Early Liver Transplantation is a Viable Treatment Option in Severe Acute Alcoholic Hepatitis.

Liver transplantation is lifesaving for patients with severe acute alcoholic hepatitis (SAH) with preliminary data demonstrating favorable early post-transplant outcomes. Using the United Network for Organ Sharing database, we demonstrate that liver transplantation for SAH in the USA has steadily increased and is associated with similar 1- and 3-year post-transplant survival as well as comparable 30-day waitlist mortality to acute liver failure due to drug-induced liver injury.

An early look at the Organ Procurement and Transplantation Network explant pathology form data.

In April 2012, the Organ Procurement and Transplantation Network (OPTN) implemented an online explant pathology form for recipients of liver transplantation who received additional wait-list priority for their diagnosis of hepatocellular carcinoma (HCC). The purpose of the form was to standardize the data being reported to the OPTN, which had been required since 2002 but were submitted to the OPTN in a variety of formats via facsimile. From April 2012 to December 2014, over 4500 explant forms were submitted, allowing for detailed analysis of the characteristics of the explanted livers. Data from the explant pathology forms were used to assess agreement with pretransplant imaging. Explant data were also used to assess the risk of recurrence. Of those with T2 priority, 55.7% were found to be stage T2 on explant. Extrahepatic spread (odds ratio [OR] = 6.8; P < 0.01), poor tumor differentiation (OR = 2.8; P < 0.01), microvascular invasion (OR = 2.6; P < 0.01), macrovascular invasion (OR = 3.2; P < 0.01), and whether the Milan stage based on the number and size of tumors on the explant form was T4 (OR = 2.4; P < 0.01) were the strongest predictors of recurrence. In conclusion, this analysis confirms earlier findings that showed an incomplete agreement between pretransplant imaging and posttransplant pathology in terms of HCC staging, though the number of patients with both no pretransplant treatment and no tumor in the explant was reduced from 20% to <1%. In addition, several factors were identified (eg, tumor burden, age, sex, region, ablative therapy, alpha-fetoprotein, Milan stage, vascular invasion, satellite lesions, etc.) that were predictive of HCC recurrence, allowing for more targeted surveillance of high-risk recipients. Continued evaluation of these data will help shape future guidelines or policy recommendations. Liver Transplantation 22 757-764 2016 AASLD.

The impact of broader regional sharing of livers: 2-year results of "Share 35".

In June of 2013, the Organ Procurement and Transplantation Network (OPTN) implemented regional sharing for Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) candidates with scores reaching 35 and above ("Share 35"). The goal of this distribution change was to increase access to lifesaving transplants for the sickest candidates with chronic liver disease and to reduce the waiting-list mortality for this medically urgent group of patients. To assess the impact of this change, we compared results before and after policy implementation at 2 years. Overall, there were more liver transplants performed under Share 35 and a greater percentage of MELD/PELD 35+ candidates underwent transplantation; waiting-list mortality rates in this group were also significantly lower in the post-policy period. Overall adjusted waiting-list mortality was decreased slightly, with no significant changes in mortality by age group or ethnicity. Posttransplant graft and patient survival was unchanged overall and was unchanged for the MELD/PELD 35+ recipients. In conclusion, these data demonstrate that the Share 35 policy achieved its goal of increasing access to transplants for these medically urgent patients without reducing access to liver transplants for pediatric and minority candidates. Although the variance in the median MELD at transplant as well as the variance in transport distance increased, there was a decrease in overall liver discard rates and no change in overall cold ischemia times following broader sharing of these organs. The OPTN will continue to monitor this policy, particularly for longer-term posttransplant survival outcomes.

Liver transplantation for hepatocellular carcinoma: analysis of factors predicting outcome in 1074 patients in OPTN Region 5.

