Current Concepts: Hepatocellular Carcinoma

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TEACHING TOPICS from the New England Journal of Medicine

Source Information

From the Section of Gastroenterology and Hepatology, E. DeBakey Veterans

Affairs Medical Center; Baylor College of Medicine; and the Houston Center for

Quality of Care and Utilization Studies — all in Houston.

Address reprint requests to Dr. El-Serag at the E. DeBakey VA Medical

Center, 2002 Holcombe Blvd. (152), Houston, TX 77030, or at hasheme@....

Review Article

Hepatocellular Carcinoma

Hashem B. El-Serag, M.D., M.P.H.

N Engl J Med 2011; 365:1118-1127September 22, 2011

This article has no abstract; the first 100 words appear below.

Each year, hepatocellular carcinoma is diagnosed in more than half a million

people worldwide, including approximately 20,000 new cases in the United

States.1,2 Liver cancer is the fifth most common cancer in men and the seventh

in women. Most of the burden of disease (85%) is borne in developing countries,

with the highest incidence rates reported in regions where infection with

hepatitis B virus (HBV) is endemic: Southeast Asia and sub-Saharan Africa

(Figure 1).3 Hepatocellular carcinoma rarely occurs before the age of 40 years

and reaches a peak at approximately 70 years of age. Rates of liver cancer among

.. . .

Dr. El-Serag reports receiving consulting fees from Vertex Pharmaceuticals and

support from a grant from Bayer Pharmaceuticals to the Baylor College of

Medicine.

Disclosure forms provided by the author are available at NEJM.org.

No other potential conflict of interest relevant to this article was reported.

Teaching Topic

Hepatocellular Carcinoma

Review Article

Current Concepts: Hepatocellular Carcinoma

H.B. El-Serag

Each year, hepatocellular carcinoma is diagnosed in more than half a million

people worldwide, including approximately 20,000 new cases in the United States.

Clinical Pearls

What are the major risk factors for the development of hepatocellular

carcinoma?

Major risk factors for hepatocellular carcinoma include infection with HBV or

HCV, alcoholic liver disease, and possibly nonalcoholic fatty liver disease.

Less common causes include hereditary hemochromatosis, alpha1-antitrypsin

deficiency, autoimmune hepatitis, some porphyrias, and ’s disease. The

5-year cumulative risk for the development of hepatocellular carcinoma in

patients with cirrhosis ranges between 5% and 30%, depending on the cause (with

the highest risk among those infected with HCV).

What methods for screening for hepatocellular carcinoma are recommended for

high-risk patients?

The author recommends ultrasonography of the liver combined with measurement of

serum alpha-fetoprotein levels every 6 to 12 months as surveillance for

hepatocellular carcinoma in patients with cirrhosis or advanced hepatic

fibrosis, irrespective of the cause. With a cutoff point of 20 ng per

milliliter, serum levels of alpha-fetoprotein have low sensitivity (25 to 65%)

for the detection of hepatocellular carcinoma and are therefore considered

inadequate as the sole means of surveillance.

Morning Report Questions

Q. How should very-early-stage and early-stage hepatocellular carcinoma be

managed?

A. Very-early-stage hepatocellular carcinoma is currently difficult to diagnose,

since the definition requires presentation with a single, asymptomatic lesion

measuring less than 2 cm in diameter, with no vascular or distant metastases.

Surgical resection in these cases is associated with a survival rate of 90%.

Patients presenting with early-stage hepatocellular carcinoma have preserved

liver function with a solitary hepatocellular carcinoma or up to three nodules,

each measuring up to 3 cm in diameter. The most appropriate treatment for such

patients is liver transplantation, which is associated with a 5-year survival

rate of up to 75%; if transplantation is not possible, local ablation is the

next best option.

Q. How should intermediate and advanced hepatocellular carcinoma be managed?

A. Patients with compensated cirrhosis, no symptoms related to hepatocellular

carcinoma, and no vascular invasion but with large or multifocal lesions are

considered to have intermediate-stage hepatocellular carcinoma. In these

patients, transarterial chemoembolization (TACE) improves the 2-year survival

rate by 20 to 25% as compared with more conservative therapy. In recent

randomized, controlled trials patients with advanced hepatocellular carcinoma

and compensated cirrhosis who received sorafenib had a 37% increase in overall

survival (equivalent to a gain of 2 to 3 months of life), as compared with those

who received placebo.