Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Sex Disparity in Liver Transplant and Access to Living Donation.

Importance: The Model for End-stage Liver Disease (MELD)-based organ allocation system has significantly decreased mortality on the transplant waiting list for patients with end-stage liver disease. However, women have remained at a disadvantage with respect to access to deceased donor liver transplant (DDLT) even after introduction of the MELD score for organ allocation. Objective: To determine whether availability of living donation in a transplant program can offset inequity in liver transplant (LT) allocation for women. Design, Setting, and Participants: This cohort study retrospectively analyzed adult patients listed for LT at the University Health Network in Toronto, Ontario, Canada. Patients included had a potential living donor (pLD) at the moment of listing. This study was performed from November 13, 2012, to May 31, 2019. A total of 1289 listed patients (830 men; 459 women) were analyzed during the study period. Main Outcomes and Measures: This study performed survival analysis and competing-risk analysis to delineate how access to livers from living donors was associated with events in women vs men on the transplant waiting list (LT, death, or dropout). Results: Of 1289 included patients, 459 (35.6%) were women, and the mean (SD) age was 56.1 (10.0) years at assessment and listing. A total of 783 of 1289 listed patients underwent LT. Among those with no pLD at assessment, there was a higher median (range) Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score at listing (22 [6-50] vs 19 [6-50]; P < .001) and at LT (27 [6-49] vs 20 [6-52]; P < .001) in women receiving DDLT. Women were at a significant disadvantage without a pLD (hazard ratio [HR], 1.29; 95% CI, 1.04-1.60; P = .01); there was no difference in access to LT with availability of a pLD (HR, 0.93; 95% CI, 0.76,-1.14; P = .44). The instantaneous rate of receiving a transplant in men with a pLD was 1.39 times higher than men who did not have a pLD (HR, 1.39; 95% CI; P < .001) and the instantaneous rate of receiving a transplant in women with a pLD was 1.92 times higher than in women who did not (HR, 1.92; 95% CI, 1.51-2.44; P < .001). The HR was 1.38 times higher in women compared with men across the MELD-Na score strata (HR, 1.38; 95% CI, 1.03-1.84; P = .03) and 2.04 times higher when the MELD-Na score was less than 20 (HR, 2.04; 95% CI, 1.31-3.14; P = .001). Conclusions and Relevance: These study findings suggest that women can overcome the complex problem of allocation inequity with access to livers from living donors. Women with access only to DDLT were much more unwell than men independent of liver disease at the time of listing, dropout, or LT. Therefore, the wider availability of living donation liver transplant would be helpful in addressing the sex disparity in access to LT in the current MELD-Na era.

Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA.

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.

Persistent sex disparity in liver transplantation rates.

BACKGROUND: Studies have demonstrated that there are sex disparities in the rate of liver transplantation. However, little is known statistically about whether this disparity is caused by liver compartment size, Model for End-Stage Liver Disease adjustments, or regional differences. METHODS: We use retrospective data from the United Network for Organ Sharing Standard Treatment Analysis and Research data files for liver transplantation from 1995 through 2012. The final sample consists of 150,149 patients. These data contain information on all individuals who registered for the liver transplant waiting list as well as updated outcome data. Linear probability and logistic regression models were both used. RESULTS: Women were 4.8 percentage points less likely to receive a transplant. Adjustment for race, weight, body mass index, region, education, and other characteristics attenuated the sex difference by roughly 19% (from 4.8 to 3.9 percentage points). The disparity was consistent across the 11 United Network for Organ Sharing allocation regions. Comparing the heaviest women to the lightest men, the disparity flipped. Pairwise comparisons between men and women of various sizes suggest that disparities in favor of men increase with the ratio of male-to-female size. CONCLUSION: Our results document persistent sex disparity in liver transplantation, only 19% of which is explained by size differentials between men and women. Differences in rates of transplantation are increasing in the ratio of male-to-female height and weight, suggesting that some of the disparity is explained by differences in liver compartment size.

Analysis of Survival Benefits of Living Versus Deceased Donor Liver Transplant in High Model for End-Stage Liver Disease and Hepatorenal Syndrome.