Previous studies on loco-regional therapy (LRT) and alpha-fetoprotein (AFP) in predicting outcome after liver transplant (LT) for hepatocellular carcinoma (HCC) have shown inconsistent results. We analyzed the OPTN database in Region 5 from January 2004 to January 2009 and performed univariate and multivariate analysis of 11 pre-transplant recipient and donor variables in 1074 patients with HCC meeting Milan criteria to detect association with post-LT tumor recurrence or mortality. Mean waitlist time was 438 d. The 1- and 5-yr post-LT survival was 91.1% and 71.1%, respectively. In multivariate analysis, AFP before LT was the only predictor of HCC recurrence. The association between AFP and HCC recurrence was observed only in the subgroup receiving LRT but not in the subgroup without LRT. Predictors of mortality in multivariate analysis were HCC recurrence, Donor Risk Index, last AFP before LT, and MELD score. AFP before LT was the strongest predictor of post-transplant HCC recurrence or death in multivariate analysis. In conclusion, in Region 5 with prolonged waitlist time, high AFP was the only pre-transplant variable predicting post-transplant tumor recurrence and mortality for HCC meeting Milan criteria. Our results also supported the importance of the effects of LRT on AFP in predicting prognosis.

Region 11 MELD Na exception prospective study.

INTRODUCTION: Hyponatremia complicates cirrhosis and predicts short term mortality, including adverse outcomes before and after liver transplantation. MATERIAL AND METHODS: From April 1, 2008, through April 2, 2010, all adult candidates for primary liver transplantation with cirrhosis, listed in Region 11 with hyponatremia, were eligible for sodium (Na) exception. RESULTS: Patients with serum sodium (SNa) less than 130 mg/dL, measured two weeks apart and within 30 days of Model for End Stage Liver Disease (MELD) exception request, were given preapproved Na exception. MELD Na was calculated [MELD + 1.59 (135-SNa/30 days)]. MELD Na was capped at 22, and subject to standard adult recertification schedule. On data end of follow-up, December 28, 2010, 15,285 potential U.S. liver recipients met the inclusion criteria of true MELD between 6 and 22. In Region 11, 1,198 of total eligible liver recipients were listed. Sixty-two (5.2%) patients were eligible for Na exception (MELD Na); 823 patients (68.7%) were listed with standard MELD (SMELD); and 313 patients (26.1%) received HCC MELD exception. Ninety percent of MELD Na patients and 97% of HCC MELD patients were transplanted at end of follow up, compared to 49% of Region 11 standard MELD and 40% of U.S.A. standard MELD (USA MELD) patients (p < 0.001); with comparable dropout rates (6.5, 1.6, 6.9, 9% respectively; p = 0.2). MELD Na, HCC MELD, Region 11 SMELD, and USA MELD post-transplant six-month actual patient survivals were similar (92.9, 92.8, 92.2, and 93.9 %, respectively). CONCLUSION: The Region 11 MELD Na exception prospective trial improved hyponatremic cirrhotic patient access to transplant equitably, and without compromising transplant efficacy.

Hepatic artery thrombosis after adult living donor liver transplantation: the effect of center volume.

BACKGROUND: To investigate whether center volume impacts the rate hepatic artery thrombosis (HAT) and patient survival after adult living donor liver transplantation (ALDLT). METHODS: Patients with HAT who were listed as Status 1 in the Organ Procurement Transplant Network database were included in the study. Recipients of ALDLT were compared to those who received a deceased donor liver transplant (DDLT). RESULTS: Recipients of ALDLT had a higher rate of HAT than recipients of DDLT. Centers that performed less than four adult ALDLT had a higher rate of HAT than other higher volume centers. "Novice" centers had a worse graft and patient survival than those with more experience in ALDLT. Recipients who had HAT experienced a worse patient survival than those who did not. CONCLUSIONS: Centers with higher volume have a lower rate of HAT and a better patient and graft survival in ALDLT. Clearer regulations and focus on overcoming the learning curve might be needed to increase the utilization of ALDLT.

Use of a pediatric end-stage liver disease score for deceased donor allocation: the United States experience.

The Pediatric end-stage liver disease (PELD) score was developed as a measure of the severity of chronic liver disease that would predict mortality or children awaiting liver transplant. From multivariate analyses a model was derived that included five objective factors which together comprise the PELD score. The factors are growth failure, age less than 1 year, international normalized ratio (INR), serum albumin and total bilirubin.

Liver transplantation for status 1: the consequences of good intentions.

