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1.
J Hepatol ; 76(2): 371-382, 2022 02.
Article in English | MEDLINE | ID: mdl-34655663

ABSTRACT

BACKGROUND & AIMS: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. METHODS: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.


Subject(s)
Liver Transplantation/adverse effects , Outcome Assessment, Health Care/statistics & numerical data , Shock/etiology , Aged , Area Under Curve , Benchmarking/methods , Benchmarking/statistics & numerical data , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Liver Transplantation/methods , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Organ Dysfunction Scores , Outcome Assessment, Health Care/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Proportional Hazards Models , ROC Curve , Shock/epidemiology , Tissue and Organ Procurement/methods , Tissue and Organ Procurement/statistics & numerical data
2.
Transpl Int ; 34(8): 1433-1443, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33599045

ABSTRACT

The use of livers from donation after circulatory death (DCD) is historically characterized by increased rates of biliary complications and inferior short-term graft survival (GS) compared to donation after brain death (DBD) allografts. This study aimed to evaluate the dynamic prognostic impact of DCD livers to reveal whether they remain an adverse factor even after patients survive a certain period following liver transplant (LT). This study used 74 961 LT patients including 4065 DCD LT in the scientific registry of transplant recipients from 2002-2017. The actual, 1 and 3-year conditional hazard ratio (HR) of 1-year GS in DCD LT were calculated using a conditional version of Cox regression model. The actual 1-, 3-, and 5-year GS of DCD LT recipients were 83.3%, 73.3%, and 66.3%, which were significantly worse than those of DBD (all P < 0.01). Actual, 1-, and 3-year conditional HR of 1-year GS in DCD compared to DBD livers were 1.87, 1.49, and 1.39, respectively. Graft loss analyses showed that those lost to biliary related complications were significantly higher in the DCD group even 3 years after LT. National registry data demonstrate the protracted higher risks inherent to DCD liver grafts in comparison to their DBD counterparts, despite survival through the early period after LT. These findings underscore the importance of judicious DCD graft selection at individual center level to minimize the risk of long-term biliary complications.


Subject(s)
Liver Transplantation , Tissue and Organ Procurement , Brain Death , Death , Graft Survival , Humans , Proportional Hazards Models , Retrospective Studies , Tissue Donors
3.
Liver Transpl ; 25(5): 741-751, 2019 05.
Article in English | MEDLINE | ID: mdl-30615254

ABSTRACT

A recent study using US national registry data reported, using Cox proportional hazards (PH) models, that split-liver transplantation (SLT) has improved over time and is no more hazardous than whole-liver transplantation (WLT). However, the study methods violated the PH assumption, which is the fundamental assumption of Cox modeling. As a result, the reported hazard ratios (HRs) are biased and unreliable. This study aimed to investigate whether the risk of graft survival (GS) in SLT has really improved over time, ensuring attention to the PH assumption. This study included 80,998 adult deceased donor liver transplantation (LT) (1998-2015) from the Scientific Registry Transplant Recipient. The study period was divided into 3 time periods: era 1 (January 1998 to February 2002), era 2 (March 2002 to December 2008), and era 3 (January 2009 to December 2015). The PH assumption was tested using Schoenfeld's test, and where the HR of SLT violated the assumption, changes in risk for SLT over time from transplant were assessed. SLT was performed in 1098 (1.4%) patients, whereas WLT was used in 79,900 patients. In the Cox PH analysis, the P values of Schoenfeld's global tests were <0.05 in all eras, which is consistent with deviation from proportionality. Assessing HRs of SLT with a time-varying effect, multiple Cox models were conducted for post-LT intervals. The HR curves plotted according to time from transplant were higher in the early period and then decreased at approximately 1 year and continued to decrease in all eras. For 1-year GS, the HRs of SLT were 1.92 in era 1, 1.52 in era 2, and 1.47 in era 3 (all P < 0.05). In conclusion, the risk of SLT has a time-varying effect and is highest in the early post-LT period. The risk of SLT is underestimated if it is evaluated by overall GS. SLT was still hazardous if the PH assumption was considered, although it became safer over time.