BACKGROUND AND AIMS: Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End-Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS). APPROACH AND RESULTS: Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention-to-treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT-LDLT, whereas those who had none belonged to ITT-deceased donor liver transplantation (DDLT) group. ITT-overall survival (OS) was analyzed from the time of listing. Three hundred twenty-five patients were listed (ITT-LDLT n = 212, ITT-DDLT n = 113). The risk of delist/death was lower in the ITT-LDLT group (43.4% vs. 19.8%, P < 0.001), whereas the transplant rate was higher in the ITT-LDLT group (78.3% vs. 52.2%, P < 0.001). The 5-year ITT-OS was superior in the ITT-LDLT group (72.6% vs. 49.5%, P < 0.001) for patients with MELD > 25 and patients with both MELD > 25 and HRS (56% vs. 33.8%, P < 0.001). Waitlist mortality was the highest early after listing, and the distinct alteration of slope at survival curve showed that the benefits of ITT-LDLT occurred within the first month after listing. Perioperative outcomes and 5-year patient survival were comparable for patients with MELD > 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD > 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long-term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT-LDLT reduced the hazard of mortality (hazard ratio = 0.387-0.552) across all MELD strata. CONCLUSIONS: The ITT-LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long-term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.

Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis.

BACKGROUND: Hepatic encephalopathy is a devastating complication of cirrhosis. AIM: To describe the outcomes after developing hepatic encephalopathy among contemporary, aging patients. METHODS: We examined data for a 20% random sample of United States Medicare enrolees with cirrhosis and Part D prescription coverage from 2008 to 2014. Among 49 164 persons with hepatic encephalopathy, we evaluated the associations with transplant-free survival using Cox proportional hazard models with time-varying covariates (hazard ratios, HR) and incidence rate ratios (IRR) for healthcare utilisation measured in hospital-days and 30-day readmissions per person-year. We validated our findings in an external cohort of 2184 privately insured patients with complete laboratory values. RESULTS: Hepatic encephalopathy was associated with median survivals of 0.95 and 2.5 years for those ≥65 or <65 years old and 1.1 versus 3.9 years for those with and without ascites. Non-alcoholic fatty-liver disease posed the highest adjusted risk of death among aetiologies, HR 1.07 95% CI (1.02, 1.12). Both gastroenterology consultation and rifaximin utilisation were associated with lower mortality, respective adjusted-HR 0.73 95% CI (0.67, 0.80) and 0.40 95% CI (0.39, 0.42). Thirty-day readmissions were fewer for patients seen by gastroenterologists (0.71 95% CI [0.57-0.88]) and taking rifaximin (0.18 95% CI [0.08-0.40]). Lactulose alone was associated with fewer hospital-days, IRR 0.31 95% CI (0.30-0.32), than rifaximin alone, 0.49 95% CI (0.45-0.53), but the optimal therapy combination was lactulose/rifaximin, IRR 0.28 95% CI (0.27-0.30). These findings were validated in the privately insured cohort adjusting for model for endstage liver disease-sodium score and serum albumin. CONCLUSIONS: Hepatic encephalopathy remains morbid and associated with poor outcomes among contemporary patients. Gastroenterology consultation and combination lactulose-rifaximin are both associated with improved outcomes. These data inform the development of care coordination efforts for subjects with cirrhosis.