Status 1 is the listing category reserved for patients awaiting liver transplantation who are at risk of imminent death. This high allocation priority was intended to benefit patients with acute liver failure and children with severe chronic liver failure. However, the status 1 criteria were not well defined. The aims of this study, which used the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database for patients wait-listed between February 27, 2002, and September 30, 2003, were to determine the indication and numbers of children and adults at status 1 (including regional variations); examine death rates on the waiting list for children at vs. not at status 1; and examine time to death, transplant, or removal from the waiting list for both pediatric and adult status 1 candidates. During the study period, 40.3% of children and 6.1% of adults were transplanted at status 1. The indication was acute liver failure in 52.1% of adults and 31% of children. Among status 1 transplants, Regional Review Board exceptions were granted for 16.7% of children and 10.1% of adults. Death rates for children listed at status 1 by exception per patient-year at risk were substantially lower (0.51) than those of children with acute liver failure (4.06) or with chronic liver disease and Pediatric End-Stage Liver Disease score > or =25 (4.63). The percentage of adults who died while on the waiting list within 90 days of listing was more than twice that of children, whereas the percentages transplanted were similar. Patients listed and transplanted at status 1 were a heterogeneous population with an overrepresentation of children with varying degrees of chronic liver disease and other exceptions, and an associated wide variation in waiting list mortality. Recent changes in status 1 criteria provide stricter definitions, particularly for children, including the removal of the "by exception" category, with the intent that all candidates listed at status 1 share a similar mortality risk.

Selection of pediatric candidates under the PELD system.

1. The PELD score accurately predicts the 3 month probability of waiting list death for children with chronic liver disease. 2. Comparing pre and post PELD and MELD implementation, the percent of children receiving deceased donor livers increased and the percent of children dying on the list decreased after PELD/MELD implementation. 3. Excluding children transplanted at status 1, the largest percentage of children are transplanted at a PELD score < 10. 4. Before MELD/PELD 48% of all children receiving deceased donor organs were transplanted at status 1, compared to 41% in the PELD/MELD era. Wide regional variation occurs.

MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients.

The Model for End-Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan-Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF-NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P =.0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P <.0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P =.41) and did not show a significant association between survival and OLT (P =.68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF-NA candidates.

Liver transplantation for hepatocellular carcinoma: the MELD impact.

The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for end-stage liver disease (MELD) gives candidates with stage T1 or stage T2 hepatocellular carcinoma (HCC) a priority MELD score beyond their degree of hepatic decompensation. The aim of this study was to determine the impact of the new allocation policy on HCC candidates before and after the institution of MELD. The UNOS database was reviewed for all HCC candidates listed between July 1999 and July 2002. The candidates were grouped by two time periods, based on the date of implementation of new allocation policy of February 27, 2002. Pre-MELD candidates were listed for deceased donor liver transplantation (DDLT) before February 27,2002, and post-MELD candidates were listed after February 27, 2002. Candidates were compared by incidence of DDLT, time to DDLT, and dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting and after DDLT. Incidence rates calculated for pre-MELD and post-MELD periods were expressed in person years. During the study, 2,074 HCC candidates were listed for DDLT in the UNOS database. The DDLT incidence rate was 0.439 transplant/person years pre-MELD and 1.454 transplant/person years post-MELD (P < 0.001). The time to DDLT was 2.28 years pre-MELD and 0.69 years post-MELD (P < 0.001). The 5-month dropout rate was 16.5% pre-MELD and 8.5% post-MELD (P < 0.001). The 5-month waiting-list survival was 90.3% pre-MELD and 95.7% post-MELD (P < 0.001). The 5-month survival after DDLT was similar for both time periods. The new allocation policy has led to an increased incidence rate of DDLT in HCC candidates. Furthermore, the 5-month dropout rate has decreased significantly. In addition, 5-month survival while waiting has increased in the post-MELD period. Thus, the new MELD-based allocation policy has benefited HCC candidates.

The OPTN waiting list, 1988-2002.

