Search

Background: Non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) is a rising indication for liver transplantation. This unique population, with multiple comorbidities, has potential for worse post-transplant outcomes. We compared post-transplant survival of NASH and non-NASH HCC patients using a large cohort. Methods: Adults transplanted for HCC between 2008 and 2018, from United Network for Organ Sharing (UNOS) and University Health Network (UHN) databases were divided into two populations: NASH and non-NASH. Recipient characteristics and post-transplant survival were compared. Subgroup analyses were performed within and beyond Milan criteria. Results: 2071 of 20,672 (10.0%) patients underwent transplantation for NASH HCC, with annual proportional increase of 1.2%UHN (p = 0.02) and 1.3%UNOS (p < 0.001). The 1-,3-,5-year post-transplant survival were 90.8%, 83.9%, 76.3% NASH HCC versus 91.9%, 82.1%, 74.9% non-NASH HCC (p = 0.94). No survival differences were observed in populations within or beyond Milan. Competing-risk analysis demonstrated no differences in risk for cardiovascular-related death (HR1.24, 95%CI 0.87–1.55, p = 0.16), or HCC recurrence-related death (HR1.21, 95%CI 0.89–1.65, p = 0.23). NASH HCC patients had lower risk of liver-related deaths (HR0.57, 95%CI 0.34–0.98, p = 0.04). Discussion: NASH HCC is a rising indication for liver transplantation. Despite demographic differences, no post-transplantation survival differences were observed between NASH and non-NASH HCC. This justifies equivalent organ allocation, irrespective of NASH status.

Backgrounds/Aims: Within two years of surgery, 70% of resected intrahepatic cholangiocarcinoma (iCCA) recur. Better biomarkers are needed to identify those at risk of “early recurrence” (ER). In this study, we defined ER and investigated whether preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-inflammatory index were prognostic of both overall relapse and ER after curative hepatectomy for iCCA. Methods: A retrospective cohort of patients who underwent curative-intent hepatectomy for iCCA between 2005 and 2017 were created. The cut-off timepoint for the ER of iCCA was estimated using a piecewise linear regression model. Univariable analyses of recurrence were conducted for the overall, early, and late recurrence periods. For the early and late recurrence periods, multivariable Cox regression with time-varying regression coefficient analysis was used. Results: A total of 113 patients were included in this study. ER was defined as recurrence within 12 months of a curative resection. Among the included patients, 38.1% experienced ER. In the univariable model, a higher preoperative NLR (> 4.3) was significantly associated with an increased risk of recurrence overall and in the first 12 months after curative surgery. In the multivariable model, a higher NLR was associated with a higher recurrence rate overall and in the ER period (≤ 12 months), but not in the late recurrence period. Conclusions: Preoperative NLR was prognostic of both overall recurrence and ER after curative iCCA resection. NLR is easily obtained before and after surgery and should be integrated into ER prediction tools to guide preoperative treatments and intensify postoperative follow-up.

Background and Aims: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight. Methods: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0–90 days) and longer-term (90 days–5 years) outcomes. Results: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days–5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49–0.80); graft failure HR: UK: 0.72, 95% CI: 0.58–0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p

Background: Despite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated. Method: We aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant. Results: A total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23–1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intention-to-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44–1.32; P = .30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54–4.19; P = .40) were equivalent in those who initially received a living donor liver transplant. Conclusion: Patients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes.

Background & Aims: Adult-to-adult living donor liver transplantation (LDLT) offers an opportunity to decrease the liver transplant waitlist and reduce waitlist mortality. We sought to compare donor and recipient characteristics and post-transplant outcomes after LDLT in the US, the UK, and Canada. Methods: This is a retrospective multicenter cohort-study of adults (≥18-years) who underwent primary LDLT between Jan-2008 and Dec-2018 from three national liver transplantation registries: United Network for Organ Sharing (US), National Health Service Blood and Transplantation (UK), and the Canadian Organ Replacement Registry (Canada). Patients undergoing retransplantation or multi-organ transplantation were excluded. Post-transplant survival was evaluated using the Kaplan-Meier method, and multivariable adjustments were performed using Cox proportional-hazards models with mixed-effect modeling. Results: A total of 2,954 living donor liver transplants were performed (US: n = 2,328; Canada: n = 529; UK: n = 97). Canada has maintained the highest proportion of LDLT utilization over time (proportion of LDLT in 2008 – US: 3.3%; Canada: 19.5%; UK: 1.7%; p

