Scottish Liver Transplant Unit Research Articles

Effect of recipient age on prioritisation for liver transplantation in the UK: a population-based modelling study

Following the introduction of an algorithm aiming to maximise life-years gained from liver transplantation in the UK (the transplant benefit score [TBS]), donor livers were redirected from younger to older patients, mortality rate equalised across the age range and short-term waiting list mortality reduced. Understanding age-related prioritisation has been challenging, especially for younger patients and clinicians allocating non-TBS-directed livers. We aimed to assess age-related prioritisation within the TBS algorithm by modelling liver transplantation prioritisation based on data from a UK transplant unit and comparing these data with other regions. In this population-based modelling study, serum parameters and age at liver transplantation assessment of patients attending the Scottish Liver Transplant Unit, Edinburgh, UK, between December, 2002, and November, 2023, were combined with representative synthetic data to model TBS survival predictions, which were compared according to age group (25-49 years vs ≥60 years), chronic liver disease severity, and disease cause. Models for end-stage liver disease (UKELD [UK], MELD [Eurotransplant region], and MELD 3.0 [USA]) were used as validated comparators of liver disease severity. Of 2093 patients with chronic liver disease, 1808 (86%) had complete datasets and liver disease parameters consistent with eligibility for the liver transplant waiting list in the UK (UKELD ≥49). Disease severity as assessed by UKELD, MELD, and MELD 3.0 did not differ by age (median UKELD scores of 56 for patients aged ≥60 years vs 56 for patients aged 25-49 years; MELD scores of 16 vs 16; and MELD 3.0 scores of 18 vs 18). TBS increased with advancing age (R=0·45, p<0·0001). TBS predicted that transplantation in patients aged 60 years or older would provide a two-fold greater net benefit at 5 years than in patients aged 25-49 years (median TBS 1317 [IQR 1116-1436] in older patients vs 706 [411-1095] in younger patients; p<0·0001). Older patients were predicted to have shorter survival without transplantation than younger patients (263 days [IQR 144-473] in older patients vs 861 days [448-1164] in younger patients; p<0·0001) but similar survival after transplantation (1599 days [1563-1628] vs 1573 days [1525-1614]; p<0·0001). Older patients could reach a TBS for which a liver offer was likely below minimum criteria for transplantation (UKELD <49), whereas many younger patients were required to have high-urgent disease (UKELD >60). US and Eurotransplant programmes did not prioritise according to age. The UK liver allocation algorithm prioritises older patients for transplantation by predicting that advancing age increases the benefit from liver transplantation. Restricted follow-up and biases in waiting list data might limit the accuracy of these benefit predictions. Measures beyond overall waiting list mortality are required to fully capture the benefits of liver transplantation. None.

THU292 - Geographic disparities and socioeconomic determinants in liver transplantation referral at the Scottish Liver Transplant Unit

THU292 - Geographic disparities and socioeconomic determinants in liver transplantation referral at the Scottish Liver Transplant Unit

Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study).

Acute liver failure is a rare and devastating clinical condition resulting from sudden loss of hepatic parenchyma and metabolic function. The Scottish Liver Transplant Unit (SLTU) offers specialist management and emergency liver transplantation to patients with acute liver failure from across Scotland. To describe temporal changes in number of admissions, aetiology of acute liver failure, severity of disease at presentation and outcomes over a 22-year period. Retrospective analysis of the SLTU database, including all patients admitted with acute liver injury or acute liver failure between November 1992 and March 2014. There has been no change in the number of patients presenting with acute liver injury or failure secondary to paracetamol overdose, but a reduction in the number of admissions with acute liver injury or failure secondary to non paracetamol causes. Over time, disease severity at presentation has not changed in the paracetamol cohort; those with a non paracetamol aetiology have latterly presented with milder hepatic encephalopathy. Spontaneous survival rates improved significantly over time for those patients with acute liver failure due to paracetamol and non paracetamol aetiologies. The most marked improvement in survival is observed in the sickest patients meeting Kings College Hospital poor prognostic criteria. The number of admissions to the SLTU with acute liver failure is decreasing, due to reduced numbers of non paracetamol cases. Outcomes in this condition are improving, due to improvements in intensive care management and use of liver transplantation, and the increase in survival is most marked in patients meeting Kings College Hospital poor prognostic criteria.

