Same policy, different impact: Center-level effects of share 35 liver allocation.

Early studies of national data suggest that the Share 35 allocation policy increased liver transplants without compromising posttransplant outcomes. Changes in center-specific volumes and practice patterns in response to the national policy change are not well characterized. Understanding center-level responses to Share 35 is crucial for optimizing the policy and constructing effective future policy revisions. Data from the United Network for Organ Sharing were analyzed to compare center-level volumes of allocation-Model for End-Stage Liver Disease (aMELD) ≥ 35 transplants before and after policy implementation. There was significant center-level variation in the number and proportion of aMELD ≥ 35 transplants performed from the pre- to post-Share 35 period; 8 centers accounted for 33.7% of the total national increase in aMELD ≥ 35 transplants performed in the 2.5-year post-Share 35 period, whereas 25 centers accounted for 65.0% of the national increase. This trend correlated with increased listing at these centers of patients with Model for End-Stage Liver Disease (MELD) ≥ 35 at the time of initial listing. These centers did not overrepresent the total national volume of liver transplants. Comparison of post-Share 35 aMELD to calculated time-of-transplant (TOT) laboratory MELD scores showed that only 69.6% of patients transplanted with aMELD ≥ 35 maintained a calculated laboratory MELD ≥ 35 at the TOT. In conclusion, Share 35 increased transplantation of aMELD ≥ 35 recipients on a national level, but the policy asymmetrically impacted practice patterns and volumes of a subset of centers. Longer-term data are necessary to assess outcomes at centers with markedly increased volumes of high-MELD transplants after Share 35. Liver Transplantation 23 741-750 2017 AASLD.

Liver transplantation in Germany.

Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

Subjective parameters markedly limit the referral of transplantation candidates to liver transplant centres.

BACKGROUND & AIMS: Equality of access to organ transplantation is a mandatory public health requirement. Referral from a local to a university hospital and then registration on the national waiting list are the two key steps enabling access to liver transplantation (LT). Although the latter procedure is well defined using the Model for End-stage Liver Disease score that improves equality of access, the former is mostly reliant on the practices of referring physicians. The aim of this study was to clarify the factors determining this initial step. METHODS: This observational study included consecutive inpatients with cirrhosis of whatever origin in a cohort constituted between 2003 and 2008, using medical records and structured questionnaires concerning patient characteristics and the opinions of hospital clinicians. Candidates for LT were defined in line with these opinions. RESULTS: Four hundred and thirty-three patients, mostly affected by alcoholic cirrhosis, were included, 21.0% of whom were considered to be candidates for LT. Factors independently associated with their candidature were: physician empathy [odds ratio (OR) = 10.8; 95% CI: 4.0-29.5], adherence to treatment (OR = 16.6; 95% CI: 3.7-75.2), geographical area (OR = 6.8; 95% CI: 2.2-21.3) and the patient's physiological age (OR = 2.3; 95% CI: 1.1-4.7). CONCLUSIONS: Several subjective markers restrict the referral of patients from local hospitals to liver transplant centres. Their advancement to this second step is thus markedly weakened by initial subjectivity. The development of objective guidelines for local hospital physicians to assist them with their initial decision-making on LT is now necessary.

Risk for relapse of alcohol use after liver transplantation for alcoholic liver disease: a review and proposal of a set of risk assessment criteria.

BACKGROUND: Liver transplantation for end stage alcoholic liver disease is becoming an increasingly frequent procedure. Within this context assessing the risk on relapse in alcohol use is a major issue. However, up to now, there is a clear lack in validated criteria that can be used to assess future relapse risk. METHOD: Literature review based upon Medline search identifying all new studies that have been published after the latest meta-analysis on this subject (2007-2009). RESULTS: Five new original studies were identified. They provide new evidence for the prospective validity of different criteria; pretransplant abstinence duration, diagnosis of alcohol dependence versus abuse, level of social support, additional psychiatric co morbidity. CONCLUSIONS: These criteria seem promising as to the prediction of relapse in alcohol after livertransplantation. Based upon these results a new comprehensive assessment scale is proposed.

