Age at surgery and native liver survival in biliary atresia: a systematic review and meta-analysis

Abstract

IntroductionBiliary atresia (BA) is a childhood rare disease of the liver and bile ducts that requires prompt surgical intervention. Age at surgery is an important prognostic factor; however, controversy exists with regards to the bene t of early Kasai procedure (KP). We aimed to conduct a systematic review and meta-analysis to examine the relationship between the age at KP and native liver survival (NLS) of BA patients. MethodsWe performed the electronic database search using Pubmed, EMBASE, Cochrane, and Ichushi Web and included all relevant studies published from 1968 up to May 3, 2022. Studies which examined the timing of KP at age 30,45, 60, 75, 90, 120, and/or 150 days were included. The outcome measures of interest were NLS rates at 5, 10, 15, 20, and 30 years post-KP and the hazard ratio or risk ratio for NLS. The quality assessment was used using the ROBINS-I tool. ResultsAmong 1,653 potentially eligible studies, 9 articles met the inclusion criteria for the meta-analysis. Meta-analysis for hazard ratios revealed that there was signi cantly faster time to liver transplantation in the group of patients who had KP at later timing as compared with earlier KP (HR=2.12, 95% CI 1.51-2.97). The risk ratio comparing KP <30 days and KP >31 days on native liver survival was 1.22 (95%CI 1.13-1.31). The sensitivity analysis showed that comparing KP <30 days and KP 31-60 days, the risk ratio was 1.13, 95%CI 1.04-1.22. ConclusionOur meta-analysis showed the importance of early diagnosis and surgical interventions ideally before 30 days of life in infants with BA on native liver survival on 5, 10, and 20 years. Therefore, effective newborn screening of BA targeting KP <30 days is needed to ensure prompt diagnosis of affected infants. IntroductionBiliary atresia (BA) is a childhood rare disease of liver and bile ducts presenting with biliary obstruction exclusively in the neonatal period (1). BA is the most common cause of neonatal jaundice requiring prompt surgical intervention (the Kasai procedure [KP]) that aims to restore bile ow, and is the most frequent indication for liver transplantation in children. Age at surgery is an important prognostic factor of BA (1) (2). The success of KP, such as the clearance of jaundice and native liver survival (NLS), is associated with infant age at the time of surgery (3). Over the past decade, the average age at KP has remained between 60 to 70 days, and the 10-year NLS is 52.8% in Japan(4) (5). Due to medical advances enabling early diagnosis, the age at BA diagnosis and surgery have decreased in recent years. This has resulted in shifts in surgery being performed at earlier ages at less than 60 days with studies showing better prognosis of KP performed at less than 30 days (6). In contrast, several studies have also observed that the timing of surgery does not impose a signi cant in uence on the clinical outcomes (7) (8).The previous systematic review by Jimenez-Rivera et al. conducted in 2013 (9) investigated the relationship between the timing of KP and patient outcomes. The...

Navigating cholestasis: identifying inborn errors of bile acid metabolism for precision diagnosis

“…The diagnosis of BA is made through a comprehensive evaluation of laboratory data, including [1] blood biochemical tests showing the presence of cholestasis, in which elevated GGT and TBA levels can be seen; [2] ultrasonography of the porta hepatis to confirm the presence of a triangular cord sign; [3] bile sampling using a duodenal sonde to measure bilirubin; and [4] hepatobiliary scintigraphy. Based on the results of these tests, it may be necessary to confirm that no bile is flowing from the liver into the intestinal tract, and the Kasai procedure should be performed as early as possible (7). In IEBAM, STBA and GGT are generally in the normal range despite the presence of cholestasis; thus, measuring both of these parameters can help distinguish IEBAM from BA (Figure 1).…”

“…BA, by contrast, is the most common disease involving obstructive jaundice, with an incidence in Japan of approximately 1/10,000. The need for early detection of BA and early surgery has been noted (7). Because GGT and STBA levels are usually elevated in BA patients, the measurement of these two markers, along with determination of direct bilirubin level, should be performed to first rule out IEBAM before performing invasive inspections such as open cholangiography.…”

Major surgical conditions of childhood and their lifelong implications: comprehensive review

“…As the KPE performed before 60 days of life has been shown to improve native liver survival, early diagnosis and treatment is vital. Patients who fail to normalize their serum bilirubin by 3 months after KPE are likely to require liver transplantation by the age of 2 years 156 , 157 . Individual centres’ expertise and BA subtype also impact patient outcome 158 .…”