61-Year-Old Man With Stage IV Hepatocellular Carcinoma

Pierre Gholam, MD: The case we are presenting today is a 61-year-old man who presented with nausea, vomiting, decreased appetite, and occasional generalized itching. These are all fairly nonspecific symptoms that we frequently encounter in our patients who have liver disease in general.

This person’s medical history was notable for diabetes, which was medically controlled. He also happens to have hepatitis C and hepatitis B at the same time, which are 2 infections that we often see coexisting in the setting of shared risk factors. He was treated for hepatitis C 6 years ago, we presume with cure, which is a fairly common outcome of hepatitis C these days. We can’t usually cure hepatitis B, but we can very effectively control it with antiviral medication, which I’m assuming he had initiated at the time. He was diagnosed with hepatocellular carcinoma, an unfortunate but fairly common consequence of long-standing liver disease, in December 2018.

His physical exam at the time of presentation revealed scleral icterus, jaundice. The spleen was palpable, down to 4 cm below the coastal margin, which clearly indicates that he has splenomegaly. This is another tell-tale sign of portal hypertension, and the presence of cirrhosis, which would have set up for the development of hepatocellular carcinoma.

He had a work-up done that included an alpha-fetoprotein, which was elevated at 436 ng/mL. He has a bilirubin level of 1.6 mg/dL, which is above the normal of up to 1.0 mg/dL. His AST [aspartate aminotransferase] was 105 U/L with an ALT [alanine aminotransferase] of 110 U/L and an alkaline phosphatase of 390 U/L. He also had an INR [international normalized ratio] that was prolonged at 1.9, an albumin level that was within the upper limit of normal at 3.8 g/dL, a BUN [blood urea nitrogen] level of 13 mg/dL, and a creatinine level of 1.0 mg/dL, which is normal. His platelet count was 95,000, another indication that he likely had portal hypertension and cirrhosis. As I mentioned, he had exposure to both hepatitis B and hepatitis C, although he was treated for the latter.

His abdominal ultrasound revealed 3 small hepatic lesions. His chest and abdominal pelvic and pelvic CT [computed tomography] scan confirmed 2 focal nodules in the right and 1 in the left hepatic lobe. These measured 3.6, 4.9, and 5.2 cm. He had a suspicious lesion in the right lower lung lobe, which we unfortunately sometimes detect on scanning of the abdomen and pelvis because that frequently captures the lower part of the lung. He had fairly widespread lymphadenopathy—additional circumstantial evidence, which we will confirm in a second, that he might indeed have metastatic disease.

His biopsy showed findings of hepatocellular carcinoma. We are told that he had grade 3 disease. Grade is 1 of those things that in hepatocellular carcinoma can be given a fair amount of attention or not. In the setting of metastatic disease, this is probably not as much. He had marked fibrosis consistent with the diagnosis of cirrhosis.

As with any reasonable work-up for a person who is newly diagnosed with hepatocellular carcinoma, surgical consultation is reasonable, and a reasonable surgeon would indeed conclude based on review of this case that this patient has unresectable disease due to tumor size and location. This would not be a controversial or by any means unusual decision.

Therefore, for the burden of assessing this person’s comorbidities and in terms of planning care, in terms of treatment, it would not be on the surgical end of things but more on the medical end, with a multidisciplinary team decision to initiate what would almost certainly be systemic therapy.

We know from the laboratory findings and the imaging that we just went over that this person has Child-Pugh A cirrhosis. So he had fairly good liver function. We also know that he has what we call the Barcelona Clinic Liver Cancer, or BCLC, stage C disease. Stage C characterizes persons who typically have a fairly large tumor burden, as does this person. Also he would be having either extrahepatic disease, as he does with the lungs, or macrovascular invasion, which we are not told yet. But unequivocally in this case, this patient has BCLC stage C disease. The preponderance of evidence with the BCLC guidelines indicates that such a patient would be best served by initiating systemic therapy.

We also are told that the ECOG performance status, which our audience would be very well familiar with, is 1. That means that while the person is not 100% independent in all activities of daily living, they certainly have a higher level of functionality that would allow them to be able to tolerate systemic therapy reasonably well.

After this work-up is done and the multidisciplinary team meets and decides on a plan of care, the patient has lenvatinib of the dosage of 400 mg po [orally] every 12 hours initiated. He starts treatment and experiences diarrhea within 2 weeks. But this resolved without any specific intervention. It’s not an uncommon finding in patients who initiate TKIs [tyrosine kinase inhibitors] in general and lenvatinib in this particular case.

They are also told very encouragingly that he achieved a partial response, something that we love to see in patients who initiate tyrosine kinase inhibitor therapy. In 2020, 2 years later, there is another spectacular outcome in someone who is on TKIs for metastatic disease. We have imaging that shows a new lung lesion. At the time, a second-line therapy is contemplated. Indeed, the multidisciplinary team recommends initiation of cabozantinib at the dosage of 60 mg po once a day. This treatment is indeed an issue.

Transcript edited for clarity.

Case: A 61-Year-Old Man with Stage 4 Hepatocellular Carcinoma

Initial presentation

• A 61-year-old man presented with nausea, vomiting, decreased appetite and occasional generalized itching
• PMH: diabetes, medially controlled; hepatitis C and B coinfection diagnosed and treated 6 years ago; diagnosed with HCC December 2018
• PE: scleral icterus; jaundice; spleen palpable 4-cm below the costal margin
  
  

Clinical workup

• Labs: AFP 436 ng/mL, bilirubin 1.6 mg/dL, AST 105 U/L, ALT 110 U/L, ALP 390 U/L, INR 1.9, albumin 3.8 g/dL, BUN 13 mg/dL, creatinine 1 mg/dL, plt 95,000
• HBV+, HCV+
• Abdominal ultrasound revealed 3 small hepatic lesions
• Chest/abdominal/pelvic CT scan confirmed 2 focal nodules in the right and 1 in the left hepatic lobe measuring 3.6 cm, 4.9 cm and 5.2 cm, a suspicious lesion in the right lower lung lobe; wide-spread lymphadenopathy was noted
• Biopsy findings showed grade 3 hepatocellular carcinoma with marked fibrosis
• Surgical consult: unresectable due to tumor size and location
• Child-Pugh A; BCLC stage C
• ECOG 1
  
  

Treatment and Follow-Up

• 2018: treated with lenvatinib 400 mg PO q12hr; he experienced diarrhea for 2 weeks which resolved; achieved PR
• 2020: Imaging showed a new lung lesion
  • Treatment was with cabozantinib 60 mg PO qDay was initiated