Subject(s)
Graft Rejection/epidemiology , Graft Survival , Liver Transplantation/adverse effects , Tissue Donors/statistics & numerical data , Transplant Recipients/statistics & numerical data , Adolescent , Adult , Allografts/supply & distribution , Allografts/surgery , Data Interpretation, Statistical , Female , Follow-Up Studies , Graft Rejection/etiology , Humans , Liver/surgery , Liver Transplantation/methods , Male , Middle Aged , Registries/statistics & numerical data , Time Factors , Treatment Outcome , United States/epidemiology , Young Adult
4.
Liver Transpl ; 25(8): 1241-1250, 2019 08.
Article in English | MEDLINE | ID: mdl-31119826

ABSTRACT

This study estimated the utility of technical variant grafts (TVGs), such as split/reduced liver transplantation (SRLT) and living donor liver transplantation (LDLT), in pediatric acute liver failure (PALF). PALF is a devastating condition portending a poor prognosis without liver transplantation (LT). Pediatric candidates have fewer suitable deceased donor liver transplantation (DDLT) donor organs, and the efficacy of TVG in this setting remains incompletely investigated. PALF patients from 1995 to 2015 (age <18 years) were identified using the Scientific Registry of Transplant Recipients (n = 2419). Cox proportional hazards model and Kaplan-Meier curves were used to assess outcomes. Although wait-list mortality decreased (19.1% to 9.7%) and successful transplantations increased (53.7% to 62.2%), patients <1 year of age had persistently higher wait-list mortality rates (>20%) compared with other age groups (P < 0.001). TVGs accounted for only 25.7% of LT for PALF. In the adjusted model for wait-list mortality, among other factors, increased age (subhazard ratio [SHR], 0.97 per year; P = 0.020) and access to TVG were associated with decreased risk (SHR, 0.37; P < 0.0001). LDLT recipients had shorter median waiting times compared with DDLT (LDLT versus DDLT versus SRLT, 3 versus 4 versus 5 days, respectively; P = 0.017). In the adjusted model for post-LT survival, LDLT was superior to DDLT using whole grafts (SHR, 0.41; P = 0.004). However, patient survival after SRLT was not statistically different from DDLT (SHR, 0.75; P = 0.165). In conclusion, despite clear advantages to reduce wait-list mortality, TVGs have been underutilized in PALF. Early access to TVG, especially from LDLT, should be sought to further improve outcomes.


Subject(s)
Liver Failure, Acute/surgery , Liver Transplantation/methods , Living Donors , Waiting Lists/mortality , Adolescent , Age Factors , Allografts/statistics & numerical data , Allografts/supply & distribution , Child , Child, Preschool , Female , Follow-Up Studies , Graft Survival , Humans , Infant , Kaplan-Meier Estimate , Liver Failure, Acute/diagnosis , Liver Failure, Acute/mortality , Liver Transplantation/statistics & numerical data , Liver Transplantation/trends , Male , Prognosis , Registries/statistics & numerical data , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors , Time-to-Treatment , Treatment Outcome
5.
Hepatology ; 68(4): 1448-1458, 2018 10.
Article in English | MEDLINE | ID: mdl-29604231

ABSTRACT

Patients with hepatocellular carcinoma (HCC) are screened at presentation for appropriateness of liver transplantation (LT) using morphometric criteria, which poorly specifies risk. Morphology is the crux of measuring tumor response to locoregional therapy (LRT) using modified Response Evaluation Criteria in Solid Tumors (mRECIST). This study investigated the utility of following a continuous risk score (hazard associated with liver transplantation in hepatocellular carcinoma; HALTHCC) to longitudinally assess risk. This multicenter, retrospective study from 2002 to 2014 enrolled 419 patients listed for LT for HCC. One cohort had LRT while waiting (n = 351), compared to the control group (n = 68) without LRT. Imaging studies (n = 2,085) were collated to laboratory data to calculate HALTHCC, MORAL, Metroticket 2.0, and alpha fetoprotein (AFP) score longitudinally. Cox proportional hazards evaluated associations of HALTHCC and peri-LRT changes with intention-to-treat (ITT) survival (considering dropout or post-LT mortality), and utility was assessed with Harrell's C-index. HALTHCC better predicted ITT outcome (LT = 309; dropout = 110) when assessed closer to delisting (P < 0.0001), maximally just before delisting (C-index, 0.742 [0.643-0.790]). Delta-HALTHCC post-LRT was more sensitive to changes in risk than mRECIST. HALTHCC score and peri-LRT percentage change were independently associated with ITT mortality (hazard ratio = 1.105 [1.045-1.169] per point and 1.014 [1.004-1.024] per percent, respectively). CONCLUSIONS: HALTHCC is superior in assessing tumor risk in candidates awaiting LT, and its utility increases over time. Peri-LRT relative change in HALTHCC outperforms mRECIST in stratifying risk of dropout, mortality, and recurrence post-LT. With improving estimates of post-LT outcomes, it is reasonable to consider allocation using HALTHCC and not just waiting time. Furthermore, this study supports a shift in perspective, from listing to allocation, to better utilize precious donor organs. (Hepatology 2018).