Chances and limitations of non-invasive tests in the assessment of liver fibrosis in liver transplant patients.

Because fibrosis progression resulting in liver cirrhosis represents the main reason for graft lost in patients after liver transplantation, an early detection of liver fibrosis is crucial. In recent years, several non-invasive tests for the assessment of liver fibrosis have been developed. We prospectively assessed the stage of liver fibrosis of 135 liver transplant patients (94 hepatitis C virus [HCV], 41 alcoholic cirrhosis) using liver biopsy, transient elastography, and serum markers. In the HCV group, the area under the receiver operating characteristic curve (AUROC) for diagnosis of significant fibrosis (F ≥ 2) and cirrhosis (F = 4) was 0.81 (negative predictive value [NPV] = 0.58, positive predictive value [PPV] = 0.9) and 0.87 (NPV = 0.94, PPV = 0.56), respectively. In the alcoholic cirrhosis group, significant fibrosis (F ≥ 2) was diagnosed with an AUROC of 0.83 (NPV = 1.00, PPV = 0.23). In both groups, higher AUROC values were reached in patients with a body mass index of <25 kg/m(2) , and both serum markers showed no significant correlation to liver fibrosis. The transient elastography is a reliable test for exclusion of liver cirrhosis in HCV transplant and significant liver fibrosis in alcoholic transplant patients. For the diagnosis of significant liver fibrosis in HCV transplant patients, the transient elastography reaches good results but cannot replace liver biopsy. Both serum markers AST-to-platelet ratio index and FIB-4 are not feasible to assess liver fibrosis in liver transplant patients.

Liver transplantation: from Child to MELD.

The widespread availability of transplantation in most major medical centers in the United States, together with a growing number of transplant candidates, has made it necessary for primary care providers, especially internal medicine and family practice physicians to be active in the clinical care of these patients before and after transplantation. This review provides an overview of the liver transplantation process, including indications, contraindications, time of referral to a transplant center, the current organ allocation system, and briefly touches on the expanding field of living donor liver transplantation.

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list.

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.

Determining priority for liver transplantation: a comparison of cost per QALY and discrete choice experiment-generated public preferences.

OBJECTIVE: A comparison of the implications of the application of the principles of equity and efficiency as two desirable but competing attributes of the organ allocation system. Efficiency is defined in economic terms as the standard cost per QALY model and equity considerations are included in a model based on public preferences generated from a discrete choice experiment in determining priority for donor liver graft allocation. METHODS: A survey of the general public (n = 303) using a discrete choice experiment was undertaken. The results enabled estimation of the relative weights attached to several key factors which might be used to prioritise patients on the waiting list for liver transplantation. These weights were then used to develop a patient-specific index (PSI) for all patients diagnosed with one of three main chronic liver diseases who had received a liver transplant during an 18-month period at all Department of Health designated liver transplant centres in England and Wales (n = 207). The cost per QALY model comprised net total costs from assessment to 27 months following assessment as the numerator of the ratio. Net survival over the same time period, adjusted for HR-QOL using population values for the EQ-5D descriptive system, formed the denominator. RESULTS: Priority for liver transplantation differed markedly according to whether patients were ranked according to efficiency (net cost per QALY) or equity considerations (PSI) and the differences in ranks were found to be statistically significant (Wilcoxon signed rank test p < 0.001). CONCLUSIONS: This study emphasises that the priorities of the general public may not accord with those arising from a pure efficiency objective and quantifies the extent of the efficiency loss in terms of lost QALYs and increased net programme costs associated with the incorporation of equity concerns as reflected in public preferences for the allocation of donor livers for transplantation.

[Liver transplantation in Germany]. / Lebertransplantation in Deutschland.

