Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Methods: Data on adult LT recipients who received MELD exception for HCC between 2/29/02-12/31/13 and had CT scan anytime 6 months prior to LT were reviewed (N=118). All available CT scan DICOM (Digital Imaging and Communications in Medicine) files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB®. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat and bone mineral density (BMD) were taken at the bottom of the 11th thoracic vertebral level. Results: Thirty-two patients (28%) died during the median follow up of 4.4 years. Number of HCC lesions (HR=2.72; P<0.001), BMD (HR=0.90/HU; P=0.03), pre-LT loco-regional therapy (HR=0.34; P<0.001) and donor age (HR=1.05; P<0.001) were the independent predictors of post-LT mortality. DMG area did not affect post-LT survival. Conclusion: In addition to number of HCC lesions and pre-LT loco-regional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes.
In the changing landscape of liver transplantation (LT), we are now evaluating older and sicker patients with more cardiovascular comorbidities, and the spectrum of cardiovascular disease is uniquely physiologically impacted by end‐stage liver disease. Cardiac complications are now the leading cause of morbidity and mortality in LT recipients, and the pretransplant risk is exacerbated immediately during the transplant operation and continues long term under the umbrella of immunosuppression. Accurate risk estimation of cardiac complications before LT is paramount to guide allocation of limited health care resources and to improve both short‐term and long‐term clinical outcomes for patients. Current screening and diagnostic testing are limited in their capacity to accurately identify early coronary disease and myocardial dysfunction in persons with end‐stage liver disease physiology. Furthermore, a number of testing modalities have not been evaluated in patients with end‐stage liver disease. As a result, there is wide variation in cardiac risk assessment practices across transplant centers. In this review, we propose a definition for defining cardiac events in LT, evaluate the current evidence for surgery‐related, short‐term and long‐term cardiac risk assessment in LT candidates, propose an evidence‐based testing algorithm, and highlight specific gaps in knowledge and current controversies, identifying areas for future research.
PurposeThe prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is often uncertain. We aimed to utilize analytic morphomics, a high-throughput imaging analysis, to assess if body composition is predictive of post-TACE survival.Materials and MethodsWe included patients from a single center (Ann Arbor VA)who had TACE as the primary treatment forHCC and had a pre-treatment computed tomography scans. Univariate analysis and multivariate conditional inference tree analysis were utilized to identify the morphomic characteristics predictive of 1-year survival. Results were validated in an external cohort(University of MichiganHealth System) ofHCC patientswho underwent TACE as their primary treatment.ResultsIn the 75 patients in the derivation cohort, median survival was 439 (interquartile range, 377 to 685) days from receipt of TACE, with 1-year survival of 61%. Visceral fat density (VFD) was the only morphomic factor predictive of overall and 1-year survival (p < 0.001). Patients with VFD above the 56th percentile had a 1-year survival of 39% versus 78% for those below the 56th percentile. VFD also correlated with 1-year survival in the external validation cohort (44% vs. 72%, p < 0.001). In a secondary analysis, patients with higher VFD were significantly more likely to experience hepatic decompensation after TACE (p < 0.001).ConclusionVFD served as an objective predictor of mortality in patients undergoing TACE, possibly through its ability to predict hepatic decompensation. VFD may serve as a radiographic biomarker in predicting TACE outcomes.
We aimed to understand the contemporary changes in the characteristics and the determinants of outcomes among simultaneous liver-kidney transplantation (SLKT) recipients at 6 liver transplantation centers in the United States. We retrospectively enrolled SLKT recipients between 2002 and 2017 in the US Multicenter SLKT Consortium. We analyzed time-related trends in recipient characteristics and outcomes with linear regression and nonparametric methods. Clustered Cox regression determined the factors associated with 1-year and overall survival. We enrolled 572 patients. We found significant changes in the clinical characteristics of SLKT recipients: as compared with 2002, recipients in 2017 were older (59 versus 52 years; P < 0.001) and more likely to have chronic kidney disease (71% versus 33%; P < 0.001). There was a marked improvement in 1-year survival during the study period: 89% in 2002 versus 96% in 2017 (P < 0.001). We found that the drivers of 1-year mortality were SLKT year, hemodialysis at listing, donor distance, and delayed kidney allograft function. The drivers of overall mortality were an indication of acute kidney dysfunction, body mass index, hypertension, creatinine at SLKT, ventilation at SLKT, and donor quality. In this contemporary cohort of SLKT recipients, we highlight changes in the clinical characteristics of recipients. Further, we identify the determinants of 1-year and overall survival to highlight the variables that require the greatest attention to optimize outcomes.
Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m 2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (β = −6.22 ± 2.16 mL/minute/1.73 m 2 ; P = 0.004), NASH (β = −7.27 ± 3.27 mL/ minute/1.73 m 2 ; P = 0.027), and delayed kidney graft function (β = −7.25 ± 2.26 mL/minute/1.73 m 2 ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients.
Background/Aim Transarterial chemoembolization (TACE) is the recommended treatment for patients with Barcelona stage B hepatocellular carcinoma; however, community practice varies from these American Association for the Study of Liver Diseases guidelines. In this study, we sought to assess factors determining outcome after TACE and examine adherence to guidelines. Methods From January 2006 to December 2012, 308 patients with newly diagnosed HCC were treated at the Veterans Affairs (VA) Ann Arbor Healthcare System. Of these, 109 patients underwent TACE. The primary outcome measured mortality. Kaplan–Meier analysis was used to determine the cumulative probability of death. Cox regression was used to assess the predictors of mortality. Results The median age of the 109 patients was 60 years (48–90), 97 % were males and 82 % had chronic HCV infection. The median size of the largest lesion was 4 cm, 51 % were multifocal, and portal vein thrombosis was present in 3.6 %. Sixty-two patients died after median 333 days from the index TACE treatment. Median overall survival from index TACE was 11.2 months. Unadjusted 1-, 2-, and 3-year survival was 64, 35, and 24 %, respectively. CTP score (B vs. A: HR 2.51, p = 0.002; C vs. A: HR 7.96, p < 0.0001) and presence of complete response to TACE (HR 0.51, p = 0.004) were independent predictors of mortality. Barcelona stage (p = 0.88) and performance status as measured by ECOG (p = 0.98) were not associated with mortality after TACE. Conclusions In this community based, single VA center study, we found a significant number of patients beyond Barcelona stage B were treated with TACE. Advanced TNM stage, poor liver synthetic function and achieving CR with TACE were better predictors of mortality than guideline-directed decisions based on Barcelona stage. These factors may be useful to guide future patient selection for TACE.
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/7-2-reading-su.html a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/7-2-interview-su.html the interview with the author
Objectives:Existing prognostic models for patients with hepatocellular carcinoma (HCC) have limitations. Analytic morphomics, a novel process to measure body composition using computational image-processing algorithms, may offer further prognostic information. The aim of this study was to develop and validate a prognostic model for HCC patients using body composition features and objective clinical information.Methods:Using computed tomography scans from a cohort of HCC patients at the VA Ann Arbor Healthcare System between January 2006 and December 2013, we developed a prognostic model using analytic morphomics and routine clinical data based on multivariate Cox regression and regularization methods. We assessed model performance using C-statistics and validated predicted survival probabilities. We validated model performance in an external cohort of HCC patients from Parkland Hospital, a safety-net health system in Dallas County.Results:The derivation cohort consisted of 204 HCC patients (20.1% Barcelona Clinic Liver Cancer classification (BCLC) 0/A), and the validation cohort had 225 patients (22.2% BCLC 0/A). The analytic morphomics model had good prognostic accuracy in the derivation cohort (C-statistic 0.80, 95% confidence interval (CI) 0.71–0.89) and external validation cohort (C-statistic 0.75, 95% CI 0.68–0.82). The accuracy of the analytic morphomics model was significantly higher than that of TNM and BCLC staging systems in derivation (P<0.001 for both) and validation (P<0.001 for both) cohorts. For calibration, mean absolute errors in predicted 1-year survival probabilities were 5.3% (90% quantile of 7.5%) and 7.6% (90% quantile of 12.5%) in the derivation and validation cohorts, respectively.Conclusion:Body composition features, combined with readily available clinical data, can provide valuable prognostic information for patients with newly diagnosed HCC.
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