Introduction Paracetamol hepatoxicity is the most common cause of fulminant hepatic failure in the UK 1 and NHSBT criteria for super-urgent liver transplantation in these patients are well described.2 While potentially life-saving, transplanted patients must live with the consequences of immunosuppression and life-long follow up. Patients transplanted for paracetamol overdose have an increased risk of post-transplant death compared to patients transplanted for other indications, particularly due to suicide, trauma & non-adherence to treatment.3Outcome after transplantation may be adversely affected by persisting physical/psychological/psychiatric/social & addiction circumstances that may make adherence unmanageable, even with full social support. Given the shortage of organ donors, rationing is inevitable and not all patients who fulfil the NHSBT criteria are listed for transplantation, despite a predicted poor/fatal outcome without. There is currently no clear way of pre-operatively predicting the risk of poor outcomes after transplant for paracetamol overdose. Our aim was to identify factors in the presenting history that could suggest that these patients might be unlikely to fully benefit from undergoing liver transplantation.
Methods We retrospectively analysed all patients transplanted for fulminant liver failure due to paracetamol overdose at University Hospitals Birmingham from 2000–2014, using standard clinical and transplant databases. Survival and graft related outcomes were assessed using Kaplan-Meier survival curves, with log-rank tests used to make comparisons across factors. Patients with DNAs and non-compliance were then compared to compliant patients using Mann-Whitney tests, for continuous variables, and Fisher’s exact test, for categorical variables.
Results 59 patients were transplanted for POD during this period with median follow up of 6 years, mean age of 35 (range 17–57 years). 59% of patients were female. 57% of patients had a pre-existing psychiatric diagnosis however only 36% had a history of previous overdose. 12 patients died before discharge from hospital (main causes of death were multi-organ failure & sepsis) with a further 6 patients dying after initial discharge (all associated with non-compliance and 33% were due to suicide). Overall 5 year survival was 69%, which rose to 87% if the patient survived to discharge from hospital. Having a history of domestic abuse was associated with a higher risk of death (p = 0.001). Of 36 patients under long-term follow up at our centre, 15 have had at least one episode of biopsy proven rejection (41.7%) with a 5 year rejection rate of 46%. To date this has resulted in two patient deaths and two re-grafts. Patients aged 16–35 were significantly more likely to experience rejection than the older cohort (p = 0.04). 73% of patients with rejection had a history of non-compliance with medication compared to 27% in compliant patients (p = 0.031). In the 2007–2015 patient cohort, both staggered and mixed overdosed were found to give significantly increased risk of rejection (p = 0.027 and 0.011 respectively).
Conclusion Patients transplanted for paracetamol overdose have poorer long term survival and graft function than other transplant patients. There remains no clear way of predicting post-operative mortality/graft dysfunction from pre-admission factors. However, domestic abuse may be associated with increased patient mortality and patients under 35, staggered and mixed overdoses are at higher risk of graft rejection. These results are unlikely to change the decision to list for transplantation, but could help identify those at higher risk post-discharge and aid in tailoring follow up.
References 1 Riordan S, Williams R. Cause and prognosis in acute liver failure. Liver Transpl 2003;5(1):86–89.
2 Mitchell I, Bihari D, Chang R, Wendon J, Williams R. Earlier Identification of patients at risk from acetominophen-induced acute liver failure. Cri Care Med 1998;26(2):279–284.
3 Germani G, Theocharidou E, Adam R, Karam V, Wendon J, et al. Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol 2012;57:288–296.
Disclosure of Interest None Declared