Understanding Liver Cancer (Hepatocellular Carcinoma – HCC)

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Introduction

In Malaysia, liver cancer ranked eighth most common cancer amongst Malaysian population, with males to female ratio around 2:1.

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Liver

Mostly, around 80%, present at late stages (III, IV).

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Malaysia liver cancer (HCC) data

Risk factors

Main risk of developing liver cancer is liver cirrhosis, which is liver impairment caused by scarring/ fibrosis of liver.

  • One third of patients with cirrhotic liver develop liver cancer/ HCC in their lifetime (1–8% of patients with cirrhosis develop liver cancer per year)
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Liver cirrhosis/ fibrosis

Liver cirrhosis are caused mainly by:

  • Chronic liver infection (Hepatitis B/ C), 
  • Heavy and long term alcohol consumption
  • Metabolic disorders (obesity, diabetes causing non-alcoholic fatty liver disease, etc)
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Hepatocellular carcinoma (HCC) = Liver cancer AND liver cirrhosis

Prevention of Liver Cancer 

In order to prevent liver cancer, one must avoid causes that can lead to liver cirrhosis

  • To prevent Hepatitis B infection, there is effective vaccination against the disease. Get yourself tested to see your level of Hepatitis B antibody. If it’s low or zero, get yourself immunised.
  • And for Malaysian with hepatitis C infection, you can get treated with very effective antiviral treatment (high cure rate) at very low cost.
  • Avoid heavy and prolonged alcohol consumption
  • Treatment of diabetes and avoiding obesity
  • Drinking coffee (yes!)

Surveillance

Surveillance is reserved mainly for high risk group, not for everyone.

High risk groups are those with liver cirrhosis (85%-95% of liver cancer patients had liver cirrhosis) and chronic liver infection (hepatitis B/ C).

Surveillance aim is to detect liver cancer at earlier stage, which will translate to higher cure rate and longer survival.

Surveillance is not meant to be performed once only, but at regular interval of 4 – 6 monthly.

Studies showed 37% reduction in death for hepatitis B carriers who underwent surveillance. Also, 3-year survival rate is higher by 11% – 23% for high risk group (patients with liver cirrhosis) who underwent surveillance.

Majority (77.6%) of liver cancer cases in Japan were detected by surveillance whereas in Hong Kong is less than 20%. Average survival was 52 months and 7 months in Japan and Hong Kong respectively. This is likely due to 62% of Japanese patients had early disease at diagnosis and 63% received curative treatment. The comparable figures for Hong Kong were 8% and 16% respectively.

Recommended surveillance modalities are ultrasound liver and/ or tumor marker (alpha fetoprotein).

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USG liver surveillance
  • Variable ultrasound features (iso-, hyper-, hypoechoic)
    • Contrast enhanced ultrasound (80%+ accuracy)
    • Intraoperative ultrasound (90%+ accuracy)
  • Alpha fetoprotein is raised in 70%+ of HCC and values more than 100ng/mL is suggestive of HCC (or progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma)
  • Alpha fetoprotein also help to predict treatment response
  • Detection at early stage means higher chances of cure from liver cancer

Diagnosis/ confirmation of liver cancer

Tissue biopsy (CT guided biopsy, etc), recommended for non-cirrhotic liver

Treatment can be initiated based on radiological imaging alone without tissue biopsy confirmation (unlike other cancers) in cirrhotic liver

  • Imaging with multiphase MRI or CT liver, both have similar performance characteristics,
  • Stringent imaging criteria with high specificity for ≥10 mm HCC have been developed by the American College of Radiology (ACR), include arterial phase hyperenhancement in combination with washout appearance and/or capsule appearance

Staging

Unlike other cancers, I like to use the Barcelona Clinic Liver Cancer (BCLC) to stage liver cancer instead of AJCC TNM staging system.

BCLC takes into account the tumor status, liver function and performance status.

The stage in BCLC is then linked to the different treatments available (see below).

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Barcelona Clinic Liver Cancer (BCLC) classification
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Classification of Liver Cirrhosis – degree of liver dysfunction

Treatments

  • For liver cancer, determination of treatment selection and treatment outcomes are based on
    • Staging (Barcelona Clinic Liver Cancer 0, A-D, TNM stage 1-4)
    • Liver function (Child Puch A-C)
    • Patient performance status (ECOG 1-4)
  • Treatments for Early Stage Liver Cancer
    • Aim is curative
    • Treatments include liver tumor resection, ablation, liver transplant
  • Treatment for Borderline Liver Cancer
    • Aim is conversion; hoping to convert unresectable liver cancer to resectable and hence increase chances of achieving cure
    • Treatment include liver directed treatment (TACE, SIRT)
  • Treatments for Advanced Stage Liver Cancer
    • Aim is to control disease and prolong survival
    • Treatments include liver directed therapy, targeted therapy and immunotherapy
  • Treatment for Late Stage Liver Cancer
    • Aim is for best supportive care with palliative referral to improve symptoms (pain, abdominal distention, constipation, anorexia, amnesia, shortness of breath) and not to prolong death

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