Hepatocellular Carcinoma

John P. Christodouleas and Salma Jabbour

Background

What liver Dz is associated with hepatocellular carcinoma (HCC)?

Most HCCs develop in pts with cirrhosis from liver parenchymal Dz. Exposures and Dz that cause chronic hepatitis and cirrhosis are almost uniformly associated with HCC.

HCC is most common in what 2 regions in the world?

Most common regions for HCC:

Asia (East > Southeast)
Africa (middle > East > West)

Name 2 viruses associated with HCC.

Most important viral causes of HCC:

Hepatitis B virus (HBV; carrier state without associated cirrhosis is also a cause)
Hepatitis C virus (HCV)

Name the 2 most important environmental exposures associated with HCC.

Environmental exposures associated with HCC:

Heavy ethanol consumption, which leads to cirrhosis
Aflatoxin B, a mycotoxin that contaminates corn, soybeans, and peanuts, generally in sub-Saharan Africa and East and Southeast Asia

Name 3 hereditary conditions associated with HCC.

Relatively common hereditary conditions associated with HCC:

Hemachromatosis
α1-antitrypsin deficiency
Wilson Dz

Is there a gender predilection for HCC?

Yes. Males are 3 times more likely to develop HCC.

Worldwide, where does HCC rank as a cause of cancer death?

Worldwide, HCC is the 4^th leading cause of cancer death (3^rd for men), but rates vary dramatically by region.

HCC incidence peaks in what decade of life?

HCC incidence peaks in the 6^th decade of life.

What is the most common clinical presentation of HCC?

The most common clinical presentation of HCC is rising AFP in the setting of worsening pre-existing liver Dz.

Who should be screened for HCC and how?

Pts with cirrhosis, hepatitis B carrier state, or nonalcoholic steatohepatitis should be screened for HCC. Screen with AFP and liver US every 6–12 mos.

Do most pts with HCC present with localized or metastatic Dz?

90% of HCC pts present with localized Dz.

In HCC, what are the most common sites of metastatic spread?

HCC most commonly metastasizes to intra-abdominal LNs and lungs. Less common sites of mets include bone, brain, and adrenal glands.

Workup/Staging

What is the workup of suspected HCC?

Suspected HCC workup: H&P, AFP, CBC, CMP with LDH, LFTs, PT/INR, hepatitis panel (HBV/HCV studies), triphasic CT abdomen or MRI liver, chest imaging, and percutaneous Bx if necessary

For a pt with suspected HCC, when is a Bx unnecessary to establish the Dx?

In HCC, a Bx is not necessary to establish Dx if:

A liver lesion is >2 cm, has classic appearance by 1 imaging modality (CT, US, MRI, angiography), and is associated with AFP > 200 ng/mL
A liver lesion is 1–2 cm and has classic appearance by 2 imaging modalities

Note: If a liver lesion is <1 cm, then the pt should be followed with serial imaging.

In what HCC variant is the AFP level often normal?

AFP levels are normal in the majority of pts with fibrolamellar carcinoma (FLC, a variant of HCC. It is found commonly in females and has a good prognosis. Note that some authors argue that FLC is not truly a variant of HCC since it usually occurs in the absence of cirrhosis.

What are the characteristic triphasic CT and MRI findings of an HCC liver lesion?

On dynamic CT: early phase, tumor is seen as hyperintense b/c of increased vascularity. In the later phase, the tumor is hypodense.
On MRI T1-weighted images: low signal intensity and intermediate signal intensity on T2; HCC appears hypervascular, has increased T2 signal, and shows venous invasion

What is the AJCC 7^th edition (2009) TNM staging for HCC?

Note: Bold text highlights 7^th edition changes.