Liver Transplantation In US Research Articles

Use of rapid Model for End-Stage Liver Disease (MELD) increases for liver transplant registrant prioritization after MELD-Na and Share 35, an evaluation using data from the United Network for Organ Sharing.

The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a ‘delay and cap’ policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant’s change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need.

2960 National Variation in Approach to HCV in Patients Listed for Liver Transplant

INTRODUCTION: Due to recent progress in the treatment of hepatitis C virus (HCV), many providers specializing in transplant medicine face the difficult clinical decision of whether to treat HCV in patients before or after liver transplantation (LT). Eradicating HCV in the pre-LT population has a powerful impact on both the LT waitlist and on the types of donors offered to recipients. Concurrently, increasing availability of organs from high-risk donors is occurring, largely due to the US overdose epidemic. We sought to better understand how some of these clinical and social dynamics impact decisions at US transplant centers. METHODS: We surveyed all medical and surgical transplant directors from adult US. LT centers via an online survey in 2017. The survey queried directors about their program's specific approach to waitlisted patients with HCV pre-LT. The survey posed broad questions about patient demographics as well as more specific questions relating to the frequency with which Public Health Service-increased risk (PHS-IR) and HCV+ donors are offered, the degree to which PHS-IR and HCV+ offers are declined due to a lack of waitlisted patients with HCV, and the existence of any cutoffs for transplantation. RESULTS: 28 respondents (17% response rate), representing programs in 10/11 UNOS regions, answered the survey. Respondents were primarily from university-affiliated LT programs (92.3%) and represented variably-sized programs (LT volume ≤50 in 46.4%, 51-100 in 35.7%, >100 in 17.9%). 93% of programs reported seeing >10% are PHS-IR offers, and 19% of programs reported >30% PHS-IR offers. 39.3% of programs reported >10% offers are from HCV+ donors. 50% of programs reported turning down offers for HCV+ organs due to lack of available HCV+ recipients on the waitlist. A minority of programs (14.3%) continue to use donor age cutoffs for HCV+ recipients and many programs do not attempt to treat chronic HCV in non-HCC patients with CPT-B (42.3%) and CPT-C (77.8%) cirrhosis. CONCLUSION: Significant heterogeneity in US LT centers' approach to HCV patients on the waitlist exists. There is a trend to leave the sickest HCV+ patients untreated, though organs may be discarded due to lack of available HCV+ recipients in some parts of the country. As utilization of HCV+ organs into HCV- recipients begins to increase in the US, consideration for a separate allocation strategy for these organs may be warranted.

Portopulmonary Hypertension: A Survey of Practice Patterns and Provider Attitudes.

The role of liver transplantation (LT) in the management of portopulmonary hypertension (POPH) is poorly understood. The aim of this study was to better understand provider attitudes and practice patterns regarding the management of patients with POPH and to assess the concordance between clinical practice and current guidelines. We performed a multicenter survey study of hepatologists and pulmonary hypertension (PH) physicians at US LT centers that performed >50 transplants per year. Survey responses are summarized as number (%). Associations were assessed using a Wilcoxon-rank sum, chi-square, or Fisher exact test, as appropriate. Seventy-four providers from 35 centers were included. There was marked variability regarding screening practices, management, and attitudes. Forty-two percent responded that POPH nearly always or often improves with LT, and 15.5% reported that POPH rarely or never improves. In contrast to current guidelines, 50.7% agreed that treated POPH should be an indication for LT in patients with compensated cirrhosis. Hepatologists were more likely than PH physicians to agree that POPH should be an indication for LT (P = 0.02). Forty-nine percent of respondents thought that the current POPH Model for End-stage Liver Disease exception criteria should be modified, and management of patients with an elevated mean pulmonary arterial pressure and normal pulmonary vascular resistance differed from current policies. There is marked variability in provider attitudes and practice patterns regarding the management of POPH. This study highlights the need for prospective studies to inform practice and for improved implementation of practice guidelines in order to standardize care.

The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis.