Patients with the worst outcomes after paracetamol (acetaminophen)-induced liver failure have an early monocytopenia.

Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited. The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome. On admission, patients with worst outcomes after POD-ALF had a significant monocytopenia, characterised by reduced classical and expanded intermediate monocyte population. This was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a 'cytokine storm' and increased concentrations of cytokines associated with monocyte egress from the bone marrow. Gene expression array did not differentiate patient outcome. At day 4, there was no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes. Severe paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes. This is not seen in patients with non-paracetamol-induced liver failure. Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention.

The impact of proton pump inhibitor therapy on patients with liver disease.

Proton pump inhibitor (PPI) therapy has been reported to be an independent mortality risk factor in patients with cirrhosis. To identify the prevalence of PPI prescription, the appropriateness of this therapy and to investigate the relationship between PPI therapy and overall survival in patients with liver disease. This retrospective cohort study used patient data for 2012 to 2014 collected from the Scottish Liver Transplant Unit and the Hepatology Ward at the New Royal Infirmary of Edinburgh. A total of 64% of the 198 patients discharged from the Hepatology ward were prescribed a PPI. Of the 206 patients assessed and listed for orthotopic liver transplant (OLT), 55% were prescribed a PPI. These percentages are significant, particularly as the majority had no recorded appropriate indication for this therapy. For patients listed for OLT, a logistic regression model revealed significant associations between PPI treatment and male sex, higher model of end-stage liver disease (MELD) scores and patient encephalopathy. A multivariate Cox regression model showed that MELD and UK model for end-stage liver disease scores were independent predictors of patient mortality, while alcoholic liver disease aetiology was a protective factor. There was no statistically significant difference in survival between patients who were prescribed a PPI at assessment and those who were not. Associations between PPI use, encephalopathy and higher MELD scores imply caution should be exercised in prescribing gastric acid suppressants to patients with cirrhosis, particularly in the absence of clear indications.

Hepatitis E virus and transfusion transmitted infection in Scotland

No: 1784 Presentation at ESCV 2015: Poster 2 Hepatitis E virus and transfusion transmitted infection in Scotland L. Scobie1,∗, C. Crossan1, J. Davidson1, L. Jarvis2, K. Simpson3 1 Glasgow Caledonian University, Glasgow, UK 2 Scottish National Blood Transfusion Service, Edinburgh, UK 3 Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK Background: Hepatitis E (HEV) is an increasingly recognised cause of severe acute liver injury in developed countries. In addition, HEV is now well accepted as a cause of chronic hepatitis in immune-compromised patients such as post-transplant patients and HIV infected patients. There have also been several cases of HEV infection via blood transfusion and one reported case via liver transplantation. Here we assess the incidence of HEV in the posttransplant population in Scotland. Methods: Patients attending the Scottish Liver Transplant Unit for routinepost-transplant checkupwereasked toprovide a sample for HEV screening. Patients were asked to complete a questionnaire regarding exposure to knownHEV risk factors (such asdietary factors, travel history and occupational exposure). Samples were screened for anti-HEV IgM and IgG antibodies by ELISA (Wantai, Beijing, China) and for HEV RNA by qRT-PCR. The patient demographic (n=317) ranged from 18 to 85years (× 56.4 13.6) with a male to female ratio of 1:1.07. The time post-transplant ranged up to 20 years (× 5.0 5.3). Results: The IgG seroprevalence within the cohort was 13.0%, and three IgM positive patients were identified (0.9%). Among the IgG seropositive patients there was no significant correlation with known HEV risk factors. A 46 year old male, was identified as HEV viraemic with a viral load of 1.6×106 IU/ml, despite being anti-HEV IgM and IgG seronegative. Prior to transplant this patient had suffered from primary sclerosing cholangitis, resulting in the development of chloangiocarcinoma. During this routine clinic appointment it was suspected that the patient had recurrent metastatic disease. The patient was admitted to hospital and died 14 days later (82 days post-transplant). Sequencing of the vRNA isolated from the patient’s serum showed the patient was infected with genotype HEV3C. Retrospective screening of an archived serum sample from this patient (3 months prior to transplant) tested HEV RNA negative and antibody negative. The patient received a transfusion from a pool of fresh frozen plasma which also tested positive for HEV RNA. Sequence analysis confirmed the identity of the two samples to be 99.8%. Conclusion: This is the first incidence of a potentially transfusion transmitted HEV infection in the Scotland. Overall, the HEV IgG seroprevalence in this cohort was considerably higher than the reported IgG seroprevalence of the Scottish blooddonor population (4.7%). The fact that a patient with high viraemia and no antibody response emphasizes the need for molecular screening of HEV in transplant patients. http://dx.doi.org/10.1016/j.jcv.2015.07.288

