Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers

BACKGROUND & AIMS: Carriage of rs738409:G in patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with PNPLA3 rs738409:G. This study explores the risk-associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including: 1,031 with alcohol-related cirrhosis and HCC; 1,653 with alcohol-related cirrhosis without HCC; 2,588 alcohol misusers with no liver disease; and 899 healthy controls. Genetic associations with the risks for alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for both cirrhosis (OR 0.79 [95% CI 0.72-0.88], p=8.13×10-6) and HCC (OR 0.77 [95% CI 0.68-0.89], p=2.27×10-4), while carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR 1.70 [95% CI 1.54-1.88], p=1.52x10-26) and HCC (OR 1.77 [95% CI 1.58-1.98], p=2.31×10-23). These associations remained significant after adjusting for age, sex, body mass index, type II diabetes mellitus and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women but the protective effect against the subsequent development of HCC was only observed in men (p=1.72×10-4; ORallelic, 0.75; 95% CI, 0.64-0.87). CONCLUSIONS: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population

Calculation of Volumetric Sound Field of Pulsed Air-Coupled Ultrasound Transducers Based on Single-Plane Measurements

Quantitative and reproducible air-coupled ultrasound (ACU) testing requires characterization of the volumetric pressure fields radiated by ACU probes. In this paper, a closed-form reradiation method combining the Rayleigh-Sommerfeld integral and time-reversal acoustics is proposed, which allows calculation of both near- field and far-field based on a single-plane measurement. The method was validated for both 3-D (circular, square) and 2-D (rectangular) planar transducers in the 50-230 kHz range. The pressure fields were scanned with a calibrated microphone. The measurement window was at least four times the size of the transducer area and the grid step size was one third of the wavelength. Best results were observed by acquiring the measurement plane at near-field distance. The method accurately reproduces pulsed ultrasound waveforms and pressure distributions (RMSE <2.5% in far field and <5.5% in near field), even at the transducer radiation surface. The effects of speed of sound drifts during the scan in the pressure were negligible (RMSE <0.3%). The reradiation method clearly outperforms conventional baffled piston models. Possible applications are transducer manufacture control (imperfections at radiation surface) and calibration (on-axis pressure, side lobes, and beamwidth) together with generation of accurate source functions for quantitative nondestructive evaluation inverse problems

Acoustic Field Characterization of Medical Array Transducers Based on Unfocused Transmits and Single-Plane Hydrophone Measurements

Medical ultrasonic arrays are typically characterized in controlled water baths using measurements by a hydrophone, which can be translated with a positioning stage. Characterization of 3D acoustic fields conventionally requires measurements at each spatial location, which is tedious and time-consuming, and may be prohibitive given limitations of experimental setup (e.g., the bath and stage) and measurement equipment (i.e., the hydrophone). Moreover, with the development of new ultrasound sequences and modalities, multiple measurements are often required to characterize each imaging mode to ensure performance and clinical safety. Acoustic holography allows efficient characterization of source transducer fields based on single plane measurements. In this work, we explore the applicability of a re-radiation method based on the Rayleigh–Sommerfeld integral to medical imaging array characterization. We show that source fields can be reconstructed at single crystal level at wavelength resolution, based on far-field measurements. This is herein presented for three practical application scenarios: for identifying faulty transducer elements; for characterizing acoustic safety parameters in focused ultrasound sequences from 2D planar measurements; and for estimating arbitrary focused fields based on calibration from an unfocused sound field and software beamforming. The results experimentally show that the acquired pressure fields closely match those estimated using our technique.ISSN:1424-822

C-Myc plays a crucial role in chronic liver injury

Host-parasite interactio

C-Myc is a central regulator of liver regeneration in mice with chronic liver injury

Host-parasite interactio