The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two "SharePeds" allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Organ Procurement and Transplantation Network [OPTN] 12-2017). The 2017 Liver Simulated Allocation Model and Scientific Registry of Transplant Recipients data on all US liver transplant candidates and liver offers 7/2013 to 6/2016 were used to predict waitlist deaths, transplants, and post-transplant deaths under the OPTN 12-2017 and SharePeds schema. Prioritizing national sharing of pediatric donor livers with children (SharePeds 1) would decrease waitlist deaths for infants (<2 years, P = 0.0003) and children (2-11 years, P = 0.001), with no significant change for adults (P = 0.13). Prioritizing national sharing of all younger than 35-year-old deceased donor livers with children and Status 1A adults (SharePeds 2) would decrease waitlist deaths for infants, children, and all Status 1A/B patients (P < 0.0001 for each). SharePeds 1 and 2 would increase the number of liver transplants done in infants, children, and adolescents compared to the OPTN-2017 schema (P < 0.00005 for all age groups). Both SharePeds schema would increase the percentage of pediatric livers transplanted into pediatric recipients. Waitlist deaths could be significantly decreased, and liver transplants increased, for children and the sickest adults, by prioritizing children for pediatric livers and with broader national sharing of deceased donor livers.

Improved liver transplant waitlist mortality and lower risk of disease progression among chronic hepatitis C patients awaiting liver transplantation after the introduction of direct-acting antiviral therapies in the United States.

Direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection achieve high cure rates, reducing HCV-related disease progression to cirrhosis and hepatocellular carcinoma. We aim to evaluate the impact of DAAs on US liver transplant (LT) waitlist outcomes. We retrospectively evaluated US adults (age ≥18) with and without chronic HCV listed for LT before and after the widespread use of sofosbuvir, allowing a 6-month period after approval (Era 1: 1/1/2002-5/31/2014 vs Era 2: 6/1/2014-12/31/2016) using the United Network for Organ Sharing registry. Overall, LT waitlist survival and likelihood of receiving LT were evaluated with multivariate Cox regression models. From 2002 to 2016, 158045 patients were listed for LT. While the number of patients listed for HCV has been decreasing since 2012, the proportion of HCV patients with concurrent HCC is increasing by 3.33% per year (R2 : 0.99, P<0.001 by simple linear regression). While there was no difference in likelihood of LT between HCV and non-HCV patients, those listed in Era 2 had lower likelihood of LT (HR: 0.91, P<0.001), more pronounced in the HCV cohort (HR: 0.83, P<0.001) compared to the non-HCV cohort (HR: 0.93, P<0.001). Compared to non-HCV patients, higher waitlist mortality was seen in HCV patients in Era 1 (HR: 1.08, P<0.001) but not in Era 2 (HR: 1.02, P=0.75). Since the introduction of DAAs for HCV treatment, number of patients with HCV listed for LT has declined. In the post-DAA era, HCV patients on the LT waitlist had improved waitlist mortality.

Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis.

Liver transplantation (LT) has a demonstrated survival benefit in select patients with severe acute alcoholic hepatitis (SAH) who do not respond to steroids, but prior studies suggest low adoption among US LT centers. Our study explored current perceptions and practice patterns of LT for SAH in the United States. We administered a Web-based survey to medical directors of US LT centers between May and October of 2017 to characterize practice patterns and perceptions of LT for SAH. We obtained responses from 45 (41.3%) of 109 surveyed centers, representing all 11 (100%) United Network for Organ Sharing regions. Half (n = 23; 51.1%) reported performing at least 1 LT for SAH, although most (n = 19; 82.6%) of those had performed ≤5 LTs for that indication. Centers expressed near consensus for selection criteria, requiring strong social support (100%), no prior presentations with SAH (91.3%), absence of a severe coexisting psychiatric disorder (91.3%), and official psychosocial evaluation (87.0%). Reported posttransplant survival of SAH patients was excellent, with 17 (73.9%) centers reporting 1-year posttransplant survival exceeding 90%. Among centers that had not performed LT for SAH, the most commonly cited reason was perceived high risk of alcohol relapse. In conclusion, our data demonstrate that LT is increasingly adopted as a therapeutic intervention for patients with SAH and that careful selection allows for excellent 1-year posttransplant survival. Despite this, nearly half of US centers do not perform LT for this indication due to perceived high risk of alcohol relapse. Our data support the use of LT for well-selected patients with SAH.

Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia

Excellent Outcomes of Deceased Donor Liver Transplantation Using Grafts From Older Donors: A U.S. Single-Center Experience

Introduction: One of the major challenges in deceased donor liver transplantation (DDLT) is the scarcity of donor allografts, which results in high wait-list mortality. Transplant centers tackle the donor graft scarcity by utilizing expanded criteria donors including older donors. UNOS reported that the percentage of donor age > 50 years rose from 24% in 1989 to 33% in 2013. The literature on the impact of older donor age on liver graft function, survival and complications have described contradictory results. In this study, we aim to evaluate patient and graft survival outcomes of DDLT recipients in 2 groups: donor age ≥65 years and donor age < 65 years. Methods: Setting: Single center Retrospective cohort study at a large volume US liver transplant center Inclusion criteria: All primary deceased liver transplants (DDLT) in our institution between October 2012 to October 2016 Exclusion criteria: age <18, split and reduced-size livers and multi-organ transplants were excluded from the study Outcomes: Comparison of 1-year /overall patient and graft survival in 2 groups: donor age ≥65 years and donor age < 65 years. Results: In total, 646 patients met inclusion criteria. Among patients who underwent DDLT, 70 (11%) received DDLT from older (>65 years) donors. There was no difference in age, sex, ethnicity, hepatocellular carcinoma, warm/cold ischemia time, donor sex, donor ethnicity, donor BMI in both groups. Patients who received liver transplantation from donor age >65 had lower HCV infection (20% vs 41%), lower MELDNa score (19±6 vs 21±9), and lower donor HCV-positive graft (3% vs 13%) [Table 1]. Recipients of donor age ≥65 had similar outcomes including 1-year patient survival (96% vs 92%, p = NS), 1-year graft survival (93% vs 90%, p =NS), overall patient survival (94% vs 86%, p =NS) and overall graft survivals (90% vs 84%, p=NS) comparing to recipients of donor age <65, respectively [Table 2 and Figure 1].1014_A Figure 1. Baseline charecteristicsConclusion: In our study, careful allocation of grafts from older donors to appropriate recipients resulted in excellent 1-year and longer-term patient and graft survival comparable with outcomes in recipients from donor grafts age <65 years. Increasing utilization of grafts from older donors can expand the donor pool to decrease the national organ donor shortage.1014_B Figure 2. Results1014_C Figure 3. Kaplan Meier survival graphs

Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey.

With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.

Center-driven and Clinically Driven Variation in US Liver Transplant Maintenance Immunosuppression Therapy: A National Practice Patterns Analysis.

Variation in the use of immunosuppression regimens after liver transplant has not been well described. Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003). Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.

The effects of p-NaK-tide and SW033299 on nash associated cirrhosis in the rodent

Background: NASH and its complications ESLD and HCC have become the second most common cause for liver transplantation in US. The purpose of the present studies was to test the efficacy of two compounds developed by our group, “pNa/K-tide “and “SW033299 “in reversing the liver disturbances produced by NASH. Methods: C57Bl 6J mice (n = 7) were exposed to normal chow (Control -) or high fat diet + fructose (HFD). The mice on HFD was non treated (Control+) or treated with i) p-Na/K- tide, ii) with SW033299 or iii) exposed to an exercise protocol. Livers/plasma were collected “at weeks 7, 12, 16, 20, 24”. Body composition was determined by MRI spectroscopy. The proportion of cells undergoing mitosis or in cell arrest was determined against liver apoptotic index and collagen deposition by standard stains using morphometric techniques. Quantitative protein expression of genes p53, p21, p16, mTOR1, STAT33, SIRT7, FOX01, Grb2 were determined by Western Blots. Metabolic profiles were measured on treated plasma by LC/MS-MS. Results: The total body weight corrected by aging increased significantly in the HFD (HFD vs normal chaw, p < 005 by ANOVA). The amount of liver fat accumulation, the number of cells in senescence and the apoptotic index were significantly decreased in both the pNaK and SW groups when compared to the HFD (p < 00.5 by ANOVA). In addition, the deposition of collagen was significantly lower in the pNaK and SW groups when compared to the HFD group. Glutathione ratio, mitochondrial ß-lipid oxidation function and Na/K-exchange pump activity after censored for aging followed similar trends among groups (p < 0.05 by ANOVA). Metabolic prints were significantly different among groups. Conclusion: pNaK-tide and SW033299 not only prevent but reverse NASH due to high fat diet in the rodent model.

Liver Transplantation in the Obese Cirrhotic Patient

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.

Immunosuppression Practices in Liver Transplantation: A Survey of North American Centers.

