Abstract: We found two randomised controlled trials fulfilling the inclusion criteria of our review. The trials provided data for meta-analysis. We judged the two trials as trials at low risk of bias. The two trials randomised a total of 213 infants to glucocorticosteroids versus placebo. In our Trial Sequential Analysis, the required information size (that is, the meta-analytic sample size) was not reached for any outcome. Trials were funded by charities, public organisations, and received support from private sector companies, none of which seemed to have an interest in the outcome of the respective trials. The effect of glucocorticosteroids after Kasai portoenterostomy on all-cause mortality is uncertain; the confidence interval is consistent with appreciable benefit and harm (RR 1.00; 95% CI 0.14 to 6.90; low-certainty evidence). The results showed little or no difference in adverse effects between the use of glucocorticosteroids or placebo after Kasai portoenterostomy, however this analysis was based on a single trial and we have low certainty in the result (RR 1.02; 95% CI 0.87 to 1.20;). Available data suggest that the proportions of infants who do not clear their jaundice at six months is similar between the two groups (RR 0.89; 95% CI 0.67 to 1.17; low-certainty evidence). All-cause mortality or liver transplantation did not differ at two years between the two groups (RR 1.00; 95% CI 0.72 to 1.39; low-certainty evidence). There were no data regarding health-related quality of life. Our searches also yielded 19 observational studies, some of them containing limited information on harmful effects of glucocorticosteroid treatment. We presented the extracted information narratively. We identified one further ongoing trial with no currently available results. The two meta-analysed randomised clinical trials present insufficient evidence to determine the effects of using glucocorticosteroids versus placebo after Kasai portoenterostomy in infants with biliary atresia on any of the primary or secondary review outcomes. There is insufficient evidence to support glucocorticosteroid use in the postoperative management of infants with biliary atresia for long-term outcomes of all-cause mortality or liver transplantation. It is also unclear if glucocorticosteroids are able to reduce the numbers of infants who did not clear their jaundice by six months. Further randomised, placebo-controlled trials are required to be able to determine if glucocorticosteroids may be of benefit in the postoperative management of infants with biliary atresia treated with Kasai portoenterostomy. Such trials need to be conducted as multicentre trials.

Plain-language summary: We performed a search which included studies up to 20 December 2017. We identified two randomised clinical trials (where participants are divided by chance into the trial groups) which met the requirements for our review and followed-up the participants for at least two years. We identified 19 further observational studies from which we were able to report some findings on harms in a narrative form. The randomised trials included 107 infants who were given glucocorticosteroids and 104 who were given placebo. Trials were funded by charities, public organisations, and received support from private sector companies, all of which did not seem to have any interest in the outcome of the respective trials. Funding The included trials outlined their sources of funding, and the review authors deemed that there were no conflicts of interest. Review authors did not receive funding to carry out this review. Key results We did not find any differences between the groups of infants treated with glucocorticosteroids compared with placebo in terms of mortality, adverse events, ability to clear jaundice, or need for a liver transplant. Quality of the evidence We assessed the two trials as having low risk of bias (we had no concerns that their design and reporting may deviate from the truth), but they were at high risk of imprecision (inexact evaluations of outcomes). They used different categories for adverse events, and we were unable to combine the data from the trials. We could not include enough infants in our analyses (only two published trials) in order to detect small differences between the two intervention groups. The certainty of the evidence was low for mortality, adverse events, ability to clear jaundice, or need for a liver transplant outcomes. One further ongoing trial was identified, with no currently available results. Future steps We need further randomised clinical trials that compare glucocorticosteroids with placebo in order to find out if glucocorticosteroids are of benefit in the postoperative management of infants with biliary atresia. Such trials need to be conducted at different clinical centres.