Bile duct enlargement by infusion of L-proline: potential significance in biliary atresia

Abstract

The normal signals of control of bile duct morphogenesis and growth are unknown. Consequently, aberrant development is poorly understood, as for example in those infants with biliary atresia or hypoplasia. A previous report by Isseroff et al., showed that a possible mechanism for the common bile duct enlargement by the parasite Fasciola hepatica was excess L-proline secreted by this parasite. This suggested to us that L-proline might be a specific growth factor for bile duct epithelium, and therefore possibly useful in the understanding and treatment of biliary maldevelopment. We now report an experimental study demonstrating the effect of L-proline on the normal biliary tree of the mouse. We also present a summary to date of an ongoing clinical restrospective study. These experimental findings suggest: (1) there may be a specific requirement for L-proline during the rapid growth of the biliary tract during neonatal life; (2) bile duct hypoplasia and atresia may result from a defect in proline metabolism; (3) proline administration during the early phase of biliary atresia may possibly be therapeutic.