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.

Changes in liver acceptance patterns after implementation of Share 35.

The Share 35 policy was implemented June 2013. We sought to evaluate liver offer acceptance patterns of centers under this policy. We compared three 1-year eras (1, 2, and 3) before and 1 era (4) after the implementation date of the Share 35 policy (June 18, 2013). We evaluated all offers for liver-only recipients including only those offers for livers that were ultimately transplanted. Logistic regression was used to develop a liver acceptance model. In era 3, there were 4809 offers for Model for End-Stage Liver Disease (MELD) score ≥ 35 patients with 1071 acceptances (22.3%) and 10,141 offers and 1652 acceptances (16.3%) in era 4 (P < 0.001). In era 3, there were 42,954 offers for MELD score < 35 patients with 4181 acceptances (9.7%) and 44,137 offers and 3882 acceptances (8.8%) in era 4 (P < 0.001). The lower acceptance rate persisted across all United Network for Organ Sharing regions and was significantly less in regions 2, 3, 4, 5, and 7. Mean donor risk index was the same (1.3) for all eras for MELD scores ≥ 35 acceptances and the same (1.4) for MELD score < 35 acceptances. Refusal reasons did not vary throughout the eras. The adjusted odds ratio of accepting a liver for a MELD score of 35 + compared to a MELD score < 35 patient was 1.289 before the policy and 0.960 after policy implementation. In conclusion, the Share 35 policy has resulted in more offers to patients with MELD scores ≥ 35. Overall acceptance rates were significantly less compared to the same patient group before the policy implementation. Centers are less likely to accept a liver for a patient with a MELD score of 35 + after the policy change. Decreased donor acceptance rates could reflect more programmatic selectivity and ongoing donor and recipient matching.

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.

Delayed hepatocellular carcinoma model for end-stage liver disease exception score improves disparity in access to liver transplant in the United States.

UNLABELLED: The current system granting liver transplant candidates with hepatocellular carcinoma (HCC) additional Model for End-Stage Liver Disease (MELD) points is controversial due to geographic disparity and uncertainty regarding optimal prioritization of candidates. The current national policy assigns a MELD exception score of 22 immediately upon listing of eligible patients with HCC. The aim of this study was to evaluate the potential effects of delays in granting these exception points on transplant rates for HCC and non-HCC patients. We used Scientific Registry of Transplant Recipients data and liver simulated allocation modeling software and modeled (1) a 3-month delay before granting a MELD exception score of 25, (2) a 6-month delay before granting a score of 28, and (3) a 9-month delay before granting a score of 29. Of all candidates waitlisted between January 1 and December 31, 2010 (n = 28,053), 2773 (9.9%) had an HCC MELD exception. For HCC candidates, transplant rates would be 108.7, 65.0, 44.2, and 33.6 per 100 person-years for the current policy and for 3-, 6-, and 9-month delays, respectively. Corresponding rates would be 30.1, 32.5, 33.9, and 34.8 for non-HCC candidates. CONCLUSION: A delay of 6-9 months would eliminate the geographic variability in the discrepancy between HCC and non-HCC transplant rates under current policy and may allow for more equal access to transplant for all candidates.

Reducing morbidity and mortality among pregnant obese.

Obesity is increasing; in the UK, almost 20% of pregnant women have a body mass index (BMI) of ≥30 kg/m(2). Obese mothers have increased risks of pregnancy complications including miscarriage, congenital anomaly, gestational diabetes, pre-eclampsia, macrosomia, induction of labour, caesarean section, anaesthetic and surgical complications, post-partum haemorrhage, infection and venous thromboembolism. Complications tend to be greater in those with the highest BMIs. In recent triennia, obesity (27-29%) was over-represented in maternal mortality figures. Strategies to reduce morbidity and mortality include calculating BMI at booking visit to identify obese mothers and plan their antenatal care and delivery. This should include nutritional and lifestyle advice, screening for gestational diabetes and pre-eclampsia, thromboembolism risk assessment, antenatal anaesthetic review if BMI is ≥ 40 kg/m(2), ensuring availability of robust theatre tables and other equipment and involving senior doctors, especially in the labour ward. Afterwards, continuing weight reduction should be encouraged to reduce future pregnancy and health risks.

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.

Saving Mothers' Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.

In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006­2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States.

