Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.

BACKGROUND & AIMS: Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. Previously we reported that the liver graft assessment following transplantation (L-GrAFT7) risk score was superior to binary EAD or the model for early allograft function (MEAF) score for estimating 3-month graft failure-free survival in a single-center derivation cohort. Herein, we sought to externally validate L-GrAFT7, and compare its prognostic performance to EAD and MEAF. METHODS: Accuracies of L-GrAFT7, EAD, and MEAF were compared in a 3-center US validation cohort (n = 3,201), and a Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion (NMP) trial cohort (n = 222); characteristics were compared to assess generalizability. RESULTS: Compared to the derivation cohort, patients in the validation and NMP trial cohort had lower recipient median MELD scores; were less likely to require pretransplant hospitalization, renal replacement therapy or mechanical ventilation; and had superior 1-year overall (90% and 95% vs. 84%) and graft failure-free (88% and 93% vs. 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; p <0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT7 maintained an excellent validation AUROC of 0.78, significantly superior to binary EAD (AUROC 0.68, p = 0.001) and MEAF scores (AUROC 0.72, p <0.001). In post hoc analysis of the COPE NMP trial, the highest tertile of L-GrAFT7 was significantly associated with time to liver allograft (hazard ratio [HR] 2.17, p = 0.016), Clavien ≥IIIB (HR 2.60, p = 0.034) and ≥IVa (HR 4.99, p = 0.011) complications; post-LT length of hospitalization (p = 0.002); and renal replacement therapy (odds ratio 3.62, p = 0.016). CONCLUSIONS: We have validated the L-GrAFT7 risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to existing scores. L-GrAFT7 may standardize grading of early hepatic allograft function and serve as a clinical endpoint in translational studies (www.lgraft.com). LAY SUMMARY: Early allograft dysfunction negatively affects outcomes following liver transplantation. In independent multicenter US and European cohorts totaling 3,423 patients undergoing liver transplantation, the liver graft assessment following transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure-free survival and post-liver transplantation complications.

Assessment of Anastomotic Biliary Complications in Adult Patients Undergoing High-Acuity Liver Transplant.

Importance: Anastomotic biliary complications (ABCs) constitute the most common technical complications in liver transplant (LT). Given the ever-increasing acuity of LT, identification of factors contributing to ABCs is essential to minimize morbidity and optimize outcomes. A detailed analysis in a patient population undergoing high-acuity LT is lacking. Objective: To evaluate the rate of, risk factors for, and outcomes of ABCs and acuity level in LT recipients. Design, Setting, and Participants: This retrospective cohort study included adult LT recipients from January 1, 2013, through June 30, 2016, at a single large urban transplant center. Patients were followed up for at least 12 months after LT until June 30, 2017. Of 520 consecutive adult patients undergoing LT, 509 LTs in 503 patients were included. Data were analyzed from May 1 through September 13, 2017. Exposure: Liver transplant. Main Outcomes and Measures: Any complications occurring at the level of the biliary reconstruction. Results: Among the 503 transplant recipients undergoing 509 LTs included in the analysis (62.3% male; median age, 58 years [interquartile range {IQR}, 50-63 years), median follow-up was 24 months (IQR, 16-34 months). Overall patient and graft survival at 1 year were 91.1% and 90.3%, respectively. The median Model for End-stage Liver Disease (MELD) score was 35 (IQR, 15-40) for the entire cohort. T tubes were used in 199 LTs (39.1%) during initial bile duct reconstruction. Overall incidence of ABCs included 103 LTs (20.2%). Anastomotic leak occurred in 25 LTs (4.9%) and stricture, 77 (15.1%). Exit-site leak in T tubes occurred in 36 (7.1%) and T tube obstruction in 16 (3.1%). Seventeen patients with ABCs required surgical revision of bile duct reconstruction. Multivariate analysis revealed the following 7 independent risk factors for ABCs: recipient hepatic artery thrombosis (odds ratio [OR], 12.41; 95% CI, 2.37-64.87; P = .003), second LT (OR, 4.05; 95% CI, 1.13-14.50; P = .03), recipient hepatic artery stenosis (OR, 3.81; 95% CI, 1.30-11.17; P = .02), donor hypertension (OR, 2.79; 95% CI, 1.27-6.11; P = .01), recipients with hepatocellular carcinoma (OR, 2.66; 95% CI, 1.23-5.74; P = .01), donor death due to anoxia (OR, 2.61; 95% CI, 1.13-6.03; P = .03), and use of nonabsorbable suture material for biliary reconstruction (OR, 2.45; 95% CI, 1.09-5.54; P = .03). Conclusions and Relevance: This large, single-center series identified physiologic and anatomical independent risk factors contributing to ABCs after high-acuity LT. Careful consideration of these factors could guide perioperative management and mitigate potentially preventable ABCs.

