Liver functional assessment using time-associated change in the liver-to-spleen signal intensity ratio on enhanced magnetic resonance imaging: a retrospective study.

BACKGROUND: Liver-to-spleen signal intensity ratio (LSR) is evaluated by magnetic resonance imaging (MRI) in the hepatobiliary phase and has been reported as a useful radiological assessment of regional liver function. However, LSR is a passive (non-time-associated) assessment of liver function, not a dynamic (time-associated) assessment. Moreover, LSR shows limitations such as a dose bias of contrast medium and a timing bias of imaging. Previous studies have reported the advantages of time-associated liver functional assessment as a precise assessment of liver function. For instance, the indocyanine green (ICG) disappearance rate, which is calculated from serum ICG concentrations at multiple time points, reflects a precise preoperative liver function for predicting post-hepatectomy liver failure without the dose bias of ICG or the timing bias of blood sampling. The aim of this study was to develop a novel time-associated radiological liver functional assessment and verify its correlation with traditional liver functional parameters. METHODS: A total of 279 pancreatic cancer patients were evaluated to clarify fundamental time-associated changes to LSR in normal liver. We defined the time-associated radiological assessment of liver function, calculated using information on LSR from four time points, as the "LSR increasing rate" (LSRi). We then investigated correlations between LSRi and previous liver functional parameters. Furthermore, we evaluated how timing bias and protocol bias affect LSRi. RESULTS: Significant correlations were observed between LSRi and previous liver functional parameters such as total bilirubin, Child-Pugh grade, and albumin-bilirubin grade (P < 0.001 each). Moreover, considerably high correlations were observed between LSRi calculated using four time points and that calculated using three time points (r > 0.973 each), indicating that the timing bias of imaging was minimal. CONCLUSIONS: This study propose a novel time-associated radiological assessment, and revealed that the LSRi correlated significantly with traditional liver functional parameters. Changes in LSR over time may provide a superior preoperative assessment of regional liver function that is better for predicting post-hepatectomy liver failure than LSR using the hepatobiliary phase alone.

The Assessment of Regional Liver Function Before Major Hepatectomy Using Magnetic Resonance Imaging.

BACKGROUND: The liver-to-spleen signal intensity ratio (LSR) on magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid has been used as a parameter to assess liver function. LSR of the future remnant liver region (FR-LSR) is included in preoperative assessment of regional liver function. The aim of this study was to investigate the predictability of post-hepatectomy liver failure (PHLF) by FR-LSR. METHODS: Between May 2013 and May 2019, 127 patients underwent standardized EOB-MRI for diagnosis of liver tumor before major hepatectomy. The FR-LSR on EOB-MRI was calculated by a semiautomated three-dimensional volumetric analysis system. The cutoff value of FR-LSR in association with clinically relevant PHLF was determined according to the areas under the receiver operating characteristic curves. Then, FR-LSR and clinical variables were analyzed to assess the risk of clinically relevant PHLF. RESULTS: In patients with preoperative biliary drainage, metastatic liver tumor, estimated future remnant liver volume <50%, biliary reconstruction, operation time ≥ 480 min, estimated blood loss ≥ 1000 g, blood transfusion and a FR-LSR < 2.00 were associated with clinically relevant PHLF (P < .05 for all) in univariable analysis. The liver-to-spleen signal intensity ratio of the future remnant liver region < 2.00 was the only independent risk factor for clinically relevant PHLF in multivariable risk analysis (OR, 27.90; 95% CI: 7.99-136.40; P < .05). DISCUSSION: The present study revealed that FR-LSR calculated using a 3-dimensional volumetric analysis system was an independent risk factor for clinically relevant PHLF. The liver-to-spleen signal intensity ratio of the future remnant liver region might be a reliable preoperative parameter in liver functional assessment, enabling safe performance of major hepatectomy.

Novel Method of Evaluating Liver Transplant Surgery Fellows Using Objective Measures of Operative Efficiency and Surgical Outcomes.

