Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 57-year-old man is evaluated during a routine examination. His medical history is notable for chronic hepatitis C infection with cirrhosis, which was diagnosed 3 years ago. He undergoes surveillance ultrasound for hepatocellular carcinoma every 6 months.

On physical examination, temperature is 36.8 °C (98.2 °F), blood pressure is 110/82 mm Hg, pulse rate is 65/min, and respiration rate is 18/min; BMI is 22. Muscle wasting and scleral icterus are noted. There is no flank dullness and no asterixis.

Ultrasound demonstrates three new liver masses. A four-phase CT demonstrates three lesions (1.8 cm, 2.5 cm, and 2.9 cm in size) that show arterial enhancement with venous washout. Splenomegaly and esophageal varices are also noted.

Which of the following is the most appropriate next step in management?

A. Liver biopsy
B. Liver transplantation evaluation
C. Sorafenib
D. Surgical resection
E. Transarterial chemoembolization

MKSAP Answer and Critique

The correct answer is B. Liver transplantation evaluation.

The most appropriate next step in management is to refer this patient for liver transplantation evaluation. A diagnosis of hepatocellular carcinoma can be made in a patient with cirrhosis in the presence of lesions larger than 1 cm that enhance in the arterial phase and have washout of contrast in the venous phase. Patients who meet the Milan criteria (up to three hepatocellular carcinoma tumors ≤3 cm or one tumor ≤5 cm) have excellent 5-year survival rates after liver transplantation. Patients who meet Milan criteria and have a tumor 2 cm or larger with arterial enhancement and venous washout on CT or MRI are eligible to receive Model for End-Stage Liver Disease (MELD) exception points, placing them at a higher priority for liver transplantation.

This patient does not require a biopsy of the liver masses because the radiographic characteristics of his liver tumors meet criteria for a diagnosis of hepatocellular carcinoma. The vast majority of hepatocellular carcinomas in the context of cirrhosis can be diagnosed with radiologic criteria alone. There is also a small risk (1%-3%) of seeding the needle track with tumor cells with percutaneous biopsy of hepatocellular carcinoma.

Sorafenib, a compound that targets growth signaling and angiogenesis, should be reserved for patients with Child-Turcotte-Pugh class A or B cirrhosis, good performance status, and vascular, lymphatic, or extrahepatic spread of the tumor. This patient has no evidence of angiolymphatic or extrahepatic involvement, and the tumor sizes are within Milan criteria; therefore, he should be evaluated for liver transplantation rather than started on sorafenib.

Surgical resection is not an appropriate option in this patient with evidence of hyperbilirubinemia and portal hypertension; he would be at high risk for postsurgical hepatic decompensation.

Transarterial chemoembolization (TACE) should not be performed before referral to a transplant center. Ultimately, patients who are expected to be on the waiting list for longer than 6 months are recommended to receive locoregional therapy such as TACE to control the tumor while awaiting a transplant. However, TACE should only be performed after the liver transplant evaluation is completed.

Key Point

• Patients with cirrhosis who meet the Milan criteria (up to three hepatocellular carcinoma tumors ≤3 cm or one tumor ≤5 cm) are best treated with liver transplantation and have excellent 5-year survival rates.

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