ASCORBIC acid (AA) supplementation could potentially reduce post-reperfusion syndrome (PRS) during liver transplantation, according to new research from Hospital Universitario Ramón y Cajal, Madrid, Spain. AA, which has antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic strategy to prevent PRS, a haemodynamic complication that reduces mean arterial pressure and is associated with increased morbidity and mortality, ischaemia-reperfusion injury, and systemic inflammation. This is supported by evidence of low levels of AA in donors and recipients, possibly due to inadequate dietary intake, chronic inflammation, and immunosuppressive therapies.
The team randomised 39 patients undergoing liver transplantation at the hospital in a single-centre, double-blind RCT to receive either 1,500 mg intravenous AA during the anhepatic phase, when the liver is removed (19 patients), or placebo (0.9% saline; 20 controls). The primary endpoint of the study was PRS incidence, and secondary endpoints were post-operative renal function, inflammatory cytokine levels, and patient/graft survival.
The team noted a PRS incidence of 10.5% in the AA group, compared to 30.0% in the control group (p=0.235). Of note, there were more instances of post-operative renal failure in the AA group (68.4%), compared to the control group (35.0%; p=0.037). Re-transplantation had to be performed in four patients treated with AA. Researchers hypothesised that this could be due to the more severe haemodynamic changes or an unknown interaction with renal physiology. The team further reported increases in IL-6, IL-8, and IL-10 in patients with PRS, which suggests a stronger inflammatory response.
In conclusion, this study suggests that administering AA during liver transplantation may be beneficial in reducing PRS; however, larger, multicentre trials are needed to confirm efficacy, determine the optimal dosing and timing strategy, and evaluate whether the protective effects could be enhanced through combination therapy with other antioxidants.
Reference:
Gajate Martin L et al. A randomized trial of ascorbic acid for the prevention of post-reperfusion syndrome during liver transplantation. Hepatol Commun. 2025;9(8):e0777.
