Clinical update on the efficacy of anti-SARS-CoV-2 mRNA vaccines in patients on the waiting list for liver transplantation and in liver transplant recipients.
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ABSTRACT:
SUBMITTER: Toniutto P
PROVIDER: S-EPMC8318693 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Clinical update on the efficacy of anti-SARS-CoV-2 mRNA vaccines in patients on the waiting list for liver transplantation and in liver transplant recipients.
Toniutto Pierluigi P Aghemo Alessio A Grossi Paolo P Burra Patrizia P
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 20210729 10
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Project description:BackgroundSarcopenia at the time of liver transplantation (LT) is an established risk factor for mortality following LT. However, most studies in this context have defined sarcopenia by one-time, static measurements. The aims of this study were (I) to determine the impact of the rate of muscle loss in waitlisted LT recipients on post-LT outcomes and (II) to identify patterns of serum metabolites associated with patients with more progressive sarcopenia.MethodsPatients undergoing liver transplant from 2008 to 2018 who received more than one computed tomography (CT) scans within 12 months prior to liver transplant were included (n=61). The psoas muscle index (PMI) was calculated using Slice-O-Matic software and corrected for patient height (m2). Patients were classified into two groups based the rate of reduction in PMI-high wasting [HW; change in PMI (ΔPMI) ≤-1%/month] and low wasting (LW; ΔPMI >-1%/month). Pre-transplant serum metabolic profiles were collected using nuclear magnetic resonance (NMR) spectroscopy. Living kidney donor sera was used as healthy controls.ResultsMedian ΔPMI was -2.0%/month in HW and -0.15%/month in LW patients (P<0.001). Post-transplant 1-year mortality was significantly higher in HW patients. There were no significant differences in metabolite concentrations between HW and LW patients. However, perturbations in taurine, sarcosine, betaine and the aromatic amino acids (AAAs), were observed in patients with liver disease as compared to healthy controls. Liver disease was also associated with a decrease in lipoprotein profiles, especially high-density lipoprotein (HDL) particles.ConclusionsIn patients undergoing LT, the rate of progression of sarcopenia is a strong prognostic indicator of post-LT death. Serum metabolite profiles were not characteristically unique to HW patients, and most closely resemble derangements associated with chronic liver disease.
| S-EPMC11634410 | biostudies-literature
Project description:BackgroundUnder the current liver-transplantation policy, donor organs are offered to patients with the highest risk of death.MethodsUsing data derived from all adult candidates for primary liver transplantation who were registered with the Organ Procurement and Transplantation Network in 2005 and 2006, we developed and validated a multivariable survival model to predict mortality at 90 days after registration. The predictor variable was the Model for End-Stage Liver Disease (MELD) score with and without the addition of the serum sodium concentration. The MELD score (on a scale of 6 to 40, with higher values indicating more severe disease) is calculated on the basis of the serum bilirubin and creatinine concentrations and the international normalized ratio for the prothrombin time.ResultsIn 2005, there were 6769 registrants, including 1781 who underwent liver transplantation and 422 who died within 90 days after registration on the waiting list. Both the MELD score and the serum sodium concentration were significantly associated with mortality (hazard ratio for death, 1.21 per MELD point and 1.05 per 1-unit decrease in the serum sodium concentration for values between 125 and 140 mmol per liter; P<0.001 for both variables). Furthermore, a significant interaction was found between the MELD score and the serum sodium concentration, indicating that the effect of the serum sodium concentration was greater in patients with a low MELD score. When applied to the data from 2006, when 477 patients died within 3 months after registration on the waiting list, the combination of the MELD score and the serum sodium concentration was considerably higher than the MELD score alone in 32 patients who died (7%). Thus, assignment of priority according to the MELD score combined with the serum sodium concentration might have resulted in transplantation and prevented death.ConclusionsThis population-wide study shows that the MELD score and the serum sodium concentration are important predictors of survival among candidates for liver transplantation.
