Chapter 088. Hepatocellular Carcinoma (Part 2) pot

Hepatocellular Carcinoma Part 2 Epidemiology Endemic hot spots occur in areas of China and sub-Saharan Africa, which are associated with both high endemic hepatitis B carrier rates an

Chapter 088 Hepatocellular

Carcinoma

(Part 2)

Epidemiology

Endemic hot spots occur in areas of China and sub-Saharan Africa, which are associated with both high endemic hepatitis B carrier rates and mycotoxin contamination of foodstuffs, stored grains, drinking water, and soil Environmental factors are important; Japanese in Japan have a higher incidence than those living

in Hawaii, who in turn have a higher incidence than those living in California

Etiologic Factors

Chemical Carcinogens

Probably the best-studied and most potent ubiquitous natural chemical

carcinogen is a product of the Aspergillus fungus, called aflatoxin B1 This mold and aflatoxin product can be found in stored grains in hot, humid places, where peanuts and rice are stored in unrefrigerated conditions Aflatoxin contamination

of foodstuffs correlates well with incidence rates in Africa and to some extent in China In endemic areas of China, even farm animals such as ducks have HCC The most potent carcinogens appear to be natural products of plants, fungi, and bacteria, such as bush trees containing pyrrollizidine alkaloids as well as tannic acid and safrole Pollutants such as pesticides and insecticides are known rodent carcinogens

Hepatitis

Both case-control and cohort studies have shown a strong association between chronic hepatitis B carrier rates and increased incidence of HCC In Taiwanese male postal carriers who were hepatitis B surface antigen (HBsAg)-positive, a 98-fold greater risk for HCC was found compared to HBsAg-negative individuals The incidence of HCC in Alaskan natives is markedly increased related to a high prevalence of HBV infection HBV-based HCC may arise from rounds of hepatic destruction with subsequent proliferation and not necessarily from frank cirrhosis The increase in Japanese HCC incidence rates in the past three decades is thought to be from hepatitis C A large-scale intervention study sponsored by the World Health Organization (WHO) is currently underway in

Asia involving HBV vaccination of the newborn HCC in African blacks is not associated with severe cirrhosis but is poorly differentiated and very aggressive Despite uniform HBV carrier rates among the South African Bantu, there is a ninefold difference in HCC incidence between Mozambicans living along the coast and inland These differences are attributed to the additional exposure to dietary aflatoxin B1 and other carcinogenic mycotoxins A typical interval between HCV-associated transfusion and subsequent HCC is ~30 years HCV-associated HCC patients tend to have more frequent and advanced cirrhosis, but in HBV-associated HCC, only half the patients have cirrhosis; the remainder have chronic active hepatitis (Chap 300)

Other Etiologic Conditions

The 75–85% association of HCC with underlying cirrhosis has long been recognized, more typically with macronodular cirrhosis in Southeast Asia but also with micronodular cirrhosis (alcohol) in Europe and the United States (Chap 302)

It is still not clear whether cirrhosis itself is a predisposing factor to the development of HCC or whether the underlying causes of the cirrhosis are actually the carcinogenic factors However, ~20 % of U.S patients with HCC do not have underlying cirrhosis Several underlying conditions are associated with an increased risk for cirrhosis-associated HCC (Table 88-2), including hepatitis, alcohol abuse, autoimmune chronic active hepatitis, cryptogenic cirrhosis, and nonalcoholic steatohepatitis (NASH) A less common association is with primary

biliary cirrhosis and several metabolic diseases, including hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, tyrosinemia, porphyria cutanea tarda, glycogenesis types 1 and 3, citrullinemia, and orotic aciduria The etiology of HCC in those 20% of patients who have no cirrhosis is unclear, and their HCC natural history not well-defined

Table 88-2 Risk Factors for Hepatocellular Carcinoma

Cirrhosis from any cause Primary biliary cirrhosis

Hepatitis B or C chronic infection Hemochromatosis

Ethanol chronic consumption α1 Antitrypsin deficiency

Nonalcoholic steatohepatitis (NASH) Glycogen storage diseases Aflatoxin B1 orother mycotoxins Citrullinemia

Porphyria cutanea tarda Hereditary tyrosinemia Wilson's disease