BACKGROUND: The majority of liver transplantations (LTs) in North America are performed by transplant surgery fellows with attending surgeon supervision. Although a strict case volume requirement is mandatory for graduating fellows, no guidelines exist on providing constructive feedback to trainees during fellowship. STUDY DESIGN: A retrospective review of all adult LTs performed by abdominal transplant surgery fellows at a single American Society of Transplant Surgeons-accredited academic institution from 2005 to 2019 was conducted. Data from the most recent 5 fellows were averaged to generate reference learning curves for 8 variables representing operative efficiency (ie total operative time, warm ischemia time, and cold ischemia time) and surgical outcomes (ie intraoperative blood loss, unplanned return to the operating room, biliary complication, vascular complication, and patient/graft loss). Data for newer fellows were plotted against the reference curves at 3-month intervals to provide an objective assessment measure. RESULTS: Three hundred and fifty-two adult LTs were performed by 5 fellows during the study period. Mean patient age was 56 years; 67% were male; and mean Model for End-Stage Liver Disease score at transplantation was 22. For the 8 primary variables, mean values included the following: total operative time 330 minutes, warm ischemia time 28 minutes, cold ischemia time 288 minutes, intraoperative blood loss 1.59 L, biliary complication 19.6%, unplanned return to operating room 19.3%, and vascular complication 2.3%. A structure for feedback to fellows was developed using a printed report card and through in-person meetings with faculty at 3-month intervals. CONCLUSIONS: Comparative feedback using institution-specific reference curves can provide valuable objective data on progression of individual fellows. It can aid in the timely identification of areas in need of improvement, which enhances the quality of training and has the potential to improve patient care and transplantation outcomes.

Viscoelastic testing in liver transplantation.

Despite the lack of large randomized clinical studies, viscoelastic tests (VETs) have been a critical armamentarium for hemostatic control in liver transplantation (LT) since the 1960s. Many transplant institutions have adopted VETs in their clinical practice. Several small-size randomized clinical trials on LT patients have suggested that VET-guided hemostatic treatment algorithms have led to decreased indications for and amounts of transfused blood products, especially fresh-frozen plasma, compared to standard laboratory-based hemostatic management. VETs have also been reported to offer insight into the diagnosis and prediction of LT patients' development of hypercoagulability-related morbidity and mortality. There is still a need for VET device-specific hemostatic algorithms in LT, and clinicians must take into account the tendency to underestimate the coagulation capacity of VETs in patients with end-stage liver disease where hemostasis is rebalanced.

Comparison of Quality of Life and Caregiving Burden of 2- to 4-Year-Old Children Post Liver Transplant and Their Parents.

A literature search determined there are no studies on children between 2 and 4 years of age who have had a liver transplant and their parents. For this reason, this study aimed to compare the quality of life of children between 2 and 4 years of age who have had a liver transplant, and the caregiving burden of their parents. The study was carried out as a descriptive cross-sectional study on 47 children who visited Inonu University Liver Transplant Institute outpatient clinic between March 2017 and March 2018. This study found that 59.6% of the children with transplants were male and 38.3% had their organ donated by their mother. There was a positive relationship between the quality of life of the parents and the quality of life and subdimensions of the children. There was a negative relationship between parental quality of life and care burden. This study found that the quality of life of children with liver transplants and their parents was low and, as the quality of life of children was impaired, the caregiving burden of parents increased. Healthcare professionals' awareness of the effect of caregivers' care load on quality of life after liver transplantation can positively affect the healing process.

EVALUATION AND SELECTION OF CANDIDATES FOR LIVER TRANSPLANTATION: AN ECONOMIC PERSPECTIVE.

