working? The patient s general health, including whether there is cirrhosis of the liver Outcomes of Liver Cancer It is an aggressive tumor Survival 6 20 months after diagnosis Therapeutic options depend upon Patient s liver reserve Stage of tumor Mainstay of therapy: surgical Treatment options Localized resectable The cancer is found in the liver only, has not spread, and can be completely removed by surgery. Localized and locally advanced unresectable The cancer is found in the liver only and has not spread, but cannot be completely removed by surgery. Advanced Cancer has spread throughout the liver or has spread to other parts of the body, such as the lungs and bone Screening for Liver Cancer Optimal screening is unknown Doubling time of liver cancer is 3 to 4 months. Need for screening in 3 to 6 months Suggested frequency of screening AFP levels in every 6 months U/S of liver in every 6 months 7
Who should be Screened? Candidates for Screening Cirrhosis Chronic Viral hepatitis with elevated AFP Chronic liver diseases, age > 50 yrs and male > female Family history of liver cancer Previously resected liver Cancer Screening not necessary HCV without cirrhosis and age < 40 yrs (without family history) Possibly patients who are not surgical candidates Natural History of HCC Acute Hepatitis Chronic Hepatitis Cirrhosis HCC How do we prevent liver cancer? Prevention of HCC Prevention Primary Prevention Secondary Prevention Tertiary Prevention 8
Prevention of HCC Primary Prevention Aimed at preventing occurrence of chronic liver diseases Secondary Prevention Prevention of HCC among patients with chronic liver diseases with/without cirrhosis Tertiary Prevention Preventing recurrence and/or the development of new HCC lesions after successful surgical or non-surgical treatment of HCC. Prevention of HCC Primary Prevention Prevention of acquired Liver diseases Early treatment of acute liver diseases Prevention of HCC Acute Hepatitis Primary Prevention Chronic Hepatitis Secondary Prevention Cirrhosis Tertiary Prevention HCC Primary Prevention How do we prevent acquiring any liver diseases? Avoiding: alcohol, toxins Avoiding high risk behaviors: IVDA, high risk sexual behaviors Hepatitis B vaccination: high risk groups, pregnant women Universal precautions for body fluid and blood products in health care settings 9
Primary Prevention (Cont.) What measures do we need take for the early treatment of acute liver diseases? Recognition of acute liver problems Alcoholism and alcohol related problems Early treatment of Acute Hepatitis C Early diagnosis of inherited liver diseases Hemochromatosis Wilson s diseases Tertiary Prevention Early diagnosis & treatment of liver cancer Screening for liver Cancer Resection of HCC in non-cirrhotic liver Liver transplantation of cirrhotic liver with small HCC (appropriate candidates) Paliative care for advanced HCC Chemoembolization and/or radiofrequency ablation Anticancer therapy for unresectable HCC Participate in the clinical trials for HCC Secondary Prevention Interventions for the prevention of progression of chronic hepatitis to cirrhosis Treatment of chronic Hepatitis B, C and D Treatment of cholestatic, autoimmnue and inherited liver diseases Interventions to prevent the development of HCC from cirrhosis Similar to above, patients with cirrhosis should be treated Summary HCC is one of the most common cancer world wide Primary and secondary preventions are main goals to prevent HCC by blocking the progression to chronic liver disease including cirrhosis depending on specific type of liver diseases. Early diagnosis and treatment of HCC are considered as tertiary prevention including palliative care for large or advanced HCC. 10