- File Under liver cancer
ISSUE: JUNE 2011
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by Christina Frangou
The American Association for the Study of Liver Diseases (AASLD) has issued a new practice guideline on the management of hepatocellular carcinoma (HCC), after recent data made a 2005 version obsolete. The authors called for greater surveillance of high-risk groups as well as changes to diagnostic, surveillance and staging techniques, including dropping alpha-fetoprotein (AFP) from the list of recommended tests and adding sorafenib to the list of acceptable treatments..
Gastroenterologist Lewis R. Roberts, MB, ChB, PhD, called the document a “very important” aid for clinicians. “There were no major surprises in the guideline,” said Dr. Roberts, professor of medicine at Mayo Clinic in Rochester, Minn. “It reflects the preponderance of evidence for screening diagnosis and therapy for HCC. And it recognizes our change in viewpoint that HCC has become a cancer that can be detected at an early stage and effectively treated or transformed into a chronic disease.”
In a letter to Hepatology, Jorge A. Marrero, MD, associate professor of internal medicine at the University of Michigan, Ann Arbor, and Hashem B. El-Serag, MD, professor of medicine at Baylor College of Medicine, Houston, criticized the omission of AFP, saying the guidelines “ignore a significant amount of data” about its efficacy in surveillance of patients at risk of HCC (2011;53:1060-1061). “In the absence of randomized studies in patients with cirrhosis, the current evidence points to US [ultrasonography] combined with serum AFP as the most effective surveillance strategy for patients at risk for HCC. The guidelines should be revised to recommend US with AFP as the best-available surveillance strategy,” they wrote.
The guideline authors responded, saying they stand by their recommendation of surveillance by US every six months.
“Although the randomized controlled study of HCC screening used both AFP and US, we believe that contribution of AFP to the outcome was minimal and maintain our position that it should not be used. US is a better test, and we should not be recommending inferior tests in guidelines such as this,” they said.
Screening and Surveillance
Much of the guidelines focus on improving surveillance for HCC. Surveillance is considered cost effective if the expected risks exceed 1.5% per year in patients with hepatitis C and 0.2% in patients with hepatitis B. Screening is recommended every six months for Asian male hepatitis B carriers over age 40; Asian female hepatitis B carriers over age 50; hepatitis B carriers with a family history of HCC; African/North American blacks with hepatitis B; cirrhotic hepatitis B carriers; and patients with hepatitis C cirrhosis, stage 4 primary biliary cirrhosis, genetic hemochromatosis and cirrhosis, alpha-1 antitrypsin deficiency and cirrhosis.
Diagnosis should be based on imaging techniques and/or biopsy. Staining for glypican 3, heat shock protein 70 and glutamine synthetase can help reinforce expert pathology diagnoses. Positive results on two of the three stains confirm HCC. The authors do not recommend contract-enhanced US, saying it may offer false-positive HCC diagnosis in patients with cholangiocarcinoma. Moreover, they recommend diagnostic imaging criteria be applied only to patients with cirrhosis of any etiology and patients with chronic hepatitis B who may not have fully developed cirrhosis or regressed cirrhosis.
The standard for staging has changed as well. The authors said that the Barcelona-Clinic Liver Cancer staging system has become the “de facto system that is used.”
Sorafenib, the first approved targeted agent for the treatment of HCC, is now considered the “first-line treatment” in patients with HCC who can no longer be treated with potentially more effective therapies.
“These patients did not have any effective option until now and the availability of a treatment option represents a major advancement,” said Dr. Bruix.