Liver cancer is the third-highest cause of cancer-related deaths worldwide, and incidence of primary liver cancer in the US has tripled in the last four decades. While chronic viral hepatitis is the leading pathway to liver cancer in the US, noninfectious causes such as morbid obesity, type-2 diabetes, non-alcoholic fatty liver disease (NAFLD), and associated non-alcoholic steatohepatitis (NASH) have been growing rapidly. We will describe each of these pathways, starting with viral hepatitis (HCV and HBV), and alcoholic cirrhosis.


There is a morbid saying that cancer gets us all in the end, unless something else gets us first.

While some cancers have no amenable prevention at present, some can be effectively prevented. Hepatocellular carcinoma (HCC) is one of those that can be preventable, but once HCC is established and symptomatic, the survival rates diminish sharply. While liver cancer is the 8th leasing site of cancer by prevalence (Figure 1), it is the 3rd leading cause of death (Figure 2). HCC has a high mortality profile with a median survival following diagnosis of 6-20 months, and in the US, it has a 5-year survival rate of only 10% (Golabi, et al., 2017)

Top 10 Cancer Sites by Cases

Figure 1. Top 10 Cancer Sites by Cases (Sung et al, 2021)


Top 10 Cancer Sites by Deaths

Figure 2. Top 10 Cancer Sites by Deaths (Sung et al, 2021)


The COVID-19 pandemic has rightfully occupied the minds and efforts of almost everyone in healthcare for the past two years, but HCC has not disappeared and is still causing daily harm. HCC was the 4th leading cause of cancer-related death in 2019 (Yang, et al., 2019), and has been climbing steadily – it has tripled in the US (Rawla, Sunkara, Muralidharan, & Raj, 2018).

Although your daily odds of encountering a patient with HCC are still small, they are increasing year on year, and there is a serious risk of missing the window of opportunity to prevent full-blown HCC.

This blog will describe how to be alert for causes and cases of HCC, and we will provide you with some tools and resources to help you to identify HCC, ways to link your patient to suitable specialists, and help you find appropriate studies and trials for your patient.

There are four main HCC risk factors:

  1. Hepatitis B (HBV)
  2. Hepatitis C (HCV)
  3. Excessive alcohol consumption
  4. Nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH)

How Are You Likely to Encounter Hepatocellular Carcinoma in Patients?

For the near future, the chances are slim that any specific patient you see will already have HCC. That is great, but also a problem because you are therefore less likely to immediately recognize it. For HCC, delay is the killer.

However, you are very likely to see a patient that, regardless of their chief complaint, is already on one or more of the four leading HCC pathways. The picture is also skewed when race is considered – while the overall HBV infection rate has dropped significantly since 1991, it remains of concern for the African American population. In 2017, non-Hispanic African Americans were 1.5x as likely to die as a result of viral hepatitis than whites, and almost twice as likely to die as a result of HCV. (HHS-OMH “Hepatitis and African Americans”)

Anything you can do to increase vaccination rates for HBV, and prevent infection with HCV, will help to keep your patients off the viral pathway. It is therefore important to use HBV and HCV testing, and strongly encourage HBV vaccination even if patients are not in the high-risk categories. Likewise, addressing alcohol use and encouraging your patients to keep within guidelines, will help keep them off the alcohol pathway to HCC.

The NAFLD/NASH pathway speaks to lifestyle changes that are inherently healthier, and worth discussing. Discussing eating a healthy diet, limiting portion sizes, and maintaining a healthy weight with your patients may help keep them off this pathway.

Patient history that should increase your index of suspicion includes past unprotected sex, needle use, excessive alcohol use or binge drinking, or increasing obesity. However, it is important to bear in mind that many patients who had no obvious risk factors in their history, nevertheless went on to have HCC. Although atypical, HCC can be the result of maternal HBV or HCV infection passed on to children. For an example, see “Better Off Bald: A Life in 147 Days


How to Discuss Staging With the Patients

Discussing staging with patients can be difficult, and the literature is often either aimed at clinicians, or contains misleading information. Blue Faery provides clinically accurate but understandable materials to assist you in describing the staging, and help the patient to understand where they are in the spectrum.

These materials include:

  • The HCC patient education brochures is written in layman’s terms, and intended for the patient to read.
  • The Blue Faery and Exelixis staging discussion pad contains anatomical graphics and easily understood text. Each double-sided sheet has space for the physician to add notes for their patient to use after the appointment.
  • The Patient Resource Guide for Liver Cancer is a 20-page booklet with explanations and resources pertinent to HCC patients and their caregivers.

Blue Faery will send these materials to any requesting physician, free of charge.

How to Find Hepatocellular Carcinoma Specialists, Treatment Options & Clinical Trials

The treatment of HCC is best approached with a multidisciplinary team coordinated by a primary care physician. The most effective approach will likely require the expertise of multiple medical professionals, including the primary care physician, and may include an oncologist with experience in HCC, a gastroenterologist, hepatologist, interventional radiologist, radiation oncologist, surgical oncologist, and a transplant surgeon.


Where to Find Hepatocellular Carcinoma-Specific Clinical Trials

To find all clinical trials, the best option is but this website can be confusing and difficult to navigate. To assist the physician in guiding their patients to relevant trials, Blue Faery has a custom HCC clinical trial navigator.

Where Can Patients Find Community Support?

Patient communities are very helpful in providing patients with practical tips for their care journey, and are often a source of emotional support by people who understand the experience.

The Blue Faery Liver Cancer Community is a free HIPAA-compliant online community where both patients and caregivers are welcome to join, and to seek or exchange information relevant to HCC care. Members ask questions, discuss concerns, and find common ground as they navigate their cancer journeys. The forum moderators include Community Ambassadors who were former caregivers of HCC patients.

For one-on-one patient support, Blue Faery has partnered with Imerman Angels, a nonprofit organization that provides peer-to-peer support services for the liver cancer community. Blue Faery and Imerman Angels believe that no one should face cancer alone.


With adequate screening, testing, and inoculation, the viral pathway to HCC can often be interrupted. Blue Faery provides free patient-readable and clinically accurate materials to assist physicians in discussing their patients’ staging, options, and resources.