| S-EPMC4374557 | biostudies-literature
Project description:ImportanceWith continuing improvements in medical devices and more than a decade since the 2006 United Network for Organ Sharing (UNOS) allocation policy, it is pertinent to assess survival among patients on the heart transplantation waiting list, especially given the recently approved 2018 UNOS allocation policy.ObjectivesTo assess survival outcomes among patients on the heart transplant waiting list during the past 3 decades and to examine the association of ventricular assist devices (VADs) and the 2006 UNOS allocation policy with survival.Design, setting, and participantsA retrospective cross-sectional used the UNOS database to perform an analysis of 95 323 candidates wait-listed for heart transplantation between January 1, 1987, and December 29, 2017. Candidates for all types of combined transplants were excluded (n = 2087). Patients were followed up from the time of listing to death, transplantation, or removal from the list due to clinical improvement. Competing-risk, Kaplan-Meier, and multivariable Cox proportional hazards regression analyses were used.Main outcomes and measuresThe analysis involved an unadjusted and adjusted survival analysis in which the primary outcome was death on the waiting list. Because of changing waiting list preferences and policies during the study period, the intrinsic risk of death for wait-listed candidates was assessed by individually analyzing, comparing, and adjusting for several candidate risk factors.ResultsIn total, 95 323 candidates (72 915 men [76.5%]; mean [SD] age, 51.9 [12.0] years) were studied. In the setting of changes in listing preferences, 1-year survival on the waiting list increased from 34.1% in 1987-1990 to 67.8% in 2011-2017 (difference in proportions, 0.34%; 95% CI, 0.32%-0.36%; P < .001). The 1-year waiting list survival for candidates with VADs increased from 10.2% in 1996-2000 to 70.0% in 2011-2017 (difference in proportions, 0.60%; 95% CI, 0.58%-0.62%; P < .001). Similarly, in the setting of changing mechanical circulatory support indications, the 1-year waiting list survival for patients without VADs increased from 53.9% in 1996-2000 to 66.5% in 2011-2017 (difference in proportions, 0.13%; 95% CI, 0.12%-0.14%; P < .001). In the decade prior to the 2006 UNOS allocation policy, the 1-year waiting list survival was 51.1%, while in the decade after it was 63.9% (difference in proportions, 0.13%; 95% CI, 0.12%-0.14%; P < .001). In adjusted analysis, each time period after 1987-1990 had a marked decrease in waiting list mortality.Conclusions and relevanceThis study found temporally associated increases in heart transplant waiting list survival for all patient groups (with or without VADs, UNOS status 1 and status 2 candidates, and candidates with poor functional status).
| S-EPMC7675100 | biostudies-literature
Project description:Sarcopenia predicts morbidity and mortality in adults with end-stage liver disease (ESLD) and is determined by total psoas muscle area (tPMA) measurement from computed tomography (CT) imaging. Recently developed pediatric age- and sex-specific tPMA growth curves provide the opportunity to ascertain prevalence and impact of sarcopenia in children awaiting liver transplantation (LT). This retrospective single-center study evaluated sarcopenia in children between 1 and 16 years with ESLD and a clinically indicated abdominal CT less than 3 months before first isolated LT. Sarcopenia was defined as tPMA z score less than -2 measured at the intervertebral L4-5 level. Patient demographic, biochemical, and outcome data were recorded. tPMA was compared with other measures of nutritional status using univariate and multivariate logistic analyses. Outcome measures included 1-year morbidity events and mortality after LT. CT images from 25 (64% female) children with median age of 5.50 (interquartile range [IQR], 3.75-11.33) years were reviewed. Ten children (40%) had a tPMA z score less than -2. Sarcopenia was associated with lower z scores for weight (odds ratio [OR], 0.38; P = 0.02), height (OR, 0.32; P = 0.03), and nutritional support before LT (OR, 12.93; P = 0.01). Sarcopenic children had a longer duration of pediatric intensive care unit (PICU) stay (3.50 [IQR, 3.00-6.00] versus 2.00 [IQR, 2.00-3.50] days; P = 0.03). Sarcopenia was prevalent in 40% of children with ESLD awaiting LT, and lower tPMA z score was associated with deficient anthropometrics and need for nutritional support before LT. Post-LT PICU duration was increased in children with sarcopenia, reflecting adverse outcomes associated with muscle loss. Further studies are needed to elucidate the underlying mechanisms of sarcopenia in children with ESLD.
