ABSTRACT
BACKGROUND: The utilization of kidneys donated after circulatory death (DCD) is an important strategy to address the ongoing shortage of organs suitable for transplantation in the United States. However, the nonuse rate of DCD kidneys remains high compared with kidneys donated after brain death (DBD) because of concerns regarding the injury incurred during donor warm ischemia time (DWIT). Therefore, we investigated the impact of DWIT on the risk of death-censored graft failure after DCD kidney transplantation (KT). METHODS: Retrospective analysis was conducted on DCD KTs using the Standard Transplant Analysis and Research data set. The association of DWIT with death-censored graft failure was evaluated using multivariable Cox proportional hazard regression, with reference to DCD KTs with Kidney Donor Risk Index (KDRI) of ≤0.78 and the median DWIT of 26 min. RESULTS: A total of 28 032 DCD kidney-alone transplants between January 2010 and December 2021 were studied. When stratified by KDRI, increasing DWIT was associated with a clinically significant increased risk for death-censored graft failure only in the subset of kidneys with KDRI >1.14 but not in those with KDRI >0.78-≤0.94 and >0.94-≤1.14, compared with the reference group. CONCLUSIONS: We suggest that clinicians should not decline kidneys on the basis of DWIT in favor of potential offers of DBD or other DCD kidneys with shorter DWIT, provided that their KDRI scores are within an acceptable limit. Our study highlights opportunities for more efficient usage of DCD kidneys and improving the shortage of transplantable organs.
ABSTRACT
Importance: Normothermic regional perfusion (NRP) is an emerging recovery modality for transplantable allografts from controlled donation after circulatory death (cDCD) donors. In the US, only 11.4% of liver recipients who are transplanted from a deceased donor receive a cDCD liver. NRP has the potential to safely expand the US donor pool with improved transplant outcomes as compared with standard super rapid recovery (SRR). Objective: To assess outcomes of US liver transplants using controlled donation after circulatory death livers recovered with normothermic regional perfusion vs standard super rapid recovery. Design, Setting, and Participants: This was a retrospective, observational cohort study comparing liver transplant outcomes from cDCD donors recovered by NRP vs SRR. Outcomes of cDCD liver transplant from January 2017 to May 2023 were collated from 17 US transplant centers and included livers recovered by SRR and NRP (thoracoabdominal NRP [TA-NRP] and abdominal NRP [A-NRP]). Seven transplant centers used NRP, allowing for liver allografts to be transplanted at 17 centers; 10 centers imported livers recovered via NRP from other centers. Exposures: cDCD livers were recovered by either NRP or SRR. Main Outcomes and Measures: The primary outcome was ischemic cholangiopathy (IC). Secondary end points included primary nonfunction (PNF), early allograft dysfunction (EAD), biliary anastomotic strictures, posttransplant length of stay (LOS), and patient and graft survival. Results: A total of 242 cDCD livers were included in this study: 136 recovered by SRR and 106 recovered by NRP (TA-NRP, 79 and A-NRP, 27). Median (IQR) NRP and SRR donor age was 30.5 (22-44) years and 36 (27-49) years, respectively. Median (IQR) posttransplant LOS was significantly shorter in the NRP cohort (7 [5-11] days vs 10 [7-16] days; P < .001). PNF occurred only in the SRR allografts group (n = 2). EAD was more common in the SRR cohort (123 of 136 [56.1%] vs 77 of 106 [36.4%]; P = .007). Biliary anastomotic strictures were increased 2.8-fold in SRR recipients (7 of 105 [6.7%] vs 30 of 134 [22.4%]; P = .001). Only SRR recipients had IC (0 vs 12 of 133 [9.0%]; P = .002); IC-free survival by Kaplan-Meier was significantly improved in NRP recipients. Patient and graft survival were comparable between cohorts. Conclusion and Relevance: There was comparable patient and graft survival in liver transplant recipients of cDCD donors recovered by NRP vs SRR, with reduced rates of IC, biliary complications, and EAD in NRP recipients. The feasibility of A-NRP and TA-NRP implementation across multiple US transplant centers supports increasing adoption of NRP to improve organ use, access to transplant, and risk of wait-list mortality.
