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The positive correlation of bile acid levels in biliary atresia to myocardial structural changes highlights their potential causative association with cardiomyopathy in these patients.

Cirrhotic cardiomyopathy comprises pathologic cardiac structural and functional changes in cirrhotic patients. It has a prevalence of approximately 30% and is a major cause of morbidity and peri-operative mortality in these patients. Cardiotoxic effects of elevated bile acids in cirrhosis are well documented in experimental models; however, their role in biliary atresia (BA) is undetermined. A recent study published in the journal  Hepatology Communications established a potential causative link between excess serum bile acids and cardiac structural abnormalities in children with BA. The study beckons further clinical trials to substantiate this as a modifiable factor in the treatment of these patients. 

 Study Population

The study cohort comprised 40 pediatric patients with BA enlisted for liver transplantation (LT) over 10 years. The median age was 14 months and 52% of the patients were female.

Correlation Between Bile Acid Concentrations and Pathologic Cardiac Remodeling

A significant dose-dependent positive association was found between serum bile acid levels and the following structural cardiac parameters on 2D echocardiography: left ventricular mass index, left ventricular mass, left ventricular internal diameter, and fractional shortening.
No association was established between bile acids and relative wall thickness, septal and posterior wall thickness, or left atrial volume index on echocardiography and electrocardiography parameters.  
Bile Acid Threshold Values Predicting Cirrhotic Cardiomyopathy Changes

A bile acid concentration value of ≥ 152 μmol/L was determined (through the ROC curve and best Youden index) as the cut-off point correlating with the detection of pathologic left ventricular changes, having a sensitivity of 70% and specificity of 64%. 

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Clinical and Demographic Features of Subjects Above and Below the Threshold

Patients in the group having bile acid concentrations above the cut-off value (group A) of 152 μmol/L showed higher markers of hepatic injury (AST, ALT) and cholestasis (conjugated bilirubin) as compared to the group below the cut-off value (group B). The following parameters were found to be comparable in both groups: age at echocardiography, waitlist time for LT, pediatric end-stage liver disease score, international normalized ratio, pre-albumin nutritional status, the severity of portal hypertension, percentage of patients who underwent Kasai portoenterostomy, and stage of fibrosis at Kasai portoenterostomy.

Comparison of Perioperative Outcomes Between Both Groups

Comparison of peri-LT outcomes between the groups revealed notably increased overall hospital length of stay, lesser ventilator-free days, and higher chances of serious adverse events in group A. The amount of surgical time and blood loss was similar in both groups.

Testing for Takeda G-Protein-Coupled Receptor Type 5

Effects of bile acids on the cardiovascular system are modulated through bile acid-specific receptors such as Takeda G-protein-coupled receptor type 5 (TGR5), which was positively identified in the cardiovascular samples of the study population.

Source:

Virk, M. K., Mian, M. U. M., Bashir, D. A., Wilkes, J. K., Schlingman, T., Flores, S., Kennedy, C., Lam, F., Arikan, A. A., Nguyen, T., Mysore, K., Galvan, N. T. N., Coss-Bu, J., Karpen, S. J., Harpavat, S., & Desai, M. S. (2023). Elevated bile acids are associated with left ventricular structural changes in biliary atresia. Hepatology Communications, 7(5). https://doi.org/10.1097/hc9.0000000000000109