| S-EPMC8248423 | biostudies-literature
Project description:Patients with chronic liver disease and patients after solid organ transplantation (SOT) are vulnerable to severe coronavirus disease 2019 (COVID-19). We evaluated fears, attitudes, and opinions associated with COVID-19 in 365 SOT recipients (95% liver, 5% pancreas/kidney), 112 SOT candidates, and 394 immediate household contacts in 2 German transplant centers. Seven (1.5%) patients and 10 (2.5%) controls had contact with confirmed COVID-19 cases. Fear of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was expressed by 65% of SOT recipients and by 55% of SOT candidates. SOT recipients had higher levels of fear of infection and more often wore personal protective gear than household controls. Female sex, steroid treatment, and using the local newspaper as a primary source of information were independently associated with expressed fear of infection in SOT recipients. Younger age and more recent transplantation correlated with concerns about severe COVID-19 expressed by patients and with concerns about worse medical care expressed by household controls. One third of the patients expressed fear that immunosuppression could worsen COVID-19 but only 15% used the transplantation center as a source of information. These data show that fears associated with the SARS-CoV-2 pandemic are frequently expressed but measures to prevent infection are regularly followed by patients before and after SOT.
| S-EPMC7300874 | biostudies-literature
Project description:BackgroundLiver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear.MethodsWe longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs (n = 44) and LTRs (n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4+ and CD8+ T-cell responses.ResultsHere, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4+ T-cell responses. However, spike-specific CD4+ T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8+ T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4+ and CD8+ T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8+ T-cell responses after a third vaccination in HDs or LTRs.ConclusionsThe third mRNA vaccination improves both humoral responses and spike-specific CD4+ T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8+ T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8+ T-cell responses in LTRs and HDs.
| S-EPMC10897323 | biostudies-literature
Project description:The availability of oral direct-acting antivirals has altered the hepatitis C virus (HCV) treatment paradigm for both pre-liver transplant (LT) and post-LT patients. There is a perceived trade-off between pre-LT versus post-LT treatment of HCV-treatment may improve liver function but potentially decrease the likelihood of a necessary LT. Our objective was to identify LT-eligible patients with decompensated cirrhosis who would benefit (and not benefit) from pre-LT treatment based on their Model for End-Stage Liver Disease (MELD) scores. We simulated a virtual trial comparing long-term outcomes of pre-LT versus post-LT HCV treatment with oral direct-acting antivirals for patients with MELD scores between 10 and 40. We developed a Markov-based microsimulation model, which simulated the life course of patients on the transplant waiting list and after LT. Simulation of LT integrated data from recent trials of oral direct-acting antivirals (SOLAR 1 and 2), the United Network for Organ Sharing (UNOS), and other studies. The outcomes of the model included life expectancy, 1-year and 5-year patient survival, and mortality. Model-predicted patient survival was validated with UNOS data. We found that, at the national level, treating HCV before LT increased life expectancy if MELD was ≤27 but could decrease life expectancy at higher MELD scores. Depending on the UNOS region, the threshold MELD score to treat HCV pre-LT varied between 23 and 27 and was lower for UNOS regions 3, 10, and 11 and higher for regions 1, 2, 4, 5, 8, and 9. Sensitivity analysis showed that the thresholds were stable.ConclusionOur findings suggest that the optimal MELD threshold below which decompensated cirrhosis patients should receive HCV treatment while awaiting LT is between 23 and 27, depending on the UNOS region. (Hepatology 2017;65:777-788).
| S-EPMC5319880 | biostudies-literature
Project description:We investigated the possibility that patients with hepatocellular carcinoma (HCC) listed for liver transplant with tumors just outside stage T2 size criteria may be inaccurately reported as just meeting the tumor size criteria for transplant. The United Network for Organ Sharing/Standard Transplant Analysis and Research database identified 12,958 patients listed for liver transplants with HCC exception points from 2006 to 2013, 9,168 of whom were listed with one tumor. A logistic power peak function was fitted to the single-tumor size histogram, with the fitted values representing unbiased expected values. The difference between the observed and expected tumor counts for 2.0 cm and 5.0 cm was 238 (22%) and 66 (57%), respectively. This suggests that up to 304 (3.0%) patients with tumors outside of transplant criteria had their measurements recorded at the margins of eligibility. A risk-adjusted Poisson model evaluated the ratio of observed to expected HCC recurrence by tumor size. There were 435 HCC recurrences among 6,049 transplants. Only 2.0-cm tumors had observed to expected recurrence differing from 1 (ratio 0.73, 95% confidence interval 0.57-0.94), indicating a 27% lower than expected rate of recurrence.ConclusionHigher than expected observed tumor counts at the lower transplant criteria margin were corroborated by lower than expected HCC recurrence, suggesting that tumor sizes at the margins of HCC transplant criteria may be subject to inaccurate reporting. (Hepatology 2017;66:1144-1150).