Background: The use of neoadjuvant chemotherapy (NAC) in patients with intrahepatic cholangiocarcinoma (iCCA) is increasing. The objective of this study was to compare the 30-day post-operative complications and length-of-stay (LOS) between patients undergoing hepatectomy for iCCA with and without NAC. Methods: A retrospective study was conducted using the ACS-NSQIP database queried from 2014 to 2018. Patients with NAC receipt were propensity-score matched into 1:3 ratio with controls using the greedy-matching algorithm and a caliper of 0.2. Logistic and Poisson regression models were used to estimate the effect sizes. Results: A total of 1508 patients who underwent hepatectomy for iCCA were included. 706 patients remained after matching and balance were achieved. The NAC group had 110 (60.1%) complications vs. 289 (55.3%) complications in the non-NAC group (p = 0.29). NAC was not associated with worse 30-day postoperative complications [OR 1.24, 95% CI: 0.87–1.76; p = 0.24]. Post-operative LOS in the NAC group was 8.56 days (mean, SD 7.4) vs. non-NAC group 9.27 days (mean, SD 8.41, p = 0.32). NAC was not associated with longer post-operative LOS [RR 0.93, 95% CI:0.80, 1.08; p = 0.32]. Conclusion: NAC may be safely administered without increasing the risk of 30-day complications or post-operative hospital LOS.

Objective In the era of organ shortage, redo liver transplantation (reLT) is frequently discussed in terms of expected poor outcome, high cost and therefore wasteful resources. However, there is a lack of benchmark data to reliably assess outcomes after reLT. The aim of this study was to define the ideal reLT case, and to establish clinically relevant benchmark values for best achievable outcome in reLT. Methods We collected data on reLT between January 2010 and December 2018 from 22 high volume transplant centers on three continents. Benchmark cases were defined as recipients with model of end-stage liver disease score Results Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: =3a complications and the CCI at 1 year: Conclusion ReLT remains associated with high morbidity and mortality. The availability of benchmark values for outcome parameters of reLT may serve for comparison in any future analyses of individuals, patient groups, or centers, but also in the evaluation of new therapeutic strategies and principles.

Background: Recurrence rates of intrahepatic cholangiocarcinoma (iCCA) after curative hepatectomy are as high as 50% to 70%, and about half of these recurrences occur within 2 years. This systematic review aims to define prognostic factors (PFs) for early recurrence (ER, within 24 months) and 24-month disease-free survival (DFS) after curative-intent iCCA resections. Methods: Systematic searching was performed from database inception to 14 January 2021. Duplicate independent review and data extraction were performed. Data on 13 predefined PFs were collected. Meta-analysis was performed on PFs for ER and summarized using forest plots. The Quality in Prognostic Factor Studies tool was used for risk-of-bias assessment. Results: The study enrolled 10 studies comprising 4158 patients during an accrual period ranging from 1990 to 2016. In the risk-of-bias assessment of patients who experienced ER after curative-intent iCCA resection, six studies were rated as low risk and four as moderate risk (49.6%; 95% confidence interval [CI], 49.2–50.0). Nine studies were pooled for meta-analysis. Of the postoperative PFs, multiple tumors, microvascular invasion, macrovascular invasion, lymph node metastasis, and R1 resection were associated with an increased hazard for ER or a reduced 24-month DFS, and the opposite was observed for receipt of adjuvant chemo/radiation therapy. Of the preoperative factors, cirrhosis, sex, HBV status were not associated with ER or 24-month DFS. Conclusion: The findings from this systematic review could allow for improved surveillance, prognostication, and treatment decision-making for patients with resectable iCCAs. Further well-designed prospective studies are needed to explore prognostic factors for iCCA ER with a focus on preoperative variables.

