69-Year-Old Man With Stage IV Hepatocellular Carcinoma

Anthony El-Khoueiry, MD: Today we are discussing a case of a patient with hepatocellular carcinoma [HCC]. This is a 69-year-old man who presented with vague right-upper-quadrant abdominal discomfort, low appetite, and occasional nausea and vomiting. His past medical history is significant for diabetes that’s medically controlled as well as hepatitis B, for which he is on antiviral therapy starting 8 years ago. He has a previous history of alcohol use at the rate of 2 to 3 drinks per day. On physical exam, he’s noted to have mild tenderness in the epigastric and right-upper-quadrant areas.

On laboratory evaluation, his alpha-fetoprotein is 425 ng/mL, bilirubin of 1.2 mg/dL, AST [aspartate aminotransferase] of 102 U/L, ALT [alanine aminotransferase] of 116 U/L, alkaline phosphatase of 380 U/L, INR [International Normalized Ratio] of 1.6, albumin of 3.6 g/dL, BUN [blood urea nitrogen] of 15 mg/dL, creatinine of 1.5 mg/dL, and platelet count of 205,000 per mm3. As far as serologies, he’s hepatitis B surface antigen positive, hepatitis B core antibody positive, and hepatitis C antibody negative. As far as his work-up, we did an abdominal ultrasound, which shows 2 hepatic lesions. This is followed by a CT [computed tomography] scan of the chest, abdomen, and pelvis, and the abdomen component is a multiphase scan. It again confirms the presence of 2 lesions—2 masses measuring 3.2 cm and 5.5 cm, respectively, both of which show arterial enhancement and venous washout. There’s also a peri-centimeter nodule in the left lung, which is indeterminate, as well as enlarged lymph nodes in the abdomen measuring about 1.5 cm.

The biopsy of the liver lesion reveals hepatocellular carcinoma as fully differentiated with marked fibrosis in the normal liver. A consultation is made with surgery that determines that the patient has advanced disease and therefore is not a resection candidate. The Child-Pugh score is A, and upon determination of the staging, he’s determined to be BCLC [Barcelona Clinic Liver Cancer] stage C because of the presence of extra hepatic disease. The ECOG performance status is 1.

The patient is initiated on treatment with atezolizumab combined with bevacizumab. The first imaging shows stable disease at 2 months. Subsequent imaging at 4 months shows 2 new lung lesions that are determined to be definitive for new metastatic disease. He’s taken off treatment and started on second-line treatment with cabozantinib at 60 mg daily.

Let’s start by discussing the work-up of a patient with HCC, including the diagnostic work-up and some discussion related to liver function. When a patient has known risk factors for hepatocellular carcinoma, such as viral hepatitis or known liver cirrhosis, there are standard criteria for imaging-based diagnosis, meaning without the necessary need for a biopsy. If the patient has multiphase imaging that shows a liver mass that’s 1 cm or larger with arterial enhancement and corresponding venous or delayed washout on multiphase CT or multiphase MRI, that would be sufficient to make the diagnosis of hepatocellular carcinoma in the right clinical setting—meaning the patient has viral hepatitis or known liver cirrhosis.

If the patient does not have viral hepatitis or known liver cirrhosis, these criteria do not apply and a biopsy would be required. Similarly, if the patient does not have the typical arterial enhancement and corresponding venous or delayed phase washout, a biopsy would be required. Please note that the alpha-fetoprotein is not part of the diagnostic criteria of HCC anymore since we know that alpha-fetoprotein is nonspecific and can be elevated for multiple reasons, including other space-occupying lesions in the liver.

In regard to liver function when treating hepatocellular carcinoma, we are always treating 2 diseases at once. We are treating or taking into consideration the underlying liver disease and liver cirrhosis as well as the cancer. We know that the underlying liver function is prognostic by itself. Patients who have Child-Pugh A cirrhosis do better than patients with Child-Pugh B cirrhosis with equal cancer staging. The Child-Pugh function is prognostic in these patients. We also know that the safety and efficacy of all the adopted clinical treatment regimens for advanced HCC have been studied in the setting of Child-Pugh A cirrhosis. Very few have data for more advanced liver disease, such as Child-Pugh B. That’s important and is an important part of the discussion when we are deciding on how to treat a patient who presents with a new diagnosis of hepatocellular carcinoma.

Patients with more advanced cirrhosis, high Child-Pugh B—meaning 8 or 9—or Child-Pugh C, who are requiring therapeutic paracentesis, who have active hepatic encephalopathy, are usually not candidates to treat their cancer. This is because their mortality is probably more driven by the advanced cirrhosis, and we do not have sufficient safety information about treating their cancer as well.

Transcript edited for clarity.

Case: A 69-Year-Old Man with Stage 4 Hepatocellular Carcinoma

Initial presentation

• A 69-year-old man presented with vague right upper quadrant abdominal discomfort, decreased appetite and occasional nausea and vomiting
• PMH: diabetes, medially controlled; hepatitis B virus diagnosed and treated 8 years ago
• SH: moderate amount of alcohol use (2-3 drinks a day)
• PE: abdominal discomfort on palpation
  
  

Clinical workup

• Labs: AFP 425 ng/mL, bilirubin 1.2 mg/dL, AST 102 U/L, ALT 116 U/L, ALP 380 U/L, INR 1.6, albumin 3.6 g/dL, BUN 15 mg/dL, creatinine 1.5 mg/dL, plt 205,000
• HBV+, HCV-
• Abdominal ultrasound revealed 2 hepatic lesions
• Chest/abdominal/pelvic CT scan confirmed 2 lesions in the right hepatic lobe measuring 3.2 cm and 5.5 cm, a suspicious lesion in the left lung lobe, and wide-spread lymphadenopathy noted
• Biopsy findings showed grade 3 HCC with marked fibrosis
• Surgical consult: unresectable due to tumor size and location
• Child-Pugh A; BCLC stage C
• ECOG 1
  
  

Treatment and Follow-Up

• Treatment with atezolizumab + bevacizumab was initiated
  • First imaging shows stable disease at 2 months; imaging at 4-month follow-up showed 2 new lung lesions
  • Treatment was subsequently changed to cabozantinib 60 mg PO qDay