LINKED CONTENT
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
Display omitted
•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.
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.).
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.
Telaprevir for retreatment of HCV infection Zeuzem, Stefan; Andreone, Pietro; Pol, Stanislas ...
New England journal of medicine/The New England journal of medicine,
06/2011, Volume:
364, Issue:
25
Journal Article
Peer reviewed
Open access
Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.
In this randomized, phase 3 ...trial, we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug.
Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%).
Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Pharmaceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.).
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.
https://www.wileyhealthlearning.com/Activity/7201351/disclaimerspopup.aspx
Background and Aims
The United Network for Organ Sharing’s Model for End‐Stage Liver Disease (UNOS‐MELD) score is the basis of liver allocation in the Eurotransplant region. It was constructed ...20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the United States. Therefore, this study refits the MELD (reMELD) for the Eurotransplant region.
Approach and Results
All adult patients listed for a first liver transplantation between January 1, 2007, and December 31, 2018, were included. Data were randomly split in a training set (70%) and a validation set (30%). In the training data, generalized additive models with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log‐likelihood were chosen for the final models. The refit models were tested in the validation data with C‐indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS‐MELD. The correlation between scores and survival of prioritized patients was calculated. A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7‐2.5, bilirubin 0.3‐27, international normalized ratio 0.1‐2.6, and sodium 120‐139. ReMELD and reMELD‐Na showed C‐indices of 0.866 and 0.869, respectively. ReMELD‐Na prioritized patients with 1.6 times higher 90‐day mortality probabilities compared to UNOS‐MELD.
Conclusions
Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD‐Na was significantly higher than UNOS‐MELD. ReMELD prioritized patients with higher 90‐day mortality rates. Thus, reMELD(‐Na) should replace UNOS‐MELD for liver graft allocation in the Eurotransplant region.
Liver function is measured regularly in liver transplantation (LT) candidates. Currently, these previous disease development data are not used for survival prediction. By constructing and validating ...joint models (JMs), we aimed to predict the outcome based on all available data, using both disease severity and its rate of change over time. Adult LT candidates listed in Eurotransplant between 2007 and 2018 (n = 16 283) and UNOS between 2016 and 2019 (n = 30 533) were included. Patients with acute liver failure, exception points, or priority status were excluded. Longitudinal MELD(‐Na) data were modeled using spline‐based mixed effects. Waiting list survival was modeled with Cox proportional hazards models. The JMs combined the longitudinal and survival analysis. JM 90‐day mortality prediction performance was compared to MELD(‐Na) in the validation cohorts. MELD(‐Na) score and its rate of change over time significantly influenced patient survival. The JMs significantly outperformed the MELD(‐Na) score at baseline and during follow‐up. At baseline, MELD‐JM AUC and MELD AUC were 0.94 (0.92–0.95) and 0.87 (0.85–0.89), respectively. MELDNa‐JM AUC was 0.91 (0.89–0.93) and MELD‐Na AUC was 0.84 (0.81–0.87). The JMs were significantly (p < .001) more accurate than MELD(‐Na). After 90 days, we ranked patients for LT based on their MELD‐Na and MELDNa‐JM survival rates, showing that MELDNa‐JM‐prioritized patients had three times higher waiting list mortality.
Dynamic prediction of waitlist survival using joint modeling of liver disease development over time better predicts survival, compared to the model for end‐stage liver disease sodium score, for both Eurotransplant and UNOS liver transplant candidates. See Bittermann and Abt's editorial on page 3511‐3512.
Background
Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2‐4 weeks. The ...safety and efficacy of both strategies have been unexplored.
Methods
We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (<2 weeks) or delayed AZA initiation (≥2 weeks). Primary outcome was discontinuation of AZA in the first year of treatment. Cox regression and propensity score matching was performed to determine difference in outcomes between groups.
Results
Patients with early AZA initiation had significantly lower transaminases and bilirubin at baseline. Discontinuation rates of AZA did not differ between early and delayed starters (16.6% vs 14.2%), which did not reach statistical significance (hazard ratio 0.97, 95% confidence interval 0.61‐1.55, P = .90). Stratification according to baseline disease activity or propensity score matching did not alter the results. Main reason for AZA discontinuation was intolerance to treatment (14.0% vs 13.2%, P = .78) with nausea and vomiting as main side effects. AIH remission rates were comparable among groups.
Conclusion
The discontinuation rate of AZA in AIH treatment is ~15% in the first year of treatment. Early or delayed AZA initiation does not differ in remission and discontinuation rates in AIH induction therapy. Our data suggest that either strategy may be used as part of AIH treatment.
PDF