A tool to measure the impact of inaction toward elimination of hepatitis C: A case study in Korea.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and its sequelae present a significant source of economic and societal burden. Introduction of highly effective curative therapies has made HCV elimination attainable. The study used a predictive model to assess the clinical and economic impact of implementing national screening and treatment policies toward HCV elimination in Korea. METHODS: A previously validated Markov disease progression model of HCV infection was employed to analyze the clinical and economic impact of various strategies for HCV diagnosis and treatment in Korea. In this analysis, the model compared the clinical and economic outcomes of current HCV-related interventions in Korea (7,000 patients treated and 4,200 patients newly diagnosed annually, starting in 2017) to four elimination scenarios: 1) initiating sufficient diagnosis and treatment interventions to meet the World Health Organization's GHSS elimination targets by 2030, 2) delaying initiation of interventions by one year, 3) delaying initiation of interventions by two years and 4) accelerating initiation of interventions to meet elimination targets by 2025. Modelled historical incidence of HCV was calibrated to match a viremic HCV prevalence of 0.44% in 2009. Elimination scenarios required 24,000 treatments and 34,000 newly diagnosed patients annually, starting in 2018, to reach the 2030 targets. RESULTS: Compared to current "status quo" interventions, elimination (or accelerated elimination by 2025) would avert 23,700 (27,000) incident cases of HCV, 1,300 (1,400) liver-related deaths (LRDs) and 2,900 (3,100) cases of end-stage liver disease (ESLD) over the 2017-2030 time period. Postponing interventions by one (or two) years would avert 21,100 (18,600) new HCV infections, 920 (660) LRDs and 2,000 (1,400) cases of ESLD by 2030. Following elimination or accelerated elimination strategies would save 860 million USD or 1.1 billion USD by 2030, respectively, compared to the status quo, requiring an up-front investment in prevention that decreases spending on liver-related complications and death. CONCLUSIONS: By projecting the impact of interventions and tracking progress toward GHSS elimination targets using modelling, we demonstrate that Korea can prevent significant morbidity, mortality and spending on HCV. Results should serve as the backbone for policy and decision-making, demonstrating how aggressive prevention measures are designed to reduce future costs and increase the health of the public.

Prevalence and Profile of Discarded Liver Donors in a Tertiary Health Service in Brazil From 2015 to 2018.

BACKGROUND: Little has changed in donor management and liver utilization rates in Brazil over the last decade. With a growing demand for liver donations, organ waste is an important obstacle toward better patient care. The study of discarded donors helps to shed light on the possibilities of increasing organ usage, including by using extended criteria donors. METHODS: We retrospectively analyzed all discarded liver donors in a high-volume Brazilian transplant center from January 2015 to December 2018. Pertinent clinical and laboratorial data were collected from the donors' electronic health records. RESULTS: In our study period, there were 248 liver harvests, of which 67 (27.0%) were discarded. Most discarded donors were male (65.7%). More than three-quarters of donors were Caucasian (79.1%). Median donor body mass index was 26.27 kg/m2, and most discarded donors presented no comorbidities. Donor liver injury tests were abnormal in 56 (83.5%) out of 67 discarded donors. Forty-three (64.1%) donors presented elevated transaminases. Alanine aminotransferase levels were elevated in 35 (52.2%) discarded donors, with a median value of 38 U/L. Half of all discarded livers were due to graft-related issues. Twenty-eight organs (41.79%) presented external pathologic alterations. Organ refusal due to donor clinical and laboratorial condition was reported in 24 cases. CONCLUSION: It is clear there is a considerable issue of organ waste in Brazil, with the subjective judgment of graft quality and inadequate interpretation of donor's laboratorial exams leading to excessive denial of organs that could be fitted into extended criteria for donation.

State-Based Liver Distribution: Broad Sharing With Less Harm to Vulnerable and Underserved Communities Compared With Concentric Circles.

Allocation of livers for transplantation faces regulatory pressure to move toward broader sharing. A current proposal supported by the United Network for Organ Sharing Board of Directors relies on concentric circles, but its effect on socioeconomic inequities in access to transplant services is poorly understood. In this article, we offer a proposal that uses the state of donation as a unit of distribution, given that the state is a recognized unit of legal jurisdiction and socioeconomic health in many contexts. The Scientific Registry of Transplant Recipients liver simulated allocation model algorithm was used to generate comparative estimates of regional transplant volume and the impact of these considered changes with regard to vulnerable and high-risk patients on the waiting list and to disparities in wait-list access. State-based liver distribution outperforms the concentric circle models in overall system efficiency, reduced discards, and minimized flights for organs. Furthermore, the efflux of organs from areas of greater sociodemographic vulnerability and lesser wait-list access is more than 2-fold lower in a state-based model than in concentric circle alternatives. In summary, we propose that a state-based system offers a legally defensible, practical, and ethically sound alternative to geometric zones of organ distribution.

Health Care Utilization and Costs for Patients With End-Stage Liver Disease Are Significantly Higher at the End of Life Compared to Those of Other Decedents.