| S-EPMC5605395 | biostudies-literature
Project description:Sarcopenia is a prevalent condition that predicts prognosis in patients awaiting liver transplantation (LT). The gold standard for the diagnosis of sarcopenia is the assessment of the muscular area at L3 with computed tomography (CT) scan (skeletal muscle index [SMI]), but the routine use of CT scan is limited in clinical practice. Thus, we designed a single-center observational study aimed to evaluate the clinical factors associated with the presence of sarcopenia by SMI, and to build a score capable of predicting or excluding the presence of sarcopenia in patients on the LT waiting list (WL). Binary logistic regression analysis was performed to establish the factors independently associated with sarcopenia, and the Sarcopenia Hospital Italiano de Buenos Aires (HIBA) score was built from the resulting model after internal validation analysis by bootstrapping and correction for optimism. The predictive capability of mortality on the WL was evaluated with competing risk regression analysis. A total of 215 patients with cirrhosis on the LT WL were included. The independent factors associated with the presence of sarcopenia were male sex (odds ratio [OR]: 6.09, p < 0.001), body mass index (OR: 0.74, p < 0.001), Child Pugh (OR: 1.44, p < 0.001), and the ratio creatinine/Cystatin C (OR: 0.03, p = 0.007). The Sarcopenia HIBA score constructed with these variables showed an area under the curve of 0.862. During follow-up, 77 (36%) patients underwent LT, 46 (21%) died, and 92 (43%) remained alive. After adjusting for Model for End-Stage Liver Disease-Sodium, Sarcopenia HIBA score was an independent predictor of WL mortality (subhazard ratio: 1.19; 95% confidence interval 1.01-1.40; p = 0.042). Sarcopenia HIBA score is an easy-to-use, objective, and reliable diagnostic and predictive tool that can be useful to improve the prognostic evaluation and allow identifying a group of patients with a higher risk of death while awaiting LT.
| S-EPMC9234615 | biostudies-literature
Project description:The prevalence of advanced liver disease and listing for liver transplantation is increasing. Prior assessments of quality of care neither incorporate nor emphasize the patient perspective on quality of care, which may impact clinical outcomes. Our aim was to identify patients' perceptions on what constitutes high quality of care, comparing the findings to existing frameworks and assessments to determine if a patient-derived tool assessing quality of care could facilitate efforts to improve health care. We conducted semistructured interviews of patients wait-listed for liver transplantation, asking patients to describe the quality of their health care with a specific focus on how coordination, communication, office visits, hospitalizations, and cost affect their perceptions of the quality of their care. Data collection conducted concurrently with analyses determined emerging themes and saturation. Themes were mapped to an existing quality-of-care conceptual framework. Qualitative analysis revealed thematic saturation after 15 interviews, and an additional 15 interviews were analyzed that confirmed thematic saturation, maximizing the strength of the results. The 30 patients had a median age of 56 years (range, 32-72 years) and included 15 (50%) men. Although patients believed they received a high quality of care, which was substantiated on current existing measures, a qualitative analysis suggested that patient priorities emphasized 5 themes not currently assessed: managing expectations, providing education, responding to patient needs, executing the care plan efficiently, and utilizing interdisciplinary communication and coordination of care. In conclusion, transplant candidates perceived 5 themes that constitute quality of care, and existing quality-of-care measures do not assess these domains, suggesting a role for creating a patient-derived quality-of-care tool to improve health care and clinical outcomes.
| S-EPMC8363064 | biostudies-literature