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Last updated: August 19, 2022
Revisions: 36

Last updated: August 19, 2022
Revisions: 36

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Introduction

Liver cancer can either be metastatic (90%) or primary (10%). In this article, we will mainly focus on hepatocellular carcinoma (HCC), followed by a brief description of secondary liver cancers.

Hepatocellular carcinoma is the sixth most common cancer worldwide and the third leading cause of cancer death. Incidence rates vary significantly across the globe – in China there are 401 cases per 100,000 people, whilst in the UK there are just 13 cases per 100,000 people. The majority of cases occur in those >70 years and around 65% of cases occurring in males.

HCC arises as a result of a chronic inflammatory process affecting the liver. The aetiology of the inflammation varies, yet worldwide it is most commonly due to viral hepatitis. Other causes for HCC are chronic alcohol excess, hereditary haemochromatosis, primary biliary cirrhosis (PBC), and aflatoxin exposure (a toxic fungal metabolite)

Risk Factors

The main risk factors for HCC are:

  • Viral hepatitis infection, mainly Hepatitis B virus and Hepatitis C virus
  • Alcohol excess
  • Smoking
  • Advanced age (>70yrs)
  • Positve family history

In certain low and middle income countries, viral hepatitis can accounts for up to 90% of HCC cases, however this is as low as 15% of cases in many developed countries.

Figure 1 – Lobes and ligaments of the Liver

Clinical Features

Many cases in developed countries are picked up on surveillance imaging, in those patients identified as high risk (e.g. known liver cirrhosis patient).

Less commonly, patients may present with non-specific symptoms, such as fatigue or weight loss. Abdominal pain in HCC is uncommon, especially in early stages of the disease.

On examination, classically an irregular enlarged liver is palpable, however in early HCC disease, this may not be present. Those with already established liver disease may present with features of decompensated liver disease, such as ascites, jaundice, or confusion.

Fig 2 - Ascites, an indicator of late stage liver disease.

Figure 2 – Ascites, an indicator of late stage liver disease.

Investigations

Laboratory Tests

A patient with suspected HCC should have routine bloods, including full blood count, liver function tests and a clotting profile.

An alpha fetoprotein (AFP) level should be measured in all suspected cases, as it is raised in 70% of HCC cases. It is used to monitor treatment response and recurrence.

Imaging

Ultrasound scanning is the initial imaging modality of choice for suspected HCC, however is also used in screening programmes for high-risk individuals (along with AFP measurements). HCC lesions show as hypodense lesions on ultrasound, however are often difficult to distinguish from any background cirrhosis if present.

MRI or CT imaging (Fig. 3) are both useful to further assess suspicious lesions identified from ultrasound. These imaging modalities typically show the mass with vivid enhancement during the late arterial phase and a subsequent rapid wash out.

Diagnosis is normally made through tumour markers and imaging alone, yet in cases of diagnostic uncertainty, then image-guided percutaneous biopsy may be required (albeit with risks of bleeding and tumour seeding)

Figure 3 – A CT scan demonstrating a hepatocellular carcinoma

Staging

The Barcelona Clinic Liver Cancer staging system (BCLC) is the most accepted staging system for HCC. It takes into account the tumour stage, liver function, physical status and cancer related symptoms to provide guidance on what treatment is most suitable.

Risk assessment tools, such as the Child-Pugh and MELD scores, can be used to assess the risk of mortality from cirrhosis and to predict potential effectiveness from potential treatment options.

Liver Cirrhosis Risk Scores

The well-known and widely used Child-Pugh score uses parameters of serum bilirubin, albumin, INR, degree of ascites, and evidence of encephalopathy to calculate prognosis of patients with liver cirrhosis.

However, recent scores such as the MELD score have been shown to be a better predictor of mortality. The latest MELD score calculator includes parameters of creatinine, bilirubin, INR, sodium, and the use of dialysis (at least twice per week).

A MELD score can also be used to predict the likelihood of a patient tolerating a potential liver transplant.

Management

Treatment for hepatocellular carcinoma should be organised through a multidisciplinary team approach. Surgical resection and transplantation are the only curative options, but are limited by tumour size and liver function, alongside any co-morbidities present

  • Surgical resection – the treatment of choice in patients without cirrhosis and with a good baseline health status. Five-year recurrence of HCC post-resection occurs in 50-60% of cases
  • Transplantation – can be considered in patients that fulfil the Milan Criteria: (1) one lesion is smaller than 5cm or three lesions are smaller than 3cm (2) no extrahepatic manifestations (3) no vascular infiltration
Fig 3 - Left lobe liver tumour in a 50 year old male. A) Removal of the tumour; B) The liver after resection.

Figure 4 – Left lobe liver tumour in a 50 year old male. A) Removal of the tumour; B) The liver after resection.

Non-Surgical Management

Image-Guided Ablation

Image-guided ablation is indicated for patients with early HCC (BCLC 0 or A). Ultrasound probes (or microwave probes) are placed in the tumour mass to induce necrosis.

Alcohol ablation can also be trialled, involving the injection of alcohol into the tumour, acting to destroy the malignant tissue. It is most effective on small tumours in those with well-functioning livers, also being the treatment of choice in those with small inoperable cancers.

Transarterial Chemoembolisation (TACE)

Transarterial Chemoembolisation (TACE) is reserved for patients with BCLC stage B (a large multinodular tumour), whereby high concentrations of chemotherapy drugs are injected directly into the hepatic artery and an embolising agent is then added to induce ischaemia.

Radiological techniques are used to selectively inject and embolise the branches of the hepatic artery supplying the tumour, which preserves the majority of the liver.

Prognosis

The prognosis of hepatocellular carcinoma depends on the extend of the underlying cirrhosis, as this plays a large role in determining how aggressively the cancer can be treated. Median survival time from diagnosis is around 6 months.

Secondary Liver Metastasis

The most common cancers that metastasise to the liver are those from bowel (via the portal circulation), breast, pancreas, gastric, and lung.

These are typically picked up on staging imaging following the initial diagnosis. However patients can present with jaundice, right upper quadrant pain, or deranged LFTs.

Fig. 4 - Metastatic liver (A) metastatic liver deposits from a colon primary, seen on post-mortem (B) CT scan showing metastatic liver deposits

Figure 5 – Metastatic liver (A) metastatic liver deposits from a colon primary, seen on post-mortem (B) CT scan showing metastatic liver deposits

Generally, patients with multiple metastatic deposits are not curable, therefore palliative chemotherapy is the mainstay of treatment in the majority of cases.

A small proportion of patients who have limited number of deposits in the liver (especially in bowel cancer patients) with no further evidence of disease elsewhere, with surgically resectable disease, who are clinically fit enough, liver metastatectomies for curative intent may be considered.

Non-surgical options, such as transarterial chemoembolisation or selective internal radiotherapy, can be trialled.

Key Points

  • Hepatocellular carcinoma (HCC) is most commonly associated hepatitis virus and excessive alcohol intake
  • AFP levels can be used for diagnosis and monitor response to treatment
  • Surgical options are the only definitive cure, and include resection or transplantation
  • The most common cancers that metastasise to the liver are those from bowel, breast, pancreas, gastric, and lung