Digestive and Liver Disease 43 (2011) 484–490 Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld Liver, Pancreas and Biliary Tract Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography—A prospective study Bita Boozari a,* , Bisharah Soudah b , Kinan Rifai a , Sabine Schneidewind a , Arndt Vogel a , Hartmut Hecker c , Andreas Hahn c , Jerome Schlue b , Christoph F. Dietrich d , Matthias J. Bahr a , Stefan Kubicka a , Michael P. Manns a , Michael Gebel a a Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany b Hannover Medical School, Institute of Pathology, Hannover, Germany c Hannover Medical School, Department of Biometrics, Hannover, Germany d Caritas-Krankenhaus Bad Mergentheim, Department of Internal Medicine II, Hannover, Germany article info Article history: Received 22 April 2010 Accepted 4 January 2011 Available online 5 March 2011 Keywords: Contrast enhanced ultrasound Hepatocellular carcinoma Tumour grading abstract Background: Outcome of patients with hepatocellular carcinoma is influenced by their histological grade. Invasive biopsy of the lesions is the gold standard in this regard. Aims: We therefore analysed the diagnostic accuracy of contrast enhanced ultrasound for non-invasive grading of hypervascular hepatocellular carcinoma in liver cirrhosis. Methods: According to the tumour perfusion kinetics on contrast enhanced ultrasound two grading groups were prospectively defined: well-differentiated hepatocellular carcinoma (US-G1) and higher grade hep- atocellular carcinoma (US-G2/G3). Immediately after contrast enhanced ultrasound-grading, biopsies of hepatocellular carcinoma-lesions (n = 95, 1.2–12.5 cm) were obtained and analysed for tumour grad- ing (G). Descriptive statistics, sensitivity, specificity positive and negative predictive values, diagnostic likelihood ratios and interoperator reproducibility were calculated (). Results: Histologically 77 (81.1%) patients had G2–G3 and 18 (18.9%) had G1 tumours. Higher grade hepa- tocellular carcinoma showed more often a washout in the portal or late phase (p < 0.0001). The sensitivity, specificity, positive predictive values and negative predictive values of contrast enhanced ultrasound for grading of hepatocellular carcinoma for all patients were 94% (CI: 72–99%), 95% (CI: 88–99%), 81% and 99% and for patients with tumours < 5 cm 100%(95% CI: 79–100), 96% (95% CI: 80–99), 92% and 100%. Positive and negative diagnostic likelihood ratios’ were 18 and 26 and 0.06 and 0, respectively.  = 0.941 (p < 0.001). Conclusions: Contrast enhanced ultrasound has a high diagnostic value and reproducibility for non- invasive grading of hypervascular hepatocellular carcinoma >1 cm in patients with liver cirrhosis. © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction In the majority of cases, hepatocellular carcinoma (HCC) origi- nates from liver cirrhosis [1]. The molecular events leading to the development of HCC in a cirrhotic liver are currently incompletely understood. They may even differ according to various aetiologies [2]. The same variability is seen in the morphological appearance making the detection of HCC in a cirrhotic liver a challenge for all imaging modalities. * Corresponding author at: Medical School of Hannover, Department Gastroen- terology, Hepatology and Endocrinology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Tel.: +49 511 532 3415; fax: +49 511 532 5059. E-mail address: boozari.bita@mh-hannover.de (B. Boozari). Hepatocarcinogenesis is a multistep process [2]. It is assumed that many HCC develop from high grade dysplastic nodules [3] with a further progression from well differentiated to poorly dif- ferentiated HCC. The histopathological grade of HCC is a well established prognostic factor [4]. Furthermore, grading of HCC is also considered as an important issue in the planning of the thera- peutic strategy. Patients with high grade HCC, for example, show a higher rate of HCC recurrence after resective surgery and orthotopic liver transplantation (OLT) [5,6]. Also the therapeutic results after radiofrequency ablation are influenced by the histological grade of HCC [7]. Therefore, it is of great clinical interest to diagnose HCC at an early stage and to gain information regarding the tumour grade. There have been attempts to correlate CT and MRI findings with the grading of HCC [8,9]. However, to detect HCC at an early stage an imaging modality with a very high temporal and spatial resolution 1590-8658/$36.00 © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2011.01.001