A national conference was held to better characterize the long-term outcomes of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) and to assess whether it is justified to continue the policy of assigning increased priority for candidates with early-stage HCC on the transplant waiting list in the United States. The objectives of the conference were to address specific HCC issues as they relate to liver allocation, develop a standardized pathology report form for the assessment of the explanted liver, develop more specific imaging criteria for HCC designed to qualify LT candidates for automatic Model for End-Stage Liver Disease (MELD) exception points without the need for biopsy, and develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions. At the completion of the meeting, there was agreement that the allocation policy should result in similar risks of removal from the waiting list and similar transplant rates for HCC and non-HCC candidates. In addition, the allocation policy should select HCC candidates so that there are similar posttransplant outcomes for HCC and non-HCC recipients. There was a general consensus for the development of a calculated continuous HCC priority score for ranking HCC candidates on the list that would incorporate the calculated MELD score, alpha-fetoprotein, tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors would receive additional HCC priority points.

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.

Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database.

Assignment of liver allocation priority for hepatocellular carcinoma is predicated on accurate imaging staging. We analyzed radiographically defined stage (radiologic stage [RS]) at listing and most recent extension and pathologic stage (PS) data from 789 liver transplant recipients for whom no pretransplant ablative treatment was given. There were no predetermined imaging or pathological protocols in this retrospective analysis of wait list data. Seventy-two (9.1%), 690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively. Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used with no difference in time to transplant for listing or most recent scan among the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different if original listing RS or most recent RS was used for comparison with PS. No one type of imaging technique had superior accuracy (P = 0.13); however, CT scan used alone or in combination compared to not being used at all, had higher odds of being accurate (odds ratio [OR] 1.38 [1.03-1.84], P = 0.031). In addition, imaging done less than 90 days before transplant had higher odds of being accurate (OR 1.49 [1.06-2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70-11.11], P < 0.0001). We observed considerable variation in RS accuracy among the United Network for Organ Sharing and Organ Procurement and Transplantation Network regions that is unexplained. In conclusion, current imaging requirements for RS prior to liver transplantation are unacceptably inaccurate. Future policy should require more accurate modalities or combinations of techniques.

Regional sharing for adult status 1 candidates: reduction in waitlist mortality.

The intent of regional sharing for status 1 candidates is to promote timely access to donor livers. Presumably this decreases waitlist mortality. Little published data exists that supports this policy. Organ Procurement and Transplantation Network data was used to calculate region 4 and national adult waitlist death and transplant rates 4 yr prior to (period A) and after (period B) implementation of the sharing agreement in July 1999. Death and transplant rates were calculated using a competing risk analysis. Regional sharing resulted in a reduction in adult status 1 waitlist death rate and an increase in transplant rate for region 4 candidates at 7 and 14 days (P > 0.05) without a change in the death rate at 90 days for the non-status 1 candidates. National data showed a significant increase in transplant rate at 7 days and reduction in waitlist death rate at 14 days after listing (P < 0.05). Status 1 waiting time was decreased from 10 to 3 days (P < 0.05). Adult patient survival was not significantly different between the periods. In conclusion, regional sharing for status 1 candidates results in an increased transplant rate and a reduction in waitlist mortality. Sharing did not impact waitlist mortality for non-status 1 candidates.

Introducing 'Palcall': an innovative out-of-hours telephone service led by hospice nurses.

Palcall is an out-of-hours telephone service providing support and advice to palliative care patients, their carers and health professionals. Each patient who is registered with the scheme consents to named friends or relatives having access to the dedicated Palcall number. Telephone calls to the service are taken by the most senior palliative care nurse on duty in the hospice. The nurse has ready access to details of the medical condition and current medications of every patient who is registered. If required, the nurse can contact a more senior nursing colleague or the on-call hospice GP. The day following the telephone call, the Palcall administrator forwards written details to the patient's GP and any healthcare professional involved in the care of the patient. Quality control measures are in place to continually enhance the service.

Does MELD work for relisted candidates?

1. Based on OPTN data, the ability of the model for end-stage liver disease (MELD) to predict short-term pretransplant and posttransplant outcomes was assessed. 2. Concordance with pretransplant mortality was excellent. 3. Concordance with pretransplant mortality was better for candidates listed for a primary transplant. 4. Of the MELD components, there were no statistically significant differences in the effects on pretransplant mortality between candidates listed for a primary or a repeat transplant. 5. Concordance with posttranplant outcomes was poor.

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.