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•Sarcopenia is associated with waiting list mortality in liver transplant patients.•Adding sarcopenia to the MELD score does not have any added value for prioritization.•However, ...patients with a low MELD score and sarcopenia may be under prioritized.•Our model may be used to identify patients at risk for waiting list mortality.
Frail patients with low model for end-stage liver disease (MELD) scores may be under-prioritised. Low skeletal muscle mass, namely sarcopenia, has been identified as a risk factor for waiting list mortality. A recent study proposed incorporating sarcopenia in the MELD score (MELD-Sarcopenia score). We aimed to investigate the association between sarcopenia and waiting list mortality, and to validate the MELD-Sarcopenia score (i.e. MELD + 10.35 * Sarcopenia).
We identified consecutive patients with cirrhosis listed for liver transplantation in the Eurotransplant registry between 2007–2014 and measured skeletal muscle mass on computed tomography. A competing risk analysis was used to compare survival of patients with and without sarcopenia, and concordance (c) indices were calculated to assess performance of the MELD and MELD-Sarcopenia score. We created a nomogram of the best predictive model.
We included 585 patients with a median MELD score of 14 (interquartile range 9–19), of which 254 (43.4%) were identified as having sarcopenia. Median waiting list survival was shorter in patients with sarcopenia than those without (p <0.001). This effect was even more pronounced in patients with MELD ≤15. The discriminative performance of the MELD-Sarcopenia score (c-index 0.820) for three-month mortality was lower than MELD score alone (c-index 0.839). Apart from sarcopenia and MELD score, other predictive variables were occurrence of hepatic encephalopathy before listing and recipient age. A model including all these variables yielded a c-index of 0.851.
Sarcopenia was associated with waiting list mortality in liver transplant candidates with cirrhosis, particularly in patients with lower MELD scores. The MELD-Sarcopenia score was successfully validated in this cohort. However, incorporating sarcopenia in the MELD score had limited added value in predicting waiting list mortality.
In this study among patients with liver cirrhosis listed for liver transplantation, low skeletal muscle mass was associated with mortality on the waiting list, particularly in patients who were listed with low priority based on a low MELD score. However, adding these measurements to the currently used system for donor and organ allocation showed no added value.
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This article is linked to Huang et al and Lee and Huang papers. To view these articles, visit https://doi.org/10.1111/apt.15887 and https://doi.org/10.1111/apt.15994
A simple, analytical method for predicting transport of uncharged organic solutes through nanofiltration (NF) and reverse osmosis (RO) membranes is presented in this paper. The method requires ...characterization of key solute and membrane parametersnamely, solute size, membrane pore size, and solute−membrane affinity. All three parameters can be experimentally determined from relatively simple permeation tests and contact angle analyses. The parameters are fed into an analytical model of solute transport, which accounts for hindered convection and diffusion of solutes in the membrane pores, as well as the combined effects of steric exclusion and solute−membrane affinity on solute partitioning from the feed solution into the membrane pores. Overall model predictions for organic solute rejection agreed well with experimental data for three different solutes and two different polymeric NF membranes. Further, the model demonstrates the dramatic influence of solute−membrane affinity on organic rejection by NF and RO membranes. Solute transport predictions made assuming only steric exclusion significantly overestimated rejections for solutes with strong affinity for membrane polymers and similarly underestimated rejections for solutes that were strongly repelled by membrane polymers.
Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers ...may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.
In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.
A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval CI, 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.
Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).
Extensive population‐based studies are much needed to accurately establish epidemiology and disease course in patients with primary sclerosing cholangitis (PSC). We aimed to obtain population‐based ...prevalence and incidence figures, insight in disease course with regard to survival, liver transplantation (LT), and occurrence of malignancies, as well as risk factors thereof. Four independent hospital databases were searched in 44 hospitals in a large geographically defined area of the Netherlands, comprising 50% of the population. In addition, all PSC patients in the three Dutch liver transplant centers and all inflammatory bowel disease (IBD) patients in the adherence area of a large district hospital were identified. All medical records were reviewed on‐site, verifying diagnosis. Five hundred and ninety PSC patients were identified, resulting in an incidence of 0.5 and a point prevalence of 6.0 per 100,000. Median follow up was 92 months. Estimated median survival from diagnosis until LT or PSC‐related death in the entire cohort was 21.3 years, as opposed to 13.2 years in the combined transplant centers cohort (n = 422; P < 0.0001). Colorectal carcinoma (CRC) risk was 10‐fold increased, as compared to ulcerative colitis controls, and developed at a much younger age (39 years; range, 26‐64), compared to IBD controls (59 years; range, 34‐73; P = 0.019). Colonoscopic surveillance was associated with significantly better outcome. Conclusion: This study exemplifies that, for relatively rare diseases, it is paramount to collect observational data from large, population‐based cohorts, because incidence and prevalence rates of PSC are markedly lower and survival much longer than previously reported. The selection of a bias‐free, population‐based cohort showed a significantly longer survival, compared to the tertiary referral cohort. CRC can develop at an early age, warranting surveillance from time of PSC diagnosis. (Hepatology 2013; 58:2045–2055)
The MELD score is used in the Eurotransplant (ET) region to allocate liver grafts. Hyponatremia in cirrhotic patients is an important predictor of death but is not incorporated in MELD. This study ...investigated the performance of the MELD‐Na score for the ET region. All adult patients with chronic liver disease on the ET liver transplantation waiting list (WL) allocated through lab MELD scores were included. The MELD‐corrected effect of serum sodium (Na) concentration at listing on the 90‐day WL mortality was calculated using Cox regression. The MELD‐Na performance was assessed with c‐indices, calibration per decile and Brier scores. The reclassification from MELD to MELD‐Na score was calculated to estimate the impact of MELD‐Na‐based allocation in the ET region. For the 5223 included patients, the risk of 90‐day WL death was 2.9 times higher for hyponatremic patients. The MELD‐Na had a significantly higher c‐index of 0.847 (SE 0.007) and more accurate 90‐day mortality prediction compared to MELD (Brier score of 0.059 vs 0.061). It was estimated that using MELD‐Na would reduce WL mortality by 4.9%. The MELD‐Na score yielded improved prediction of 90‐day WL mortality in the ET region and using MELD‐Na for liver allocation will very likely reduce WL mortality.