BACKGROUND & AIMS: Patients with end-stage liver disease (ESLD) have progressively complex medical needs. However, little is known about their end-of-life health care utilization or associated costs. We performed a population-based study to evaluate the end-of-life direct utilization and costs for patients with ESLD among health care sectors in the province of Ontario. METHODS: We used linked Ontario health administrative databases to conduct a population-based retrospective cohort study of all decedents from April 1, 2010, through March 31, 2013. Patients with ESLD were compared with patients without ESLD with regard to total health care utilization and costs in the last year and last 90 days of life. RESULTS: The median age at death was significantly lower for ESLD decedents (65 y; interquartile range, 56-75 y) than for individuals without ESLD (80 y; interquartile range, 68-88 y). The median cost in the last year of life was significantly greater for patients with ESLD ($51,235 vs $44,456 without ESLD) (P < .001). Median ESLD end-of-life care costs also significantly exceeded those associated with 4 of the 5 most resource-intensive chronic conditions ($69,040 for ESLD vs $59,088 for non-ESLD) (P < .001). Cost differences were most pronounced in the final 90 days of life. During this period, patients with ESLD spent 4.7 more days in the hospital (95% CI, 4.3-5.1 d) than patients without ESLD (P < .0001), had significantly higher odds of dying in an institutional setting (odds ratio, 1.8; 95% CI, 1.7-1.9) (P < .0001), and incurred an additional $4201 in costs (95% CI, $3384-$5019; P < .0001). CONCLUSIONS: In a population-based study in Canada, we found that patients with ESLD incur significantly higher end-of-life care costs than decedents without ESLD, predominantly owing to increased time in the hospital during the final 90 days of life.

Increasing Health Care Burden of Chronic Liver Disease Compared With Other Chronic Diseases, 2004-2013.

BACKGROUND & AIMS: Chronic liver disease (CLD) is a common and expensive condition, and studies of CLD-related hospitalizations have underestimated the true burden of disease. We analyzed data from a large, diverse health care system to compare time trends in CLD-related hospitalizations with those in congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD). METHODS: We collected data from a large health care system in Texas on hospitalizations related to CLD (n = 27,783), CHF (n = 60,415), and COPD (n = 34,199) from January 1, 2004 through December 31, 2013. We calculated annual hospitalization rates (per 100,000) and compared hospital course, inpatient mortality, ancillary services, and readmissions. RESULTS: Compared with patients with CHF (median age, 71 years) or COPD (median age, 69 years), patients with CLD were significantly younger (median age, 57 years) (P < .01 vs CHF and COPD). Higher proportions of patients with CLD were uninsured (11.7% vs 5.4% for CHF and 5.4% for COPD, P < .01) and Hispanic (17% for CLD vs 9.3% for CHF and 5.0% for COPD, P < .01). A lower proportion of patients with CLD had Medicare (41.5% vs 68.6% with CHF and 70.1% with COPD, P < .01). From 2004 through 2013, the rate of CLD-related hospitalization increased by 92% (from 1295/100,000 to 2490/100,000), compared with 6.7% for CHF (from 3843/100,000 to 4103/100,000) and 48.8% for COPD (from 1775/100,000 to 2642/100,000). During this time period, CLD-related hospitalizations covered by Medicare increased from 31.8% to 41.5%, whereas hospitalizations covered by Medicare did not change for CHF (remained at 70%) or COPD (remained at 70%). Patients with CLD had longer hospital stays (7.3 days vs 6.2 days for CHF and 5.9 days for COPD, P < .01). A higher proportion of patients with CLD died or were discharged to hospice (14.2% vs 11.5% of patients with CHF and 9.3% of patients with COPD, P < .01), and a smaller proportion had access to postacute care (13.2% vs 23.2% of patients with CHF and 27.4% of patients with COPD, P < .01). A higher proportion of patients with CLD were readmitted to the hospital within 30 days (25% vs 21.9% of patients with CHF and 20.6% with COPD, P < .01). CONCLUSIONS: Patients with CLD, compared with selected other chronic diseases, had increasing rates of hospitalization, longer hospital stays, more readmissions, and, despite these adverse outcomes, less access to postacute care. Disease management models for CLD are greatly needed to manage the anticipated increase in hospitalizations for CLD.