Evaluation of Early Allograft Function Using the Liver Graft Assessment Following Transplantation Risk Score Model.

Importance: Early allograft dysfunction (EAD) following a liver transplant (LT) unequivocally portends adverse graft and patient outcomes, but a widely accepted classification or grading system is lacking. Objective: To develop a model for individualized risk estimation of graft failure after LT and then compare the model's prognostic performance with the existing binary EAD definition (bilirubin level of ≥10 mg/dL on postoperative day 7, international normalized ratio of ≥1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level of >2000 U/L within the first 7 days) and the Model for Early Allograft Function (MEAF) score. Design, Setting, and Participants: This retrospective single-center analysis used a transplant database to identify all adult patients who underwent a primary LT and had data on 10 days of post-LT laboratory variables at the Dumont-UCLA Transplant Center of the David Geffen School of Medicine at UCLA between February 1, 2002, and June 30, 2015. Data collection took place from January 4, 2016, to June 30, 2016. Data analysis was conducted from July 1, 2016, to August 30, 2017. Main Outcomes and Measures: Three-month graft failure-free survival. Results: Of 2021 patients who underwent primary LT over the study period, 2008 (99.4%) had available perioperative data and were included in the analysis. The median (interquartile range [IQR]) age of recipients was 56 (49-62) years, and 1294 recipients (64.4%) were men. Overall survival and graft-failure-free survival rates were 83% and 81% at year 1, 74% and 71% at year 3, and 69% and 65% at year 5, with an 11.1% (222 recipients) incidence of 3-month graft failure or death. Multivariate factors associated with 3-month graft failure-free survival included post-LT aspartate aminotransferase level, international normalized ratio, bilirubin level, and platelet count, measures of which were used to calculate the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score. The L-GrAFT model had an excellent C statistic of 0.85, with a significantly superior discrimination of 3-month graft failure-free survival compared with the existing EAD definition (C statistic, 0.68; P < .001) and the MEAF score (C statistic, 0.70; P < .001). Compared with patients with lower L-GrAFT risk, LT recipients in the highest 10th percentile of L-GrAFT scores had higher Model for End-Stage Liver Disease scores (median [IQR], 34 [26-40] vs 31 [25-38]; P = .005); greater need for pretransplant hospitalization (56.8% vs 44.8%; P = .003), renal replacement therapy (42.9% vs 30.5%; P < .001), mechanical ventilation (35.8% vs 18.1%; P < .001), and vasopressors (22.9% vs 11.0%; P < .001); longer cold ischemia times (median [IQR], 436 [311-539] vs 401 [302-506] minutes; P = .04); greater intraoperative blood transfusions (median [IQR], 17 [10-26] vs 10 [6-17] units of packed red blood cells; P < .001); and older donors (median [IQR] age, 47 [28-56] vs 41 [25-52] years; P < .001). Conclusions and Relevance: The L-GrAFT risk score allows a highly accurate, individualized risk estimation of 3-month graft failure following LT that is more accurate than existing EAD and MEAF scores. Multicenter validation may allow for the adoption of the L-GrAFT as a tool for evaluating the need for a retransplant, for establishing standardized grading of early allograft function across transplant centers, and as a highly accurate clinical end point in translational studies aiming to mitigate ischemia or reperfusion injury by modulating donor quality and recipient factors.

Damage Control as a Strategy to Manage Postreperfusion Hemodynamic Instability and Coagulopathy in Liver Transplant.