Hepatitis E virus in patients with acute severe liver injury.

To examine the incidence of hepatitis E (HepE) in individuals with acute liver injury severe enough to warrant treatment at a transplant unit. Hepatitis E virus (HEV) is an emerging pathogen in developed countries causing severe illness, particularly in immunocompromised patients or those with underlying chronic liver disease. HepE infection is often under diagnosed, as clinicians can be reluctant to test patients who have not travelled to regions traditionally considered hyperendemic for HepE. There are few data regarding the significance of HEV in patients with very severe acute liver injury in developed countries. Eighty patients with acute severe liver injury attending the Scottish Liver Transplant unit were tested for HEV and anti-HEV IgG and IgM. Severe acute liver injury was defined as a sudden deterioration in liver function confirmed by abnormal liver function tests and coagulopathy or presence of hepatic encephalopathy. Eighty percent of these patients were diagnosed with paracetomol overdose. No patients had a history of chronic or decompensated chronic liver disease at time of sampling. IgG positive samples were quantified against the World Health Organization anti-HEV IgG standard. Samples were screened for HEV viral RNA by quantitative reverse transcription polymerase chain reaction. Four cases of hepatitis E were identified. Three of the four cases were only diagnosed on retrospective testing and were initially erroneously ascribed to drug-induced liver injury and decompensated chronic liver disease, with the cause of the decompensation uncertain. One case was caused by HEV genotype 1 in a traveller returning from Asia, the other three were autochthonous and diagnosed on retrospective testing. In two of these cases (where RNA was detected) HEV was found to be genotype 3, the most prevalent genotype in developed countries. Three patients survived, two of whom had been misdiagnosed as having drug induced liver injury. The fourth patient died from sepsis and liver failure precipitated as a result of hepatitis E infection and previously undiagnosed cirrhosis. Histopathology data to date is limited to mainly that seen for endemic HepE. All patients, with the exception of patient 1, demonstrated characteristics of HepE infection, as seen in previously described locally acquired cases. In patients with acute severe liver injury, HEV testing should be part of the initial diagnostic investigation algorithm irrespective of suspected initial diagnosis, age or travel history.

925 FACTORS ASSOCIATED WITH POOR OUTCOME IN PRIMARY BILIARY CIRRHOSIS

925 FACTORS ASSOCIATED WITH POOR OUTCOME IN PRIMARY BILIARY CIRRHOSIS M. Carbone, G. Mells, H.J. Cordell, M.A. Heneghan, J.M. Neuberger, P.T. Donaldson, A.J. Bathgate, A.K. Burroughs, M.H. Davies, D.B. Day, S. Rushton, M.F. Dawwas, S. Thomson, G.J. Alexander, D.E. Jones, R.N. Sandford, UK Primary Biliary Cirrhosis (PBC) Consortium. Academic Department of Medical Genetics, University of Cambridge, Department of Medicine, Division of Gastroenterology and Hepatology, Cambridge University Hospitals, Cambridge, Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, Institute of Liver Studies, King’s College Hospital, London, Liver Unit, Queen Elizabeth Hospital, Birmingham, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, Liver Transplantation and Hepato-Biliary Medicine Unit, Royal Free Hospital, London, Liver Unit, St James’s University Hospital, Leeds, Organ Donation and Transplantation, NHS Blood and Transplant, Bristol, UK E-mail: marco.carbone@uniroma2.it

