ORIGINAL ARTICLE Magnitude of contrast-enhanced ultrasonography as a noninvasive predictor for hepatic fibrosis: comparison with liver stiffness measurement and serum-based models Akinobu Tawada • Hitoshi Maruyama • Hidehiro Kamezaki • Taro Shimada • Hiroyuki Ishibashi • Masanori Takahashi • Tatsuo Kanda • Keiichi Fujiwara • Fumio Imazeki • Osamu Yokosuka Received: 5 November 2011 / Accepted: 6 April 2012 / Published online: 27 April 2012 Ó Asian Pacific Association for the Study of the Liver 2012 Abstract Purpose To elucidate the efficiency of contrast-enhanced ultrasonography alone and in combination with other noninvasive models for grading hepatic fibrosis. Methods This prospective study included 74 patients with four grades (F1–F4) of chronic liver disease (17, 20, 18, and 19 patients, respectively). Diagnostic performances of the contrast parameter (time to the maximum intensity ratio between the right portal vein and liver parenchyma from the onset of contrast enhancement in the right portal vein) assessed by ultrasonography, liver stiffness measurement (LSM), FIB-4 test, and type IV collagen 7s were compared with histological findings. Results Greatest areas under the receiver operating characteristics curve (Az) with the single model were 0.83 (95 % confidence interval 0.71–0.91) for marked fibrosis (CF2) by FIB-4 test; 0.85 (0.73–0.92) for advanced fibrosis (CF3) by LSM, and 0.92 (0.83–0.96) by type IV collagen 7s for cirrhosis (F4). When combined, Az for marked fibrosis was C0.82; the best Az value was 0.87 (0.74–0.94) for the combination of contrast parameter with FIB-4. Similarly, the Az for advanced fibrosis was C0.82, and the best Az value was 0.89 (0.78–0.94) for the combination of contrast parameter with LSM. The Az for cirrhosis was C0.95, and the best Az was 0.99 (0.97–1.00) for the combination of contrast parameter with LSM. Conclusions The contrast parameter is a promising pre- dictor for grading hepatic fibrosis when combined with LSM or FIB-4. Keywords Ultrasonography Á Liver stiffness Á Fibrosis Á Cirrhosis Á FIB-4 Á Type IV collagen 7s Abbreviations AIH Autoimmune hepatitis Az Area under the receiver operating characteristics curve CHB Chronic hepatitis B CHC Chronic hepatitis C IVcol7s Type IV collagen 7s LSM Liver stiffness measurement NASH Nonalcoholic steatohepatitis NPV Negative predictive value PPV Positive predictive value ROC Receiver operating characteristics curve Introduction The hepatic fibrosis grade is a definitive indicator of the severity of disease in patients with chronic liver disease. The most advanced stage is cirrhosis, which confirms a poor prognosis for patients with chronic liver diseases because of the risk of developing hepatocellular carcinoma, portal hypertension, and/or hepatic failure [1–3]. Clinical management of chronic liver disease should be imple- mented on the basis of the stage of fibrosis. Liver biopsy remains the gold standard for evaluating the grade of hepatic fibrosis [4, 5]. However, its application A. Tawada Á H. Maruyama (&) Á H. Kamezaki Á T. Shimada Á H. Ishibashi Á M. Takahashi Á T. Kanda Á K. Fujiwara Á F. Imazeki Á O. Yokosuka Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan e-mail: maru-cib@umin.ac.jp 123 Hepatol Int (2013) 7:749–757 DOI 10.1007/s12072-012-9370-7