Background: The role of viral hepatitis status in post-hepatectomy outcomes has yet to be delineated. This large, multicentred contemporary study aimed to evaluate the effect of viral hepatitis status on 30-day post-hepatectomy complications in patients treated for hepatocellular carcinoma (HCC). Methods: Patients from the National Surgical Quality Improvement Program (NSQIP) database with known viral hepatitis status, who underwent hepatectomy for HCC between 2014 and 2018, were included. Patients were classified as HBV-only, HCV-only, HBV and HCV co-infection (HBV/HCV), or no viral hepatitis (NV). Multivariable models were used to assess outcomes of interest. The primary outcome was any 30-day post-hepatectomy complication. The secondary outcomes were major complications and post-hepatectomy liver failure (PHLF). Subgroup analyses were performed for cirrhotic and noncirrhotic patients. Results: A total of 3234 patients were included. The 30-day complication rate was 207/663 (31.2%) HBV, 356/1077 (33.1%) HCV, 29/81 (35.8%) HBV/HCV, and 534/1413 (37.8%) NV (p = 0.01). On adjusted analysis, viral hepatitis status was not associated with occurrence of any 30-day post-hepatectomy complications (ref: NV, HBV odds ratio (OR) 0.89 [95% confidence interval (CI): 0.71–1.12]; HCV OR 0.91 [95% CI: 0.75–1.10]; HBV/HCV OR 1.17 [95% CI: 0.71–1.93]). Similar results were found in cirrhotic and noncirrhotic subgroups, and for secondary outcomes: occurrence of any major complications and PHLF. Conclusions: In patients with HCC managed with resection, viral hepatitis status is not associated with 30-day post-hepatectomy complications, major complications, or PHLF compared with NV. This suggests that clinical decisions and prognostication of 30-day outcomes in this population likely should not be made based on viral hepatitis status.

Background Laparoscopic liver resections for malignancy are increasing worldwide, and yet data from North America are lacking. We aimed to assess the long-term outcomes of patients undergoing laparoscopic liver resection and open liver resection as a treatment for hepatocellular carcinoma. Methods Patients undergoing liver resection for hepatocellular carcinoma between January 2008 and December 2019 were retrospectively studied. A propensity score matching was performed using patient demographics, laboratory parameters, etiology of liver disease, liver function, and tumor characteristics. Primary outcomes included overall survival and cumulative incidence of recurrence. Kaplan-Meier and competing risk cumulative incidence were used for survival analyses. Multivariable Cox regression and Fine-Gray proportional hazard regression were performed to determine hazard for death and recurrence, respectively. Results Three hundred and ninety-one patients were identified (laparoscopic liver resection: 110; open liver resection: 281). After propensity score matching, 149 patients remained (laparoscopic liver resection: 57; open liver resection: 92). There were no significant differences between groups with regard to extent of hepatectomy performed and tumor characteristics. The laparoscopic liver resection group experienced a lower proportion of ≥Clavien-Dindo grade III complications (14% vs 29%; P = .01). In the matched cohort, the 1-, 3-, and 5-year overall survival rate in the laparoscopic liver resection versus open liver resection group was 90.9%, 79.3%, 70.5% vs 91.3%, 88.5%, 83.1% (P = .26), and the cumulative incidence of recurrence 31.1%, 59.7%, 62.9% vs 18.9%, 40.6%, 49.2% (P = .06), respectively. Conclusion This study represents the largest single institutional study from North America comparing long-term oncologic outcomes of laparoscopic liver resection and open liver resection as a treatment for primary hepatocellular carcinoma. The combination of reduced short-term complications and equivalent long-term oncologic outcomes favor the laparoscopic approach when feasible.

Background The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC. Methods Patients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders. Results Of the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p = 0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p = 0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71–1.78, p = 0.61) or OS (HR 1.04, 95%CI 0.71–1.54, p = 0.83). Conclusion Perioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.