952 THE IMPACT OF PRIMARY BILIARY CIRRHOSIS (PBC) ON PERCEIVED QUALITY OF LIFE (QoL): THE UK-PBC NATIONAL STUDY

G. Mells, M. Carbone, G. Pells, J. Newton, A. Bathgate, A. Burroughs, M. Heneghan, J. Neuberger, D. Day, S. Ducker, R. Sandford, G. Alexander, D. Jones, The UK-PBC Consortium. Academic Department of Medical Genetics, Cambridge University, Department of Hepatology, Cambridge University Hospitals, Cambridge, Institute of Cellular Medicine, NIHR Biomedical Research Centre in Ageing and Chronic Disease, Newcastle University, Newcastle-upon-Tyne, Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, Hepatology Dept, Royal Free Campus, University College London, Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, The Liver Unit, Queen Elizabeth Hospital, Birmingham, UK E-mail: greta.pells@ncl.ac.uk

Authors' response to Dr Reiter

Authors' response to Dr Reiter

Re: Remien et al.: Mathematical modeling of liver injury and dysfunction after acetaminophen overdose

We read with interest the recent analysis by Remien et al.1 of the prognostic accuracy of the Model for Acetaminophen-induced Liver Damage (MALD). By combining serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and international normalized ratio INR, the authors demonstrate a negative predictive value (NPV) of 100% for predicting death when applied to a mixed cohort of 53 acetaminophen overdoses. This complex model has several limitations to its use at present, including the difficulty in calculating the formula at the patients' bedside, and in the use of serum AST, which may not always be routinely available in some centers. However, the study does highlight the importance of accurate triage when considering the potential need for liver transplantation following acetaminophen overdose. We similarly demonstrated an extremely high NPV following acetaminophen overdose by utilizing the Sequential Organ Failure Assessment (SOFA) score, where a SOFA score <7 by 96 hours following single timepoint overdose had a NPV of 98.2%.2 The SOFA score is similarly helpful at ruling out death following multiple timepoint (staggered) acetaminophen overdose, with a SOFA score <6 at tertiary care admission carrying an NPV of 100.0% (Craig DG, unpubl. data). SOFA is a simple scoring system that can be rapidly recalculated at the bedside throughout admission, and, because it is an ordinal rather than a dichotomous variable, a rising SOFA score could function as a gatekeeper to identify deteriorating patients at an early stage and expedite transfer to liver centers. Although the MALD score appears promising as a triage marker, we would urge caution before adopting it as a primary transplant listing criterion. In keeping with several other prognostic studies, the authors compared the prognostic accuracy of their model with the King's College Criteria (KCC) at a single timepoint (hospital admission) rather than dynamically throughout admission, as originally intended, which is likely to invalidate comparisons with the KCC.3 Furthermore, MALD does not explicitly include hepatic encephalopathy, thereby raising the possibility of undertaking liver transplantation inappropriately in patients with high MALD scores from other (nonacetaminophen) etiologies. As ever, there remains a balance between ensuring patients at risk of death are not missed through the inappropriate use of highly specific listing criteria, such as the KCC, as triage markers, while minimizing unnecessary transplantation of patients who might spontaneously survive. Further evaluation of the MALD and SOFA scores as triage markers in prospective studies between several large centers would be welcome. Drren G. Craig M.R.C.P.*, Kenneth J. Simpson MD, Ph.D.*, * Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.

PWE-282 The role of α-fetoprotein in hepatocellular carcinoma surveillance

IntroductionThe most efficient and cost-effective programme for HCC surveillance is the subject of ongoing debate. Current UK standard practice for HCC surveillance in high risk populations consists of 6 monthly...