Subject(s)
Graft Survival , Liver Transplantation , Perfusion , Humans , Female , Male , Retrospective Studies , Middle Aged , Perfusion/methods , United States/epidemiology , Adult , Organ Preservation/methods , Tissue DonorsABSTRACT
The imbalance between organ supply and demand continues to limit the broader benefits of organ transplantation. Machine perfusion (MP) may increase the supply of donor livers by expanding the use of extended-criteria donors. Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network and the Standard Transplant Analysis and Research dataset, we reviewed the effect of MP implementation on the behavior of transplant centers. We identified 15 high-utilizing MP centers that were matched to suitable controls based on volume and geographical proximity. We conducted a differences-in-differences analysis using linear regression to estimate the impact of MP adoption on the transplant centers' donor utilization. We found a significant increase in cold ischemia time and organs with donor warm ischemia time over 30 minutes (P < .05). After removing one outlier center, the analysis showed that these centers through MP accepted overall more donation after circulatory death donors, donation after circulatory death donors over 50 years old, donors with macrovesicular steatosis greater than 30% on liver biopsy, and donor warm ischemia time over 30 minutes (P < .05). MP has allowed centers to expand their use of extended-criteria donors beyond traditional cutoffs and to increase patient access to liver transplantation.
ABSTRACT
PURPOSE OF REVIEW: Over the past decade, donation after circulatory death (DCD) liver transplantation has expanded in the United States due to improved surgical experience and perioperative management. Despite these advances, there remains a reluctance towards broader utilization of DCD liver allografts due to lack of standardized donation process, concern for inferior graft survival, and risk of ischemic cholangiopathy associated with temporary lack of oxygenated perfusion during withdrawal of life-supporting treatment during procurement. RECENT FINDINGS: New perfusion technologies offer potential therapeutic options to mitigate biliary complications and expand utilization of marginal DCD grafts. As these modalities enter routine clinical practice, DCD utilization will continue to increase, and liver allocation policies in turn will evolve to reflect this growing practice. This review describes recent progress in DCD LT, current challenges with utilization of DCD liver allografts, and how novel technologies and policies could impact the future of the field.
Subject(s)
Liver Transplantation , Tissue and Organ Procurement , Humans , United States , Tissue Donors , Death , Perfusion , Retrospective StudiesABSTRACT
The donor operation and the hemodynamics during declaration resulting in donor warm ischemia time have been linked to the outcomes in donation after circulatory death (DCD) liver transplantation (LT). Scrutiny of the donor hemodynamics at the time of withdrawal of life support concluded that a functional donor warm ischemia time may be associated with LT graft failure. Unfortunately, the definition for functional donor warm ischemia time has not reached a consensus-but has almost always incorporated time spent in a hypoxic state. Herein, we reviewed 1114 DCD LT cases performed at the 20 highest volume centers during 2014 and 2018. Donor hypoxia began within 3 minutes of withdrawal of life support for 60% of cases and within 10 minutes for 95% of cases. Graft survival was 88.3% at 1 year and 80.3% at 3 years. Scrutinizing the time spent under hypoxic conditions (oxygen saturation ≤ 80%) during the withdrawal of life support, we found an increasing risk of graft failure as hypoxic time increased from 0 to 16 minutes. After 16 minutes and up to 50 minutes, we did not find any increased risk of graft failure. In conclusion, after 16 minutes of time in hypoxia, the risk of graft failure in DCD LT did not increase. The current evidence suggests that an over-reliance on hypoxia time may lead to an unnecessary increase in DCD liver discard and may not be as useful for predicting graft loss after LT.
Subject(s)
Liver Transplantation , Tissue and Organ Procurement , Humans , Warm Ischemia/adverse effects , Liver Transplantation/adverse effects , Liver Transplantation/methods , Oxygen Saturation , Donor Selection , Risk Factors , Tissue Donors , Hypoxia/etiology , Graft Survival , Retrospective Studies , DeathABSTRACT
HCC recurrence following liver transplantation (LT) is highly morbid and occurs despite strict patient selection criteria. Individualized prediction of post-LT HCC recurrence risk remains an important need. Clinico-radiologic and pathologic data of 4981 patients with HCC undergoing LT from the US Multicenter HCC Transplant Consortium (UMHTC) were analyzed to develop a REcurrent Liver cAncer Prediction ScorE (RELAPSE). Multivariable Fine and Gray competing risk analysis and machine learning algorithms (Random Survival Forest and Classification and Regression Tree models) identified variables to model HCC recurrence. RELAPSE was externally validated in 1160 HCC LT recipients from the European Hepatocellular Cancer Liver Transplant study group. Of 4981 UMHTC patients with HCC undergoing LT, 71.9% were within Milan criteria, 16.1% were initially beyond Milan criteria with 9.4% downstaged before LT, and 12.0% had incidental HCC on explant pathology. Overall and recurrence-free survival at 1, 3, and 5 years was 89.7%, 78.6%, and 69.8% and 86.8%, 74.9%, and 66.7%, respectively, with a 5-year incidence of HCC recurrence of 12.5% (median 16 months) and non-HCC mortality of 20.8%. A multivariable model identified maximum