As in other western countries the major challenge of liver transplantation in Germany is to expand the number of liver transplantations in respect to the increasing disparity of qualified patients on the waiting list and the still static availability of brain death donor organs. The problem of death on the waiting list has become overt since the German transplantation law has been installed, which has changed the former center-oriented to a patient-oriented allocation weighting waiting time over medical urgency criteria. The more liberal acceptance of so called marginal cadaveric donor livers will probably impair further improvements in the acute and long-term outcome of liver transplantation. This problem can be partially compensated by the use of novel surgical techniques, such as splitting a donor liver to be transplanted into two adult recipients or, more commonly and safe, into an adult and one child. Another alternative to increase the donor pool is living donor liver transplantation, which was first introduced for pediatric recipients but is now increasingly used in adults. In 2001, a constant number of 757 liver transplantations were performed in Germany, including 12.5 % living donor transplantations. Recently, general guidelines for the selection of patients with end-stage liver disease and acute liver failure have been published by the Bundesärztekammer. Additional developments have contributed to improve the results of liver replacement including individualized immunosuppression strategies and novel treatment options to avoid recurrent viral disease following transplantation.

Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: In patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), prognostic scores may identify those with a poor prognosis or even those with a clear survival benefit. The Child-Pugh score (CPS) is well established but several drawbacks have led to development of the model of end stage liver disease (MELD). AIM: The aim of the study was to compare the predictive power of CPS and MELD, to validate the original MELD formula, and to assess the predictive value of the determinants used in the two prognostic scores outside of a study setting. PATIENTS: A total of 501 patients underwent elective TIPS placement and 475 patients fulfilled the inclusion criteria. METHODS: Data of all patients undergoing elective TIPS in one university hospital and four community hospitals in Vienna, Austria, between 1991 and 2001, were analysed retrospectively. The main statistical tests were Cox proportional hazards regression model, the log rank test, Kaplan-Meier analysis, and concordance c statistics. RESULTS: Median follow up was 5.2 years and median survival was 4.6 years. During follow up, 230 patients died, 75 within three months after TIPS placement. In stepwise proportional hazards analyses, independent predictors of death were creatinine level, bilirubin level, age, and refractory ascites. MELD was better in predicting survival in a stepwise Cox model but both scores were equally predictive in c statistics for one month, three month, and one year survival. Renal function was the strongest independent predictor of survival. CONCLUSIONS: Although MELD was the primary predictor of overall survival in multivariate analysis, c statistics showed that both scores can be used for patients undergoing TIPS with equal accuracy. For assessing prognosis in patients undergoing TIPS implantation, there seems little reason to replace the well established Child-Pugh score.

Allocation of transplantable organs: do people want to punish patients for causing their illness?

Some people believe patients with alcoholic cirrhosis should not receive equal priority for scarce transplantable organs. This may reflect a belief that these patients (1) are personally responsible for causing their own illnesses, (2) have poor transplant prognoses, or (3) are unworthy because they have engaged in socially undesirable behavior. We explore the roles that social desirability and personal responsibility have in people's judgments about transplant allocation. We presented prospective jurors with 4 scenarios, asking them to distribute 100 transplantable organs among 2 groups of 100 patients each. In each scenario, 1 group of patients, but not the other, was described as having a history of unhealthy behavior (alcohol or cigarette use) associated with a poorer prognosis. In some scenarios, alcohol or cigarette use was said to cause the organ failure. In others, it only contributed to the patients' transplant prognosis. We also obtained self-reports of subjects' own smoking status. Subjects allocated significantly fewer than half the organs to those with unhealthy behaviors and worse prognoses (33%; P <.001), but the specific behavior (alcohol versus cigarette use) was not significantly associated with subjects' allocation choices. Significantly fewer organs were allocated to patients with behavior responsible for causing their diseases than to other patients (P <.0001). Subjects who never smoked discriminated the most and current smokers discriminated the least against patients with a history of unhealthy behavior (P <.0001). The public's transplantation allocation preferences are influenced by whether patients' behaviors are said to have caused their organ failure.

Indications for liver transplantation in British Columbia's Aboriginal population: a 10-year retrospective analysis.

