Search

Background and Aims: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown., Approach and Results: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97)., Conclusions: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization., (© 2021 American Association for the Study of Liver Diseases.)

Background and Aims: Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard-of-care therapy., Approach and Results: Thirty-nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow-up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan-Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length-of-stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6-month follow-up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long-term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%., Conclusions: TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation., (© 2021 by the American Association for the Study of Liver Diseases.)

Background and Aims: Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality., Approach and Results: Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79., Conclusions: LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates., (© 2020 by the American Association for the Study of Liver Diseases.)

Brain edema is a major complication of fulminant hepatic failure and is responsible for death in a large percentage of patients. We previously demonstrated the progressive accumulation of water in grey matter areas of the brain in the rabbit with galactosamine-induced fulminant hepatic failure. We now report the electron microscopic morphology of the brain in the same model of acute hepatic failure following the intravenous injection of horseradish peroxidase, an intravascular tracer which forms an electron-dense reaction product. Rabbits with both mild and severe encephalopathy had normal blood pressures and blood gases at the time of study. Fixation of brain tissue was obtained by whole-body perfusion. Marked swelling of the cytoplasm, perineuronal and perivascular processes of astrocytes were noted in cortical gray, but not white, matter areas; the other cellular components of the brain had normal morphology. Capillary endothelial cells were normal, and there was no evidence of horseradish peroxidase in endothelial cell vesicles, basement membranes or the brain parenchyma, suggesting that the blood-brain barrier was impermeable to large molecules. Histologic evidence of brain edema is seen in this model, with swelling of astrocytes as the primary manifestation of the accumulation of water. Damage to astrocytes or inhibition of their function may contribute to the pathogenesis of hepatic encephalopathy in this model.