Hepatocellular carcinoma

Written by Qiyun Ren

Last Reviewed: April 2019

Review Due: April 2020



'hepatocellular carcinoma (HCC) is a primary malignancy of the liver derived from hepatocytes that usually develops on the background of chronic liver disease, such as cirrhosis'



The aetiology of HCC is complex with no single definite cause. Most patients with HCC also have liver cirrhosis, but other factors have a direct impact on the disease course of HCC.

Important risk factors of HCC include


HBV infection

HCV infection

Autoimmune hepatitis


Alcoholic liver disease

Other less common but equally impactful risk factors include drugs and toxins, genetic metabolic diseases, and vascular abnormalities.


Underlying liver disease

Loss of appetite

Nausea and vomiting

General malaise


Tumour mass

Abdominal mass


Abdominal pain

Bile obstruction


Most common sites are lung, bone, mesentery, adrenal glands and brain



The various risk factors contribute to a process of hepatitis, associated with liver cell necrosis, inflammation, regeneration, and fibrosis.


Proliferation of hepatocytes in regeneration and the oxidative stress in inflammation may cause DNA damage and eventually acquisition of sufficient genetic damage leads to dysregulation of the normal cell cycle.

HBV has an additional role in the pathophysiology of the development of HCC, as the integration of HBV DNA during its replication cycle can induce DNA damage as well as chromosomal abnormalities.



Investigations involve making the diagnosis of HCC, evaluation of the underlying liver condition, and staging of HCC.

AFP (Alpha feto protein)

is useful as a serum marker for the monitoring of recurrent disease. AFP may also provide prognostic information

Ultrasound (US)

Can assess for masses and cirrhosis 


is extremely accurate in confirming the diagnosis of HCC. The classic CT finding is a lesion showing arterial enhancement with venous or delayed phase washout


 has similar sensitivity and specificity to those of multiphase CT imaging. Dynamic gadolinium contrast can be used to improve characterisation of HCC tumours


is indicated when radiological investigations are inconclusive, and the tumour size is between 1-2 cm

The protocol for staging scans differ in each centre and usually involve one or more of the following -CT chest abdomen and pelvis, nuclear bone scan, and PET scan.



Surgical resection is the treatment of choice for patients with single nodules, good liver function, and no underlying cirrhosis. 

Radiofrequency ablation (RFA) can also be used for small tumours and have obtained results comparative to surgical resection and the benefit of being less expensive and less invasive.

Transcatheter arterial chemoembolization (TAZE) is the delivery of high-dose local chemotherapy agents by an interventional radiologist. It is the standard treatment for larger tumours or multifocal HCC without evidence of metastatic spread.

Liver transplantation is potentially curative and the best option for patients with cirrhosis. The Milan criteria can be used to assess suitability and the MELD score can be used to assign priority on the transplant waiting list.


The worldwide epidemiology of HCC is closely linked to HBV and HCV epidemiology.


In European and North American countries, alcoholic and non-alcoholic fatty liver disease has also resulted in an increased incidence of HCC.


HCC is more common in man (>2:1 ratio of man to women) and the incidence increases with age, with peak incidence in the 85-89 age group (UK). The total incidence for the UK is 5736 per 100,000 population in 2015. HCC accounts for 2% of all new cancer cases.




Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1. Published 2017 May 29. doi:10.4103/jcar.JCar_9_16

Sanyal AJ, Yoon SK, Leniconi R. The Etiology of Hepatocellular Carcinoma and Consequences for Treatment. The Oncologist 2010; 15:14-22; doi:10.1634/theoncologist.2010-S4-14

Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol. 2014;20(15):4115–4127. doi:10.3748/wjg.v20.i15.4115

Bialecki ES, Di Bisceglie AM. Diagnosis of hepatocellular carcinoma. HPB (Oxford). 2005;7(1):26–34. doi:10.1080/13651820410024049