Outcomes of liver transplantation for paracetamol (acetaminophen)-induced hepatic failure

Abstract

Paracetamol (acetaminophen) hepatotoxicity, whether due to intentional overdose or therapeutic misadventure, is an indication for liver transplantation in selected cases. However, there is a concern that long-term outcomes may be compromised by associated psychopathology that may predispose patients to further episodes of self-harm or poor treatment adherence. We therefore undertook a retrospective analysis of patients transplanted for paracetamol-induced fulminant hepatic failure (FHF) to determine their long-term outcomes, psychiatric problems, and compliance and whether these issues could be predicted from pretransplant information. Records from patients undergoing liver transplantation for paracetamol-associated liver failure in this unit and 2 comparison groups (patients undergoing liver replacement for FHF from other causes and for chronic liver diseases) were examined. Of 60 patients transplanted for paracetamol-induced FHF between 1989 and 2007, 44 (73%) survived to discharge. Currently, 35 patients (58%) are surviving at an average of 9 years post-transplantation. The incidence of psychiatric disease (principally depression) and 30-day mortality were greatest in the paracetamol group, but for those who survived 30 days, there was no difference in long-term survival rates between the groups. Adherence to follow-up appointments and compliance with immunosuppression were lowest in the paracetamol overdose group. Poor adherence was not predicted by any identifiable premorbid psychiatric conditions. Two patients grafted for paracetamol FHF died from self-harm (1 from suicide and 1 from alcoholic liver disease after 5 years). This study suggests that, notwithstanding the shortage of donor liver grafts, transplantation is an appropriate therapy in selected patients, although close follow-up is indicated. Liver Transpl 15: 1351-1357, 2009.

Acetaminophen hepatotoxicity: an updated review

“…Patients receiving liver transplantation for acetaminophen-related ALF have a 73 % rate of survival to discharge. With the higher incidence of psychiatric illness and prior suicide attempts in these patients, long-term survival can be affected by repeated suicide attempts, substance abuse, and nonadherence to medications (Cooper et al 2009;Karvellas et al 2010). A review of the Acute Liver Failure Study Group data showed better long-term survival following acetaminophen overdose with transplantation than with spontaneous recovery, possibly due to the need for closer follow up with healthcare professionals after transplantation (Fontana et al 2014).…”

Role of Liver Transplantation in Acute Liver Failure

“…Less than 5% of those transplanted for APAP overdose reattempted overdose. There was worse 30-day mortality for the APAP-ALF patients, and a greater probability of post-OLT medical nonadherence and adverse events in those who had taken APAP for deliberate self-harm compared with both non-APAP-ALF patients and chronic liver disease patients (Cooper et al, 2009).…”

“…Risk of repeated overdose appears to be less common; however, if the patient was transplanted, perhaps due to the intensity of postoperative care. In two series from the United Kingdom, APAP-ALF patients who underwent OLT showed similar long-term survival (median 5 years and 9 years) compared with patients transplanted for chronic liver disease (Cooper et al, 2009;Karvellas et al, 2010). Less than 5% of those transplanted for APAP overdose reattempted overdose.…”

Detecting mRNA Predictors of Acetaminophen-Induced Hepatotoxicity in Mouse Blood Using Quantitative Real-Time PCR

“…[10][11][12][13] Notably, 30 to 50% of cases of APAP hepatotoxicity admitted to hospitals nowadays result from a "therapeutic misadventure," wherein the daily dose may not have greatly exceeded the recommended safe limits but where specific risk factors are present. 10,14,15) Previously, it has been reported the APAP-induced hepatotoxicity correlates with various factors.…”