alpha-fetoprotein (HR = 1.35 per-log SD, 95% CI,1.22-1.50, p < 0.001), neutrophil-lymphocyte ratio (HR = 1.16 per-log SD, 95% CI,1.04-1.28, p < 0.006), pathologic maximum tumor diameter (HR = 1.53 per-log SD, 95% CI, 1.35-1.73, p < 0.001), microvascular (HR = 2.37, 95%-CI, 1.87-2.99, p < 0.001) and macrovascular (HR = 3.38, 95% CI, 2.41-4.75, p < 0.001) invasion, and tumor differentiation (moderate HR = 1.75, 95% CI, 1.29-2.37, p < 0.001; poor HR = 2.62, 95% CI, 1.54-3.32, p < 0.001) as independent variables predicting post-LT HCC recurrence (C-statistic = 0.78). Machine learning algorithms incorporating additional covariates improved prediction of recurrence (Random Survival Forest C-statistic = 0.81). Despite significant differences in European Hepatocellular Cancer Liver Transplant recipient radiologic, treatment, and pathologic characteristics, external validation of RELAPSE demonstrated consistent 2- and 5-year recurrence risk discrimination (AUCs 0.77 and 0.75, respectively). We developed and externally validated a RELAPSE score that accurately discriminates post-LT HCC recurrence risk and may allow for individualized post-LT surveillance, immunosuppression modification, and selection of high-risk patients for adjuvant therapies.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Risk Factors , Neoplasm Recurrence, Local/pathology , Retrospective Studies , RecurrenceABSTRACT
Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.
Subject(s)
Fatty Liver , Image Processing, Computer-Assisted , Liver Transplantation , Humans , Alanine Transaminase , Aspartate Aminotransferases , Bilirubin , Biopsy , Fatty Liver/diagnostic imaging , Fatty Liver/pathology , Liver/diagnostic imaging , Liver/pathology , Liver Transplantation/methods , Software , Image Processing, Computer-Assisted/methodsABSTRACT
NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Adult , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/epidemiology , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/surgery , Liver Transplantation/adverse effects , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Risk FactorsABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has disrupted normal operating procedures at transplant centers. With the possibility that COVID-19 infection carries an overall 4% mortality rate and potentially a 24% mortality rate among the immunocompromised transplant recipients, many transplant centers considered the possibility of slowing down and even potentially pausing all transplants. Many proposals regarding the need for pausing organ transplants exist; however, much remains unknown. Whereas the impact of the COVID-19 pandemic on the overall healthcare system is unknown, the potential impact of pausing organ transplants over a period can be estimated. This study presents a model for evaluating the impact of pausing liver transplants over a spectrum of model for end-stage liver disease-sodium (MELD-Na) scores. Our model accounts for two potential risks of a pause: (1) the waitlist mortality of all patients who do not receive liver transplants during the pause period, and (2) the impact of a longer waiting list due to the pause of liver transplants and the continuous accrual of new patients. Using over 12 years of liver transplant data from the United Network for Organ Sharing and a system of differential equations, we estimate the threshold probability above which a decision maker should pause liver transplants to reduce the loss of patient life months. We also compare different pause policies to illustrate the value of patient-specific and center-specific approaches. Finally, we analyze how capacity constraints affect the loss of patient life months and the length of the waiting list. The results of this study are useful to decision makers in deciding whether and how to pause organ transplants during a pandemic. The results are also useful to patients (and their care providers) who are waiting for organ transplants.
ABSTRACT
Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.
Subject(s)
Carcinoma, Hepatocellular , Kidney Transplantation , Liver Neoplasms , Tissue and Organ Procurement , Adult , Death , Graft Survival , Humans , Middle Aged , Organ Preservation/methods , Perfusion/methods , Retrospective Studies , Tissue Donors , United StatesABSTRACT
PURPOSE OF REVIEW: Living organ donation provides improved access to transplantation, thereby shortening transplant wait times and allowing for more deceased organ transplants. However, disparity in access to living donation has resulted in decreased rates of living donor transplants for some populations of patients. RECENT FINDINGS: Though there have been marked improvements in deceased donor equity, there are still challenges as it relates to gender, racial/ethnic, and socio-economic disparity. Improvements in living donation rates in Hispanic and Asian populations are tempered by challenges in African American rates of organ donation. Socio-economic disparity may drive gender disparities in organ donation resulting in disproportionate female living donors. Tailored approaches relating to language-specific interventions as well as directed educational efforts have helped mitigate disparity. Additionally, the use of apolipoprotein1 testing and modifications of glomerular filtration rate calculators may improve rates of African American donation. This review will evaluate recent data in living donor disparity as well as highlight successes in mitigating disparity. SUMMARY: Though there are still challenges in living donor disparity, many efforts at tailoring education and access as well as modifying living donor evaluation and identifying systemic policy changes may result in improvements in living donation rates.