Liver transplantation in the Kingdom of Saudi Arabia.

The first liver transplantation (LT) in Saudi Arabia was performed in 1991; however, it was not until 1994 that the first structured LT program was launched. Until 1997, all LTs in the Kingdom of Saudi Arabia (KSA) were deceased donor liver transplantations. Programs performing LTs needed the authorization of the Saudi Center for Organ Transplantation (SCOT), which provides the essential support for organ procurement and allocation as well as regulatory support for organ transplantation in the country. Currently, there are 4 LT centers in the KSA. Three centers are in Riyadh, the capital city of KSA, and 1 is in the city of Dammam in the Eastern province. Pediatric living donor liver transplantation (LDLT) began in 1997, while the adult LDLT program started 4 years later in 2001. Currently, more than 2000 LTs have been performed by the 4 centers in the KSA. Over 50% of those were performed at King Faisal Specialist Hospital and Research Center in Riyadh. The outcomes of these transplants have been comparable with the international standards. The aim of this review is to provide an overview of LT in KSA. Liver Transplantation 23 1312-1317 2017 AASLD.

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

Obese children with fatty liver: Between reality and disease mongering.

Following the current epidemic of obesity, the worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with potential serious health implications. While it is established that in adults NAFLD can progress to end-stage liver disease in many cases, the risk of progression during childhood is less well defined. Since most obese children are not adherent to lifestyle modifications and hypocaloric diets, there is a growing number of studies on pharmacological interventions with the risk of disease mongering, the practice of widening the boundaries of illness in order to expand the markets for treatment. Here, we propose a critical appraisal of the best available evidence about long-term course of pediatric NAFLD and efficacy of treatments other than hypocaloric diet and physical exercise. As a result, the number of NAFLD children with a poor outcome is small in spite of the alarming tones used in some papers; large-scale longitudinal studies with long-term follow-up of pediatric NAFLD patients are lacking; the studies on ancillary pharmacological interventions have been performed in few patients with inconclusive and conflicting results.

Tackling the burden of the hepatitis C virus in the UK: characterizing and assessing the clinical and economic consequences.

OBJECTIVES: The hepatitis C virus (HCV) remains a significant public health issue. This study aimed to quantify the clinical and economic burden of chronic hepatitis C in the UK, stratified by disease severity, age and awareness of infection, with concurrent assessment of the impact of implementing a treatment prioritization approach. STUDY DESIGN AND METHODS: A previously published back projection, natural history and cost-effectiveness HCV model was adapted to a UK setting to estimate the disease burden of chronic hepatitis C and end-stage liver disease (ESLD) between 1980 and 2035. A published meta-regression analysis informed disease progression, and UK-specific data informed other model inputs. RESULTS: At 2015, prevalence of chronic hepatitis C is estimated to be 241,487 with 22.20%, 33.72%, 17.22%, 16.67% and 10.19% of patients in METAVIR stages F0, F1, F2, F3 and F4, respectively, but is estimated to fall to 193,999 by 2035. ESLD incidence is predicted to peak in 2031. Assuming all patients are diagnosed and treatment is prioritized in F3 and F4 using highly efficacious direct-acting antiviral (DAA) regimens, a 69.85% reduction in ESLD incidence is predicted between 2015 and 2035, and the cumulative discounted medical expenditure associated with the lifetime management of incident ESLD events is estimated to be £1,202,827,444. CONCLUSIONS: The prevalence of chronic hepatitis C is expected to fall in coming decades; however, the ongoing financial burden is expected to be high due to an increase in ESLD incidence. This study highlights the significant costs of managing ESLD that are likely to be incurred without the employment of effective treatment approaches.

National Assessment of Hospitalization Rates for Incident End-Stage Renal Disease After Liver Transplantation.

