What Is Hepatocellular Carcinoma?

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Cancers are usually very worrisome with any suspicious symptom raising anxiety and in this article, the discussion is going to focus on hepatocellular carcinoma (HCC). You should be able to identify its signs and symptoms and how it is managed and treated when the diagnosis is made.

HCC refers to the primary tumour of the liver.1 This means that the cancer cells originate from the liver tissues and keep growing causing damage to the liver and adjacent structures, affecting the function of the liver system and may spread to other parts of the body.

In this article, you will understand the differences between HCC and other types of cancer. You will also be able to understand its distribution in the population, its prognosis, and life expectancy, along with many other important information. 

Overview

The word ‘Hepat- is a prefix derived from the Greek word hêpar, meaning “liver.” That is why inflammation or infection of the liver is called hepatitis. Therefore, hepatocellular means ‘originating from the liver cells’ and this distinguishes HCC from other forms of tumours affecting the liver as a secondary metastasis. 

HCC is more common in men with a ratio of 2.4:1 and it represents the 7th most common contributor to cancer incidence and the 2nd in terms of mortality.2,,3 Asia and Africa represent areas with the highest incidence rates.4 This form of cancer is seen in 80-90% of patients with liver cirrhosis.1,5 Cirrhosis means scarring of the liver tissue due to chronic damage by infection or toxins . 

Causes of hepatocellular carcinoma

Generally, cancers arise when normal cells undergo a transformation from pre-cancerous to cancerous stages, a process known as caricinogenesis.

In the vast majority of cancers, the specific cause is not known, however there are certain risk factors. 

Some risk factors for hepatocellular carcinoma include:1,5

  • Hepatitis B virus (HBV) infection
  • Hepatitis C virus (HCV) infection
  • Alcohol consumption
  • Non-alcoholic fatty liver disease (NAFLD) 
  • Non-alcoholic steatohepatitis (NASH)
  • Aflatoxins
  • Iron overload
  • Glycogen storage disease
  • Wilson disease6
  • Alpha-1-antitrypsin disease
  • Hypercitrullinemia7
  • Alagille syndrome8
  • Acute intermittent porphyrias

A feature unique to HBV is the ability to lead to HCC in the absence of cirrhosis. In patients with cirrhosis, infection with both HBV and HCV increases the risk of HCC.

Signs and symptoms of hepatocellular carcinoma

The median age of presentation of HCC is 69 years.1 Some cases of HCC may be asymptomatic, especially the non-cirrhotic categories. In the cirrhotic related subtypes, symptoms of decompensated liver disease are seen. Decompensated liver disease is a situation of an acute worsening of liver function seen in those with cirrhosis.8 The most common symptom is abdominal pain, others include:1

  • Worsening jaundice, which may be obstructive
  • Ascites
  • Upper abdominal swelling
  • Fever
  • Malaise
  • Weight loss
  • Early satiety 
  • Malaise
  • Cachexia9
  • Pruritus
  • Bleeding - variceal, or intraperitoneal
  • Hepatic encephalopathy 

HCC can also present with symptoms as a result of the release of hormones or similar molecules, causing abnormal reactions in the body. This is the so-called paraneoplastic syndrome exhibited by malignant tumours. In HCC, these symptoms include:

HCC can metastasize (spread) to the lungs, lymph nodes in the abdomen, bone, and adrenal glands. 

Management and treatment for hepatocellular carcinoma

The management of HCC is multidisciplinary (involving various health professionals), requiring careful assessment and evaluation to select the best available option. Management is based on tumour size and site, hepatic function, and the extent of spread in the body.10  

People who have a heightened risk of developing HCC are candidates for surveillance.11 This means regularly screening them for early signs and symptoms, a practice proven to improve early diagnosis, lead to better prognosis, and avail patients of a range of treatment options.11 According to the American Association for the Study of Liver Diseases (AASLD), the following are the high-risk groups recommended for surveillance:11

  1. HBV carriers who are Africans, African-Americans, Asian men >40 years, Asian women >50 years, those who have cirrhosis, and those with a family history of HCC (begin screening at an even earlier age)
  2. All patients with cirrhosis

Screening is done with imaging and blood investigations. Imaging involves doing an ultrasound scan, computed tomography (CT) scan, and magnetic resonance imaging (MRI). The main blood investigation done in serum alpha fetoprotein (AFP).11 

Staging is useful in HCC and it is the process of clinically evaluating the tumour to measure the severity and to select the appropriate treatment. The most common staging system is the Tumour, Node, and Metastasis (TNM) classification which uses measurement of the tumour size, its spread to surrounding structures (such as lymph nodes), and spread to other parts of the body (distant metastasis) .

In terms of treatment, at early stages, HCC can be cured using surgical resection or liver transplantation.10 Resection is preferred when the  tumour is confined to the liver and has a low risk of recurrence. Liver transplantation is the next option when the tumour is not resectable. 

