Patient Prognosis and Risk Factors in HCC and Cirrhosis

Anthony El-Khoueiry, MD: When you look at the patient that we are presented with in this situation, we see that the patient has evidence of extrahepatic disease in the form of lymph nodes and potentially a lung nodule on presentation. The presence of extrahepatic disease immediately puts the patient in the Barcelona Clinic Liver Cancer [BCLC] staging system at stage C. Similarly, if the patient had portal venous invasion, macrovascular invasion in the liver, that would put the patient in BCLC stage C. If the patient had liver-limited disease only, without extrahepatic metastases, without portal vein invasion, and they had either a single large lesion or multifocal disease in the liver with more than 3 lesions—with lesions more than 3 cm—that also puts them in BCLC stage B. These are the 2 scenarios, for BCLC stages B and C, where medical oncologists get involved the most. Naturally, the prognosis is poorer with BCLC stage C compared with B. In this case, the imaging criteria met the criteria for diagnosis of HCC [hepatocellular carcinoma]. Nonetheless, the patient ended up having a biopsy.

As far as risk factors for this patient and others, the presence of viral hepatitis and the history of alcohol use and dependence are the most common risk factors for liver cirrhosis and HCC. But more and more we are seeing a rise in the incidence of HCC that’s driven by nonalcoholic fatty liver disease or NASH [nonalcoholic steatohepatitis]. This is linked to metabolic syndrome as well as obesity and diabetes. This is becoming a more common and ever-rising etiology for hepatocellular carcinoma that one needs to keep in mind.

In the case of the patient we are discussing, he had hepatitis B that he’s on treatment for but also a history of taking 2 to 3 alcoholic drinks per day. We know that patients who consume 3 or more alcoholic drinks per day already put themselves at the risk of chronic alcoholic liver disease. This patient may have actually 2 etiologies for his HCC and for his cirrhosis as well.

It is critically important to realize that HCC is best treated in the multidisciplinary setting. This disease involves patients having underlying liver disease, potentially viral hepatitis, liver cirrhosis, as well as potentially concomitant substance abuse challenges. The treatments available are quite broad in range and include surgical modalities, liver-directed modalities, and systemic treatment modalities.

It is critically important that such patients are discussed in a multidisciplinary setting to determine if a treatment approach that’s strategic based on all the information available and all the treatment options available to the patient. If you are not practicing in a setting where you have multidisciplinary care, it would be important to do this in a different way. This could be done by perhaps partnering with a neighboring academic center, where the patient could be presented at a tumor board, and perhaps a recommendation can be rendered to you as the treating physician about the best approach. But there are more data showing that a multidisciplinary approach can lead to better outcomes for these patients as well as more coordinated care than not. I’d like to emphasize this as an important approach to patients with hepatocellular cancer.

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