The Specific Bile Acid Profile of Shock: A Hypothesis Generating Appraisal of the Literature

Harnisch, Lars-Olav; Moerer, Onnen

doi:10.3390/jcm9123844

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…Bile acids have been reported to be capable of solubilizing GGT from the membrane surface of cholangiocytes by their detergent action [ 44 , 45 , 46 , 47 ]. Since bile acids have been reported to be elevated in serum in many states of disease, including ARDS [ 48 ] (Harnisch et al, submitted), this increase in bile acids could be sufficient to solubilize enough GGT from cholangiocyte membranes to increase plasma levels. In fact, we found the serum levels of total bile acids to be correlated to serum levels of GGT on day 0 and 3 and in a trend also on day 5.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

et al. 2021

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Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 (p = 0.019) and day 0 to day 5 (p < 0.001), but not between day 3 and day 5 (p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 (p < 0.001), day 3 (p = 0.02), and in a trend on day 5 (p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO2. Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to paO2, prone position, ECMO treatment, or mean PEEP, but correlated to total bile acid levels.

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Section: Discussionmentioning

confidence: 99%

Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

et al. 2021

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A reduced glycine-to-taurine ratio of conjugated serum bile acids signifies an adaptive mechanism and is an early marker of outcome in acute respiratory distress syndrome

et al. 2022

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Determination of individual bile acids in acute respiratory distress syndrome reveals a specific pattern of primary and secondary bile acids and a shift to the acidic pathway as an adaptive response to the critical condition

Harnisch

Mihaylov

Bein

et al. 2022

Clinical Chemistry and Laboratory Medicine (CCLM)

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Objectives Cholestasis and elevated serum bile1 acid levels are common in critically ill patients. This study aims to define the specific pattern of bile acids associated with acute respiratory distress syndrome (ARDS) and the changes in pattern over time. Methods Prospective observational study. Serum samples of 70 ARDS patients were analyzed for primary bile acids (cholic acid, chenodeoxycholic acid) and secondary bile acids (deoxycholic acid, litocholic acid, and ursodeoxycholic acid) as well as their glycine and taurine glycation products. Results Primary bile acid levels increased from day zero to day five by almost 50% (p<0.05). This change bases on a statistically significant increase in all primary bile acids between day 0 and day 5 (cholic acid [CA] p=0.001, taurocholic acid [TCA] p=0.004, glycocholic acid [GCA] p<0.001, chenodeoxycholic acid [CDCA] p=0.036, taurochenodeoxycholic acid [TCDCA] p<0.001, glycochenodeoxycholic acid [GCDCA] p<0.001). Secondary bile acids showed predominantly decreased levels on day 0 compared to the control group and remained stable throughout the study period; the differences between day zero and day five were not statistically significant. Non-survivors exhibited significantly higher levels of TCDCA on day 5 (p<0.05) than survivors. This value was also independently associated with survival in a logistic regression model with an odds ratio of 2.24 (95% CI 0.53–9.46). Conclusions The individual bile acid profile of this ARDS patient cohort is unique compared to other disease states. The combination of changes in individual bile acids reflects a shift toward the acidic pathway of bile acid synthesis. Our results support the concept of ARDS-specific plasma levels of bile acids in a specific pattern as an adaptive response mechanism.

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The Specific Bile Acid Profile of Shock: A Hypothesis Generating Appraisal of the Literature

Cited by 3 publications

References 35 publications

Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

A reduced glycine-to-taurine ratio of conjugated serum bile acids signifies an adaptive mechanism and is an early marker of outcome in acute respiratory distress syndrome

Determination of individual bile acids in acute respiratory distress syndrome reveals a specific pattern of primary and secondary bile acids and a shift to the acidic pathway as an adaptive response to the critical condition

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