Background
Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte, generally leading to death within 6-20 months. Hepatocellular carcinoma frequently arises in the setting of cirrhosis, appearing 20-30 years following the initial insult to the liver. However, 25% of patients have no history or risk factors for the development of cirrhosis. The extent of hepatic dysfunction limits treatment options, and as many patients die of liver failure as from tumor progression.
Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma (HCC) in an 80-year-old man without cirrhosis. Although it is currently one of the most common worldwide causes of cancer death, a major impact on the incidence of hepatocellular carcinoma should be achieved through current vaccination strategies for hepatitis B virus (HBV) infection, screening and treatment for hepatitis C virus (HCV) infections, and from the reduction of alcoholic liver disease. However, because the latency period from hepatic damage to hepatocellular carcinoma development is very long, it may be many years until the incidence of hepatocellular carcinoma decreases as a result of these interventions.
Pathophysiology
Tumors are multifocal within the liver 75% of the time. Late in the disease, metastases may develop in the lung, portal vein, periportal nodes, bone, or brain (see images below).
Hepatic carcinoma, primary. Dilated collateral superficial abdominal veins in a 67-year-old man with cirrhosis, hepatocellular carcinoma (HCC), and portal vein occlusion.
Hepatic carcinoma, primary. Unusual location of a bone metastasis from hepatocellular carcinoma (HCC). Epidemiology
Frequency
United States
Although hepatocellular carcinoma is uncommon, comprising only 2% of all malignancies, since the mid-1980s the incidence of hepatocellular carcinoma has been rising at an alarming rate.[1, 2, 3] The age-adjusted incidence rates increased 2-fold between 1980 and 1998. Much of this increase is likely due to hepatitis C infection, a known risk factor for hepatocellular carcinoma.[4] More recently, the tremendous rise in obesity and diabetes is also thought to be contributing to the increased incidence of hepatocellular carcinoma. Fatty liver and nonalcoholic steatorrheic hepatitis, especially in men, may lead to cirrhosis and hepatocellular carcinoma.[5]
The American Cancer Society estimates that 26,190 new cases of hepatocellular carcinoma and intrahepatic bile duct cancers were diagnosed in 2011, with 19,260 cases in men and 6930 cases in women. An estimated 19,590 patients (13,260 men and 6330 women) were expected to die of hepatocellular carcinoma and intrahepatic bile duct cancer in 2011.[6]
International
Hepatocellular carcinoma is the fifth most common cancer in men and the eighth most common cancer in women worldwide. An estimated 560,000 new cases are diagnosed annually. The incidence of hepatocellular carcinoma worldwide varies according to the prevalence of hepatitis B and C infections. Areas such as Asia and sub-Saharan Africa with high rates of infectious hepatitis have incidences as high as 120 cases per 100,000.[7]
Mortality/Morbidity
Cure, usually through surgery, is possible in less than 5% of all patients.
Median survival from time of diagnosis is generally 6 months. Length of survival depends largely on the extent of cirrhosis in the liver; cirrhotic patients have shorter survival times and more limited therapeutic options; portal vein occlusion, which occurs commonly, portends an even shorter survival.
Complications from hepatocellular carcinoma are those of hepatic failure; death occurs from cachexia, variceal bleeding, or (rarely) tumor rupture and bleeding into the peritoneum.
Race
Hepatocellular carcinoma is most commonly found among Asian persons, due to childhood infections with hepatitis B. However, due to the implementation of childhood hepatitis B vaccination programs in many Asian countries, a decrease in the incidence of hepatocellular carcinoma among Asians is expected.
Sex
Hepatocellular carcinoma occurs more commonly in men than in women.
In the United States, 74% of hepatocellular carcinoma cases occur in men.
In high-risk areas (China, sub-Saharan Africa, Japan), the difference in incidence between the sexes is more pronounced, with male-to-female ratios as high as 8:1.
Age
Age at diagnosis varies widely according to geographic distribution.
In the United States and Europe, the median age at diagnosis is 65 years. Hepatocellular carcinoma is rarely diagnosed in persons younger than 40 years. However, between 1975 and 1998, the 45- to 49-year age group had the highest rate, a 3-fold increase in the incidence of hepatocellular carcinoma.
In Africa and Asia, age at diagnosis is substantially younger, occurring in the fourth and fifth decades of life, respectively. Diagnosis at a younger age is thought to reflect the natural history of hepatitis B and C related hepatocellular carcinoma.[8]
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