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Diagnosis and management of early-stage hepatocellular carcinoma

The global incidence of hepatocellular carcinoma has risen in several countries over the past two decades driven by higher levels of obesity and type 2 diabetes , leading to non-alcoholic fatty liver disease . Several effective treatment modalities are available provided that the disease is identified at an early stage , highlighting the importance of surveillance programmes
Arman Reza Chowdhury Consultant Oncologist , Evercare Hospital , Dhaka , Bangladesh
Md . Salim Reza Consultant Oncologist , Square Hospital , Dhaka , Bangladesh
Primary liver cancer is the seventh most frequently occurring cancer in the world and the second most common cause of cancer mortality . 1 Hepatocellular carcinoma ( HCC ), which is a tumour of the parenchymal cells in the liver , is the most common form of liver cancer , accounting for 90 % of all cases . The rate of HCC has been rising worldwide over the last 20 years and the highest incidence rates of liver cancer are found in Asian and African countries , although rates are likely to become much higher in some countries such as the United States , whereas in other countries , e . g ., China and Japan , the incidence has started to decline . 2 The reason for the higher rates in the United States is due to greater levels of both obesity and type 2 diabetes , which lead to non-alcoholic fatty liver disease ( NAFLD ) and its most severe form , non-alcoholic steatohepatitis ( NASH ). The presence of NAFLD can result in liver fibrosis and ultimately cirrhosis , which is an important cause of HCC . 3 Overall incidence rates of HCC are directly correlated with advancing age and the cancer is 2 – 4-times more common in men than women . 4 The prognosis of HCC is relatively poor especially has patients often present at a later stage of the disease so that there is little difference between incidence and mortality . For example , in 2018 , the estimated global incidence rate of liver cancer per 100,00 person-years was 9.3 with a corresponding mortality rate of 8.5 . 1
Both hepatitis B ( HBV ) and C are established risk factors for HCC and HBV vaccination programmes are a key preventative strategy for HCC . In fact , data from Taiwan has shown an 80 % decline in HCC incidence and a 92 % mortality reduction in cohorts born after the introduction of a vaccination programme . 5 Furthermore , treatment of HBV with nucleotide analogues led to a significant reduction in the subsequent development of HCC . 6
Surveillance Early diagnosis of HCC enables aggressive treatment , prolonging patients ’ long-term survival and , as a result , many international societies have introduced surveillance programmes , involving the repeated use of screening tools in at-risk patients 3 and for those with cirrhosis , irrespective of its aetiology . Surveillance of non-cirrhotic , hepatitis-infected patients should also be considered in chronic HBV carriers or HCV-infected patients with bridging fibrosis who are at a higher risk than the general population . Specifically , among Asian patients , serum HBV-DNA above 10,000 copies / ml was associated with a significantly higher risk of HCC higher risk compared with those with lower viral loads . 7 Surveillance of patients at risk should be carried out every 6 – 12 months using liver ultrasound . 8
Diagnosis Currently , ultrasound tests are the recommended imaging modality for the assessment and early detection of HCC , although contrast-enhanced computed tomography ( CT ) and magnetic resonance imaging ( MRI ) can also be used . Levels of serum alpha fetoprotein ( AFP ) are also assessed although AFP has a low sensitivity and specificity for early HCC . Imaging techniques are also recommended for the detection of liver nodules > 1cm and the hallmark imaging features for a diagnosis of HCC are arterial phase hyperenhancement ( APHE ) and portal / delayed washout , which represent the characteristic vascular profile of HCC on dynamic CT or MRI . 9
In an effort to improve standardisation and consensus with respect to the reporting and data collection of CT and MRI for HCC , the Liver Imaging Reporting and Data System ( LI-RADS ) was introduced . LI-RADS classifies new hepatic lesions into five classes based on their size , extent of interval growth and patterns of enhancement . 10
Work-up The diagnostic work-up of a patient with an HCC-suspicious nodule is given in Table 1 .
Staging of liver cancer The staging of HCC is mainly undertaken with the Barcelona Clinic Liver Cancer ( BCLC ) system , 12 which has four stages ( A to D ) and assesses :
• Tumour extent ( contrast-enhanced MRI or helical CT are recommended ).
• Liver function ( using the Child-Pugh score / ALBI score ).
• Clinical performance status ( Eastern Cooperative Oncology Group ( ECOG ) performance status ).
Child-Pugh classification of cirrhosis This is designed to predict mortality in cirrhosis patients . Liver function is assessed using the Child-Pugh system , 13 which looks at :
• Bilirubin levels
• Albumin levels
• Prothrombin time
• Ascites
• Encephalopathy hospitalpharmacyeurope . com | 21