Introduction: Primary liver cancer is among the top five causes of cancer related death worldwide. 905,700 people were diagnosed with liver cancer worldwide in 2020. 830,200 people died with liver cancer globally in the same year. There is estimated to be a 55% rise in the number of new diagnoses and deaths from liver cancer by 2040.1
October is Liver Cancer Awareness month. Raising public awareness is vital in improving outcomes for patients with liver cancer. Not only because it is a major health problem itself, but it is also associated with liver disease and cirrhosis. Prevention and early detection of primary liver cancer through public health measures, surveillance programmes, education and health promotion are key in the battle against this disease.
There are 2 main types of primary liver cancer, hepatocellular carcinoma (HCC) originating in hepatocytes, and cholangiocarcinoma (CCA) forming in the cells of the biliary tree. HCC is the most prominent type, accounting for approximately 90% of cases worldwide. HCC generally occurs on a background of liver cirrhosis, therefore the most common risk factor is chronic liver disease. This article will focus on HCC.
Liver cirrhosis is a chronic disease due to constant liver damage from a recurring insult e.g. excess fat in the liver, viral hepatitis, alcohol abuse, haemochromatosis, plus other aetiologies. Over time, as hepatocytes are in a constant state of injury and repair, mutations develop in the cells leading to carcinogenesis and the formation of HCC. Patients with liver cirrhosis have a 1– 8% cumulative annual risk of developing HCC, therefore liver cirrhosis and HCC tend to be managed simultaneously by Hepatologists, in conjunction with Hepatopancreaticobiliary Surgeons, Interventional Radiologists, Oncologists and Specialist Nurses.
Diagnosis and Staging
HCC is one of the few cancers which can be diagnosed radiologically if the patient has liver cirrhosis, or chronic hepatitis B virus (HBV) in the absence of cirrhosis. The Liver Imaging Reporting and Data System (LI-RADS) classification is widely used to guide non-invasive diagnosis of HCC. LI-RADS category LR-1 is considered a definitely benign lesion, whereas LR-5 is consistent with definite HCC.2 If a patient does not have cirrhosis or chronic HBV, or a LI-RADS classification of LR-M (definite or probable malignancy, not specific for HCC), a histopathological diagnosis is required.
Liver cancer can be staged with various systems. The staging of HCC and its treatment algorithm differ from that of other cancers, as the background liver disease and level of liver function is a major determining factor in treatment selection. A patient may have a small cancer which would ordinarily be considered for curative resection in an organ without a synchronous pathology e.g. breast. However, when a patient has dual pathologies like HCC and liver cirrhosis, the level of liver dysfunction from the chronic liver disease will increase the mortality risk from interventions like surgery. Conservative management with a life prolonging treatment plan may become the clinical pathway of choice then, regardless of the small cancer size. There are validated scores available in the literature to assess the level of liver dysfunction and risk of mortality for patients with cirrhosis based on their clinical data. These include the Model for End Stage Liver Disease (MELD) score, which predicts the 3-month mortality risk for patients with liver cirrhosis. As well as, the Child Turcotte Pugh (CTP) score, which stratifies the severity of liver disease and predicts surgical mortality for patients with liver cirrhosis. For HCC management, the Barcelona Clinic Liver Cancer (BCLC) Staging Classification is a widely accepted treatment algorithm which stages the cancer and guides clinicians to appropriate treatment modalities considering both HCC burden and extent of the background liver disease determined by the CTP score.3 The MELD, CTP and BCLC are internationally recognised and recommended for use in the management of HCC and can provide prognostic information for these patients.
All patients with a new diagnosis of liver cancer should have their case discussed at a specialist liver cancer multidisciplinary team meeting (MDM) with an expert consensus decision made regarding recommended treatment.4,5 The specialist liver cancer MDM in St Vincent’s University Hospital (SVUH) is an example of this. Treatment for HCC can be divided into 2 categories, those with curative intent and those which are life prolonging.
Surgical options include liver resection and liver transplantation. Surgical resection removes the part of the liver affected by the cancer. Factors affecting consideration for resection include tumour size, location, vascular invasion, presence of metastases and level of background liver function. Liver Transplant involves the removal of the patient’s native liver and replacing it with a new healthy donor liver. Strict criteria must be met before a patient is considered for a liver transplant.
If deemed appropriate, they then undergo a period of assessment to ensure their suitability for this type of major surgery. Both surgical treatments are curative in nature, however liver transplantation is considered superior as it not only removes the existing liver cancer, but also the background liver cirrhosis which caused it, and is a continued risk factor for further HCC development.
Non-surgical options include thermal ablation (curative intent), transarterial chemoembolisation (TACE), selective internal radiation therapy (SIRT) and systemic therapy, both of which are noncurative in nature. Thermal ablation uses extreme temperature (heat or cold) to ablate the liver cancer and is used to treat lesions ≤3cm in size. TACE works by injecting chemotherapy directly into the blood supply feeding the HCC as well as blocking off the arterial blood supply to it. SIRT is similar to TACE, however radiation is injected into the liver this time, which damages the cancer cells internally. Systemic therapy is used for patients who have advanced liver cancer with preserved liver function. Immunotherapy (IV) and tyrosine kinase inhibitors (oral) are used for this type of treatment. For patients with deranged liver function and / or poor performance status, best supportive care and palliation is the treatment of choice regardless of the liver cancer burden.
SVUH is the only centre nationally equipped to offer the full array of approved treatment modalities here in Ireland.
