BA is a fibrotic inflammation involving the intrahepatic and extrahepatic bile ducts, causing intrahepatic and extrahepatic biliary obstruction, leading to liver cirrhosis and end-stage liver disease about 2 years old[1, 2]. The global incidence rate of BA was ranged from 0.2/10,000 to 0.6/10,000. Occidente was from 0.5/10,000 to 0.8/10,000. Taiwan was estimated to be about 1.5/10000[7–9]. Bile drainage can be achieved by Kasai portoenterostomy, a preferred treatment for BA currently, for some infants to extend the survival time of the autologous liver. However, the best time for the operation is within 60 days after birth, and the latest time should not exceed 90 days. After surgical treatment of BA in infants over 90 days, the rate of removing jaundice is significantly descended, and direct liver transplantation is recommended[4, 5]. In this study, 19.4% of infants missed Kasai surgery treatment because their parents did not pay attention to this disease or repeated visits to several hospitals for treatment. A simple method of judging BA may help patients get diagnosis and treatment sooner.
Serum Dbil is an indicator of liver injury. Elevated Dbil indicates hepatic dysfunction or IC, with impaired bile flow[10]. The GGT in the liver is mainly in the side of the hepatocyte capillary bile duct and the whole bile duct system. Elevated GGT indicates biliary obstruction disease and liver injury[11]. Dbil gradually increases after the birth of the newborn. In western countries, early detection of BA through Dbil measurement has been advocated [12, 13]. In Japan and China Taiwan, it is advocated to use the stool color card for early BA diagnosis, which has improved the autologous liver survival rate of infants with BA[14, 15]. The Chinese mainland uses Dbil and GGT as indicators for early BA detection, for their high sensitivity and specificity in diagnosis [16].
Sanjiv Harpavatet et al.[17] performed a two-stage Dbil screening on 124,385 newborns after birth. In the first stage, newborns within 60 hours after birth were tested for Dbil. In the second stage, newborns with more than 95% Dbil were screened again in the next two weeks. It was found that patients with BA had higher Dbil than the reference range, with a sensitivity of 100%, specificity of 99.9%. The results confirmed that Dbil is a valuable indicator of the BA diagnosis. According to reports[16], for infants within 90 days with obstructive jaundice, when GGT>328 U/L, BA should be considered, with a sensitivity of 69.7% and a specificity of 83.9%. Dillman JR et al.[18] determined a sensitivity of 100.0% and a specificity of 77.8% for the diagnosis of BA in infants within three months with obstructive jaundice. In Japan, the stool color card is used for early BA screening. This method reduces the mean age of Kasai surgery for BA infants from 68.2 days to 59.7 days and increases the 12-year autologous liver survival rate from 36.6–48.5%[19]. China Taiwan has enabled more infants to receive early diagnosis and treatment using the stool color card and has reduced the mortality rate of BA infants from 26.2–15.9% [20]. These studies have confirmed the importance of stool color, Dbil, and GGT in the early diagnosis of BA.
This study combined the above factors to explore a simple and effective method for BA diagnosis. Infants with BA and IC aged less than 90 days were selected as observation subjects. The stool color card divides stool colors into 9 kinds, but there was certain subjectivity in judgment. It was difficult to popularize in practice. The stool color was divided into 3 categories, including clay color, light color, and normal color. In this study, 90.6% IC and 89.6% BA infants underwent conservative treatment (including steroid hormones, ursodeoxycholic acid, liver protection) with no significant differences between the two groups. It was observed that 58.3% BA infants had clay-colored stools. Dbil and GGT of BA infants were higher than those of IC infants, and the GGT of BA infants increased with the increase of age. In this study, infants with clay -colored stool had a 2.3 times higher rate of BA than IC, with a specificity of 82.4%, which was possibly be related to the degree of extrahepatic biliary obstruction. Infants with Dbil>75.3umol/L had high sensitivity (94.8%) but low specificity (34.1%) in the BA diagnosis because BA jaundice is more severe than IC. Infants with GGT > 252U/L had a high specificity (85.7%) in the BA diagnosis. Generally, liver injury and cirrhosis are more serious in BA, which is possibly be related to the high specificity of GGT. There are some limitations in the clinical diagnosis of diseases by a single index. The three factors combined diagnosis can improve the accuracy of BA diagnosis. In this study, the combination of clay-colored stool, Dbil > 75.3 umol/L, and GGT > 252 U/L BA diagnosis can reach an 80.0% specification and a 91.1% accuracy. This study emphasizes simplicity and effectiveness in diagnosis. Generally, Dbil and GGT are easy to obtain, which can be quickly tested in medical institutions. This approach allows more jaundiced infants to be diagnosed early and receive treatments early.
There are some limitations of this study. Because some parents did not agree with screening for genetic metabolic liver disease, the IC genetic metabolic liver disease might have had a certain impact on the study results. The early diagnosis and treatment of BA still have a long way to go because of different medical conditions and attention to the disease.