Taner, C. Burcin

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.

Background. There is limited information concerning whether social determinants of health affect postliver transplant (LT) outcomes. This study aims to understand to what extent the health of LT recipients’ counties of residence influence long-term LT outcomes. Methods. We used the United Network for Organ Sharing data to identify adult LT recipients transplanted between January 2010 and June 2018. Patient-level data were matched to county-level County Health Ranking (CHR) data using transplant recipient zip code, and nationwide CHRs were created. Mixed-effects Cox proportional hazards models were used to examine associations between CHRs and graft and patient survival post-LT. Results. Health outcomes rank was significantly associated with posttransplant graft and patient survival, with worst tertile counties showing a 13% increased hazard of both graft failure and patient mortality compared to the best tertile counties. Conclusions. Although county health is associated with LT outcomes, it also appears that LT recipient selection is effective at mitigating major disparities based on county of residence and helps yield equitable outcomes in this respect.

AbstractLittle is known about the surgical challenges and outcomes of kidney transplantation (KT) in the face of severe iliac occlusive disease (IOD). We aim to examine our institution's experience and outcomes compared with all KT patients. Retrospective review of our multi-institutional transplant database identified patients with IOD requiring vascular surgery involvement for iliac artery endarterectomy at time of KT from 2000 to 2018. Clinical data, imaging studies, and surgical outcomes of 22 consecutive patients were reviewed. Our primary end-point was allograft survival. Secondary end-points included mortality and perioperative complications. A total of 6,757 KT were performed at our three sites (Florida, Arizona, and Minnesota); there were 22 (0.32%) patients receiving a KT with concomitant IOD requiring iliac artery endarterectomy. Mean patient age was 61.45 ± 7 years. There were 13 (59.1%) male patients. The most common etiology of renal failure was diabetic nephropathy in 10 patients (45.5%) followed by a combination of hypertensive/diabetic nephropathy in five patients (22.7%), and hypertensive nephrosclerosis in three patients (13.6%). The majority (n = 16, 72.7%) of patients received renal allografts from deceased donors and six (27.3%) were recipients from living donors. Mean time from dialysis to transplantation was 2.9 ± 2.9 years. Mean follow-up was 3.5 ± 2.5 years. Mean length of hospital stay was 6.3 ± 4.3 days (range: 3–18 days). Graft loss within 90 days occurred in two (9.1%) patients, one due to renal vein thrombosis and another due to acute tubular necrosis. Overall allograft survival was 90.1% at 1-year and 86.4% at 3-year follow-up. Overall mortality occurred in 6 (27.3%) patients. Perioperative complications (Clavien-Dindo Grade 2–4) occurred in 13 (59.1%) patients, including 10 (45.5%) with acute blood loss anemia requiring transfusion, 2 (9.1%) reoperations for hematoma evacuation, 1 (4.5%) ischemic colitis requiring total abdominal colectomy, and 1 (4.5%) renal vein thrombosis requiring nephrectomy. IOD patients selected for KT are not common and although challenging, they have similar outcomes to our standard KT patients. The 1- and 3-year allograft survivals were 90.1 and 86.4% versus 96.0 and 90.3% in the general KT patient population. With these excellent outcomes, we recommend expanding the criteria for KT to include patients with IOD with prior vascular surgery consultation to prevent progression of IOD or prevention of wait list removal in select patients who are otherwise good candidates for KT.

The number of steatotic deceased donor livers encountered has continued to rise as a result of the obesity epidemic. Little is known about the histological characteristics of moderately macrosteatotic livers over time in the recipient following liver transplantation (LT). All recipients undergoing LT at Mayo Clinic Florida with donor livers with moderate macrosteatosis (30%‐60%) from 2000‐2017 were identified (n = 96). Routine protocol liver biopsies were performed 1‐week and 6‐months following LT. All liver donor and protocol biopsies were read by an experienced liver pathologist. Of the 96 moderate macrosteatosis LTs, 70 recipients had post‐LT protocol liver biopsies available and comprised the study cohort. Median donor allograft macrosteatosis at the time of transplant was 33% (IQR, 30%‐40%) compared with 0% (IQR, 0%‐2%) at 1‐week (P < 0.001) and 0% (IQR, 0%‐0%) at 6‐months (P < 0.001) following LT. Biopsies at 1‐week post‐LT displayed pericentral necrosis in 57.1% of recipients and lipopeliosis in 34.3% of recipients. In the 6‐month post‐LT biopsies, cholestasis was seen in 3 (4.3%) of the recipients, whereas grade 2 fibrosis was seen in 6 recipients (8.6%). Graft survival at 5 years in the present cohort was 74.0%. Moderate macrosteatosis (30%‐60%) in the donor allograft demonstrates complete reversal on liver biopsies performed as early as 7 days following LT and remains absent at 6‐months following LT. Both pericentral necrosis and lipopeliosis are common features on day 7 biopsies. Despite these encouraging findings, the perioperative risks of using these livers (postreperfusion cardiac arrest and primary nonfunction) should not be understated. Long‐term graft survival is acceptable in patients who are able to overcome the immediate perioperative risk of using moderately steatotic donor livers.

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.

