AJM Theme Issue: GastroenterologyReviewHepatocellular Cancer: A Guide for the Internist
Section snippets
Epidemiology
Hepatocellular cancer is a major health problem; more than half a million cases are reported yearly worldwide. The geographic areas most affected are located in Southeast Asia and sub-Saharan Africa. More recently, an increasing number of cases have been identified in Western countries. A large, retrospective cohort study confirmed an almost 2-fold increase in the incidence of hepatocellular cancer from 1975 to 1998 in the United States.2, 3 This increase is primarily related to the spread of
Cause
The major clinical risk factor for the development of hepatocellular cancer is cirrhosis of the liver. Chronic infections with hepatitis B virus (HBV) and HCV and chronic heavy alcohol use are the most important risk factors for the development of cirrhosis. HBV accounts for the majority of hepatocellular cancer in China and Africa, where most of the infection is acquired early in life either from mother to the offspring or by horizontal transmission.8, 9 In contrast, HCV accounts for most of
Clinical Features
The typical clinical manifestations of hepatocellular cancer are right upper quadrant abdominal pain, early satiety, and weight loss. However, more and more hepatocellular cancers are now detected at an asymptomatic stage because of the growing awareness of these tumors in patients with chronic liver disease and cirrhosis.19 Other clinical presentations, such as spontaneous rupture of the tumor into the peritoneal cavity, obstructive jaundice, and bony pain from metastasis, are extremely
Diagnosis
A consensus statement from the European Association for the Study of Liver Diseases (EASL) has been formulated to help clinicians standardize diagnostic approaches20 (Table 2).
Screening
Although there is no definite evidence that screening in hepatocellular cancer improves survival, many physicians screen patients in high-risk groups with either serum alpha-fetoprotein or ultrasound of the liver or both. Two recent randomized controlled trials completed in China demonstrated a significant reduction in hepatocellular cancer-related mortality in patients who underwent screening.37, 38 Ultrasound of the liver is the preferred screening test because it has a sensitivity of 84% and
Natural History and Prognosis
Prospective studies have shown that most hepatocellular cancers develop through a progressive pathway from premalignant nodular lesions to cancerous lesions in the cirrhotic liver.43 Progression takes an average of approximately 2 to 4 decades from the initial time of infection with HBV or HCV to the development of cirrhosis. Thereafter, the annual risk of hepatocellular cancer is 2% to 3% for HBV, 1% to 7% for HCV, and 1% for alcohol-induced cirrhosis.10, 44 Hepatocellular cancer can develop
Management
The definitive treatment of hepatocellular cancer is liver transplantation; this cures both the cancer and the underlying cancer-prone cirrhotic liver (Figure 2).
Future Trends
Proteomics has led to the discovery of new molecular markers, such as des-gamma carboxyprothrombin and human hepatocyte growth factor, for screening hepatocellular cancer, and these are being validated for clinical use. Antiangiogenesis agents such as vascular endothelial growth factor antibodies and thalidomide, nonspecific inhibitors of carcinogenesis such as Sandostatin and arsenic, and better means of delivering radiation such as yttrium microspheres are all being actively investigated for
Conclusion
The incidence of hepatocellular cancer is increasing in the Western world, including the United States. Although HBV, HCV, and alcohol use constitute the most important risk factors for the development of hepatocellular cancer, diabetes and obesity may contribute to increased carcinogenicity. Primary care physicians taking care of patients with chronic viral hepatitis and cirrhosis will need to have a heightened awareness of hepatocellular cancer, because the translation of bench research into
Acknowledgments
We are indebted to Drs Richard Goodgame, Hashem El-Serag, and Prashant Kapoor for their critical review of this article.
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