Due to late recognition and presentation in the majority of patients, only a few cases of HCC qualify for these treatment modalities. In those with advanced HCC (metastatic liver disease), the following are the treatment options:10

  • Chemotherapy using systemic cytotoxics (antitumour drugs)
  • Radiofrequency ablation (RFA)
  • Microwave ablation
  • Cryoablation
  • Radioembolization
  • Transarterial chemoembolization
  • Radiation therapy
  • Stereotactic radiotherapy
  • Percutaneous ethanol injection
  • Molecular therapy 

FAQs

How is hepatocellular carcinoma diagnosed?

The definitive diagnosis is made by liver biopsy. Contrast CT or MRI are the imaging techniques used to reliably confirm the diagnosis. In addition, used alone, serum AFP can also be a good predictive marker if highly raised.12

How can I prevent hepatocellular carcinoma?

Some of the preventive measures include:

  • Ensuring you are vaccinated against HBV and screening blood donations are proven preventive methods13 
  • Strategies and treatments that slow or prevent progression to cirrhosis are also useful. Reduction of alcohol intake and exposure to aflatoxins can help prevent HCC13
  • Maintaining a healthy lifestyle by avoiding tobacco, healthy dietary habits and regular exercise are general health tips that are recommended

Who is at risk of hepatocellular carcinoma?

  • Those infected with viral hepatitis (HBV and HCV)
  • Excessive alcohol consumption
  • Those exposed to aflatoxins
  • Those who smoke tobacco
  • Excessive consumers of iron, eg from iron tablets
  • Those with metabolic syndrome, obesity, or diabetes
  • Those with genetic mutations in genes such as in cases of haemochromatosis, alpha-1-antitrypsin deficiency, porphyrias, tyrosinemia, Wilson’s disease etc

How common is hepatocellular carcinoma?

Primary liver cancer is the 7th most common cancer. It is more common in Asia and Africa, and more common in males than females.

What is the life expectancy of people with hepatocellular carcinoma?

The 5-year relative survival rate of HCC is 18.4%, but this varies widely depending on the stage of the cancer, with those with advanced disease (metastatic liver cancer) having only 2.4% 5-year survival rate.

When should I see a doctor?

Seek medical attention when you have symptoms of liver disease such as yellowness of eyes, upper abdominal swelling, early satiety and unintended weight loss. 

Summary

HCC is a malignant tumour of the liver tissue with a poor prognosis that mostly occurs in the setting of cirrhosis developing from several causes. Most patients present late with symptoms such as yellowness of eyes, abdominal mass and weight loss. Disease surveillance is recommended in at-risk groups and early diagnosis, staging, and treatment can improve treatment outcome. Prevention can be achieved by vaccination against viral hepatitis and adequate screening of blood donation.

References

  1. Asafo-Agyei KO, Samant H. Hepatocellular carcinoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Feb 1]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK559177/ 
  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424. 
  3. Petrick JL, Florio AA, Znaor A, Ruggieri D, Laversanne M, Alvarez CS, et al. International trends in hepatocellular carcinoma incidence, 1978–2012. Int J Cancer [Internet]. 2020 Jul 15 [cited 2023 Feb 2];147(2):317–30. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ijc.32723 
  4. Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2007 Aug;5(8):938–45, 945.e1-4.  
  5. Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. Journal of Hepatology [Internet]. 2020 Feb 1 [cited 2023 Feb 2];72(2):250–61. Available from: https://www.journal-of-hepatology.eu/article/S0168-8278(19)30519-7/fulltext 
  6. Chaudhry HS, Anilkumar AC. Wilson disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Feb 2]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK441990/ 
  7. Quinonez SC, Lee KN. Citrullinemia type i. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Feb 2]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1458/ 
  8. Mansour D, McPherson S. Management of decompensated cirrhosis. Clin Med (Lond) [Internet]. 2018 Apr 1 [cited 2023 Feb 2];18(Suppl 2):s60–5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334027/ 
  9. Baker Rogers J, Syed K, Minteer JF. Cachexia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Feb 2]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470208/ 
  10. Crissien AM, Frenette C. Current management of hepatocellular carcinoma. Gastroenterol Hepatol (N Y) [Internet]. 2014 Mar [cited 2023 Feb 3];10(3):153–61. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014047/ 
  11. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology [Internet]. 2005 Nov [cited 2023 Feb 3];42(5):1208–36. Available from: https://onlinelibrary.wiley.com/doi/10.1002/hep.20933 
  12. Bialecki ES, Di Bisceglie AM. Diagnosis of hepatocellular carcinoma. HPB (Oxford) [Internet]. 2005 [cited 2023 Feb 4];7(1):26–34. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2023919/ 
  13. Colombo M, Donato MF. Prevention of hepatocellular carcinoma. Semin Liver Dis. 2005;25(2):155–61. 

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Abdul-Azeez Kuna

Master of Public Health - MPH, University of Liverpool

Hi! I am Abdul. I recently completed my MPH degree from the University of Liverpool.
I joined the public health degree from a medical background and am currently looking forward to proceeding with a PhD. As a way of contributing to public health, I am leveraging the internet space to provide health education and awareness for people to gain knowledge and do what they can to improve their health. With many people searching for health information online, there is a huge advantage to reaching a wider audience. Providing easy-to-read articles backed by evidence is key to ensuring they are not misinformed. As you read this article, I hope it improves your understanding of this health topic and more importantly, motivates you to take preventive measures

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