BACKGROUND: Over the next 20 years, the number of patients on the waiting list for liver transplantation (LTx) is expected to increase by 23%, while pre-LTx costs should raise by 83%. OBJECTIVE: To evaluate direct medical costs of the pre-LTx period from the perspective of a tertiary care center. METHODS: The study included 104 adult patients wait-listed for deceased donor LTx between October 2012 and May 2016 whose treatment was fully provided at the study transplant center. Clinical and economic data were obtained from electronic medical records and from a hospital management software. Outcomes of interest and costs of patients on the waiting list were compared through the Kruskal-Wallis test. A generalized linear model with logit link function was used for multivariate analysis. P-values <0.05 were considered statistically significant. RESULTS: The costs of patients who underwent LTx ($8,879.83; 95% CI 6,735.24-11,707.27; P<0.001) or who died while waiting ($6,464.73; 95% CI 3,845.75-10,867.28; P=0.04) were higher than those of patients who were excluded from the list for any reason except death ($4,647.78; 95% CI 2,469.35-8,748.04; P=0.254) or those who remained on the waiting list at the end of follow-up. CONCLUSION: Although protocols of inclusion on the waiting list vary among transplant centers, similar approaches exist and common problems should be addressed. The results of this study may help centers with similar socioeconomic realities adjust their transplant policies.

Avaliação e seleção de candidatos para transplante hepático: uma perspectiva econômica / Evaluation and selection of candidates for liver transplantation: an economic perspective

ABSTRACT BACKGROUND: Over the next 20 years, the number of patients on the waiting list for liver transplantation (LTx) is expected to increase by 23%, while pre-LTx costs should raise by 83%. OBJECTIVE: To evaluate direct medical costs of the pre-LTx period from the perspective of a tertiary care center. METHODS: The study included 104 adult patients wait-listed for deceased donor LTx between October 2012 and May 2016 whose treatment was fully provided at the study transplant center. Clinical and economic data were obtained from electronic medical records and from a hospital management software. Outcomes of interest and costs of patients on the waiting list were compared through the Kruskal-Wallis test. A generalized linear model with logit link function was used for multivariate analysis. P-values <0.05 were considered statistically significant. RESULTS: The costs of patients who underwent LTx ($8,879.83; 95% CI 6,735.24-11,707.27; P<0.001) or who died while waiting ($6,464.73; 95% CI 3,845.75-10,867.28; P=0.04) were higher than those of patients who were excluded from the list for any reason except death ($4,647.78; 95% CI 2,469.35-8,748.04; P=0.254) or those who remained on the waiting list at the end of follow-up. CONCLUSION: Although protocols of inclusion on the waiting list vary among transplant centers, similar approaches exist and common problems should be addressed. The results of this study may help centers with similar socioeconomic realities adjust their transplant policies.

RESUMO CONTEXTO: Nos próximos 20 anos, estima-se um aumento de 23% no número de pacientes em lista de espera para transplante de fígado (TxF) e de 83% nos custos no período pré-TxF. OBJETIVO: Avaliar os custos médicos diretos do período pré-TxF sob a perspectiva de um centro de atenção terciária. MÉTODOS: Foram incluídos no estudo 104 adultos em lista de espera para TxF, com doador falecido, entre outubro de 2012 e maio de 2016, tratados integralmente no centro transplantador do estudo. Dados clínicos e econômicos foram obtidos do prontuário eletrônico e do software de gestão hospitalar. Os desfechos de interesse e os custos dos pacientes em lista de espera foram comparados através do teste de Kruskal-Wallis. Um modelo linear generalizado com função de ligação logarítmica foi utilizado para a análise multivariável. Valores de P<0.05 foram considerados estatisticamente significativos. RESULTADOS: Os custos com pacientes submetidos a TxF (US$ 8.879,83; IC 95% 6.735,24-11.707,27; P<0,001) ou que morreram enquanto estavam em lista (US$ 6.464,73; IC 95% 3.845,75-10.867,28; P=0,04) foram maiores do que com pacientes excluídos da lista por qualquer motivo, exceto óbito (US$ 4.647,78; IC 95% 2.469,35-8.748,04; P=0,254) ou daqueles que permaneceram em lista de espera ao final do seguimento. CONCLUSÃO: Embora os protocolos de inclusão em lista de espera variem entre os centros transplantadores, existem condutas semelhantes e problemas comuns devem ser considerados. Os resultados deste estudo podem auxiliar os centros com realidades socioeconômicas semelhantes na adequação das suas políticas de transplante.

Barriers to ideal outcomes after pediatric liver transplantation.

Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.

Patient-reported outcome measures within pediatric solid organ transplantation: A systematic review.

