Abstract
ObjectiveThe purpose of this study was to investigate the association of telomere length in peripheral blood leukocytes with the severity of biliary atresia (BA).MethodsOne hundred and fourteen BA patients and 114 age-matched healthy controls were enrolled. Relative telomere length (RTL) was assessed using a quantitative real-time polymerase chain reaction. Multivariate regression analysis was used to estimate RTL as an independent risk factor of BA. Receiver operating characteristic curve analysis was used to calculate the accuracy of biomarkers in the prediction of liver cirrhosis.ResultsBA patients had significantly shorter telomeres than healthy controls (p < 0.0001). The RTL in BA patients with jaundice was considerably lower than that of patients without jaundice (p = 0.005). Moreover, RTL was markedly shorter in patients with cirrhosis (F4), as compared to patients with mild fibrosis (F2) and non-fibrosis (F0-F1, p < 0.0001). Logistic regression analysis indicated that short RTL was associated with a higher risk of liver cirrhosis in BA. Tertile analysis showed a dose-response effect for this association (p trend < 0.0001). Additionally, RTL in BA children revealed a negative correlation with age (r = -0.50, p < 0.001). We noted an association between reduction of RTL and liver stiffness scores, adjusted for age and gender (b = -0.01, p < 0.0001). Short RTL can be employed to distinguish cirrhosis patients from non-cirrhosis patients (AUC = 0.78). Further analysis showed a linear correlation between leukocyte RTL and liver RTL in BA patients (r = 0.83, p < 0.001).ConclusionThe findings of this study provide evidence that telomere shortening is associated with an elevated risk of liver cirrhosis in BA.
Highlights
Biliary atresia (BA), the most common cause of cholestatic liver disorder in infants, is characterized by progressive fibrosclerosing cholangiopathy affecting the extra- and intrahepatic biliary ducts
Relative telomere length (RTL) was markedly shorter in patients with cirrhosis (F4), as compared to patients with mild fibrosis (F2) and non-fibrosis (F0-F1, p < 0.0001)
Logistic regression analysis indicated that short RTL was associated with a higher risk of liver cirrhosis in BA
Summary
Biliary atresia (BA), the most common cause of cholestatic liver disorder in infants, is characterized by progressive fibrosclerosing cholangiopathy affecting the extra- and intrahepatic biliary ducts. The first-line intervention for infants with BA, reestablishes bile flow to the gastrointestinal tract. Liver transplantation is another treatment option in cases where Kasai portoenterostomy fails or is not practical [2]. Environmental factors may be a cause of BA in a genetically susceptible individual during early infancy. If this is the case, variants of genes playing a role in hepatobiliary development or immunological tolerance tend to be candidates for mediating susceptibility. Evidence supporting the role of genetic factors as a cause of BA has been accumulating for a number of years [3, 4]. In addition to results from epidemiological studies, polymorphism studies, and data on twins, the concept of shortened telomere length as a genetic risk factor for liver fibrosis and BA has been proposed
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