Hepatic Nodules in Liver Cirrhosis: US and CEUS

Abstract

Hepatocellular carcinoma (HCC) is the 6th most common malignancy worldwide, 6% of all cancer. Unfortunately, HCC is a devastating cancer with 5year survival less than 5%. Among risk factors of HCC, liver cirrhosis and hepatitis B, C Virus are most important. Liver cirrhosis is a diffuse hepatic parenchymal process with extensive fibrosis and regenerative nodule formation and irreversible. In the management of hepatic nodule in liver cirrhosis, early diagnosis and treatment is necessary. For this purpose, understanding of hepatocarcinogenesis is important. There are two pathways, one is de novo pathway and the other is multistep pathway. De novo pathway is a development of HCC without background of chronic liver disease or liver cirrhosis. Multistep pathway is a development of HCC in the background of liver cirrhosis from regenerative nodule (RN) through dysplastic nodule (DN), eHCC to advanced HCC. Cellular and histopathologic change in hepatocarcinogenesis from RN to HCC include iron, glycogen, copper, and fat, vascularity, bile duct and Kupffer cell change. These cellular and histopatologic change can be visualization on imaging. For hepatic nodule, US techniques have been continuously evolved during the recent several decades from static B-scan imaging going through real-time imaging, Doppler imaging, elastography volumetric imaging and finally to virtual US and contrast imaging. US role for hepatic nodule in liver cirrhosis includes surveillance of hepatic nodule for early diagnosis of HCC, differential diagnosis hepatic nodule, intrahepatic staging of advanced HCC, evaluation of vascular lesions and portal thrombi, evaluation of liver transplantation, and planning, guidance & monitoring of biopsy and ablation of liver cancer. For detection of hepatic nodules, gray scale US is a screening and surveillance test with acceptable sensitivity and specificity, but, US shows poor performance in advanced contracted liver cirrhosis with poor depiction rate, less than 30 %. Grayscale US is sometimes useful for the Dx of liver nodule, particularly with characteristic findings. If the lesion shows peripheral halo, mosaic pattern and lateral shadowing, these findings are indicative of HCC. But, in many cases, findings of grayscale US are not specific. Doppler US can be used, and sometimes, it is useful, but in many cases of small nodule, Doppler US is not specific. In such a case, US contrast agent is useful to make a correct Dx of hepatic nodule. With an US contrast agent, we are able to make a dx. by demonstrating hemodynamic change of hepatic nodule in multiphasic images. There are two techniques of contrast-enhanced US. One is high MI and the other is low MI imaging. High MI imaging is no longer used. Low MI imaging using second generation contrast agents such as Sonovue or Definity, is a continuous bubble imaging and is useful in vascularity assessment. Another contrast agent, Sonazoid, is available in Japan, and Korea. This agent is taken up by Kupffer cells. So, we can evaluate hepatic nodule in vascular phase as well as Kupffer (post vascular) phase with this contrast agent. Advantages of CE US over CT/MR are high sensitivity to contrast, real-time imaging, disruption-replenishment sequence, no renal excretion, no ionizing radiation, purely intravascular contrast, as you see in this diagram by Dr Wilson from Canada. Other advantages of CE US are ready availability, low cost, excellent patient’s compliance, and possible repeated exams with short intervals. Recently loco-regional treatment of HCC is rapidly progressing. For local therapy, chemical ablation including ethanol injection is now replaced by thermal ablation such as radiofrequency ablation (RFA), microwave or high intensity focused US (HIFU). For regional (intravascular) therapies, in addition to conventional TACE, TACE with drug eluting beads or radioembolization is now investigated. The role of US for Tx is planning before Tx, targeting, monitoring and controlling during Tx, and assessing response after Tx for early detection of recurrence. In summary, for focal liver lesion, US improves lesion detection, allows lesion characterization, reduces the need for CT/MR, and US has been introduced into guidelines, and improves patient management. For assessment of treatment response, US allows intra-and post-procedural evaluation, and is useful in patient follow-up after therapy as an alternative to CT/MR evaluation.