Age at Surgery and Native Liver Survival in Biliary Atresia: A Systematic Review and Meta-Analysis

Introduction: Biliary 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 benefit 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. Methods We 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. Results Among 1,653 potentially eligible studies, 9 articles met the inclusion criteria for the meta-analysis. Meta-analysis for hazard ratios revealed that there was significantly 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 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. Conclusion Our 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.