Subjective evaluation of medical care and disease outcomes from patients' perspectives has become increasingly important. Patient-reported outcome measures (PROMs) play a prominent role in engaging patients, capturing their experiences and improving patient care. This systematic review sought to identify PROMs that are used in the field of pediatric solid organ transplantation, with the aim to inform the implementation of PROMs into clinical practice for this population. A systematic review of English language, peer-reviewed articles was performed on key health science databases to identify publications using PROMs in pediatric solid organ transplantation. The search yielded 3670 articles, with a final data set of 62 articles that included 47 different PROMs. The three most frequently used PROMs included the following: (a) PedsQL™ Generic Core Scales (n = 25); (b) Children's Depression Inventory (n = 6); and (c) Child Health Questionnaire (n = 6). Of the 47 PROMs, 42 were generic and five were disease-specific; only six PROMS had a documented psychometric evaluation within a pediatric solid organ transplant population. This review outlines the attributes of the instruments (eg, domains captured), as well as the psychometric properties of those evaluated. PROMs are increasingly used in the field of pediatric transplantation; however, there are limited details in the current literature about their conceptual underpinnings and psychometric properties. This review highlights the need for additional psychometric evaluation of identified measures to establish the necessary foundation to inform the implementation of PROMs into clinical care for pediatric solid organ transplant patients.

Assessment of Anastomotic Biliary Complications in Adult Patients Undergoing High-Acuity Liver Transplant.

Importance: Anastomotic biliary complications (ABCs) constitute the most common technical complications in liver transplant (LT). Given the ever-increasing acuity of LT, identification of factors contributing to ABCs is essential to minimize morbidity and optimize outcomes. A detailed analysis in a patient population undergoing high-acuity LT is lacking. Objective: To evaluate the rate of, risk factors for, and outcomes of ABCs and acuity level in LT recipients. Design, Setting, and Participants: This retrospective cohort study included adult LT recipients from January 1, 2013, through June 30, 2016, at a single large urban transplant center. Patients were followed up for at least 12 months after LT until June 30, 2017. Of 520 consecutive adult patients undergoing LT, 509 LTs in 503 patients were included. Data were analyzed from May 1 through September 13, 2017. Exposure: Liver transplant. Main Outcomes and Measures: Any complications occurring at the level of the biliary reconstruction. Results: Among the 503 transplant recipients undergoing 509 LTs included in the analysis (62.3% male; median age, 58 years [interquartile range {IQR}, 50-63 years), median follow-up was 24 months (IQR, 16-34 months). Overall patient and graft survival at 1 year were 91.1% and 90.3%, respectively. The median Model for End-stage Liver Disease (MELD) score was 35 (IQR, 15-40) for the entire cohort. T tubes were used in 199 LTs (39.1%) during initial bile duct reconstruction. Overall incidence of ABCs included 103 LTs (20.2%). Anastomotic leak occurred in 25 LTs (4.9%) and stricture, 77 (15.1%). Exit-site leak in T tubes occurred in 36 (7.1%) and T tube obstruction in 16 (3.1%). Seventeen patients with ABCs required surgical revision of bile duct reconstruction. Multivariate analysis revealed the following 7 independent risk factors for ABCs: recipient hepatic artery thrombosis (odds ratio [OR], 12.41; 95% CI, 2.37-64.87; P = .003), second LT (OR, 4.05; 95% CI, 1.13-14.50; P = .03), recipient hepatic artery stenosis (OR, 3.81; 95% CI, 1.30-11.17; P = .02), donor hypertension (OR, 2.79; 95% CI, 1.27-6.11; P = .01), recipients with hepatocellular carcinoma (OR, 2.66; 95% CI, 1.23-5.74; P = .01), donor death due to anoxia (OR, 2.61; 95% CI, 1.13-6.03; P = .03), and use of nonabsorbable suture material for biliary reconstruction (OR, 2.45; 95% CI, 1.09-5.54; P = .03). Conclusions and Relevance: This large, single-center series identified physiologic and anatomical independent risk factors contributing to ABCs after high-acuity LT. Careful consideration of these factors could guide perioperative management and mitigate potentially preventable ABCs.