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation/methods , Waiting Lists , Adult , Biomarkers, Tumor/analysis , Biopsy, Needle , Carcinoma, Hepatocellular/mortality , Case-Control Studies , Female , Follow-Up Studies , Graft Survival , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Transplantation/adverse effects , Longitudinal Studies , Male , Middle Aged , Patient Selection , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Survival Rate , Treatment Outcome , United States , alpha-Fetoproteins/metabolism
6.
Clin Transplant ; 33(11): e13723, 2019 11.
Article in English | MEDLINE | ID: mdl-31583762

ABSTRACT

OBJECTIVE: Portal vein thrombosis (PVT) does not preclude liver transplantation (LT), but poor portal vein (PV) flow after LT remains a predictor of poor outcomes. Given the physiologic tendency of the hepatic artery (HA) to compensate for low PV flow via vasodilation, we investigated whether adequate HA flow would have a favorable prognostic impact among patients with low PV flow following LT. METHODS: This study included 163 patients with PVT who underwent LT between 2004 and 2015. PV and HA flow were categorized into quartiles, and their association with 1-year graft survival (GS) and biliary complication rates was assessed. For both the HA and the PV, patients at the lowest two quartiles were categorized as having low flow and the remainder as having high flow. RESULTS: The median MELD score was 22 and 1-year GS was 87.3%. As expected, GS paralleled PV flow with patients at the lowest flow quartile faring the worst. In combination of PV and HA flows, high HA flow was associated with improved 1-year GS among patients with low PV flow (P = .03). Similar findings were observed with respect to biliary complication rates. CONCLUSIONS: Sufficient HA flow may compensate for poor PV flow. Consequently, meticulous HA reconstruction may be central to achieving optimal outcomes in PVT cases.


Subject(s)
Hepatic Artery/physiopathology , Liver Diseases/mortality , Liver Transplantation/mortality , Liver/blood supply , Portal Vein/pathology , Venous Thrombosis/mortality , Adult , Aged , Female , Follow-Up Studies , Graft Survival , Humans , Liver Circulation , Liver Diseases/surgery , Male , Middle Aged , Prognosis , Survival Rate , Venous Thrombosis/physiopathology
7.
Transpl Int ; 32(2): 117-127, 2019 02.
Article in English | MEDLINE | ID: mdl-30362294

ABSTRACT

Portal vein thrombosis (PVT) is commonly encountered during liver transplantation (LT). Depending on the grade of thrombosis, varied management strategies are indicated. The aims of this study are to clarify the contemporary role of renoportal anastomosis (RPA) in patients with splanchnic vein thrombosis (SVT) undergoing LT and to systematically analyze all reported cases of RPA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement guidelines. The study was limited to studies reported in English between January 1997 and May 2017. Only retrospective single center studies were included in the analysis. A total of 66 patients with SVT were reported to have undergone RPA during LT. Transient renal dysfunction was reported in 12 patients (18.1%), variceal hemorrhage in 2 patients (3%), early portal vein (PV) re-thrombosis in 2 patients (3%), chronic renal dysfunction in 2 patients (3%), and late PV re-thrombosis in 1 patient (1.5%). The overall patient and graft survival were each 80%. This analysis illustrates the decades-long evolution of a technique practiced across the field of transplantation. Postoperative complications and graft survival appear to be encouraging, even in the setting of SVT.


Subject(s)
Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , End Stage Liver Disease/surgery , Liver Transplantation/methods , Portal Vein/pathology , Venous Thrombosis/surgery , Adolescent , Adult , End Stage Liver Disease/complications , End Stage Liver Disease/mortality , Esophageal and Gastric Varices , Female , Graft Survival , Hemorrhage/complications , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Splanchnic Circulation , Thrombosis , Treatment Outcome , Varicose Veins/physiopathology , Vascular Surgical Procedures/methods , Waiting Lists , Young Adult
9.
Liver Transpl ; 22(11): 1469-1481, 2016 11.
Article in English | MEDLINE | ID: mdl-27600806