Living donor liver transplantation (LDLT) is an attractive alternative to deceased donor liver transplantation (DDLT). Although both modalities have similar short-term outcomes, long-term outcomes are not well studied. We compared the 20-year outcomes of 668 adults who received LDLT with1596 DDLTs at the largest liver transplantation (LT) program in Canada. Recipients of LDLT were significantly younger and more often male than DDLT recipients (P 0.001). Autoimmune diseases were more frequent in LDLT, whereas viral hepatitis and alcohol-related liver disease were more frequent in DDLT. LDLT recipients had lower Model for End-Stage Liver Disease scores (P = 0.008), spent less time on the waiting list (P 0.001), and were less often inpatients at the time of LT (P 0.001). In a nonadjusted analysis, 1-year, 10-year, and 20-year patient survival rates were significantly higher in LDLT (93%, 74%, and 56%, respectively) versus DDLT (91%, 67%, and 46%, respectively; log-rank P = 0.02) as were graft survival rates LDLT (91%, 67%, and 50%, respectively) versus (90%, 65%, and 44.3%, respectively, for DDLT; log-rank P = 0.31). After multivariable adjustment, LDLT and DDLT were associated with a similar hazard of patient and graft survival. Our data of 20 years of follow-up of LDLT from a single, large Western center demonstrates excellent long-term outcomes for recipients of LDLT.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Cholangiocarcinoma (CCA) represents the second most common primary liver malignancy after hepatocellular carcinoma and has risen in incidence globally in the past decades. Intrahepatic cholangiocarcinoma (iCCA) comprises 20% of all CCAs, with the rest being extrahepatic (including perihilar [pCCA] and distal CCA). Though long representing an absolute contraindication for liver transplantation (LT), recent analyses of outcomes of LT for iCCA have suggested that iCCA may be a potentially feasible option for highly selected patients. This has been motivated both by successes seen in outcomes of LT for other malignancies such as HCC and perihilar CCA and by several retrospective reviews demonstrating favorable results with LT for a selected group of iCCA patients with small lesions. LT for iCCA is primarily relevant within two clinical scenarios. The first includes patients with very early disease (single tumor ≤2 cm) with cirrhosis and are not candidates for liver resection (LR). The second scenario is patients with locally advanced iCCA, but where the extent of LR would be too extensive to be feasible. Preliminary single-center reports have described LT in a selected group of patients with locally advanced tumors which have responded to neoadjuvant therapy and have a period of disease stability. Currently, there are three prospective trials underway that will help clarify the role of LT in iCCA. This review seeks to explore the available studies involving LT for iCCA, the challenges of ongoing trials, and opportunities for the future.

The cover image is based on the Research Letter Acuity circles allocation policy impact on waitlist mortality and donation after circulatory death liver transplantation: A nationwide retrospective analysis by Emmanouil Giorgakis et al., https://doi.org/10.1002/hsr2.1066 [Image: see text]

Background: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. Aims: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. Materials and methods: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. Results: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) (https://childb.shinyapps.io/NomogramMajorMorbidity90days/). Conclusions: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD).Using data from the Organ Procurement and Transplantation Network and United Network for Organ Sharing registry, 77 416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens.The incidence of fatal GVHD was 0.2% (121 of 77 416), of whom 105 (87%) died within 180 d and 13 (11%) died between 181 d and 1 y. Median survival after LT was 68.0 (49.5-125.5) d. Recipient age minus donor age20 y (hazard ratio [HR], 2.57; P0.001) and basiliximab induction (HR, 1.69; P = 0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR, 0.51; P = 0.001). In an increased risk cohort of patients with recipient-donor age discrepancy20 y, MMF use was associated with a 50% decline in fatal GVHD (HR, 0.50; P0.001).Recipient age minus donor age20 y remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age20 y. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD.

The impact of hyponatremia on waitlist and post-transplant outcomes following the implementation of MELD-Na-based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD-Na-based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre-MELD-Na and post-MELD-Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120 mEq/l. Ninety-day waitlist outcomes and post-LT survival were compared using Fine-Gray proportional hazard and mixed-effects Cox proportional hazard models. A total of 118 487 patients were eligible (n = 64 940: pre-MELD-Na; n = 53 547: post-MELD-Na). In the pre-MELD-Na era, extreme hyponatremia at listing was associated with an increased risk of 90-day waitlist mortality ([ref: 135–145] HR: 3.80; 95% CI: 2.97–4.87; P < 0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38–2.01; P < 0.001). In the post-MELD-Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60–3.23; P < 0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76–2.55; P < 0.001) as patients with normal serum sodium levels (135–145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365-day post-LT survival compared to patients with normal serum sodium levels. With the introduction of MELD-Na-based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short-term post-LT survival.

The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosup-pressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prog-nosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies. (Clin Mol Hepatol 2022;28:1-16).

