Screening for Hepatocellular Carcinoma
Certain groups of patients are at particularly high risk for developing hepatocellular carcinoma. We recommend screening for the following patients:
- All patients with hepatic cirrhosis
- Patients with bridging fibrosis or "incomplete"/early cirrhosis in highest risk categories: Chronic hepatitis B, Chronic hepatitis C, Chronic hepatitis D (and B), Hereditary hemochromatosis, Alcoholic cirrhosis
- All adult chronic carriers of HBV, regardless of severity of liver disease.
- All patients with Type I hereditary tyrosinemia, acute porphyrias, glycogen storage diseases, or other hereditary diseases associated with high risks of development of HCC.
- All patients shown to have moderate to high-grade dysplasia on liver biopsy.
- Note: Risks are especially high among patients who are chronically immunosuppressed: E.g., patients with HIV infection, patients with lymphomas or other cancers; patients who have received transplanted organs or who, for other reasons, are chronically receiving immunosuppressant medications; patients with hypogammaglobulinemia.
As a general rule, all patients with well established hepatic cirrhosis should be screened for development of hepatocellular carcinoma.
The diagnosis of cirrhosis is best made by liver biopsy; although, when cirrhosis is advanced, a combination of physical signs and laboratory findings is sufficient to indicate the presence of cirrhosis with a very high degree of likelihood (greater than 90%), and liver biopsy may not be required.
In addition, patients with bridging fibrosis (or "incomplete" or "early" cirrhosis) in the highest risk categories should be screened. Such high-risk patients include those with chronic hepatitis B infection, chronic hepatitis C infection, chronic hepatitis D (and B) infection, those with hereditary hemochromatosis, and those with alcoholic cirrhosis.
It is also recommended that all adult chronic carriers of hepatitis B viral (HBV) infection, regardless of severity of liver disease, be screened for hepatocellular carcinoma. This recommendation is of special importance for adult chronic carriers of HBV who probably were infected as neonates or infants (e.g., those from Asia or Africa) and who therefore are immuno-tolerant of the infection.
Such patients, even in the absence of significant liver disease, have a marked increase in risk of development of hepatocellular carcinoma over the course of a lifetime. Specifically, the risk of HCC development is increased more than 500 fold in such patients, compared to a non-HBV-infected age- and sex-matched control population.
Patients with certain relatively rare hereditary disorders are also at high risk for development of hepatocellular carcinoma. Perhaps the most important of these is type I hereditary tyrosinemia. This disease typically causes rapidly progressive liver disease in infants, but, unless such infants receive liver transplants within the first year or two of life, they are virtually certain to suffer the development of hepatocellular carcinoma and death by age 3 or 4 years.
In addition, certain of the glycogen storage diseases are associated with marked increased risks of development of HCC, and patients with these diseases, too, should undergo prophylactic liver transplantation. Such transplantation also cures or ameliorates the underlying hereditary disease.
If patients have been shown on previous liver biopsy to have evidence of moderate or high-grade dysplasia of liver cells, regardless of the presence or absence of cirrhosis or fibrosis, they, too, should undergo regular screening, looking for evidence of HCC development as early as possible.
Risks are especially high among patients who are chronically immunosuppressed. This includes patients with HIV infection, patients with lymphomas or other cancers, patients who have received transplanted organs or who, for other reasons, are chronically receiving immunosuppressive medications, and patients with hypogammaglobulinemia or other forms of chronic immunodeficient syndromes.
The second major rationale for recommending routine screening of selected target groups of patients for HCC is the knowledge that the prognosis of this kind of cancer is chiefly dependent upon the size and stage of the tumor at the time of initial diagnosis. The current therapies for small, noninvasive, nonmetastatic HCC is much better than for large, multifocal cancers with invasion of blood vessels, lymphatic channels, bile ducts, and/or distant spread. Distant spread may be to regional lymph nodes outside the liver, the lungs, or sometimes to other organs. In addition, therapies are most effective for small, single hepatocellular carcinomas.
