SonoVue (sulphur hexafluoride microbubbles) – contrast agent for contrast-enhanced ultrasound imaging of the liver

In the context of this evaluation, the term focal liver lesion refers to any focal area of perceived difference seen on imaging that occurs in 1 specific area of the liver. Focal liver lesions can be broadly classified as benign (for example, haemangioma, focal nodular hyperplasia, focal fatty infiltration or sparing, and adenoma) or malignant (for example, primary hepatocellular carcinoma, cholangiocarcinoma and liver metastases). Identifying or excluding malignancy is the primary aim of diagnostic imaging.

The distinction between benign and malignant lesions helps to determine the prognosis and subsequent treatment strategy. Benign asymptomatic liver lesions, which comprise as many as 70% to 75% of the focal liver lesions assessed in the UK, usually do not need treatment. Depending on the type of lesion, the person may be discharged or their condition may be monitored and the lesion rescanned in 6 to 12 months. If a malignant lesion is identified it is important to distinguish between primary and secondary cancers because this is likely to affect how the condition is managed. Malignant lesions may be treated with a range of interventions, including chemotherapy, surgery and local ablative therapy.

There are 2 main types of liver cancer. A cancer that starts in the liver is known as a primary liver cancer and a cancer that spreads to the liver from another part of the body is known as metastatic cancer. Approximately 3,200 people in the UK are diagnosed with primary liver cancer each year, whereas approximately 90,000 people are diagnosed with liver metastases.

Most people with a diagnosis of primary liver cancer (approximately 85%) have a hepatocellular carcinoma. A major risk factor for developing hepatocellular carcinoma is underlying cirrhosis (scarring of liver tissue). Cirrhosis commonly results from alcoholism, hepatitis B and C, and fatty liver disease. Primary liver cancer is the second most rapidly increasing cancer in men and the third in women (increases of 38% and 28% respectively in the past decade).

Primary liver cancer in adults has a poor prognosis because it tends to be diagnosed in the advanced stages. Only a minority of cases of primary liver cancer are diagnosed in the early stages when surgery may help. The prognosis of primary liver cancer depends on the extent of disease and underlying liver function. About 20% of people with primary liver cancer live for at least 1 year after diagnosis. Around 5% live for at least 5 years.

The primary cancers most commonly leading to metastases in the liver originate in the breast, lung and bowel (colorectal). The origin of the primary cancer is important because the cells of the liver metastases are the same as those of the primary cancer, and liver metastases are likely to be treated according to the cell type of the primary cancer. The prognosis of liver metastases depends on the extent of the disease and comorbidities. For example, 40% to 60% of people with stage 4 colorectal cancer with resectable liver metastases will live for 5 years after surgery.

Contrast-enhanced ultrasound could be included in the diagnostic pathway as a replacement for contrast-enhanced CT/contrast-enhanced MRI (figure 1), or as a triage step to reduce the use of contrast-enhanced CT/contrast-enhanced MRI. The available data only allowed contrast-enhanced ultrasound with SonoVue as a replacement for contrast-enhanced CT/contrast-enhanced MRI to be included in the economic analysis.

In general, care pathways for people with liver cancer are guided by prognosis. Prognosis depends on both the extent of the tumour and on comorbidity. Improvements in survival as a result of treatment largely depend on the disease stage at diagnosis: the earlier the diagnosis is made, the greater the chance for successful treatment. Detailed care pathways for the 3 indications considered in this assessment can be found in section 3.4 of the diagnostics assessment report.

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) produced guidelines and good clinical practice recommendations for contrast-enhanced ultrasound in 2004. The latest version was published in 2008 and is currently being updated.

The 2008 EFSUMB guidelines recommend the use of contrast-enhanced ultrasound for the characterisation of focal liver lesions in a range of indications. The guidelines also provide information on the typical enhancement patterns associated with various types of benign and malignant liver lesions.

The treatment of primary hepatocellular carcinoma has been addressed in published technology appraisals guidance, and NICE has issued interventional procedure guidance on a number of individual interventions for primary hepatocellular carcinoma and liver metastases (see the NICE website for details). NICE's guideline on colorectal cancer recommends the use of CT in staging of colorectal cancer, which includes the identification of liver metastases. Expert opinion suggests that there may be significant regional variation within the NHS in the characterisation of focal liver lesions.