Hepatocellular carcinoma: Clinical sciences

Hepatocellular carcinoma, or HCC for short, is primary cancer of the liver parenchyma arising from hepatocytes. Most cases occur in patients with cirrhosis from chronic liver diseases like chronic alcohol consumption or viral hepatitis infection. Because patients can remain asymptomatic until the tumor grows substantially, screening patients with risk factors is important.

Alright, the first step in evaluating a patient with a chief concern suggestive of hepatocellular carcinoma is to perform a focused history and physical examination. Let’s start with screening. These patients are asymptomatic but have risk factors for HCC like cirrhosis or non-cirrhotic chronic liver disease, which can include long-standing hepatitis B or C infections and non-alcoholic fatty liver disease. Exam will likely be normal, but some can have hepatomegaly and ascites. In this case, your next step is to obtain labs such as liver function tests, or LFTs, and alpha-fetoprotein, or AFP, as well as imaging like an ultrasound of the liver.

Before we go on with the findings, let’s talk about symptomatic patients. If the patient is symptomatic, they might report jaundice, anorexia, weight loss, malaise, and vague upper abdominal pain. History might also reveal risk factors like cirrhosis or non-cirrhotic chronic liver disease.

On exam, you might find hepatomegaly, ascites, as well as jaundice of the eyes or the skin. With these findings, your next step is to order labs including LFTs and AFP, in addition to an ultrasound of the liver.

Now, if labs are normal and the liver ultrasound is normal with no nodules, the patient likely does not have HCC and can be followed up with routine surveillance every 6 months. If the patient was symptomatic, you will need to do additional workup to find out what is causing their symptoms.

For patients with normal LFTs and negative AFP, but the liver ultrasound shows a nodule smaller than 10 millimeters, you should suspect high-risk liver nodule and follow up with repeat AFP and ultrasound in 3 to 6 months. As before, symptomatic patients might need additional workup to find the cause of their symptoms.

Lastly, if the patient has abnormal LFTs, elevated AFP and a liver ultrasound shows a nodule that is equal to or greater than 10 millimeters, you should suspect a malignant liver nodule. In this case, the next step is to assess LI-RADS to determine the diagnosis and appropriate treatment.

Okay, to do that, you need to get additional imaging with a CT or MRI of the abdomen to better visualize the mass. Typically, a dedicated CT scan called “triple phase liver protocol” is used to make radiographic diagnosis of HCC. So, liver lesions that show hyperenhancement, meaning white in the arterial phase and washout, or turning gray again in the portal venous phase are consistent with hepatocellular carcinoma.

Here’s a clinical pearl! The Liver Imaging Reporting and Data System, or LI-RADS is a system for categorizing liver tumors based on their appearance on CT or MRI. The categories range from LI-RADS 1 benign lesions to LI-RADS 5 which represents HCC. Tumors that meet criteria for LR 5 are diagnostic of HCC and do not require a biopsy for confirmation.

Additionally, multiple masses in the liver are suspicious for liver metastasis from another primary cancer like colon, breast or lung cancer. Keep in mind, metastatic lesions to the liver are more common than primary liver cancer like HCC. In these cases, refer the patient for other cancer screenings such as colonoscopy, mammogram, skin exams, or chest x-ray. You can also order associated cancer markers including CEA and CA 19-9 to help make your diagnosis.

Alright, let's talk about LI-RADS 1 and 2. If the CT or MRI of the abdomen shows a liver lesion consistent with a LI-RADS 1 or 2, you can diagnose a benign liver mass. These lesions are typically simple liver cysts, hemangiomas, confluent fibrosis or a focal scar. They are all considered benign with low risk for development of malignancy. Management includes routine surveillance to monitor for any changes with liver ultrasound and AFP every 3 to 6 months. You can consider a follow up CT or MRI for high-risk patients with a LI-RADS 2 lesion.

Now, a CT or MRI showing a LI-RADS 3 lesion is consistent with intermediate probability for HCC. These lesions are definitely not benign but also not definitely HCC. Management includes repeating the ultrasound, CT or MRI every 3 to 6 months for 2 years or more, monitoring for any changes in the lesion. If there are no changes after 2 years, they can be routinely surveilled with liver ultrasound and AFP. Keep in mind that these patients might also need a biopsy.