Heimbach, Julie K.

Background Sex-based disparities in liver transplantation (LT) are incompletely understood. We assessed the role of height, Model for End-Stage Liver Disease (MELD), MELD-Na, and exception points in the disparate access to LT. Methods Adults waitlisted for LT at Organ Procurement and Transplantation Network between 2002 and 2013 were included. Covariates associated with likelihood of LT were analyzed by Cox proportional model. In a separate cohort of waitlisted adults with glomerular filtration rate measurement by iothalamate clearance (n = 611), we determined the number of creatinine-derived MELD points in men versus women, across all ranges of glomerular filtration rate. The impact of correcting the MELD score deficit in women on LT was modeled. Results Among 90 720 Organ Procurement and Transplantation Network registrants, women had higher mortality than men (4 years after listing: 22% vs 18%, P < 0.0001), and lower likelihood of LT (49% vs 58%, P < 0.0001); women were 20% less likely to be transplanted (hazard ratio, 0.80; 95% confidence interval, 0.78-0.81). Differences in height and MELD exception scores accounted for most of the LT deficit in women (hazard ratio, 0.91; 95% confidence interval, 0.89-0.94). Women received between 1 and 2.4 fewer creatinine-derived MELD points than men with similar renal dysfunction. MELD-Na worsened the gender disparity. Addition of 1 or 2 MELD points to women significantly impacted LT access. Conclusions Differences in height and MELD exception points explained most of the sex-based disparity in LT. Additionally, MELD score underestimated disease severity in women by up to 2.4 points and MELD Na exacerbated this disparity. The degree of underestimation based on MELD had significant impact on allocation.

Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. The aim of this study was to analyze the long‐term outcomes for obese patients undergoing LT, including a noninvasive weight loss program and combined LT and sleeve gastrectomy (SG). Since 2006, all patients referred for LT with a body mass index (BMI) ≥35 kg/m2 were enrolled. Patients who achieved weight loss (BMI <35) underwent LT alone, and those who did not underwent simultaneous LT + SG. Analysis of long‐term outcomes for patients ≥3 years posttransplant was performed. Since 2006, there were 36 in the weight loss intervention (LT cohort) and 13 in the LT + SG cohort with >3 years of follow‐up, whereas overall, a total of 29 patients underwent LT + SG. Patients in the LT cohort had less severe obesity at enrollment (40.0 ± 2.7 vs. LT + SG cohort 46.0 ± 4.5; P < 0.001). In the LT cohort, 83.3% (30 of 36) achieved >10% loss in total body weight (TBW) pre‐LT. Three years posttransplant, 29.4% of patients in the LT cohort maintained >10% loss in TBW, whereas 100% of the LT + SG patients did (P < 0.001). Patients who underwent LT + SG maintained a significantly higher percentage of total body weight loss after 3 years of follow‐up (LT cohort 3.9 ± 13.3% vs. LT + S G cohort 34.8 ± 17.3%; P < 0.001). Patients in the LT + SG also had a lower prevalence of hypertension, insulin resistance, and hepatic steatosis and required fewer antihypertensive medications and lipid agents at last follow‐up. Conclusion: Whereas weight loss before transplantation was achieved by obese patients, weight regain was common in the LT cohort. Combined LT + SG resulted in more effective and more durable weight loss, as well as fewer metabolic complications at last follow‐up. (Hepatology 2018).

Intracardiac thrombus occurs in 1.2%–6.3% of patients undergoing orthotopic liver transplant and is associated with a high mortality rate. The pathophysiology and risk factors for development of this complication are not well understood. No consensus treatment guidelines exist, and specific therapies are associated with serious risks. We present the timely and successful use of a Poole tip surgical suction device advanced into the right atrium through a cavotomy created in the inferior vena cava to remove a large right atrial thrombus during liver transplant. The thrombus was identified with transesophageal echocardiography and was causing cardiovascular collapse.

Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast–enhanced MRI, and gadoxetate‐enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow‐up with the same versus alternative imaging is best for CT‐indeterminate or MRI‐indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast–enhanced MRI or gadoxetate‐enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs <1 cm. No studies examined whether adults with cirrhosis and an indeterminate nodule are best evaluated using biopsy, repeated imaging, or alternative imaging. Concerns about publication bias, inconsistent study results, increased risk of bias, and clinical factors precluded support for exclusive use of either gadoxetate‐enhanced or extracellular contrast–enhanced MRI over CT.Conclusion:CT, extracellular contrast–enhanced MRI, or gadoxetate‐enhanced MRI could not be definitively preferred for HCC diagnosis in patients with cirrhosis; in patients with cirrhosis and an indeterminate mass, there were insufficient data comparing biopsy to repeat cross‐sectional imaging or alternative imaging. (Hepatology2018;67:401‐421).

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down‐staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow‐up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06‐1.85; I 2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060‐2.370; I 2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down‐staging therapy versus no downstaging, and this showed a significant increase in 1‐year (two studies, RR, 1.11; 95% CI, 1.01‐1.23) and 5‐year (1 study, RR, 1.17; 95% CI, 1.03‐1.32) post‐LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. Conclusion: In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (H epatology 2018;67:381‐400).

AbstractBackgroundDuration of functional warm ischemia (f‐WIT) is thought to have a causal effect on outcomes in controlled donation after circulatory death (DCD) liver transplantation (LT).MethodsA retrospective cohort study was conducted at five centers. Data were extracted on donor and recipient characteristics, with attention to parameters recorded during withdrawal of life support to in situ cold perfusion. F‐WIT was the time elapsed from any of the hemodynamic and oxygenation parameters to the start of in situ cold perfusion. Parameters were as follows: MAP ≤ 50 mm Hg; SBP ≤ 50 mm Hg; and SPO2 ≤ 60%. The primary endpoint was a composite of disseminated ischemic cholangiopathy (IC), primary non‐function (PNF), and early graft failure.Results35 patients (14%) developed one or more of the primary outcomes. On univariate analysis, older donors and longer WITs were associated with greater likelihood of complications. Of the f‐WIT variations analyzed, only f‐WIT with SpO2 ≤ 60% was longer among patients with complications. On multivariate analysis, only donor age was a significant predictor of complications.ConclusionThis study demonstrates that, of the f‐WITs, f‐WIT with SpO2 ≤ 60% is most predictive of post‐DCD complications. However, results suggest that there may be an alternate etiology for poor outcomes, and that donor age plays a key role.

Background: Familial transthyretin amyloidosis is a disease caused by misfolded transthyretin aggregates that can impair multiple organ systems. Liver transplantation is the first-line treatment for familial transthyretin amyloidosis. Research Question: Our objective is to study outcomes and survival among patients with familial transthyretin amyloidosis after transplantation. Design: All patients undergoing orthotopic liver transplant for familial transthyretin amyloidosis at Mayo Clinic between 1997 and 2012 were reviewed. Baseline clinical characteristics, organs transplanted, and posttransplant clinical course were assessed. Results: Of the 40 patients, 7 patients had the V30M mutation and 33 had other mutations. Nineteen patients received liver only, 19 liver and heart, and 2 combined liver, heart, and kidney transplants. The 5-year overall survival was 85% for those receiving multiple organ transplant and 52% for those receiving liver transplant only ( P = .057). There was no difference in overall survival based on mutation (V30M vs other mutations), but survival was confounded by varied disease involvement and organs transplanted. Those who had early death (≤24 months from liver transplant) had a higher incidence of baseline peripheral neuropathy, autonomic neuropathy, lower modified BMI, and higher alkaline phosphatase. Discussion: Outcomes of orthotopic liver transplant in familial transthyretin amyloidosis are variable due to heterogeneity in mutations and patient status at the time of transplant. Familial transthyretin amyloidosis can progress, despite liver transplantation. Patients receiving combined liver, heart/kidney transplant demonstrated improved survival compared to liver transplant alone.