The Scottish Liver Transplant Unit: current and future perspectives

The Scottish Liver Transplant Unit (SLTU) opened in 1992 and has now performed over 900 liver transplants. During this time there have been major changes in both organ donation and transplantation. Currently liver transplantation is restricted by limited organ supply. Scotland has one of the lowest rates of organ donation in Europe and one of the most rapidly increasing rates of cirrhosis. The consequent waiting list mortality has driven innovations including increasing use of marginal grafts, organs donated after cardiac death, split-liver transplants and the development of living-donor liver transplantation. To maintain liver transplantation, there is an urgent need to increase organ donation rates and to find novel treatments which optimize outcomes from marginal grafts. This review addresses the surgical aspects of liver transplantation and how these have evolved over the two past decades. Major changes are currently underway in organ donation organization, and there is continuing refinement of organ treatment and storage. A number of measures to maintain and improve organ preservation and function are currently being evaluated in clinical trials, and cell therapy holds significant potential for the future. Scotland has a rising need for liver transplantation and the SLTU continues to provide high-quality care and to be at the forefront of the latest advances in organ transplantation.

Acute liver failure in Scotland between 1992 and 2009; incidence, aetiology and outcome

To describe incidence, aetiology and outcome data for Scotland since the inception of the Scottish Liver Transplant Unit (SLTU) in 1992. Acute liver failure (ALF) is a rare but frequently fatal condition. Few studies have adequate patient numbers to draw convincing conclusions over demographic features, aetiology and outcome. Statistical analysis of prospectively collected data on aetiology, demographic, clinical and outcome of all admissions, including those with ALF, to the SLTU. Incidence data presented for admissions and ALF. Descriptive frequencies for aetiology, clinical, demographic and outcome data presented; including split analysis for paracetamol and non-paracetamol aetiologies. Univariate and multivariate analysis of admission factors predictive of outcome is described. Nine hundred and forty-nine patients were admitted to the SLTU between 1992 and 2009. Five hundred and twenty-four patients had ALF. The annual incidence of ALF in the Scottish population is 0.62 per 100,000 and paracetamol overdose (POD) was the largest causative factor; responsible for 0.43 cases of ALF per 100,000 population per year. The odds ratio (OR) of transplantation or death was 0.47 in the POD group compared to other aetiologies; yet of not being a transplant candidate having met the Kings College Hospital poor prognostic criteria OR was 4.9. Of admissions listed for transplant 76.0% were transplanted. Of those listed and not transplanted mortality was approaching 100% and 76.1% of those transplanted survived to discharge. This large, prospective, single centre study with a defined geographical area and well-recorded population provides accurate data regarding ALF between 1992 and 2009.

The effect of coingestion of aspirin and nsaids on paracetamol-induced liver failure: a single centre case controlled study

IntroductionAcute liver failure (ALF), which has a high risk of death or emergency liver transplantation, is most commonly caused by paracetamol overdose (POD) in the UK. A murine study suggested...

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity.

Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P < 0.001). The King's College poor prognostic criteria had reduced sensitivity in unintentional overdoses (77.8%, 95% confidence intervals (CI) 62.9, 88.8) compared with intentional overdoses (89.9%, 95% CI 83.4, 94.5). Unintentional overdose was independently predictive of death or liver transplantation on multivariate analysis (odds ratio 1.91 (95% CI 1.07, 3.43), P = 0.032). Unintentional paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses.

Considering adult living donor liver transplantation: A qualitative study of patients and their potential donors

In April 2006, the Scottish Liver Transplant Unit became the first NHS transplant unit in the UK to offer adult Living Donor Liver Transplantation (LDLT). However, within the first 21 months of its availability, no patients on the transplant waiting list had pursued this treatment option. A qualitative interview study was devised to elicit the views of patients and their families with regards to LDLT. Interviews were conducted with 21 patients and 20 potential donors. The main reason why recipients did not pursue LDLT was their perception of risk to their donor. The anticipated feelings of guilt if the donor was harmed resulted in LDLT being rejected. However, despite this, many recipients would possibly consider LDLT as a ‘last option’. For donors, considering becoming a donor was an automatic response, driven by their need to help their loved one to survive. However, consideration of the effects of donating upon their own immediate family often superseded their wish to donate. Whilst donors need to be given time to consider the implications of LDLT upon their own lives, it is essential that recipients understand that LDLT cannot be a last option, in order to allow them to reconsider their options realistically.

