Reply
Authors: Jose T. Altamirano, Javier Michelena, Ramon Bataller
Journal: Hepatology (2016)

Supported by National Institutes of Health grant 1U01AA021908. Potential conflict of interest: Dr. Bataller consults for Valyx. Reply: We appreciate Dr. Fujita's and Dr. Stefanescu's letters on our recent study.1 The concerns regarding possible interfering factors in measuring plasma endotoxin by the limulus amebocyte lysate assay are well known.2 In our study, the limulus amebocyte lysate QCL‐1000 assay (Lonza Walkersville, Inc., Walkersville, MA) was used to determine lipopolysaccharide (LPS) serum levels because it allows a quantitative measurement. This assay was approved by the US Food and Drug Administration because limulus amebocyte lysate tests are more sensitive and better standardized than rabbit tests.3 Importantly, blood samples were obtained and manipulated and the test performed by experienced staff in a strict germ‐free environment. In our study, a robust association was found between LPS serum levels and the development of complications and mortality in patients with alcoholic hepatitis (AH). We agree with Dr. Fujita that we have to be cautious when establishing cutoff levels, given the variability of different types of tests that measure LPS. The clinical value of our study, rather than establishing a precise cutoff level with high prognostic value, relies in the association between LPS levels and patient outcomes. In fact, there is mounting evidence suggesting a role of bacterial products in the pathogenesis of alcoholic liver disease (ALD).4 In the field of AH, this is of great importance as it could represent a novel therapeutic approach (i.e., intestinal decontamination.5 Finally, Dr. Fujita is right in that multiple measurements of endotoxemia might extend our knowledge regarding the prognostic assessment of patients with AH. We also appreciate Dr. Horia's letter on the potential value of lysophosphatidylcholine (LYPC) as a noninvasive marker of disease severity in patients with ALD. Dr. Horia's cohort was comprised of 30 hospitalized ALD patients. LYPC values inversely correlated with scoring systems indicative of disease severity and showed a good accuracy in predicting liver decompensation and mortality. We think that the preliminary results by Dr. Horia's group are very interesting and deserve further investigation. Ethanol is known to induce alterations in fatty acid‐related lipids in serum and tissues including LYPC.6 Besides its biological actions, LYPC has been found to be elevated in patients with cirrhosis and hepatocellular carcinoma, and its serum levels inversely correlate with severity in patients with sepsis.7 These preliminary data suggest that sepsis and cancer are able to modulate LYPC serum levels. The preliminary results from Dr. Horia's group have to be taken with caution. It is unclear how many of these patients had a superimposed AH because the letter does not include detailed clinical information and the test used (i.e., ASH test) has not been extensively validated in patients with AH. Future studies in well‐defined phenotypes (i.e., compensated ALD, decompensated ALD without superimposed AH, and patients with AH) should be performed to confirm these interesting data.