Screening for HCC in high-risk patients key to reducing mortality

Enhanced surveillance of at-risk population is critical for the early identification and successful treatment of hepatocellular carcinoma (HCC), at the 2008 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. Gastroenterologists and other physicians who care for patients infected with hepatitis virus should be particularly watchful for HCC.

Director of the Center for Liver Diseases, University of Miami School of Medicine said that in the United States, almost all HCC is related to HCV (hepatitis C virus) that occurs in patients with cirrhosis, with or without alcohol intake. If you have HBV (Hepatitis B virus), on the other hand, you don’t have to have cirrhosis to develop cancer.

Demographics of the disease

Approximately 20% of patients with chronic HCV who develop cirrhosis will develop HCC. However, in Asia for example, up to 40% of HCC occurs in patients infected with HBV in the absence of cirrhosis. A study of a patient with HBV in Taiwan showed that HBV DNA level is a strong predictor of risk for HCC, independent of the presence of hepatitis B early antigen, serum alanine aminitransferase levels and cirrhosis. In the study of 3,653 patients with a mean follow-up of 11.4 years, the incidence of HCC was associated with increased serum HBV DNA levels, ranging from 108 per 100,000 person-years for patients with HBV DNA levels less than 300 copies/mL to 1,152 per 100,000 person-years for those with HBV DNA levels of 1 million copies/mL or more.

Westerners with chronic HBV infection have significantly less risk for developing HCC than those from HBV-endemic countries. Both groups, however, are at risk and should be screened, adding that physicians in this country should be aware of individuals with HBV who have migrated to the United States from HBV-endemic countries.

The highest prevalence of chronic HBV infection in the United States is among immigrants from the Asian and Pacific Islands. At the Gastrointestinal Cancer Symposium, researchers from the University of Texas M.D., Anderson Cancer Center, Houston, presented an epidemiologic picture of HBV and HCV associated with HCC in islander. In their retrospective review, they identified 82 islanders with HCC treated at M.D., Anderson Cancer Center between 1992 and 2005. These patients constituted 10% of all HCC cases at the institution. Most of the cohort (60%) had chronic HBV infection, and 19% were infected with HCV. Male gender, high levels of alpha-fetoprotein (AFP) and advanced stage of disease were associated with poor survival. Patients in this cohort who received any type of treatment experienced an 80% reduction in mortality risk. Patients with early-stage HCC who underwent surgical resection had greater survival outcomes than those with chemotherapy alone (33 months, vs. nine).

Assistant professor of medicine at M.D. Anderson said that Medical Providers and community health specialist should make HBV and HCV screening and surveillance a high priority in this patient population.

Screening and surveillance

Study underscores the importance of HCC screening in patients with HCV or HBV. The American association for the Study of Liver Diseases recommends HCC surveillance of HBV carriers who are Asian males age 40 and older or Asian females 50 and older; have cirrhosis; have a family history of HCC; or are African Americans older than age 20, for all noncirrhotic HBV carriers not included in the aforementioned groups, surveillance is recommended for patients with high levels of HBV DNA and those with ongoing hepatic inflammation, in addition, surveillance for HCC should be performed in all patients with cirrhosis, including those with HCV infection, alcoholic cirrhosis and genetic hemochromatosis.

In individuals at risk for HCC, ultrasound of the liver and serologic testing of AFP should be performed every six months. The relative risk for HCC is increased if AFP is elevated, without question, but there are people with AFP in the normal or undetectable range that also have HCC. The positive predictive value is low overall, but is high (67%) when AFP is greater than 200 mg/mL; however, he said; only about 5% of all patients with HCC have such high levels, which are usually associated with advanced tumors.

Other tumors biomarkers are being used, particularly AFP-L3. In patients with elevated AFP levels, this AFP isoform has a sensitivity of 71% and specificity of 63% for the detection of HCC. When the ratio of AFP-L3 to AFP is greater than 35%, the sensitivity for detecting HCC is 33% with specificity of 100%.

Another biomarker of interest in the detection of HCC is des-carboxypothrombin (DCP). Many AFP-negative patients are DCP-positive at the time of HCC diagnosis.

Regarding diagnostic imaging, the sensitivity depends on local experience. Generally, triple-phase computed tomography (CT) and magnetic resonance imaging (MRI) are the best tools for distinguishing HCC. Ultrasound is cost-effective and generally adequate for screening and assessing portal vein thrombosis associated with a focal lesion, but disease can be missed by inexperienced operators.

One approach is to screen every six months with ultrasound and watch for changes. Patients with abnormalities can then be referred for triple-phase CT or MRI, something more accurate.

Liver biopsy for the diagnosis of HCC is not contraindicated, through usually not required. Biopsy may be warranted, however, for lesions that are less than 2 cm or for cases that appear atypical on imaging; however, follow-up imaging often accomplishes the same result. Changes seen on biopsy may be subtle; and despite an extremely low risk for seeding, biopsy does pose some risk for hemorrhage.

Be aware that a diagnosis of hemangioma is probably incorrect, if it is based on the sudden appearance of a mass where there used to be none. A hemangioma would have always been there. This is a common mistake.

Surveillance is critical. You can save many patients by identifying HCC early. Otherwise, their outlook is bleak.