Transplant Trial Watch

Effect of Adjuvant Steroid Therapy in Type 3 Biliary Atresia: A Single-Center, Open-Label, Randomized Controlled Trial.

Lu, X., et al.

Annals of Surgery 2023; 277(6): e1200-e1207.

They aim to evaluate the efficacy and side effects of additional postoperative steroid therapy for type 3 biliary atresia versus the current routine care.

Following Kasai portoenterostomy patients were randomised to receive standard care with or without 10-12 weeks of adjuvant steroid therapy.

200 paediatric patients with type 3 biliary atresia, with a post-conception age >36 weeks and weight >2000g.

The primary outcome was jaundice clearance with native liver (normal bilirubin at 6 months without liver transplantation). Secondary outcomes recorded at 3, 12 and 24 months included: bilirubin, survival with native liver, ascending cholangitis and serious adverse events (SAEs).

24 months

CET Conclusions
This large, single centre, single surgeon randomised trial demonstrated that adjuvant steroid treatment resulted in a statistically significant reduction in the need for liver transplantation at 12 (10% vs 22%, p=0.03) and 24 months (15% vs 28%, p=0.03) in this Chinese paediatric population initially treated with Kasai procedure. They also had significantly more early bile clearance at 3 months, 49% vs 22%, p<0.0001. However, there was no overall survival benefit at 24 months, 72% vs 68%, p=0.54. The steroid group had a numerically greater number of SAEs, due to higher rates of bacteraemia (34%) and GI bleeding (11%), though not statistically significant, they are worth noting. The trial is of an impressive size, and has taken place in a high-volume centre, with 200 Kasais performed specifically for type 3B atresia in 9 months by a single surgeon. The populations were much less varied than other studies, containing exclusively Asian/Chinese children, which limits generalisability. As does the exclusive use of type 3B patients, though type 1 & 2 having generally more favourable outcomes could mask the effects of the steroid. None the less the results are important given the controversy and variability of steroid use in this setting. The Davenport et al RCT performed in King’s College London had numerically similar findings with better early bile clearance and lower liver transplant rate at 1 year, though this failed to reach significance possibly due to the sample size being less than half of the present study. Both contrast with the smaller still US RCT by Peterson et al, who found no benefit and recommend steroid free treatment regimens. Lu et al have conducted a good quality high volume study on a very specific group of children, in this population the have demonstrated important benefit with their steroid regime, with significantly fewer children requiring transplantation, and thus a far better life expectancy. Given there is minimal high-quality evidence internationally in the area, it would seem they have presented evidence in which steroid regimes could be considered in larger volume multicentre RCTs in a European setting.

Jadad score

Data analysis
Modified intention-to-treat analysis

Allocation concealment

Trial registration

Funding source
Non-industry funded