OBJECTIVES: To study the indications for liver transplantation among British Columbia's First Nation population. MATERIALS AND METHODS: A retrospective analysis of the British Columbia Transplant Society's database of Aboriginal and non-Aboriginal liver transplant recipients from 1989 to 1998 was undertaken. For primary biliary cirrhosis (PBC), the transplant assessment database (patients with and without transplants) was analyzed using a binomial distribution and compared with published census data regarding British Columbia's proportion of Aboriginal people. RESULTS: Between 1989 and 1998, 203 transplantations were performed in 189 recipients. Fifteen recipients were Aboriginal (n=15; 7.9%). Among all recipients, the four most frequent indications for liver transplantation were hepatitis C virus (HCV) infection (n=57; 30.2%), PBC (n=34; 18.0%), alcohol (n=22; 11.6%) and autoimmune hepatitis (n=14; 7.4%). Indications for liver transplantation among Aboriginal people were PBC (n=8; 53.3%; P<0.001 compared with non-Aboriginal people), autoimmune hepatitis (n=4; 26.67%; P=0.017), acute failure (n=2; 13.3%) and HCV (n=1). Among all patients referred for liver transplantation with PBC (n=43), 29 (67.44%) were white and 11 (25.6%) were Aboriginal. A significant difference was found between the proportion of Aboriginal people referred for liver transplantation and the proportion of Aboriginal people in British Columbia (139,655 of 3,698,755 [3.8%]; 1996 Census, Statistics Canada) (P<0.001). CONCLUSIONS: Aboriginal people in British Columbia are more likely to be referred for liver transplantation with a diagnosis of PBC but are less likely to receive a liver transplant because of HCV or alcohol than are non-Aboriginal people.

Doppler ultrasound assessment of TIPS patency and function--the need for echo enhancers.

PURPOSE: The aim of this study was to illustrate the versatility of an i.v. administered echo enhancer for Doppler US assessment of TIPS patency and function. MATERIAL AND METHODS: A total of 22 Doppler US evaluations of TIPS patency and function were performed in 5 patients with alcoholic cirrhosis and recurrent oesophageal bleeding who had been treated with TIPS. TIPS patency was evaluated by means of colour or power Doppler US. The volume flow (VF) was assessed in the TIPS and in the portal vein by spectral Doppler. The ratio of the VF in the TIPS to the VF in the portal vein (T/P ratio) was used to express the functional status of the TIPS. If Doppler signals were inconclusive or absent, echo-enhanced US was performed. RESULTS: In 22 follow-up Doppler US examinations, echo-enhanced Doppler US was required in 7 cases (29%). The Doppler enhancement persisted in the range of 3-5 min. No adverse effects were observed. An apparently normal TIPS function reflected a T/P ratio in the range of 0.44-1.10, median 0.78 +/- 0.20 (2SD). CONCLUSION: The i.v. administration of echo enhancers would seem to be indicated in the assessment of the TIPS function if conventional Doppler US fails to prove normal TIPS patency and function. The T/P ratio may be a convenient monitoring parameter for reflecting the TIPS function.

Peritoneovenous shunts in patients with intractable ascites: palliation at what price?

Intractable ascites carries great morbidity by affecting appetite, mobility, and quality of life. Peritoneovenous shunts (PVSs) are utilized to abate intractable ascites, although long-term efficacy is unestablished. Thirty male and 18 female cirrhotics, 55 +/- 12 (standard deviation) years of age, failed multiple large-volume paracenteses and diuretic therapy before undergoing PVS. Data were collected until death or the present time. Nine patients (19%) are alive and palliated, four with working shunts [average follow-up (ave. f/u), 30 months] and five without shunts (ave. f/u, 19 months). Thirty-two (67%) patients died: 18 palliated with functional shunts (survival time, 4.4 +/- 5.7 months), 8 unpalliated with dysfunctional shunts (ave. f/u, 3.9 +/- 4.5 months), 4 unpalliated with shunts removed (ave. f/u 5.5 +/- 4.7 months), and 2 with unknown shunt function at death. Function was lost to occlusion in 26 patients, infection in 9, and ligation for disseminated intravascular coagulation in 3. Thirteen patients underwent 18 shunt replacements. At death/present time, 22 (46%) patients were palliated with functioning shunts. Seven patients were lost to follow-up. PVSs provide palliation for intractable ascites short term, but commonly occlude within 1 year. Despite palliation, complications with PVSs are high, and survival is limited.