BACKGROUND: We examined the association of incident end-stage renal disease (ESRD) after liver transplantation (LT) and resource utilization using a data linkage between the Scientific Registry of Transplant Recipients and claims data from the Centers for Medicare and Medicaid Services. METHODS: The study cohort consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003, and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7019). The association of ESRD and post-LT hospitalization was assessed by sequential stratification, which entailed prognostic score matching of ESRD-free patients to each LT recipient at ESRD onset. The prognostic score was developed from a model of time to hospitalization and included baseline factors and hospitalization history as predictors. RESULTS: The overall hospitalization rates for LT recipients with and without ESRD were 2.7 and 1.1 per patient-year at risk, respectively. The total number of days hospitalized patient per year was 23 in ESRD and 7 in non-ESRD LT recipients. The adjusted post-LT hospitalization rate was 97% higher after reaching ESRD compared to non-ESRD (hazard ratio, 1.97; P < 0.0001). CONCLUSIONS: Hospitalization rates increased significantly for LT recipients after ESRD onset. Early risk factor modification efforts targeting patients who are at high ESRD risk may reduce post-LT ESRD incidence and hence decrease morbidity and cost among LT recipients.

Liver transplantation in Japan.

As of December 31, 2014, 7937 liver transplants (7673 living donor transplants and 264 deceased donor liver transplantations [DDLTs; 261 from heart-beating donors and 3 from non-heart-beating donors]) have been performed in 67 institutions in Japan. The revised Organ Transplant Law in Japan came into effect in July 2010, which allows organ procurement from brain-dead individuals, including children, with family consent if the patient had not previously refused organ donation. However, the number of deceased donor organ donations has not increased as anticipated. The rate of deceased organ donations per million population (pmp) has remained at less than 1. To maximize the viability of the limited numbers of donated organs, a system has been adopted that includes the partnership of well-trained transplant consultant doctors and local doctors. For compensating for the decreased opportunity of on-site training, an educational system regarding quality organ procurement for transplant surgeons has also been established. Furthermore, experts in the field of liver transplantation are currently discussing adoption of the Model for End-Stage Liver Disease score for allocation, promoting split-liver transplantation, arranging in-house coordinators, and improving the frequency of proposing the option to donate organs to the families. To overcome the shortage of donors during efforts to promote organ donation, living donor liver transplantation (LDLT) has been developed in Japan. Continuous efforts to increase DDLT in addition to the successful experience of LDLT will increase the benefits of liver transplantation for more patients. Liver Transplantation 22 1401-1407 2016 AASLD.

Use of Population-based Data to Demonstrate How Waitlist-based Metrics Overestimate Geographic Disparities in Access to Liver Transplant Care.

Liver allocation policies are evaluated by how they impact waitlisted patients, without considering broader outcomes for all patients with end-stage liver disease (ESLD) not on the waitlist. We conducted a retrospective cohort study using two nationally representative databases: HealthCore (2006-2014) and five-state Medicaid (California, Florida, New York, Ohio and Pennsylvania; 2002-2009). United Network for Organ Sharing (UNOS) linkages enabled ascertainment of waitlist- and transplant-related outcomes. We included patients aged 18-75 with ESLD (decompensated cirrhosis or hepatocellular carcinoma) using validated International Classification of Diseases, Ninth Revision (ICD-9)-based algorithms. Among 16 824 ESLD HealthCore patients, 3-year incidences of waitlisting and transplantation were 15.8% (95% confidence interval [CI] : 15.0-16.6%) and 8.1% (7.5-8.8%), respectively. Among 67 706 ESLD Medicaid patients, 3-year incidences of waitlisting and transplantation were 10.0% (9.7-10.4%) and 6.7% (6.5-7.0%), respectively. In HealthCore, the absolute ranges in states' waitlist mortality and transplant rates were larger than corresponding ranges among all ESLD patients (waitlist mortality: 13.6-38.5%, ESLD 3-year mortality: 48.9-62.0%; waitlist transplant rates: 36.3-72.7%, ESLD transplant rates: 4.8-13.4%). States' waitlist mortality and ESLD population mortality were not positively correlated: ρ = -0.06, p-value = 0.83 (HealthCore); ρ = -0.87, p-value = 0.05 (Medicaid). Waitlist and ESLD transplant rates were weakly positively correlated in Medicaid (ρ = 0.36, p-value = 0.55) but were positively correlated in HealthCore (ρ = 0.73, p-value = 0.001). Compared to population-based metrics, waitlist-based metrics overestimate geographic disparities in access to liver transplantation.