Increasing Donor Body Weight to Prevent Small‐for‐Size Syndrome in Living Donor Liver Transplantation

The Hollywood actress Renee Zellweger famously put on 20 lb in weight to make her appearance more suitable for the title role in the successful film Bridget Jones’s Diary [1]. In this issue of the World Journal of Surgery, Liu and colleagues from Taipei have advocated that in certain cases, potential living liver donors could be asked to gain weight, to increase the size of the future donor liver [2]. There is a clear association between graft recipient weight ratio and risk of development of small-for-size syndrome in living donor liver transplantation. Thus increasing the future liver may be a mechanism of reducing risk to the recipient. Normally, weight gain is seen in the context of potential health disadvantage, and so this article represents a somewhat controversial but very novel approach to the problem of a potentially small liver for donation. One of the fundamental questions in this approach is whether the whole body weight gain is detrimental not only to the health of the donor but also to the quality of the liver. Current evidence seems to suggest that an excessive and long-term increase in body weight is associated with an increase in the fat content of the liver and a higher risk of developing metabolic syndrome [3]. This may lead to fatty liver diseases (NAFLD or NASH) that are a fast rising indication for transplantation. Liu and colleagues challenge this concept and demonstrate that a short and well-controlled period of body weight gain does not translate into a deterioration of the liver quality. Instead, it leads to an increase in the overall liver volume that allows for a safe donation and transplantation. It is conceivable that the changes seen by Liu et al. are partially due to the high protein and carbohydrate diet, a strict control of weight gain, and the lack of pre-existent fatty changes in the liver. This short-lived weight gain seems to be rapidly reversible. Following cessation of the weight gain in the volunteers or completion of the donation process, a return to the initial body weight parameters appears to have taken place in all patients, without any immediate ill effects. Although this answers the question of immediate risks, it remains to be seen whether this rapid fluctuation in weight has any longterm impact on the donor’s health, increasing the risk of cardiovascular disease or the susceptibility to develop a metabolic syndrome later in life. This controversial approach has paid off and recipients received an appropriately sized graft that prevented the development of small for size syndrome. Our understanding of the pathophysiology of small-for-size syndrome and its clinical implications has made tremendous progress in recent years [4]. Several strategies for improving the outcome are now well established. One could argue that a less controversial approach, concentrating on recipient measures with inflow modulation, rather than donor weight modulation, is likely to be more successful and would be ethically more acceptable. Nevertheless, in a system where living liver donation is the only realistic option, and when there are no other potential donors for a given recipient, such an approach will save the life of patients who would otherwise have no alternative. Clearly, this is not a ‘‘one for all’’ measure, and the authors point out that only a few selected (and determined, G. C. Oniscu Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK

Long-term outcome following liver transplantation for paracetamol overdose

Paracetamol overdose (POD) is a major cause of acute liver failure (ALF) requiring liver transplantation in the United Kingdom. To characterize the early and late outcome after orthotopic liver transplantation (OLT) for POD in the Scottish Liver Transplant Unit over a 14-year period (1992-2006). Data were obtained from a prospective database combined with case-note review. Of 127 liver transplants performed for ALF, 44 were for POD. The median age was 30 (range 18-51). In 18 patients (63.7%), POD was associated with alcohol/other drugs, nine (20.5%) had a staggered overdose and four patients (9.1%) accidentally overdosed. Nineteen patients (43.2%) had a history of previous overdose/psychiatric illness. Post-transplant mortality during the index admission was 30% (13 patients), whilst five patients died during follow-up. The actuarial 5-year patient survival was 54.5%, whilst graft survival was 49.5%. Some 23% of the patients were re-transplanted: primary nonfunction (1), hepatic artery thrombosis (3) and chronic rejection (2). Three patients had a subsequent transplant; three patients had two further transplants. Nine patients (35%) continue to have social/psychiatric issues. OLT for POD is associated with significant early and late morbidity and mortality. A multidisciplinary approach is required to identify the suitable candidates, in whom transplantation should be pursued promptly.

Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit

Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death (p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning.