Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

OBJECTIVE: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN: Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES: 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM: To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS: From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS: At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)]. CONCLUSION: Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Diagnosis and treatment of primary biliary cholangitis.

Primary biliary cholangitis is a cholestatic, chronic autoimmune liver disease with a wide individual variation in disease progression. The diagnosis is predominantly based on chronic elevation of alkaline phosphatase and the presence of anti-mitochondrial antibodies or other specific antinuclear antibodies (i.e. anti-gp210 and anti-sp100). Even in early-stage disease, health-related quality of life can be severely impaired by symptoms such as pruritus, fatigue, and sicca syndrome and metabolic bone disease should be assessed and treated. The prognosis of the disease is, however, largely determined by the development of cirrhosis and its complications. Ursodeoxycholic acid is associated with an improved prognosis and should be initiated and continued in all patients. Clinical outcome is related to the biochemical response to ursodeoxycholic acid, but the prognosis of those with an incomplete response is still better than those who remain untreated. Obeticholic acid was recently approved as second-line treatment and bezafibrate may serve as an adequate off-label alternative, particularly in patients with pruritus. Preliminary data suggest an additive effect of triple therapy with ursodeoxycholic acid, obeticholic acid, and bezafibrate, whereas other promising drugs are being evaluated in clinical trials.

Mortality rates among individuals diagnosed with hepatitis C virus (HCV); an observational cohort study, England, 2008 to 2016.

BackgroundMonitoring trends in mortality for individuals diagnosed with hepatitis C virus (HCV) infection are important as we expand treatment and move towards World Health Organization elimination targets.AimTo estimate mortality rates for individuals aged ≥ 15 years diagnosed with HCV infection in England 2008-16.MethodsAn observational cohort study whereby death certificate information was linked to the Sentinel Surveillance of Blood Borne Virus Testing in England. Age-sex standardised mortality rates (ASMR) for individuals diagnosed with HCV infection (2008-16) were calculated and compared to the general population.ResultsOf 43,895 individuals with HCV infection, 2,656 (6.3%) died. All-cause ASMRs were 2,834.2 per 100,000 person years (PY), 2.3 times higher than in the general population. In individuals aged 30-69 years, all-cause mortality rates were 1,768.9 per 100,000 PY among individuals with HCV, 4.7 times higher than in the general population. ASMRs had not decreased between 2010 (2,992) and 2016 (2,340; p=0.10), with no change from 2014 (p = 0.058). ASMRs were 441.0 times higher for hepatitis, 34.4 times higher for liver cancer, 8.1 times higher for end stage liver disease and 6.4 times higher for external causes than in the general population.ConclusionsMortality was higher in individuals with diagnosed HCV infection compared to the general population, highlighting health inequalities. There is a need to improve HCV diagnosis, engagement in care and treatment rates. The high mortality from external causes highlights the importance of integrated health and social care strategies and addressing the needs of this vulnerable population.

Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions.

Patients with liver cirrhosis are susceptible to infections due to various mechanisms, including abnormalities of humoral and cell-mediated immunity and occurrence of bacterial translocation from the intestine. Bacterial infections are common and represent a reason for progression to liver failure and increased mortality. Fungal infections, mainly caused by Candida spp., are often associated to delayed diagnosis and high mortality rates. High level of suspicion along with prompt diagnosis and treatment of infections are warranted. Bacterial and fungal infections negatively affect the outcomes of liver transplant candidates and recipients, causing disease progression among patients on the waiting list and increasing mortality, especially in the early post-transplant period. Abdominal, biliary tract, and bloodstream infections caused by Gram-negative bacteria [e.g., Enterobacteriaceae and Pseudomonas aeruginosa (P. aeruginosa)] and Staphylococcus spp. are commonly encountered in liver transplant recipients. Due to frequent exposure to broad-spectrum antibiotics, invasive procedures, and prolonged hospitalizations, these patients are especially at risk of developing infections caused by multidrug resistant bacteria. The increase in antimicrobial resistance hampers the choice of an adequate empiric therapy and warrants the knowledge of the local microbial epidemiology and the implementation of infection control measures. The main characteristics and the management of bacterial and fungal infections in patients with liver cirrhosis and liver transplant recipients are presented.

Association of tooth loss with liver cancer incidence and chronic liver disease mortality in a rural Chinese population.

BACKGROUND: Tooth loss has been reported to be associated with the risk of liver cancer in several prior studies in economically advantaged countries. Whether this relationship is also evident in economically disadvantaged populations is not known. METHODS: We analyzed data from the Nutrition Intervention Trials, two randomized placebo-controlled trials of vitamin/mineral supplementation in Linxian, China. Participants who reported having lost permanent teeth were examined to determine the number of teeth remaining. In the 30-year follow-up period, 329 liver cancers were diagnosed and 368 chronic liver disease deaths occurred. Tooth loss was categorized based on loess smoothed age-specific predicted quartiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the two outcomes. RESULTS: Overall, persons in the highest quartile of age-specific tooth loss had an increased risk of liver cancer (HR = 1.27, 95%CI: 0.96, 1.67) which was not statistically significant. Results varied by sex and body mass index (BMI), however. Women in the highest quartile of age-specific tooth loss had a significantly increased risk (HR = 1.64, 95%CI: 1.04, 2.59), while men did not (HR = 1.08, 95%CI = 0.75, 1.57), and persons with a BMI > 23.0 kg/m2 (HR = 1.71, 95%CI: 1.00, 2.92) had a significantly increased risk, while persons with a BMI <23.0 kg/m2 did not (HR = 1.14, 95%CI: 0.82, 1.5). No relationships with chronic liver disease mortality were observed. CONCLUSIONS: In a rural, economically disadvantaged population, persons with the highest levels of age-specific tooth loss had an increased risk of liver cancer. The results, which were stronger among women and persons with greater BMI, suggest that periodontal disease may increase risk of liver cancer.

Association of fish and long-chain omega-3 fatty acids intakes with total and cause-specific mortality: prospective analysis of 421 309 individuals.

BACKGROUND: Prevailing dietary guidelines recommend regular fish consumption. However, the associations of fish and long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFAs) intakes with mortality remain unclear. OBJECTIVES: To examine the associations of fish and LCn-3 PUFAs intakes with total and cause-specific mortality. METHODS: A total of 240 729 men and 180 580 women from NIH-AARP Diet and Health Study were prospectively followed-up for 16 years. Dietary intakes were assessed using a validated NIH Diet History Questionnaire. RESULTS: A total of 54 230 men and 30 882 women died during 6.07 million person-years of follow-up. Higher fish and LCn-3 PUFAs intakes were significantly associated with lower total mortality (P < 0.0001). Comparing the highest with lowest quintiles of fish intake, men had 9% (95% confidence interval, 6-11%) lower total mortality, 10% (6-15%) lower cardiovascular disease (CVD) mortality, 6% (1-10%) lower cancer mortality, 20% (11-28%) lower respiratory disease mortality and 37% (17-53%) lower chronic liver disease mortality, while women had 8% (5-12%) lower total mortality, 10% (3-17%) lower CVD mortality and 38% (20-52%) lower Alzheimer's disease mortality. Fried fish consumption was not related to mortality in men whereas positively associated with mortality from all causes (P = 0.011), CVD and respiratory disease in women. LCn-3 PUFAs intake was associated with 15% and 18% lower CVD mortality in men and women across extreme quintiles, respectively. CONCLUSION: Consumption of fish and LCn-3 PUFAs was robustly associated with lower mortality from major causes. Our findings support current guidelines for fish consumption while advice on non-frying preparation methods is needed.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review

ABSTRACT Introduction and aim. Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. Material and methods. Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. Results. Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review.

INTRODUCTION AND AIM: Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

BACKGROUND: Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. METHODS: We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. RESULTS: One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). CONCLUSIONS: Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients.

Lessons Learned From Review of a Single Center Experience With 500 Consecutive Liver Transplants in a Region With Insufficient Deceased-Donor Support.

OBJECTIVES: We present here the outcomes of our first 500 liver transplants and discuss the lessons learned during this time. MATERIALS AND METHODS: We retrospectively analyzed the first 500 consecutive transplants within the listing criteria of the United Network for Organ Sharing, with recipients and donors with minimum 1-year follow-up. Patient survival and donor complications were analyzed for 31 liver transplant recipients with hepatocellular carcinoma beyond the Milan criteria who had transplant performed during the same time. RESULTS: Between August 2006 and March 2013, there were 519 liver transplants performed in 500 patients (365 adult, 135 pediatric). There were 394 living-donor and 125 deceased-donor liver transplants. In addition, 31 adult liver transplants were performed in patients with hepatocellular carcinoma beyond Milan criteria (22 living-donor and 9 deceased-donor transplants). The main cause of chronic liver failure was biliary atresia in pediatric patients (30.4%) and chronic hepatitis B infection in adults (35.6%). The complication rate for primary nonfunction was 3.8%, overall biliary complications 24.0% (significantly higher after adult living-donor liver transplant, 30.3%), hepatic artery thrombosis 1.6%, portal vein thrombosis 3.0%, retransplant 3.8%, acute cellular rejection 29.6%, and bacterial infection 39.4%. Overall 1-, 3-, and 5-year patient survival rates in the first 500 consecutive transplants performed on recipients within United Network for Organ Sharing listing criteria were 87.8%, 85.0%, and 78.6%; for hepatocellular carcinoma patients beyond the Milan criteria, survival rates were 71.9%, 52.5%, and 38.2%. CONCLUSIONS: In regions without a sufficient number of deceased donors, living-donor liver transplant, with its associated problems, is the only alternative to deceased-donor liver transplant. Liver transplant requires teamwork, with all players working well together for a successful outcome. The important keys to success in liver transplant include decision-making, timing, surgical skills, experience, and close follow-up.

Efficacy of cell saver use in living-donor liver transplant.

OBJECTIVES: Liver transplant currently is the best treatment option for end-stage liver disease. During liver transplant, there is major blood loss due to surgery and primary disease. By using a cell saver, the need for blood transfusion is markedly reduced. In this study, we aimed to evaluate the efficacy of cell saver use on morbidity and mortality in living-donor liver transplant. MATERIALS AND METHODS: We retrospectively evaluated 178 living-donor liver transplants, performed from 2005 to 2013 in our center. Child-Turcotte-Pugh A patients, deceased-donor liver transplants, and liver transplants performed for fulminant hepatic failure were not included in this study. Intraoperative blood transfusion was done in all patients to keep hemoglobin level between 10 and 12 g/dL. Cell saver was used in all liver transplants except in patients with malignancy, hepatitis B, and hepatitis C. RESULTS: We included 126 patients in the study. Cell saver was used in 84 liver transplants (66%). In 42 patients (34%), liver transplant was performed without a cell saver. In living-donor liver transplant with cell saver use, 10 mL/kg blood (range, 2-50 mL/kg blood) was transfused from the cell saver; in addition, 5 to 10 mL/kg allogeneic blood was transfused. In living-donor liver transplant without cell saver, 20 to 25 mL/kg allogeneic blood was transfused. CONCLUSIONS: During liver transplant, major blood transfusion is needed because of surgery and primary disease. Cell saver use markedly decreases the need for allogeneic blood transfusion and avoids adverse events of massive transfusion.

[Liver transplantation with living donor : current aspects, perspectives and significance in Germany]. / Lebertransplantation mit Lebendspende : Aktuelles, Perspektiven und Stellenwert in Deutschland.

More than 20 years ago living donor liver transplantation was introduced into clinical practice. Specifics of this method were developed initially for children and later on for adults particularly in regions where a liver transplantation program using deceased donors was not readily available. The most sensitive aspect of living donation, namely the danger to a healthy relative in order to perform the transplantation is immanent in the system and, thus, it is definitively a secondary option as compared to deceased organ donation. Following worldwide initial euphoria the numbers have markedly decreased in the western world since the start of the new millennium. In Asian countries in particular, much work has been done to optimize the procedure so that the donor safety and the outcome quality for the recipient have been impressively demonstrated in large patient populations. There is still a severe donor organ shortage and the option to allocate an optimal (partial) organ on an individual basis by living donation has given new impact to the discussion about a further rise in the profile of living donations here as well. The new version of the German transplantation legislation implemented in summer 2012 requires a number of conditions with respect to insurance for living donors. The current state and perspectives are presented here.

[Deceased donor liver transplantation]. / Lebertransplantation mit postmortalen Organen.