IMPORTANCE: Damage control (DC) with intra-abdominal packing and delayed reconstruction is an accepted strategy in trauma and acute care surgery but has not been evaluated in liver transplant. OBJECTIVE: To evaluate the incidence, effect on survival, and predictors of the need for DC using intra-abdominal packing and delayed biliary reconstruction in patients with coagulopathy or hemodynamic instability after liver allograft reperfusion. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis of adults undergoing liver transplant at a large transplant center from February 1, 2002, through July 31, 2012. MAIN OUTCOMES AND MEASURES: Predictors of DC, effects on graft, and patient survival. RESULTS: Of 1813 patients, 150 (8.3%) underwent DC during liver transplant, with 84 (56.0%) requiring a single additional operation for biliary reconstruction and abdominal closure and 57 (38.0%) requiring multiple additional operations. Compared with recipients without DC, patients requiring DC had greater Model for End-stage Liver Disease scores (33 vs 27; P < .001); more frequent pretransplant hospitalization (72.0% vs 47.9%; P < .001), intubation (33.3% vs 19.9%; P < .001), vasopressors (23.2% vs 10.9%; P < .001), renal replacement therapy (49.6% vs 30.3%; P < .001), and prior major abdominal operations (48.3% vs 21.9%; P < .001), including prior liver transplant (29.3% vs 8.9%; P < .001); greater operative transfusion requirements (37 vs 13 units of packed red blood cells; P < .001); worse intraoperative base deficit (10.3 vs 8.4; P = .03); more frequent postreperfusion syndrome (56.2% vs 27.3%; P < .001); and longer cold (430 vs 404 minutes; P = .04) and warm (46 vs 41 minutes; P < .001) ischemia times. Patients who underwent DC followed by a single additional operation for biliary reconstruction and abdominal closure had similar 1-, 3-, and 5-year graft survival (71%, 62%, and 62% vs 81%, 71%, and 67%; P = .26) and patient survival (72%, 64%, and 64% vs 84%, 75%, and 70%; P = .15) compared with recipients not requiring DC. Multivariate predictors of DC included prior liver transplant or major abdominal operation, longer pretransplant recipient and donor length of stay, greater Model for End-stage Liver Disease score, and longer warm and cold ischemia times (C statistic, 0.75). CONCLUSIONS AND RELEVANCE: To our knowledge, this study represents the first large report of DC as a viable strategy for liver transplant recipients with coagulopathy or hemodynamic instability after allograft reperfusion. In DC recipients not requiring additional operations, outcomes are excellent and comparable to 1-stage liver transplant.

Employment and quality of life in liver transplant recipients.

The purposes of liver transplantation (LT) include the extension of survival, improvement in quality of life, and the return of the recipient as a contributing member of society. Employment is one measure of the ability to return to society. The aim of this study is to determine the factors affecting employment/subemployment after LT. A total of 308 adult liver transplant recipients who were seen at the University of California, Los Angeles were administered the Medical Outcomes Short Form 36 (SF-36) and a questionnaire regarding work history and insurance coverage. Multivariate analysis were used to identify independent variables associated with posttransplantation employment. Interaction terms were used to examine effect modification. Of 308 transplant recipients, 218 (70.8%) worked prior to transplantation, and 78 (27%) worked posttransplantation. Pretransplant variables that were independently associated with posttransplantation employment included the following: lack of disability income (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.32-7.18; P = 0.36); health maintenance organization (HMO)/preferred provider organization (PPO) insurance (OR = 3.08; 95% CI, 1.32-7.18; P < 0.01); the number of hours worked (OR = 1.17; 95% CI, 1.08-1.28; P < 0.01); and the lack of diabetes mellitus (OR = 0.23; 95% CI, 0.70-0.73; P < 0.01). An interaction term between disability income and hours worked prior to transplantation (OR = 0.16; 95 % CI, 0.03-0.83; P = 0.03) was independently associated with posttransplantation employment. In a separate regression model of SF-36 responses, posttransplantation physical functioning (OR = 1.17; 95% CI, 1.10-1.26; P < 0.01) and role-physical (OR = 1.1; 95% CI, 1.02-1.16; P < 0.01) were independently associated with employment after transplantation. In conclusion, HMO or PPO insurance, lack of disability income coverage prior to transplant, the absence of diabetes mellitus, the number of hours worked prior to transplantation, and high physical functioning were associated with posttransplantation employment.

Incidence and management of abdominal wall defects after intestinal and multivisceral transplantation.

BACKGROUND: Successful primary closure of the abdominal wall following visceral organ transplantation is not always feasible. Primary closure under tension can lead to fascial ischemia or necrosis, with subsequent dehiscence. Thus, alternate techniques to achieve abdominal wall closure are an important technical aspect in intestinal transplantation. The authors review their experience managing abdominal wall defects following intestinal or multivisceral transplantation. METHODS: A retrospective review of the transplant database revealed 28 intestinal transplants in 24 patients from program inception in 1991 to January of 2002. The management of six intestinal transplant recipients with giant posttransplant abdominal wall defects is reviewed, and a novel technique is described for initially managing defects with prosthetic grafts that were serially reduced in size until a clean granulating bed was established, at which time they underwent permanent coverage using a meshed split-thickness skin graft. RESULTS: Of the 28 transplants, primary fascial closure was possible in only 14. In the other 14 patients, the fascia could not be closed primarily at the time of transplantation. The donor weight-to-recipient weight ratio was significantly greater in patients with abdominal wall closure problems (0.64 versus 1.09; p < 0.005). The incidence of retransplantation was also higher in those with abdominal closure problems compared with those whose fascia could be closed primarily (five of 14 versus one of 14). The six patients managed with skin graft closure did not have any wound complications after grafting. CONCLUSIONS: Abdominal wall defect after intestinal and multivisceral transplantation is a common problem without an ideal solution. Use of a skin graft on granulating abdominal viscera frozen with adhesions is a simple and reasonable solution to a complex problem.