Emergency department visits and unanticipated readmissions after liver transplantation: A retrospective observational study.

Improved survival after LT are likely to result in increased healthcare resource utilization. The pattern and risk factors of emergency department (ED) visits and unanticipated readmissions, associated cost, and predictors of healthcare resource utilization after liver transplantation (LT) patients who received LT between 2011 and 2014 were analyzed. A total of 430 LT recipients were enrolled and the 1 year all-cause mortality was 1.4%. ED visits occurred in 53% (229/430) and unanticipated readmissions occurred at least once in 58.6% (252/430) of the patients. Overall risk factors for ED visits after LT included emergency operation [OR 1.56 (95%CI 1.02-2.37), p = 0.038] and warm ischemic time of >15 minutes [OR 2.36 (95%CI 1.25-4.47), p = 0.015]. Risk factors for readmissions after LT included greater estimated blood loss during LT [OR 1.09 (95%CI 1.02-1.17), p = 0.012], warm ischemic time of >15 minutes [OR 1.98 (95%CI 1.04-3.78), p = 0.038], and hospital length of stay of >2 weeks.

Cardio-hepatic risk assessment by CMR imaging in liver transplant candidates.

BACKGROUND: The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof-of-concept study the value of a one-stop-shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one-stop-shop CMR approach. METHODS: In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination. RESULTS: Over 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event-free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC. CONCLUSIONS: This study further defines the population suitable for the one-stop-shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions.

Assessment of cerebral microbleeds by susceptibility-weighted imaging at 3T in patients with end-stage organ failure.

PURPOSE: Cerebral microbleeds (CMBs) are small rounded lesions representing cerebral hemosiderin deposits surrounded by macrophages that results from previous microhemorrhages. The aim of this study was to review the distribution of cerebral microbleeds in patients with end-stage organ failure and their association with specific end-stage organ failure risk factors. MATERIALS AND METHODS: Between August 2015 and June 2017, we evaluated 15 patients, 9 males, and 6 females, (mean age 65.5 years). Patients population was subdivided into three groups according to the organ failure: (a) chronic kidney failure (n = 8), (b) restrictive cardiomyopathy undergoing heart transplantation (n = 1), and (c) end-stage liver failure undergoing liver transplantation (n = 6). The MR exams were performed on a 3T MR unit and the SWI sequence was used for the detection of CMBs. CMBs were subdivided in supratentorial lobar distributed, supratentorial non-lobar distributed, and infratentorial distributed. RESULTS: A total of 91 microbleeds were observed in 15 patients. Fifty-nine CMBs lesions (64.8%) had supratentorial lobar distribution, 17 CMBs lesions (18.8%) had supratentorial non-lobar distribution and the remaining 15 CMBs lesions (16.4%) were infratentorial distributed. An overall predominance of supratentorial multiple lobar localizations was found in all types of end-stage organ failure. The presence of CMBs was significantly correlated with age, hypertension, and specific end-stage organ failure risk factors (p < 0.001). CONCLUSIONS: CMBs are mostly founded in supratentorial lobar localization in end-stage organ failure. The improved detection of CMBs with SWI sequences may contribute to a more accurate identification of patients with cerebral risk factors to prevent complications during or after the organ transplantation.

Current policy for allocation of donor livers in the Netherlands advantages primary sclerosing cholangitis patients on the liver transplantation waiting list-a retrospective study.

Studies from the USA and Nordic countries indicate primary sclerosing cholangitis (PSC) patients have low mortality on the liver transplantation (LTx) waiting list. However, this may vary among geographical areas. Therefore, we compared waiting list mortality and post-transplant survival between laboratory model for end-stage liver disease (LM) and MELD exception (ME)-prioritized PSC and non-PSC candidates in a nationwide study in the Netherlands. A retrospective analysis of patients waitlisted from 2006 to 2013 was conducted. A total of 852 candidates (146 PSC) were waitlisted of whom 609 (71.5%) underwent LTx and 159 (18.7%) died before transplantation. None of the ME PSC patients died, and they had a higher probability of LTx than LM PSC [HR obtained by considering ME as a time-dependent covariate (HRME 9.86; 95% CI 6.14-15.85)] and ME non-PSC patients (HRME 4.60; 95% CI 3.78-5.61). After liver transplantation, PSC patients alive at 3 years of follow-up had a higher probability of relisting than non-PSC patients (HR 7.94; 95% CI 1.98-31.85) but a significantly lower mortality (HR 0.51; 95% CI 0.27-0.95). In conclusion, current LTx prioritization advantages PSC patients on the LTx waiting list. Receiving ME points is strongly associated with timely LTx.