Background and Aims: Following liver resection (LR) for HCC, the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impacts on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians. Approach and Results: Adult patients undergoing LR for HCC between January 2000 and December 2018 were retrospectively identified at a single center. Multistate analysis modeled post-LR tumor progression by describing transitions between distinct disease states. In this model, the states included surgery, intrahepatic recurrence (first, second, third, fourth, fifth), distant metastasis with or without intrahepatic recurrence, and death. Of the 486 patients included, 169 (34.8%) remained recurrence-free, 205 (42.2%) developed intrahepatic recurrence, 80 (16.5%) developed distant metastasis, and 32 (7%) died. For an average patient having undergone LR, there was a 33.1% chance of remaining disease-free, a 31.0% chance of at least one intrahepatic recurrence, a 16.3% chance of distant metastasis, and a 19.8% chance of death within the first 60 months post-LR. The transition probability from surgery to first intrahepatic recurrence, without a subsequent state transition, increased from 3% (3 months) to 17.4% (30 months) and 17.2% (60 months). Factors that could modify these probabilities included tumor size, satellite lesions, and microvascular invasion. The online multistate model calculator can be found on https://multistatehcc.shinyapps.io/home/. Conclusions: In contrast to standard single time-to-event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy.

The liver transplantation (LT) landscape is continuously evolving. We sought to evaluate trends in indications for LT in Canada and the impact of primary liver disease on post-LT outcomes using a national transplant registry. Adult patients who underwent a primary LT between 2000 and 2018 were retrospectively identified in the Canadian Organ Replacement Registry. Outcomes included post-LT patient and graft survival. A total of 5,722 LTs were identified. The number of LT per year increased from 251 in 2000 to 349 in 2018. The proportion of patients transplanted for HCV decreased from 31.5% in 2000 to 3.4% in 2018. In contrast, the percentage of transplants for HCC increased from 2.3% in 2000 to 32.4% in 2018, and those performed for NASH increased from 0.4% in 2005 to 12.6% in 2018. Year of transplant (per 1 year) was protective for both patient (HR:0.96,95%CI:0.94-0.97; P

While adverse effects of prolonged recipient warm ischemia time (rWIT) in liver transplantation (LT) have been well investigated, few studies have focused on possible positive prognostic effects of short rWIT. We aim to investigate if shortening rWIT can further improve outcomes in donation after brain death liver transplant (DBD-LT). Primary DBD-LT between 2000 and 2019 were retrospectively reviewed. Patients were divided according to rWIT (≤30, 31-40, 41-50, and >50 min). The requirement of intraoperative transfusion, early allograft dysfunction (EAD), and graft survival were compared between the rWIT groups. A total of 1,256 patients of DBD-LTs were eligible. rWIT was ≤30min in 203 patients (15.7%), 31-40min in 465 patients (37.3%), 41-50min in 353 patients (28.1%), and >50min in 240 patients (19.1%). There were significant increasing trends of transfusion requirement (P < 0.001) and increased estimated blood loss (EBL, P < 0.001), and higher lactate level (P < 0.001) with prolongation of rWIT. Multivariable logistic regression demonstrated the lowest risk of EAD in the WIT ≤30min group. After risk adjustment, patients with rWIT ≤30 min showed a significantly lower risk of graft loss at 1 and 5-years, compared to other groups. The positive prognostic impact of rWIT ≤30min was more prominent when cold ischemia time exceeded 6 h. In conclusion, shorter rWIT in DBD-LT provided significantly better post-transplant outcomes.

BACKGROUND: Accurately identifying time-varying differences in the hazard of all-cause mortality after liver transplantation (LT) between recipients with and without hepatocellular carcinoma (HCC) may inform patient selection and organ allocation policies as well as post-LT surveillance protocols. METHODS: A UK population-based study was carried out using 9586 LT recipients. The time-varying association between HCC and post-LT all-cause mortality was estimated using an adjusted flexible parametric model (FPM) and expressed as hazard ratios (HRs). Differences in this association by transplant year were then investigated. Non-cancer-specific mortality was compared between HCC and non-HCC recipients using an adjusted subdistribution hazard model. RESULTS: The HR comparing HCC recipients with non-HCC recipients was below one immediately after LT (1-mo HR = 0.76; 95% confidence interval [CI], 0.59-0.99; P = 0.044). The HR then increased sharply to a maximum at 1.3 y (HR = 2.07; 95% CI, 1.70-2.52; P < 0.001) before decreasing. The hazard of death was significantly higher in HCC recipients than in non-HCC recipients between 4 mo and 7.4 y post-LT. There were no notable differences in the association between HCC and the post-LT hazard of death by transplant year. The estimated non-cancer-specific subdistribution HR for HCC was 0.93 (95% CI, 0.80-1.09; P = 0.390) and not found to vary over time. CONCLUSION: FPMs can provide a more precise comparison of post-LT hazards of mortality between HCC and non-HCC patients. The results provide further evidence that some HCC patients have extra-hepatic spread at the time of LT, which has implications for optimal post-LT surveillance protocols.