Deceased donor liver transplantation is nowadays a routine procedure for the treatment of terminal liver failure and often represents the only chance of a cure. Under given optimal conditions excellent long-term results can be obtained with 15-year survival rates of well above 60 %.In Germany the outcome after liver transplantation has deteriorated since the introduction of an allocation policy, which is based on the medical urgency. At present 25 % of liver graft recipients die within the first year after transplantation. In contrast 1-year survival in most other countries, e.g. in the USA or the United Kingdom is around 90 % and therefore significantly better. Reasons for the inferior results in Germany are on the one hand an increasing number of critically ill recipients and on the other hand an unfavorable situation for organ donation. In comparison with other countries the organ donation rate is low and moreover the risk profile of these donors is above average. This combination of organ shortage and organ allocation represents a big challenge for the future orientation of liver transplantation and creates the potential for conflict. These cannot be solved on a medical basis but require a social consensus.Because of the present inferior results and because of the high expenses of the present system we suggest a discussion on future allocation policies as well as on future centre structures in Germany. In addition to the medical urgency the maximum benefit should also be considered for organ allocation.

Liver-protecting effects of omega-3 fish oil lipid emulsion in liver transplantation.

AIM: To investigate the liver-protecting effect of parenteral nutrition (PN) support with omega-3 fatty acids in a randomized controlled clinical trial. METHODS: Sixty-six patients with the diagnosis of end-stage liver disease or hepatic cellular carcinoma were admitted to the Affiliated Drum Tower Hospital, Nanjing University, China for orthotopic liver transplantation. The patients were randomly divided into two groups: PN group (n = 33) and polyunsaturated fatty acid (PUFA) group (n = 33). All patients received isocaloric and isonitrogenous PN for seven days after surgery, and in PUFA group omega-3 fish oil lipid emulsion replaced part of the standard lipid emulsion. Liver function was tested on days 2 and 9 after surgery. Pathological examination was performed after reperfusion of the donor liver and on day 9. Clinical outcome was assessed based on the post-transplant investigations, including: (1) post-transplant mechanical ventilation; (2) total hospital stay; (3) infectious morbidities; (4) acute and chronic rejection; and (5) mortality (intensive care unit mortality, hospital mortality, 28-d mortality, and survival at a one-year post-transplant surveillance period). RESULTS: On days 2 and 9 after operation, a significant decrease of alanine aminotransferase (299.16 U/L ± 189.17 U/L vs 246.16 U/L ± 175.21 U/L, P = 0.024) and prothrombin time (5.64 s ± 2.06 s vs 2.54 s ± 1.15 s, P = 0.035) was seen in PUFA group compared with PN group. The pathological results showed that omega-3 fatty acid supplement improved the injury of hepatic cells. Compared with PN group, there was a significant decrease of post-transplant hospital stay in PUFA group (18.7 d ± 4.0 d vs 20.6 d ± 4.6 d, P = 0.041). Complications of infection occurred in 6 cases of PN group (2 cases of pneumonia, 3 cases of intra-abdominal abscess and 1 case of urinary tract infection), and in 3 cases of PUFA group (2 cases of pneumonia and 1 case of intra-abdominal abscess). No acute or chronic rejection and hospital mortality were found in both groups. The one-year mortality in PN group was 9.1% (3/33), one died of pulmonary infection, one died of severe intra-hepatic cholangitis and hepatic dysfunction and the other died of hepatic cell carcinoma recurrence. Only one patient in PUFA group (1/33, 3.1%) died of biliary complication and hepatic dysfunction during follow-up. CONCLUSION: Post-transplant parenteral nutritional support combined with omega-3 fatty acids can significantly improve the liver injury, reduce the infectious morbidities, and shorten the post-transplant hospital stay.

Comparison of seven liver allocation models with respect to lives saved among patients on the liver transplant waiting list.

The patients with end-stage liver disease (ESLD) on the liver transplant waiting list are prioritized for transplant based on the model for end-stage liver disease (MELD) score. We developed and used an innovative approach to compare MELD to six proposed alternatives with respect to waiting list mortality. Our analysis was based on United Network for Organ Sharing data of patients with ESLD on the waiting list between January 2006 and June 2009. We compared six allocation models to MELD. Two models were based on reweighting the variables used by MELD: an "updated" MELD, and ReFit MELD. Four models also included serum sodium: MESO, MeldNa, UKELD, and ReFit MELDNa. We estimated that UKELD and the updated MELD would result in significantly fewer lives saved. There were no significant differences between the other models. Our new approach can supplement standard methods to provide insight into the relative performance of liver allocation models in reducing waiting list mortality. Our analysis suggests that UKELD and the updated MELD score would not be optimal for reducing waiting list mortality in the United States.