Prior to the introduction of sonography 40 years ago, the only non-invasive information easily available to clinicians managing patients with suspected liver disease were the collection of the patient's history, the physical examination including manual palpation, and a few laboratory values. The arrival of sonography, providing visualization of the liver size, contours and internal structure, permitted the diagnosis of parenchymal disease such as steatosis or cirrhosis 1 2 and the detection of intrahepatic lesions, such as cysts or solid tumors 1 3. To reliably visualize dilated bile ducts and the location of the duct obstruction also became possible, already in the early days of B-mode sonography 4 with increasing rates of demonstration of the obstruction causes in the following years 5 6 7. The additional use of higher frequency transducers enabled to identify even slightly nodular liver surfaces 8, particularly in the absence of ascites: this step was often decisive for detecting cirrhosis, as well as the imaging of the architecture of the hepatic vessels 9. As a result, liver cirrhosis could be detected earlier and more reliably. Today, even initial cases of liver cirrhosis can be often diagnosed thanks to the combination of sonography and clinical knowledge 10. Diagnostic liver biopsies became soon performed under sonographic guidance for the best of patients safety and with the additional opportunity to specifically target needle puncture to solid tumors 11. Additionally, abscesses could be drained or aspirated without surgery with a very high success rate. Color Doppler and duplex sonography represent afurther technical advancement introduced between the '80s and '90s. Such techniques allowed to display the intra and extrahepatic portal systems informing on blood flow direction and to better detect the diverse ectopic and portosystemic collaterals 12 13 14. Blood flow velocity measurement with clinically sufficient accuracy became possible and stimulated hepatological research 12 15 16. In clinical practice, it is important to detect portal hypertension because it is significant for the prognosis and often can be already present at the time of the initial diagnosis of cirrhosis 13 14. In the mid '90s the differentiation of various tumor entities of the liver and the determination of the extent of liver fibrosis still represented insurmountable diagnostic hurdles. In the very late '90s, however, the introduction of ultrasound contrast agents in the form of stabilized gas microbubbles and the possibility to examine the liver with a low acoustic pressure, using digital equipments provided new possibilities for metastasis detection and tumor characterization 17 leading tothe first recommendations on the clinical use of Contrast Enhanced Ultrasound (CEUS), published in 2004 18. This new technique put sonography on equal footing with CT and MRI but with higher temporal and spatial resolution 19 20. The most important and most common focal liver lesions, such as hemangioma, FNH, metastasis, and HCC, could then be noninvasively detected or characterized with a high degree of reliability without the use of radiations or puncture and in a single examination procedure 21 22 23 24. However, especially benign lesions with a diameter of less than 1cm continue to pose differential diagnostic problems 25. Dynamic contrast-enhanced ultrasound (DCE-US) as a quantitative method may provide new possibilities for improving the diagnosis of tumors and their response to new targeted molecular treatment 26 27 28. The introduction of contrast enhancement quantification went along with the introduction of liver elastography in the early years 2000 to add further possibility for ultrasound techniques. In particular ultrasonography became capable not only to show morphological aspects of the liver, but also the assessment of functional properties 29. Especially the latter, namely elastography, is having an enormous clinical impact at present. In fact, it can better and more reproducibly replace the manual palpation, which since the ancient times informs that when a liver is hard as a stone, it bears a bad prognosis, being usually cirrhotic or infiltrated by malignancy. The introduction of shear wave elastometry (SWE) by ultrasound is having an even greater impact than Doppler ultrasound. It provides simple, rapid and reliable findings about liver stiffness, which inform on the liver status and most commonly on disease stage in chronic liver disease 30. To date not only transient elastography with Fibroscan exists, a self standing equipment specifically dedicated to liver stiffness measurement, which still remains the reference standard in this field 31, but also other SWE techniques 29. The latter are Acoustic Radiation Force Imaging (ARFI) quantification, also termed point SWE (pSWE) and 2Dimensional SWE, whose technical background and recommendations for clinical applications have been reported by EFSUMB in this journal in the current year 29 32. Strain Elastography also appears of interest, despite applications to liver disease seems to suffer from more limitations than SWE 32. All the latter techniques are integrated into standard ultrasound equipments allowing the assessment of liver stiffness as an immediate add on to any liver examination. Moreover, they can be easily applied also to other organs beside the liver, such as the spleen 33 34. Hence many new functional applications have begun to be explored in hepatology. For instance splenic stiffness appeared related to the severity of portal hypertension 33 35 36 and indeed it was reported to decrease after placement of Transjugular Intrahepatic Portosystemic Shunt (TIPS) 37; liver stiffness can be utilized to assess the rate of chronic liver disease progression over time 38 and hence prognosis. In this and in a previous issue of the journal pilot studies show how Strain Elastography of liver tumors after thermal ablation is promising to be a good predictor of the extent of necrosis 39 40 and how changes in tumor stiffness occurring early after start of antiangiogenic therapy predict the long term response to treatment in a mice model 41. To summarize, ultrasound based techniques have enormously evolved over the last 40 years, providing today a broad armamentarium of tools for morphologic and functional exploration of the liver. Thus the activity of modern hepatologists nearly invariably includes the application of ultrasound based technologies, which can be easily offered by the physician in one single step.This type of hepatologist (whatever the formal background specialty) is able to receive a patient into the office and, thanks to the integration of history, laboratory exams and application of the most suitable ultrasound techniques contained in one single equipment and applied during the visit, let the patient go home nearly invariably with an accurate diagnosis. This one stop shop opportunity is offered regardless of whether the question was the assessment of chronic liver disease, the diagnosis of an incidental focal liver lesion in an otherwise healthy liver or alternatively in cirrhosis 24, the diagnosis of some biliary disease 27 or the assessment of outcomes of treatments of focal or diffuse liver disease 24 42. Morover, modern hepatologists who work in the ward, also benefit from the miniaturization of ultrasound scanners, which can be utilized hand held at the bedside to extend the physical examination and easily provide simple, but relevant diagnosis for liver patients management, such as the presence of ascites and the best location for its puncturing, the occurence of biliary tree dilation and so on. This approach was termed by EFSUMB echoscopy 43 which corresponds to a sort of first level bedside ultrasonography. Echoscopy is relatively easy to learn, whereas the full training in all liver applications requires dedication and more time, together with good teachers. However, young generations of hepatologist have clear in mind that the full exploitation of the ultrasound potential is a goal to be pursued to make their daily practice optimal. Needless to say, that the combination of ultrasound with clinical knowledge and experience known as Clinical Ultrasound stand as a most effective approach!