The National Cancer Registry of Ireland described a 300% increase in the number of liver cancer cases in Ireland in the last decade.6 In 2018, they reported 285 new cases of primary liver cancer per year in Ireland, with 290 deaths from primary liver cancer here per year.7
While primary liver cancer is a major burden globally, awareness of liver cancer is limited in this country. When I ask members of the general public about liver cancer, they describe secondary liver cancer or metastases to the liver from another primary malignancy originating elsewhere in the body. Their knowledge is lacking about primary liver cancer, its causes, surveillance options, treatments and outcomes. This liver cancer awareness month we hope to shine a light on liver disease and its associated cancer here in Ireland.
While improvements in cancer care are always welcome, prevention is better than cure! Prevention of primary liver cancer requires awareness of the risk factors for its development, mainly chronic liver disease. Globally viral hepatitis is the leading cause of liver cirrhosis, however fatty liver and alcohol excess are the leading risk factors in the western world.
A fibroscan is a quick and easy, non-invasive test used to identify the presence of fat and inflammation or scarring in the liver. Liver specific blood tests can be used to calculate scores to predict liver dysfunction. These tests, coupled with a comprehensive health history and physical assessment can make a diagnosis of liver disease and cirrhosis, prompting a surveillance protocol for liver cancer.
Strategies to tackle viral hepatitis associated HCC include vaccination against HBV. Universal vaccination programmes for newborn babies in Asia are associated with significant decreases in HCC incidence there.
In Ireland, the HBV vaccine is now given to children as part of the 6 in 1 vaccine at 2, 4 and 6 months of age.
Additional strategies involve antiviral therapy for those with HBV and hepatitis C virus (HCV). Treatment for HBV will keep the virus under control. New treatments for HCV can eradicate the virus altogether. Both treatments aim to prevent the development of significant fibrosis or cirrhosis in the liver. Antiviral therapies have shown to significantly reduce HCC risk. However, patients who have already developed cirrhosis will have a persistent risk for HCC development.
Non-alcoholic fatty liver disease (NAFLD)
The Health Service Executive (HSE) recently reported that Ireland has one of the highest levels of obesity in Europe.8 Obesity is linked with many chronic illnesses including NAFLD and liver cirrhosis. It is associated with a 1.5 – 4.5 times higher risk of HCC, contributing to nearly 10% of all HCC incidence worldwide. NAFLD is currently the fastest growing cause of HCC in liver transplant candidates and is the leading cause of HCC in the absence of liver cirrhosis.4 Weight loss and increased physical activity improves outcomes for patients with NAFLD, reducing the progression to cirrhosis.
Alcohol Action Ireland and the UCC School of Public Health attribute the number 1 cause of alcohol related deaths in Ireland to liver cancer and liver cirrhosis. The International Agency for Research on Cancer classify alcohol as a group 1 carcinogen. There is a proven link between alcohol and several types of cancer. While it is important to note that there is no safe level of alcohol consumption, low risk drinking guidelines are available recommending less than 11 standard drinks per week for women and 17 standard drinks per week for men. It is hoped that the Public Health (Alcohol) Act 2018 will help to reduce alcohol use and subsequent harms in Ireland.
Smoking is associated with risk for many cancers, but specifically a 20%-86% increased risk for HCC.4 Quitting smoking can return this risk almost to baseline after 30 years of cessation. The HSE provide resources and programmes to assist in smoking cessation.
Once a diagnosis of liver cirrhosis has been made or a patient has chronic HBV in the absence of cirrhosis, regular surveillance for primary liver cancer is recommended the world over, in the form of an ultrasound liver every 6 months, to assess for the development of primary liver cancer.4,5 Although the evidence is not strong for the use of tumour markers as part of the surveillance protocol, the measurement of alphafetoprotein (AFP) level in blood may assist in early detection of primary liver cancer.
Primary liver cancer rates are increasing in Ireland. HCC is the most common type of primary liver cancer and usually occurs on a background of liver cirrhosis. Surveillance for HCC should be offered to all patients who qualify for it. A specialist MDT should provide recommendations for management of anyone diagnosed with liver cancer. However, prevention is better than cure! Steps need to be taken in at risk groups to prevent the development of significant liver fibrosis, cirrhosis and primary liver cancer. If you would like any further information, the Irish Liver Foundation (www. liverfoundation.ie) and the Irish Cancer Society (www.cancer.ie) have excellent information pages dedicated to primary liver cancer.
1. Rumgay et al. (2022) ‘Global burden of primary liver cancer in 2020 and predictions to 2040’, Journal of Hepatology, 77, pp. 15981606.
2. LI-RADS (2023) Available online at: LI-RADS | Radiology Reference Article | Radiopaedia.org Accessed on 08/08/2023.
3. Reig et al. (2022) ‘BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update’, Journal of Hepatology, 76(3), pp.681-693.
4. AASLD (2023) ‘AASLD Practice Guidance on Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma’, Hepatology, Available online at: AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma – PubMed (nih.gov) Accessed on 14/06/2023.
5. EASL (2018) ‘EASL Clinical Practice Guidelines: Management of Hepatocellular Carcinoma’, Journal of Hepatology, 69(1), pp. 182-236
6. National Cancer Registry Ireland (2016) Cancer Trends. Available online at: https://www.ncri.ie/ sites/ncri/files/pubs/Liver%20 trendsDecember2016_0.pdf Accessed on 08/08/2023.
7. National Cancer Registry Ireland (2018) Cancer Factsheet Liver. Available online at: Factsheet liver. pdf (ncri.ie) Accessed on 08/08/2023.
8. HSE (2020) A healthy weight for Ireland Obesity policy and action plan. Available online at: ccbd6325268b48da80b8a9e5421a9eae. pdf (www.gov.ie)
Written by: Michèle Bourke, Hepatocellular Carcinoma Advanced Nurse Practitioner, St. Vincent’s University Hospital
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