Pairwise Multiple Comparison Adjustment Procedure for Survival Functions with Right-Censored Data.

The aim of this study is to propose a new pairwise multiple comparison adjustment procedure based on Genz's numerical computation of probabilities from a multivariate normal distribution. This method is applied to the results of two-sample log-rank and weighted log-rank statistics where the survival data contained right-censored observations. We conducted Monte Carlo simulation studies not only to evaluate the familywise error rate and power of the proposed procedure but also to compare the procedure with conventional methods. The proposed method is also applied to the data set consisting of 815 patients on a liver transplant waiting list from 1990 to 1999. It was found that the proposed method can control the type I error rate, and it yielded similar power as Tukey's and high power with respect to the other adjustment procedures. In addition to having a straightforward formula, it is easy to implement.

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.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). CONCLUSION: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).

Neurological disorders in liver transplant candidates: Pathophysiology and clinical assessment.

Compromised liver function, as a consequence of acute liver insufficiency or severe chronic liver disease may be associated with various neurological syndromes, which involve both central and peripheral nervous system. Acute and severe hyperammoniemia inducing cellular metabolic alterations, prolonged state of "neuroinflammation", activation of brain microglia, accumulation of manganese and ammonia, and systemic inflammation are the main causative factors of brain damage in liver failure. The most widely recognized neurological complications of serious hepatocellular failure include hepatic encephalopathy, diffuse cerebral edema, Wilson disease, hepatic myelopathy, acquired hepatocerebral degeneration, cirrhosis-related Parkinsonism and osmotic demyelination syndrome. Neurological disorders affecting liver transplant candidates while in the waiting list may not only significantly influence preoperative morbidity and even mortality, but also represent important predictive factors for post-transplant neurological manifestations. Careful pre-transplant neurological evaluation is essential to define severity and distribution of the neurological impairment, to identify the abnormalities still responsive to current treatment, and to potentially predict the inherent post-operative prognosis. The preferred specific indices of neurological pre-transplant assessment may vary among centers, however, even with the aid of the current biochemical, neurophysiological, neuropsychological and neuroimaging diagnostic tools, the correct diagnosis and differential diagnosis of various syndromes may be difficult. In this article the relevant pathophysiological and clinical aspects of the most frequent brain and peripheral nervous system diseases affecting liver transplant candidates with acute or advanced chronic liver failure are briefly reported. The practical diagnostic findings useful for the preoperative assessment and treatment, as well as the expected neurological evolution after liver transplantation are also evaluated.

The effects of Share 35 on the cost of liver transplantation.

On June 18, 2013, the United Network for Organ Sharing (UNOS) instituted a change in the liver transplant allocation policy known as "Share 35." The goal was to decrease waitlist mortality by increasing regional sharing of livers for patients with a model for end-stage liver disease (MELD) score of 35 or above. Several studies have shown Share 35 successful in reducing waitlist mortality, particularly in patients with high MELD. However, the MELD score at transplant has increased, resulting in sicker patients, more complications, and longer hospital stays. Our study aimed to explore factors, along with Share 35, that may affect the cost of liver transplantation. Our results show Share 35 has come with significantly increased cost to transplant centers across the nation, particularly in regions 2, 5, 10, and 11. Region 5 was the only region with a median MELD above 35 at transplant, and cost was significantly higher than other regions. Several other recipient factors had changes with Share 35 that may significantly affect the cost of liver transplant. While access to transplantation for the sickest patients has improved, it has come at a cost and regional disparities remain. Financial implications with proposed allocation system changes must be considered.