Living donor liver transplantation (LDLT) is an established treatment for advanced liver disease. Whether right lobe (RL) or left lobe (LL) LDLT provides the best outcomes for donors and recipients remains contentious.MedLine, Embase, PubMed, and Cochrane Central were searched to identify studies comparing RL- and LL-LDLT and reporting donor and/or recipient outcomes. Effect sizes were pooled using random-effect meta-analysis. Meta-regressions were used to explore heterogeneity.Sixty-seven studies were included. RL donors were more likely to experience major complications (relative risk [RR] = 1.63; 95% confidence interval [CI] = 1.30-2.05; I2 = 19%) than LL donors; however, no difference was observed in the risk of any biliary complication (RR = 1.41; 95% CI = 0.91-2.20; I2 = 59%), bile leaks (RR = 1.56; 95% CI = 0.97-2.51; I2 = 52%), biliary strictures (RR = 0.99; 95% CI = 0.43-1.88; I2 = 27%), or postoperative death (RR = 0.51; 95% CI = 0.25-1.05; I2 = 0%). Among recipients, the incidence of major complications (RR = 0.85; 95% CI = 0.68-1.06; I2 = 21%), biliary complications (RR = 1.10; 95% CI = 0.91-1.33; I2 = 8%), and vascular complications (RR = 0.79; 95% CI = 0.44-1.43; I2 = 0%) was similar. Although the rate of small for size syndrome (RR = 0.47; 95% CI = 0.30-0.74; I2 = 0%) and postoperative deaths (RR = 0.62; 95% CI = 0.44-0.87; I2 = 0%) was lower among RL-LDLT recipients, no differences were observed in long-term graft (hazard ratio = 0.87; 95% CI = 0.55-1.38; I2 = 74%) and overall survival (hazard ratio = 0.86; 95% CI = 0.60-1.22; I2 = 44%).LL donors experience fewer complications than RL donors, and LL-LDLT recipients had similar outcomes to RL-LDLT recipients. These findings suggest that LL-LDLT offers the best outcomes for living donors and similar outcomes for recipients when measures are taken to prevent small for size syndrome.

This study aimed to assess the differences between the United States and the United Kingdom in the characteristics and posttransplant survival of patients who received donation after circulatory death (DCD) liver allografts from donors aged60 y.Data were collected from the UK Transplant Registry and the United Network for Organ Sharing databases. Cohorts were dichotomized into donor age subgroups (donor60 y [D60]; donor ≤60 y [D ≤60]). Study period: January 1, 2001, to December 31, 2015.1157 DCD LTs were performed in the United Kingdom versus 3394 in the United States. Only 13.8% of US DCD donors were aged50 y, contrary to 44.3% in the United Kingdom. D60 were 22.6% in the United Kingdom versus 2.4% in the United States. In the United Kingdom, 64.2% of D60 clustered in 2 metropolitan centers. In the United States, there was marked inter-regional variation. A total of 78.3% of the US DCD allografts were used locally. One- and 5-y unadjusted DCD graft survival was higher in the United Kingdom versus the United States (87.3% versus 81.4%, and 78.0% versus 71.3%, respectively; P0.001). One- and 5-y D60 graft survival was higher in the United Kingdom (87.3% versus 68.1%, and 77.9% versus 51.4%, United Kingdom versus United States, respectively; P0.001). In both groups, grafts from donors ≤30 y had the best survival. Survival was similar for donors aged 41 to 50 versus 51 to 60 in both cohorts.Compared with the United Kingdom, older DCD LT utilization remained low in the United States, with worse D60 survival. Nonetheless, present data indicate similar survivals for older donors aged ≤60, supporting an extension to the current US DCD age cutoff.

Background: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes. Objective: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA. Methods: Patients undergoing LT (January 2001–October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan–Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death. Results: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52–3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28–25.30, p = 0.40). Conclusions: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.