Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world, the third-largest cause of cancer-related deaths, and accounts for approximately 75% of all liver cancers. [1] The last few decades have seen growth in non-viral causes of HCC, such as non-alcoholic fatty liver disease (NAFLD). NAFLD ranges from simple steatosis in the absence of excessive alcohol intake to non-alcoholic steatohepatitis (NASH) with or without cirrhosis.

The risk of HCC is higher in people with long-term liver diseases and if the liver is scarred by infection with hepatitis B or hepatitis C. It’s also more common in people who drink large amounts of alcohol and have an accumulation of fat in the liver.

Tests and procedures used to diagnose HCC include blood tests, imaging tests, and liver biopsy. Treatments include surgery, liver transplant surgery, cryotherapy and hyperthermia, chemotherapy, radiation therapy, targeted drug therapy, immunotherapy, and clinical trials.

When liver diseases advance to cirrhosis, the incidence of HCC is markedly increased, making it critical to closely monitor HCC. [2] Guidelines from the American Association for the Study of Liver Disease recommend that people living with cirrhosis be screened twice per year for liver cancer.

  • About 3-15% of obese patients with NASH progress to cirrhosis; [1]
  • Approximately 4-27% of NASH with cirrhosis patients transform to HCC;
  • At the outset, HCC can develop in patients with NASH without the presence of cirrhosis;
  • Liver cancer rates have more than tripled since 1980, while death rates more than doubled during this time;[3]
  • About 21,000 Americans are diagnosed with primary liver cancer each year and it is twice as common in men than in women.[4]

Individuals most at risk for developing NAFLD or NASH have obesity, Type 2 diabetes, hyperlipidemia and/or metabolic syndrome. NASH, which is mostly asymptomatic, often underdiagnosed and underreported, recently became the most common reason for a liver transplant  in women and older patients.

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Researchers have found that liver cancer, NAFLD, hepatitis C and liver transplants are prevalent in 40-80% of people who have Type 2 diabetes and in 30-90% of people who are obese. Being overweight or obese is responsible for about 85% of fatty liver disease. People with NAFLD have higher rates of several types of cancer, with the greatest increase seen for liver cancer and other gastrointestinal cancers. When liver disease advances to cirrhosis, the incidence of HCC is markedly increased, making it critical to closely monitor HCC.

More commonly, NAFLD is associated with a 2x increase in all-cause mortality in people with Type 2 diabetes over those diabetics without NAFLD and attributed to a 2x increase in cardiovascular mortality.  NASH is associated with a 3x increase in all-cause mortality in this population, attributable to the addition of liver-related mortality.[5]

Targeting liver health can address the broader needs of at-risk patients and prevent them from developing NASH. In fact, this is a critical imperative given the costs and complications associated with NASH. Although the NASH progression rate may be slower than other types of liver disease, the incidence of NASH, and its sequela hyperlipidemia, hypertension, Type 2 diabetes (T2DM), obesity and metabolic syndrome, is increasing throughout the world.

NAFLD is reversible if caught in the early stages and accompanied by lifestyle change. In many patients, a 5-7% decrease in body weight is associated with a reduction in liver fat and inflammation. The challenge is that lifestyle changes are not always sustainable or efficient. This is where a liver examination can optimize a drug-free and highly effective way to reverse liver damage.[6]

Early Detection of Liver Disease Saves Lives
Traditional approaches to assessing liver health, such as liver biopsy and advanced radiological imaging, have generated response that these tests may not be cost-effective, or accessible to the broader at-risk population.

Point-of-care examinations, monitoring and ongoing assessment of liver fat and stiffness can more cost-effectively identify individuals who are asymptomatic and undiagnosed for liver damage. It’s critical to directly measure physical properties of stiffness and fat liver to provide reproducible results and allow for both diagnosis and monitoring of liver stiffness and liver fat.

Because liver damage is serious but treatable, this presents an opportunity for primary care physicians, endocrinologists, internists and gastroenterologists to play a critical role by recognizing NAFLD early so that intervention and monitoring can be implemented.

Engaging the patient to focus on lifestyle management can help to achieve a long-term impact and prompt rapid and potentially meaningful changes in liver fat as estimated by a liver exam score, which can further validate the lifestyle interventions.

[1] Dhamija E, Paul SB, Kedia S. Non-alcoholic fatty liver disease associated with hepatocellular carcinoma: An increasing concern. Indian J Med Res. 2019 Jan;149(1):9-17. doi: 10.4103/ijmr.IJMR_1456_17. PMID: 31115369; PMCID: PMC6507546
[2] Tarao K, Nozaki A, Ikeda T, Sato A, Komatsu H, Komatsu T, Taguri M, Tanaka K. Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment. Cancer Med. 2019 Mar;8(3):1054-1065. doi: 10.1002/cam4.1998. Epub 2019 Feb 21. PMID: 30791221; PMCID: PMC6434205.
[3] Key Statistics About Liver Cancer. American Cancer Society. Online. Last accesed on May 20, 2021
[4] Six things you should know about Liver Cancer. American Liver Foundation. Online. Last accessed on May 20, 2021.
[5] Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018 Jan;67(1):123-133. doi: 10.1002/hep.29466. Epub 2017 Dec 1. PMID: 28802062; PMCID: PMC5767767.
[6] Perdomo CM, Frühbeck G, Escalada J. Impact of Nutritional Changes on Nonalcoholic Fatty Liver Disease. Nutrients. 2019 Mar 21;11(3):677. doi: 10.3390/nu11030677. PMID: 30901929; PMCID: PMC6470750.

Featured image: African American patient explaining issues to Asian doctor using a computer tablet. Photo courtesy: © 2016 – 2021 Fotolia/Adobe. used with permission.

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