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Background and Aims: This study investigated the depth-related bias and the influence of scan plane angle on performance of point-shear-wave elastometry in a chronic hepatitis C patient cohort. Materials and Methods: We included 104 patients affected by chronic liver disease related to the hepatitis C virus. Liver surface nodularity was the reference to diagnose cirrhosis. The ultrasound platform was the Siemens S2000, equipped with point-shear-wave elastometry software. Measurements were obtained in left lateral decubitus from the liver surface to the maximum depth of 8 cm in two orthogonal scan planes according to a standard sampling plane. Scatterplot and box plots explored the depth-related bias graphically. The area under the receiver operating characteristic was used to determine the point-shear-wave elastometry diagnostic performance at progressive depths according to liver surface nodularity. Results: Of the 104 patients, 68 were cirrhotics. Depth-related bias equally modified point-shear-wave elastometry in the two orthogonal scan planes. A better point-shear-wave elastometry diagnostic performance was observed between depths of 4 and 5 cm. The frontal scan plane assured better discrimination between cirrhotic patients and non-cirrhotic patients. Conclusion: Depth is crucial for point-shear-wave elastometry performance. Excellent diagnostic performance at a depth between 4 and 5 cm can also be obtained with a smaller number of measurements than previously recommended. [ABSTRACT FROM AUTHOR]