1. Additions to the OPTN waiting list decreased in 2002 for all organs except kidney and pancreas islets. 2. On November 30, 2003, there were 89,361 registrations on the combined UNOS waiting list. Of these, 67% were awaiting kidney transplantation, and 20% were awaiting liver transplantation. 3. The majority of patients on the UNOS waiting list on October 31, 2000 were of blood type O (52%), White (51%) and male (57%), and awaiting their first transplant (87%). 4. Despite lengthy waiting times, the percentage transplanted within one year following listing has increased over the past 2 years for all organs except kidney. A tremendous increase in the percentage of liver candidates transplanted within one year was observed in 2002. 5. Blood type and medical urgency have a significant impact upon the percent transplanted within one year of listing for most organ types. Patients awaiting heart, liver, pancreas, and intestinal transplants experience the highest probability of receiving a transplant within one year. 6. Death rates per patients waiting at risk have declined since 1988 for most patients awaiting life-saving organs and have remained relatively low for those awaiting a kidney, pancreas, or kidney-pancreas transplant.

Redrawing organ distribution boundaries: results of a computer-simulated analysis for liver transplantation.

For several years, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) Liver and Intestinal Transplantation Committee has been examining effects of changes and proposed changes to the liver allocation system. The Institute of Medicine recently recommended that the size of liver distribution units be increased to improve the organ distribution system. Methods to achieve this and the potential impact on patients and transplant centers of such a change are evaluated in this study. In hypothetical scenarios, we combined geographically contiguous organ procurement organizations (OPOs) in seven different configurations to increase the size of liver distribution units to cover populations greater than 9 million persons. Using the UNOS Liver Allocation Model (ULAM), we examined the effect of 17 different organ allocation sequences in these proposed realignments and compared them with those predicted by ULAM for the current liver distribution system by using the following primary outcome variables: number of primary liver transplantations performed, total number of deaths, and total number of life-years saved. Every proposed new liver distribution unit plan resulted in fewer primary transplantations. Many policies increased the total number of deaths and reduced total life-years saved compared with the current system. Most of the proposed plans reduced interregional variation compared with the current plan, but no one plan consistently reduced variation for all outcome variables, and all reductions in variations were relatively small. All new liver distribution unit plans led to significant shifts in the number of transplantations performed in individual OPOs compared with the current system. The ULAM predicts that changing liver distribution units to larger geographic areas has little positive impact on overall results of liver transplantation in the United States compared with the current plan. Enlarging liver distribution units likely will result in significant shifts in organs across current OPO boundaries, which will have a significant impact on the activity of many transplant centers.

The impact of MELD on OPTN liver allocation: preliminary results.

The OPTN implemented a revised system (MELD/ PELD) for the allocation of cadaveric livers on February 27, 2002. When compared with an earlier era, preliminary results indicate that transplant rates remain similar by gender, ethnicity, age group (adult and pediatric) and for most principal diagnoses. Both the actual number of pretransplant deaths and the pretransplant death rate has dropped under the new system. While some regional variation exists in the average MELD scores at listing, death and transplant, it accounts for only a small percentage of the total variation observed. In a multivariate analysis, MELD scores above 20 had the strongest effect and were associated with a significantly increased mortality risk on the waiting list. More data are need to analyze the impact of MELD on posttransplant outcomes.

The OPTN waiting list, 1988-2001.

1. On November 30, 2002, there were 86,452 registrations on the combined UNOS waiting list. Of these, 65% were awaiting kidney transplantation and 20% were awaiting liver transplantation. 2. The majority of patients on the UNOS waiting list on October 31, 2000 were blood type O (52%), White (53%) and male (58%), and awaiting their first transplant (87%). 3. Despite a decreasing trend in the percentage transplanted within one year of listing over the past several years, the percentage transplanted increased in 2001 for all organs except kidney and pancreas. 4. Blood type and medical urgency have a significant impact upon the percent transplanted within one year of listing for most organ types. Patients awaiting heart, pancreas, and intestinal transplants experience the highest probability of receiving a transplant within one year. 5. Death rates per patients waiting at risk have declined since 1988 for most patients awaiting life-saving organs and have remained relatively low for those awaiting a kidney, pancreas, or kidney-pancreas transplant.