There is a clear lack of clinical evidence guiding immunosuppressive management in long-term stable liver transplant recipients. As a result, anecdotal experience suggests wide variability across transplant centers. We aimed to identify patterns of immunosuppression practices in liver transplant centers across Canada and the United States. From February 9 to May 31, 2015, we invited clinicians from all liver transplant centers in Canada and the United States to answer a 6-question survey generated using SurveyMonkey. Seventeen respondents from 15 liver transplant centers completed the survey. Although immun-suppressive practices are relatively uniform for induction and early maintenance therapy, significant variations exist in the management of long-term immunosuppression in stable transplant recipients with a relative lack of minimization protocols. Our survey confirms a wide variability in immunosuppression practices across Canadian and US liver transplant centers. Research and practice priorities include design of pragmatic randomized controlled trials and development of clinical practice guidelines to standardize immunosuppressive management of long-term stable liver transplant recipients with a focus on immunosuppression minimization.

Analysis of Liver Offers to Pediatric Candidates on the Transplant Wait List

Approximately 10% of children on the liver transplant wait-list in the United States die every year. We examined deceased donor liver offer acceptance patterns and their contribution to pediatric wait-list mortality. We performed a retrospective cohort study of children on the US liver transplant wait-list from 2007 through 2014 using national transplant registry databases. We determined the frequency, patterns of acceptance, and donor and recipient characteristics associated with deceased donor liver organ offers for children who died or were delisted compared with those who underwent transplantation. Children who died or were delisted were classified by the number of donor liver offers (0 vs 1 or more), limiting analyses to offers of livers that were ultimately transplanted into pediatric recipients. The primary outcome was death or delisting on the wait-list. Among 3852 pediatric liver transplant candidates, children who died or were delisted received a median 1 pediatric liver offer (inter-quartile range, 0-2) and waited a median 33 days before removal from the wait-list. Of 11,328 donor livers offered to children, 2533 (12%) were transplanted into children; 1179 of these (47%) were immediately accepted and 1354 (53%) were initially refused and eventually accepted for another child. Of 27,831 adults, 1667 (6.0%; median, 55 years) received livers from donors younger than 18 years (median, 15 years), most (97%) allocated locally or regionally. Of children who died orwere delisted, 173 (55%) received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 143 (45%) died or were delisted with no offers. Among pediatric liver transplant candidates in the US, children who died or were delisted received a median 1 pediatric liver offer and waited a median of 33 days. Of livers transplanted into children, 47% were immediately accepted and 53% were initially refused and eventually accepted for another child. Of children who died or were delisted, 55% received an offer of 1 or more liver that was subsequently transplanted into another pediatric recipient, and 45% died or were delisted with no offers. Pediatric prioritization in the allocation and development of improved risk stratification systems is required to reduce wait-list mortality among children.

Transplantation for acute alcoholic hepatitis.

Transplantation for acute alcoholic hepatitis.

Disability in patients with end-stage liver disease: Results from the functional assessment in liver transplantation study.

Cirrhosis leads to sarcopenia and functional decline that can severely impact one's ability to function at home and in society. Self-reported disability scales to quantify disability-Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)-are validated to predict mortality in older adults. To evaluate disability in liver transplantation (LT) candidates and quantify its impact on outcomes, consecutive outpatients ≥18 years listed for LT with laboratory Model for End-Stage Liver Disease scores of ≥12 at a single high-volume US LT center were assessed for ADLs and IADLs during clinic visits. Multivariate competing risk models explored the effect of disabilities on wait-list mortality (death or delisting for illness). Of 458 patients, 36% were women, median (interquartile range [IQR]) age was 60 years (IQR, 54-64 years), and initial Model for End-Stage Liver Disease-Sodium (MELD-Na) was 17 (IQR 14-20). At first visit, 31% had lost ≥ 1 ADL, and 40% had lost ≥ 1 IADL. The most prevalent ADL deficits lost were continence (22%), dressing (12%), and transferring (11%); the most prevalent IADLs lost were shopping (28%), food preparation (23%), and medication management (22%). After adjustment for age, MELD-Na, and encephalopathy, dressing (subdistribution hazard ratio [SHR], 1.7; 95% confidence interval [CI], 1.0-2.8; P = 0.04), toileting (SHR, 1.9; 95% CI, 1.1-3.5; P = 0.03), transferring (SHR, 1.9; 95% CI, 1.1-3.0; P = 0.009), housekeeping (SHR, 1.8; 95% CI, 1.2-3.0; P = 0.009), and laundry (SHR, 2.2; 95% CI, 1.3-3.5; P = 0.002) remained independent predictors of wait-list mortality. In conclusion, ADL/IADL deficits are common in LT candidates. LT candidates would benefit from chronic disease management programs developed to address the impact of cirrhosis on their daily lives. Liver Transplantation 23 292-298 2017 AASLD.

Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults?

The classical form of alpha-1-antitrypsin deficiency (A1ATD) is known to cause liver disease in children and adults, but there is relatively little information about the risk of severe, progressive liver disease and the need for liver transplantation. To better understand how newly evolving pharmacological, genetic, and cellular therapies may be targeted according to risk for progressive liver disease, we sought to determine the age distribution of A1ATD as a cause of severe liver disease, as defined by the need for liver transplantation. Using 3 US liver transplantation databases for the period 1991-2012, we found 77.2% of 1677 liver transplants with a reported diagnosis of A1ATD were adults. The peak age range was 50-64 years. Using 2 of the databases which included specific A1AT phenotypes, we found that many of these adults who undergo liver transplantation with A1ATD as the diagnosis are heterozygotes and have other potential causes of liver disease, most notably obesity and ethanol abuse. However, even when these cases are excluded and only ZZ and SZ phenotypes are considered, severe liver disease requiring transplantation is more than 2.5 times as likely in adults. The analysis also showed a markedly increased risk for males. In the pediatric group, almost all of the transplants are done in children less than 5 years of age. In conclusion, A1ATD causes progressive liver disease most commonly in adults with males in the highest risk category. In the pediatric group, children less than 5 years of age are highest in risk. These results suggest that A1ATD most commonly causes liver disease by mechanisms similar to age-dependent degenerative diseases and more rarely in children by powerful modifiers. Liver Transplantation 22 886-894 2016 AASLD.

How we provide blood transfusion support in two large US liver transplant programs.

How we provide blood transfusion support in two large US liver transplant programs.

Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List.

Although renal dysfunction is a known complication of acute liver failure (ALF), its frequency, severity, and impact among patients with ALF on the US liver transplant list are not well defined. Organ Procurement and Transplantation data for ALF patients listed as status 1/1A from 2002 to 2012 were analyzed. The frequency and severity of renal dysfunction at the time of listing [the latter was categorized in 5 stages using estimated GFR (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation] were determined and the association between renal dysfunction and waiting list mortality was assessed using Cox proportional hazard regression analysis. There were a total of 2280 adult patients with ALF, including 56 % with renal dysfunction (defined as eGFR < 60 ml/min/1.73 m(2)) at listing. The highest proportion of patients with renal dysfunction was among those with ALF caused by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, fatty liver disease of pregnancy, heat stroke/hyperthermia, hepatitis A virus, and drug-induced liver injury due to acetaminophen APAP, phenytoin, trimethoprim-sulfamethoxazole, and macrolides. Despite the fact that 69 % (468/674) of patients with APAP-induced ALF listed as status 1/1A had renal dysfunction, only 0.9 % underwent simultaneous liver-kidney transplantation. Six-week survival probabilities in patients with ALF on the liver transplant waiting list were 71, 59, 56, 59, and 42 % with renal dysfunction stages of 1, 2, 3, 4, and 5, respectively. Multivariate analysis showed that after controlling for age, etiology of ALF, INR, total bilirubin, and region, the relative risk of death increased progressively as eGFR declined (P < 0.0001). Among patients with ALF on the liver transplant waiting list, renal dysfunction was common (overall prevalence of 56 %). Most importantly, severe renal dysfunction was associated with significantly increased mortality.

Orthotopic liver transplantation in non-alcoholic fatty liver disease patients.

Non-alcoholic fatty liver disease (NAFLD) is a frequent etiology of liver disease in Western Countries and non-alcoholic steato-hepatitis (NASH) is becoming a leading indication for liver transplantation in US, with constant increase overtime. Specific co-morbidities correlated to the presence of obesity and associated with metabolic syndrome should always be ruled out in patients affected by NASH-related end-stage liver disease, who are potential candidates for liver transplantation. Patients transplanted for NAFLD present similar outcomes compared with patients transplanted for other indications. With regards to post-transplant outcomes in obese patients, available data are contradictory, with reported increased mortality only in patients with BMI >40. A new multidisciplinary protocol of liver transplantation and sleeve gastrectomy seems to be effective and safe in obese patients who were not able to lose weight before liver transplantation. However prospective studies are needed. The NASH recurrence rate after liver transplantation ranges between 20-40%, but its variability largely depends on the methodology used for the diagnosis (i.e. liver tests, liver histology or imaging technique).