MELD fails to measure quality of life in liver transplant candidates.

Previous studies have demonstrated an association between Child Turcotte-Pugh (CTP) class and impaired quality of life. However, the relationship between the model for end-stage liver disease (MELD) score and quality of life (QOL) has not been well studied. In this study, quality of life questionnaires (Medical Outcomes Short Form 36 [SF-36] and the Chronic Liver Disease Questionnaire [CLDQ]) were administered to 150 adult patients awaiting liver transplantation. We also collected demographic data and laboratory results and recorded manifestations of hepatic decompensation. The study found that all domains of the SF-36 and CLDQ were significantly lower in our patient cohort than in normal controls (P < .001). There was a moderate negative correlation between CPT class and physical components of the SF-36 (r = -.30), while there was a weak negative correlation (r = -.10) between CPT class and the mental component. There was a negative moderate correlation between CPT class and overall CLDQ (r = -.39, P < .001) and a weak correlation (r = -.20) between MELD score and overall CLDQ score. Both encephalopathy (correlation coefficient = -.713, P = .004) and ascites (correlation coefficient = -.68, P = .006) were predictive of the QOL using CLDQ (adjusted R(2) = .1494 and f = 0.000). In conclusion, in liver transplant candidates, the severity of liver disease assessed by the MELD score was not predictive of QOL. The presence of ascites and/or encephalopathy was significantly associated with poor quality of life. CTP correlates better to QOL, probably because it contains ascites and encephalopathy.

Hepatocellular carcinoma screening in patients waiting for liver transplantation: a decision analytic model.

De novo hepatocellular carcinoma (HCC) may have a large impact on patients waiting for liver transplantation. The presence of HCC can lead to a status upgrade or removal from the waitlist. Our aim is to compare costs and outcomes of different liver cancer surveillance strategies. A Markov-based decision analytic model is created to simulate costs and health outcomes for a hypothetical cohort awaiting liver transplantation undergoing HCC screening. Three strategies of HCC screening are compared with the referent strategy of using alphafetaprotein (AFP) level alone: (1) ultrasound (U/S), (2) AFP plus U/S, and (3) computed tomography (CT). Screening is performed for all strategies at 6-month intervals. Selected tumors are treated locally. Costs and clinical outcomes are discounted. Using baseline assumptions, incremental cost-effectiveness ratios (ICERs) for U/S, U/S plus AFP, and CT are $60,300/life-year saved (LY), $74,000/LY, and $101,100/LY, respectively. The most cost-effective strategy was dependent on the relative costs of each screening modality. U/S screening becomes the dominant strategy when the cost of an AFP test is decreased. Our results show that screening with CT is associated the greatest gain in life expectancy and greatest costs. U/S screening strategy is the preferred screening strategy based on the lowest ICER. Ultimately, costs of the screening modalities determine the most cost-effective strategy.

Operative parameters that predict the outcomes of hepatic transplantation.

BACKGROUND: A growing discrepancy between the number of patients awaiting liver transplantation and the number of organs available mandates the use of even marginal organ donors in whom there is major risk of suboptimal graft function. A comprehensive analysis of operative parameters on the outcomes of liver transplantation has not been reported. STUDY DESIGN: We analyzed the impact of 24 operative variables on the survival of 942 consecutive primary liver allografts performed at a single center from June 1992 through December 1997. Univariate and Cox proportional hazards analysis was used to identify those variables with independent prognostic significance in graft survival. Resource utilization for variables with multivariate significance was also analyzed. RESULTS: Of 12 intraoperative variables found to have significance in univariate analysis, three were significant by Cox multivariate analysis: 1) lack of immediate bile production by the graft intraoperatively, 2) platelet transfusion > or = 20 U, and 3) recipient urine output < or =2.0 mL/kg/h intraoperatively. Each of the three variables was associated with marked increases in hospital and Intensive Care Unit length of stay and hospital charges accrued during the admission for transplantation. CONCLUSION: We identified three operative parameters that predict a poor outcome after liver transplantation. The presence of these indicators suggests that early retransplantation should be considered. Early identification of grafts likely to have poor function might also provide an opportunity for therapeutic intervention to salvage graft function.