Patient Presentation
A 62-year-old male with chronic hepatitis C presents with several weeks of right upper quadrant pain, unintentional weight loss, and progressive jaundice. His history includes cirrhosis and prior alcohol use, and there is a family history of liver disease.
On examination he is jaundiced with hepatomegaly and mild ascites. There is no acute hemodynamic instability described. Laboratory studies reveal an elevated alpha-fetoprotein along with abnormalities on his liver function panel.
The clinical picture—cirrhosis, HCC risk factors, RUQ pain, weight loss, and elevated AFP—raises strong concern for hepatocellular carcinoma superimposed on chronic liver disease. Your task is to complete the workup, stage the disease, assess hepatic reserve, and determine the appropriate treatment pathway.
What You'll Be Asked — and What a Strong Resident Discusses
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What is your differential diagnosis and initial workup for this patient?
Expected answer
In a cirrhotic patient with a liver lesion and elevated AFP, HCC is the leading diagnosis. Differential includes intrahepatic cholangiocarcinoma, metastatic disease, hepatic adenoma, focal nodular hyperplasia, regenerative/dysplastic nodules, and hemangioma. Initial workup: full history and physical, CBC, complete metabolic panel, coagulation studies, hepatitis serologies, liver function panel, and AFP. The key diagnostic study is dedicated liver imaging—triple-phase contrast CT of the liver or MRI abdomen.
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What radiographic features confirm the diagnosis of HCC and allow you to avoid biopsy?
Expected answer
HCC has a classic imaging signature on multiphasic CT/MRI: arterial-phase hypervascularity (enhancement) followed by venous or delayed-phase washout. In a cirrhotic patient, a lesion with these LI-RADS features is diagnostic of HCC and biopsy is generally not required, since biopsy carries a risk of tumor seeding and bleeding and can miss the lesion. AFP supports the diagnosis but has poor sensitivity and specificity and is most useful for surveillance of recurrence after treatment.
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How do you stage this patient and assess whether he can tolerate liver-directed therapy?
Expected answer
Staging requires defining tumor burden—number of tumors, lobar distribution, size, and proximity to hepatic veins, main portal veins, and biliary tree—and evaluating for vascular invasion and extrahepatic metastasis (chest imaging, cross-sectional abdominal/pelvic imaging). Hepatic reserve is assessed with Child-Pugh classification, MELD, bilirubin, presence of portal hypertension, and liver volumetry to estimate the future liver remnant. These functional data—not just the tumor—drive treatment selection.
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If extrahepatic metastasis is present, how does management change?
Expected answer
Extrahepatic metastatic disease makes the patient unresectable and not a transplant candidate. Regardless of Child-Pugh class, treatment shifts to palliative systemic therapy—sorafenib (or regorafenib after sorafenib failure) and supportive/palliative care. Aggressive local resection offers no survival benefit in the setting of metastatic disease.
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Assuming no metastasis, how do you decide between resection and transplantation?
Expected answer
With no extrahepatic disease, the goal is complete removal of tumor by resection or transplant. Child-Pugh class A patients with adequate functional liver remnant, no significant portal hypertension, acceptable bilirubin, and a favorably located tumor (generally ≤5 cm) are candidates for resection. Child-Pugh B/C patients or those with portal hypertension do not tolerate resection and should be evaluated for transplant. This patient has ascites and jaundice, suggesting decompensated cirrhosis/portal hypertension, which favors transplant evaluation over resection.
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What criteria determine transplant eligibility for HCC?
Expected answer
The standard is the Milan criteria: a single tumor ≤5 cm, or up to 3 tumors each ≤3 cm, with no extrahepatic spread and no macrovascular invasion. Some centers use the expanded UCSF criteria (single lesion ≤6.5 cm, or 2–3 lesions none >4.5 cm with total diameter ≤8 cm, no vascular invasion). Patients within criteria are listed for orthotopic liver transplant, often with bridging locoregional therapy (RFA/TACE/Y-90) to control tumor while awaiting an organ. Those beyond criteria receive palliation and systemic therapy.
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What locoregional therapies are available and when are they used?
Expected answer
RFA is used for unresectable Child-Pugh A/B patients with tumors <4 cm and as a bridge to transplant. RFA plus TACE is recommended per NCCN for intermediate-sized HCC (3–5 cm). TACE and Y-90 radioembolization are options for tumor control, downstaging, or bridging. These modalities allow treatment of patients who are not resection or transplant candidates and help maintain patients within transplant criteria while listed.
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After a major hepatic resection, what post-operative complications concern you most?
Expected answer
Post-hepatectomy liver failure (progressive coagulopathy, hyperbilirubinemia, encephalopathy) is the most feared complication, with resection mortality reaching up to 20% depending on preoperative liver function. Other concerns include bile leak, hemorrhage, ascites/decompensation, portal vein thrombosis, and infection. Management is supportive—monitor synthetic function, control ascites, treat sepsis, and be prepared to escalate. This underscores why patient selection with Child-Pugh class and volumetry is critical.
What Residents Often Miss
- Ordering percutaneous biopsy of a lesion with classic HCC imaging features in a cirrhotic patient, risking tumor seeding and bleeding when biopsy is unnecessary.
- Relying on AFP to make or exclude the diagnosis despite its poor sensitivity and specificity, rather than obtaining dedicated multiphasic imaging.
- Offering resection to a decompensated (Child-Pugh B/C) patient with portal hypertension and ascites, ignoring hepatic reserve and inviting post-hepatectomy liver failure.
- Failing to rule out extrahepatic metastasis and macrovascular invasion before committing to resection or transplant.
- Not applying Milan (or UCSF) criteria when triaging transplant candidacy, leading to inappropriate listing or missed transplant opportunity.
- Overlooking bridging/downstaging locoregional therapy (RFA/TACE/Y-90) for patients awaiting transplant.
- Continuing to pursue curative surgery in a patient with metastatic disease instead of transitioning to palliative systemic therapy.
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