Subject(s)
Kidney Transplantation , Organ Transplantation , Tissue and Organ Procurement , Black or African American , Female , Humans , Living DonorsABSTRACT
The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Aged , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/epidemiology , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Middle Aged , Retrospective Studies , Risk Assessment , Survival Rate , United States/epidemiologyABSTRACT
The rate-determining step in free radical lipid peroxidation is the propagation of the peroxyl radical, where generally two types of reactions occur: (a) hydrogen-atom transfer (HAT) from a donor to the peroxyl radical; (b) peroxyl radical addition (PRA) to a "CâC" double bond. Peroxyl radical clocks have been used to determine the rate constants of HAT reactions (kH), but no radical clock is available to measure the rate constants of PRA reactions (kadd). In this work, we modified the analytical approach on the linoleate-based peroxyl radical clock to enable the simultaneous measurement of both kH and kadd. Compared to the original approach, this new approach involves the use of a strong reducing agent, LiAlH4, to completely reduce both HAT and PRA-derived products and the relative quantitation of total linoleate oxidation products with or without reduction. The new approach was then applied to measuring the kH and kadd values for several series of organic substrates, including para- and meta-substituted styrenes, substituted conjugated dienes, and cyclic alkenes. Furthermore, the kH and kadd values for a variety of biologically important lipids were determined for the first time, including conjugated fatty acids, sterols, coenzyme Q10, and lipophilic vitamins, such as vitamins D3 and A.
ABSTRACT
BACKGROUND AND AIMS: The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013). APPROACH AND RESULTS: Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P < 0.001). CONCLUSIONS: In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
Subject(s)
Ablation Techniques/methods , Carcinoma, Hepatocellular/therapy , End Stage Liver Disease/therapy , Liver Neoplasms/therapy , Liver Transplantation/statistics & numerical data , Neoplasm Recurrence, Local/epidemiology , Ablation Techniques/statistics & numerical data , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Disease-Free Survival , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , End Stage Liver Disease/pathology , Female , Follow-Up Studies , Humans , Liver/diagnostic imaging , Liver/pathology , Liver/radiation effects , Liver/surgery , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/standards , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Radiotherapy, Adjuvant/methods , Radiotherapy, Adjuvant/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Tissue and Organ Procurement/standards , Tumor Burden/radiation effects , United States/epidemiology , Waiting Lists/mortalityABSTRACT
BACKGROUND: Currently, no surveillance guidelines for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) exist. In this retrospective, multicenter study, we have investigated the role of surveillance imaging on postrecurrence outcomes. METHODS: Patients with recurrent HCC after LT from 2002 to 2016 were reviewed from 3 transplant centers (University of California San Francisco, Mayo Clinic Florida, and University of Toronto). For this study, we proposed the term cumulative exposure to surveillance (CETS) as a way to define the cumulative sum of all the protected intervals that each surveillance test provides. In our analysis, CETS has been treated as a continuous variable in months. RESULTS: Two hundred twenty-three patients from 3 centers had recurrent HCC post-LT. The median follow-up was 31.3 months, and median time to recurrence was 13.3 months. Increasing CETS was associated with improved postrecurrence survival (hazard ratio, 0.94; P < 0.01) as was treatment of recurrence with resection or ablation (hazard ratio, 0.31; P < 0.001). An receiver operating characteristic curve (area under the curve, 0.64) for CETS covariate showed that 252 days of coverage (or 3 surveillance scans) within the first 24 months provided the highest probability for aggressive postrecurrence treatment. CONCLUSIONS: In this review of 223 patients with post-LT HCC recurrence, we found that increasing CETS does lead to improved postrecurrence survival as well as a higher probability for aggressive recurrence treatment. We found that 252 days of monitoring (ie, 3 surveillance scans) in the first 24 months was associated with the ability to offer potentially curative treatment.
Subject(s)
Carcinoma, Hepatocellular/surgery , Early Detection of Cancer , Liver Neoplasms/surgery , Liver Transplantation , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/diagnostic imaging , Tomography, X-Ray Computed , Biopsy , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Female , Florida , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/therapy , Ontario , Predictive Value of Tests , Retrospective Studies , San Francisco , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). BACKGROUND: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. METHODS: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. RESULTS: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil-lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). CONCLUSIONS: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.