Su1722 Kupffer Cell-Specific Calcium Signaling Drives Inflammation in Alcoholic Liver Disease (ALD) in Mice

Abstract

[Background] A simple method for discriminating alcoholic liver disease (ALD) from nonalcoholic fatty liver disease (NAFLD) could be helpful in the management of fatty liver disease. Although ALD/NAFLD index is known to be useful in Caucasian subjects (Dunn et al. Gastroenterology 2006;131:1057-1063), no corresponding indices for Asian subjects have been reported yet. In this study, we aimed to develop a discrimination index for Japanese subjects using readily available clinical parameters. [Materials and Methods] Between 2009 and 2010, we conducted a nationwide survey for Japanese subjects to evaluate the status of fatty liver disease and collected data from 695 subjects with biopsy-proven ALD (n = 147) or NAFLD (n = 548). The index was developed on the basis of clinical parameters that were significant on multiple logistic regression analysis. [Results] This multivariate analysis identified the following significant parameters: gender, body mass index (BMI), aspartate aminotransferase level/alanine aminotransferase level, γ-glutamyl transpeptidase level, and mean corpuscular erythrocyte volume. Discrimination index greater than 0 was suggestive of ALD and that less than 0 was suggestive of NAFLD. The index had an area under the receiver operating characteristic (ROC) curve of 0.936 (95% confidence interval, 0.910-0.962). For diagnosing ALD, following were the suggested values for assessment: sensitivity, 66.7%; specificity, 96.7%; positive predictive value, 84.5%; and negative predictive value, 91.5%. On the other hand, for diagnosing NAFLD, following were the suggested values for assessment: sensitivity, 96.7%; specificity, 66.7%; positive predictive value, 91.5%; and negative predictive value, 84.5%. The index was validated for use in subgroups classified according to histological findings or BMI. In the simple steatosis group, the sensitivity and specificity for diagnosing ALD were 42.3% and 93.5%, respectively; in the fibrosis group, the sensitivity and specificity for diagnosing ALD were 80.0% and 97.5%, respectively. In the group with BMI ,25 kg/m2, the sensitivity and specificity for diagnosing ALD were 77.2% and 92.2%, respectively; in the group with BMI ≥25 kg/m2, the sensitivity and specificity for diagnosing ALD were 43.5% and 98.7%, respectively. [Conclusions] This index is excellent for differentiating ALD from NAFLD: it is particularly helpful for ruling in ALD and ruling out NAFLD. Thus, we believe that this index should be validated in other Asian populations.