Background. Aorto-hepatic conduits can provide arterial inflow for liver transplants in cases where the native hepatic artery is unsuitable for use. Methods. Clinical outcomes of all patients undergoing liver transplantation (LT) with an aorto-hepatic conduit between 2000 and 2016 were included. Recipients were divided into 2 groups: those with a supraceliac (SC) aortic conduit (N = 22) and those with an infrarenal (IR) aortic conduit (N = 82). Results. There was no difference in calculated model for end-stage liver disease score between the 2 groups. The SC group received grafts with a higher mean donor risk index (1.69 versus 1.48; P = 0.02). Early allograft dysfunction was 18.2% in the SC group and 29.3% in the IR group (P = 0.30). In the SC group, 10.5% of patients required initiation of postoperative continuous renal replacement therapy compared to 12.1% of patients in the IR group (P = 0.69). No difference in the rate of postoperative acute kidney injury was seen between the 2 groups (P = 0.54). No significant difference in median creatinine at 1 year was seen between the SC (1.2 mg/dL; IQR 1–1.3) and IR (1.2 mg/dL; IQR 0.9–1.5) groups (P = 0.85). At a median follow-up of 5.3 years, thrombosis of the aortic conduit occurred in 0% of patients in the SC group and 6.1% of patients in the IR group (P = 0.24). Graft survival was not significantly different between the 2 groups (P = 0.47). Conclusions. No difference in renal dysfunction as demonstrated by need for post-LT continuous renal replacement therapy, acute kidney injury, or creatinine at 1 year post-LT was seen between SC and IR aortic conduits. A slight trend of higher conduit thrombosis rate was seen with IR compared to SC aortic conduits; however, this did not reach statistical significance. Both SC and IR aortic conduits represent reasonable options when the native hepatic artery is unsuitable for use.

Previous large registry studies have demonstrated inferior outcomes for simultaneous liver‐kidney transplantation (SLKT) recipients of grafts from donation after circulatory death (DCD) donors compared with those from donation after brain death (DBD) donors in the era from 2000 to 2010. Given the improving national results in liver transplantation alone using grafts from DCD donors, the present study aimed to investigate if results with DCD‐SLKT have improved in the modern era. Patients undergoing SLKT between 2000 and 2018 were obtained from the United Network for Organ Sharing Standard Analysis and Research file and divided into 2 eras based on the date of SLKT: era 1 (2000‐2010) and era 2 (2011‐2018). Improvement in DCD‐SLKT patient, liver graft, and kidney graft survival rates was seen between era 1 and era 2 (P < 0.001). Concurrently, there was a decrease in the proportion of critically ill (P = 0.02) and retransplant (P = 0.006) candidates undergoing DCD‐SLKT. When DCD‐SLKT in era 2 was compared with a propensity‐matched cohort of DBD‐SLKT in era 2, no differences in patient (P = 0.99), liver graft (P = 0.19), or kidney graft (P = 0.90) survival were observed. In addition, both bilirubin (0.5 versus 0.5 mg/dL; P = 0.86) and creatinine (1.2 versus 1.2 mg/dL; P = 0.68) at last follow‐up were not different between the DCD‐SLKT and DBD‐SLKT patients in era 2. In conclusion, in the most recent era, patients undergoing DCD‐SLKT were able to achieve similar outcomes compared with matched patients undergoing DBD‐SLKT. DCD‐SLKT represents a viable option for appropriately selected recipients.

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre‐LT predictors of potentially reversible renal injury using histological information obtained on pre‐LT renal biopsy. Data on 128 LT candidates who underwent pre‐LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End‐Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision‐making process to list patients with renal dysfunction for LT alone versus simultaneous liver‐kidney transplantation.

Liver grafts from donation after circulatory death (DCD) are a source of organs to decrease wait‐list mortality. While there have been lower rates of graft loss, there are concerns of an increased incidence of intraoperative events in recipients of DCD grafts. We aim to look at the incidence of intraoperative events between recipients of livers from DCD and donation after brain death (DBD) donors. We collected data for 235 DCD liver recipients between 2006 and 2017. We performed a 1:1 propensity match between these patients and patients with DBD donors. Variables included recipient age, liver disease etiology, biological Model for End‐Stage Liver Disease (MELD) score, allocation MELD score, diagnosis of hepatocellular carcinoma, and year of transplantation. DCD and DBD groups had no significant differences in incidence of postreperfusion syndrome (P = 0.75), arrhythmia requiring cardiopulmonary resuscitation (P = 0.66), and treatments for hyperkalemia (P = 0.84). In the DCD group, there was a significant increase in amount of total intraoperative and postreperfusion blood products (with exception of postreperfusion packed red blood cells) utilized (P < 0.05 for all products), significant differences in postreperfusion thromboelastography parameters, as well as inotropes and vasopressors used (P < 0.05 for all infusions). There was no difference in patient (P = 0.49) and graft survival (P = 0.10) at 1, 3, and 5 years. In conclusion, DCD grafts compared with a cohort of DBD grafts have a similar low incidence of major intraoperative events, but increased incidence of transient vasopressor/inotropic usage and increased blood transfusion requirements. This does not result in differences in longterm outcomes. While centers should continue to look at DCD liver donors, they should be cognizant regarding intraoperative care to prevent adverse outcomes.