This study validates the MELD‐Na for the Eurotransplant region, showing that its implementation could reduce waitlist mortality.
PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are ...disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses. Liver biopsies obtained during 1979-2010 at the Department of Paediatrics, Karolinska University Hospital, Sweden, were subjected to histological re-evaluation, immunohistochemistry and NanoString-based transcriptome profiling using a panel of 760 fibrosis plus 8 bile acid-related genes. Subjects were divided into three groups based on clinical outcomes: NCH (neonatal cholestasis, favourable outcome,
= 5), NCC (neonatal cholestasis, early cirrhosis and liver transplantation,
= 4), and NNCH (no neonatal cholestasis, favourable outcome,
= 5, six biopsies). Hepatocytes containing Z-AAT polymers were abundant in all groups whereas NCC showed higher expression of genes related to liver fibrosis/cirrhosis and lower expression of genes related to lipid, aldehyde/ketone, and bile acid metabolism. Z-AAT accumulation per se cannot explain the clinical outcomes of PiZZ children; however, changes in the expression of specific genes and pathways involved in lipid, fatty acid, and steroid metabolism appear to reflect the degree of liver injury.
Liver retransplantation (re-LT) accounts for up to 22% after primary liver transplantation (LT), and using donor livers for retransplantation can only be justified by successful outcomes.
A total of ...2,387 adult recipients with 2,778 LT, between 1979 and 2017, were analyzed to determine risk factors and outcome of re-LT in the Netherlands.
Of 2,778 LT, 336 (12.1%) were first, 43 (1.5%) were second, and 12 (0.5%) were third or fourth re-LT. The 5-year patient survival for primary LT, and first, second, and third or fourth re-LT were 74.0%, 70.8%, 63.3%, and 57.1%, respectively (P = 0.10). Recipient age (≤60 years) (OR 1.96, P < 0.001), era (1979-2006) (OR 1.56, P = 0.003), donor after circulatory death (DCD) (OR 1.96, P < 0.001), and cold ischemia time (CIT) (>9 h) (OR 1.42, P = 0.007) were significant risk factors for retransplantation after primary LT.
Recipient age, era, DCD, and prolonged CIT were identified as parameters for retransplantation. The outcome after the first re-LT was good, and comparable to those of primary transplants. Survival after multiple re-LT was not significantly different from the first retransplant group, legitimizing third and fourth re-LT to well-selected patients.
Presentation of autoimmune hepatitis (AIH) can differ from nonacute to acute autoimmune hepatitis (A‐AIH) with jaundice and acute severe autoimmune hepatitis (AS‐AIH) with jaundice and coagulopathy. ...The aim of the study was to evaluate the short‐term prognosis of different presentations of AIH and the influence of liver function improvement on short‐term prognosis. In this single‐center retrospective cohort study, AIH patients with repeatedly tested liver function at diagnosis and during at least 1 year of follow‐up were included. A‐AIH was defined as bilirubin >45 µmol and international normalized ratio (INR) <1.5. AS‐AIH was defined as bilirubin level >45 µmol/L and INR ≥1.5. Of the 81 included patients, 17 (21%) presented with A‐AIH, and 14 (17%) presented with AS‐AIH. After the start of immunosuppressive therapy, bilirubin, albumin, and INR normalized in 70%, 77%, and 69%, respectively, in a median of 2.6 months, 3 months, and 4 weeks, respectively, in patients with A‐AIH and AS‐AIH. Liver transplantation (LT)–free survival rate was 100% in nonacute AIH, 94% in A‐AIH, and 57% in AS‐AIH at 12 months after diagnosis. An increase of INR or bilirubin at 2 weeks was the best predictive factor for the need of LT within 12 months with a Youden’s index of 0.85. A‐AIH was present in 21%, and AS‐AIH was present in 17% of AIH patients. In the majority of patients, bilirubin, albumin, and INR normalized in the first months of treatment. Deterioration of liver function after 2 weeks of treatment should lead to rapid evaluation for LT and consideration of second‐line medication.
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