Maja Thiele1, Vanessa Rausch2, Gabriele Fluhr2, Maria Kjærgaard1, Felix Piecha2, Johannes Mueller2, Beate Katharina Straub3, Monica Lupșor-Platon4, Victor De-Ledinghen5, Helmut Karl Seitz2, Sönke Detlefsen6, Bjørn Madsen1, Aleksander Krag1, Sebastian Mueller7. 1. Department of Gastroenterology and Hepatology and Odense Patient data Exploratory Network (OPEN), Odense University Hospital, Odense, Denmark; Institute for Clinical Research, University of Southern Denmark, Odense, Denmark. 2. Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Heidelberg, Germany. 3. Institute for Pathology, University of Mainz, Germany and Institute for Pathology, University of Heidelberg, Germany. 4. Department of Medical Imaging, Iuliu Hatieganu, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology 'Prof. Dr. Octavian Fodor', Cluj-Napoca, Romania. 5. Center d'Investigation de la Fibrose hépatique, Hôpital Haut-Leveque, CHU Bordeaux, Pessac, 33600 Pessac, France. 6. Institute for Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark. 7. Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Heidelberg, Germany. Electronic address: sebastian.mueller@urz.uni-heidelberg.de.
Abstract
BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. METHODS: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate single-centre cohort. RESULTS: A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] ≥S1 = 0.77; 0.71-0.83 and AUC ≥S2 = 0.78; 0.72-0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (interquartile range 4-6) for detoxification, CAP decreased by 32 ± 47 dB/m (p <0.001). Body mass index predicted higher CAP in both cohorts, irrespective of drinking pattern. Obese patients with body mass index ≥30 kg/m2 had a significantly higher CAP, which did not decrease significantly during detoxification. CONCLUSIONS: CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal. LAY SUMMARY: CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusing patients were more likely to have higher CAP values than lean patients, irrespective of drinking.
BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive measure of hepatic steatosis, but it has not been evaluated in alcoholic liver disease. Therefore, we aimed to validate CAP for the assessment of biopsy-verified alcoholic steatosis and to study the effect of alcohol detoxification on CAP. METHODS: This was a cross-sectional biopsy-controlled diagnostic study in four European liver centres. Consecutive alcohol-overusing patients underwent concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured CAP before and after admission for detoxification in a separate single-centre cohort. RESULTS: A total of 562 patients were included in the study: 269 patients in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94 (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and moderate steatosis with fair accuracy (area under the receiver operating characteristic curve [AUC] ≥S1 = 0.77; 0.71-0.83 and AUC ≥S2 = 0.78; 0.72-0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP was superior to bright liver echo pattern by regular ultrasound. CAP above 290 dB/m ruled in any steatosis with 88% specificity and 92% positive predictive value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62% negative predictive value. In the 293 patients who were admitted 6.3 days (interquartile range 4-6) for detoxification, CAP decreased by 32 ± 47 dB/m (p <0.001). Body mass index predicted higher CAP in both cohorts, irrespective of drinking pattern. Obesepatients with body mass index ≥30 kg/m2 had a significantly higher CAP, which did not decrease significantly during detoxification. CONCLUSIONS: CAP has a good diagnostic accuracy for diagnosing severe alcoholic liver steatosis and can be used to rule in any steatosis. In non-obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal. LAY SUMMARY: CAP is a new ultrasound-based technique for measuring fat content in the liver, but has never been tested for fatty liver caused by alcohol. Herein, we examined 562 patients in a multicentre setting. We show that CAP highly correlates with liver fat, and patients with a CAP value above 290 dB/m were highly likely to have more than 5% fat in their livers, determined by liver biopsy. CAP was also better than regular ultrasound for determining the severity of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese) patients rapidly decrease in CAP after short-term alcohol withdrawal. In contrast, obese alcohol-overusingpatients were more likely to have higher CAP values than lean patients, irrespective of drinking.
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