ABSTRACT

Donation after circulatory death (DCD) donors show heterogeneous hemodynamic trajectories following withdrawal of life support. Impact of hemodynamics in DCD liver transplant is unclear, and objective measures of graft viability would ease transplant surgeon decision making and inform safe expansion of the donor organ pool. This retrospective study tested whether hemodynamic trajectories were associated with transplant outcomes in DCD liver transplantation (n = 87). Using longitudinal clustering statistical techniques, we phenotyped DCD donors based on hemodynamic trajectory for both mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2 ) following withdrawal of life support. Donors were categorized into 3 clusters: those who gradually decline after withdrawal of life support (cluster 1), those who maintain stable hemodynamics followed by rapid decline (cluster 2), and those who decline rapidly (cluster 3). Clustering outputs were used to compare characteristics and transplant outcomes. Cox proportional hazards modeling revealed hepatocellular carcinoma (hazard ratio [HR] = 2.53; P = 0.047), cold ischemia time (HR = 1.50 per hour; P = 0.027), and MAP cluster 1 were associated with increased risk of graft loss (HR = 3.13; P = 0.021), but not SpO2 cluster (P = 0.172) or donor warm ischemia time (DWIT; P = 0.154). Despite longer DWIT, MAP and SpO2 clusters 2 showed similar graft survival to MAP and SpO2 clusters 3, respectively. In conclusion, despite heterogeneity in hemodynamic trajectories, DCD donors can be categorized into 3 clinically meaningful subgroups that help predict graft prognosis. Further studies should confirm the utility of liver grafts from cluster 2. Liver Transplantation 22 1469-1481 2016 AASLD.


Subject(s)
End Stage Liver Disease/surgery , Graft Survival , Hemodynamics/physiology , Liver Transplantation/adverse effects , Liver/physiology , Adult , Allografts/physiology , Arterial Pressure , Cold Ischemia , Female , Humans , Male , Middle Aged , Phenotype , Prognosis , Proportional Hazards Models , Prospective Studies , Retrospective Studies , Risk Factors , Tissue Donors/classification , Tissue and Organ Procurement , Warm Ischemia
10.
Liver Transpl ; 21(12): 1494-503, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26334196

ABSTRACT

The use of liver grafts from donation after circulatory death (DCD) donors remains controversial, particularly with donors of advanced age. This retrospective study investigated the impact of donor age in DCD liver transplantation. We examined 92 recipients who received DCD grafts and 92 matched recipients who received donation after brain death (DBD) grafts at Cleveland Clinic from January 2005 to June 2014. DCD grafts met stringent criteria to minimize risk factors in both donors and recipients. The 1-, 3-, and 5-year graft survival in DCD recipients was significantly inferior to that in DBD recipients (82%, 71%, 66% versus 92%, 87%, 85%, respectively; P = 0.03). Six DCD recipients (7%), but no DBD recipients, experienced ischemic-type biliary stricture (P = 0.01). However, the incidence of biliary stricture was not associated with donor age (P = 0.57). Interestingly, recipients receiving DCD grafts from donors who were <45 years of age (n = 55) showed similar graft survival rates compared to those receiving DCD grafts from donors who were ≥45 years of age (n = 37; 80%, 69%, 66% versus 83%, 72%, 66%, respectively; P = 0.67). Cox proportional hazards modeling in all study populations (n = 184) revealed advanced donor age (P = 0.05) and the use of a DCD graft (P = 0.03) as unfavorable factors for graft survival. Logistic regression analysis showed that the risk of DBD graft failure increased with increasing age, but the risk of DCD graft failure did not increase with increasing age (P = 0.13). In conclusion, these data suggest that stringent donor and recipient selection may ameliorate the negative impact of donor age in DCD liver transplantation. DCD grafts should not be discarded because of donor age, per se, and could help expand the donor pool for liver transplantation.


Subject(s)
Liver Transplantation/statistics & numerical data , Tissue Donors/statistics & numerical data , Adult , Age Factors , Brain Death , Death , Female , Graft Survival , Humans , Male , Middle Aged , Ohio , Retrospective Studies
11.
Dig Surg ; 31(4-5): 312-7, 2014.
Article in English | MEDLINE | ID: mdl-25401989

ABSTRACT

AIM: We hereby present and evaluate a technique for hepatic parenchymal transection based on the application of Metzenbaum scissors and clips during liver ischemia. METHODS: Our technique was retrospectively evaluated in 32 noncirrhotic, noncholestatic patients with intrahepatic cholangiocarcinoma and 32 patients with hepatocellular carcinoma (23 of whom cirrhotic, 71.9%). Patient data were retrieved from our Hepatobiliary Surgery Database. Type and duration of vascular clamping, blood transfusion requirements, marginal status and immediate postoperative complications were analyzed. RESULTS: Twenty-seven extended (>4 liver segments; 42.2%) and 37 nonextended (≤4 liver segments; 57.8%) liver resections were analyzed. Warm liver ischemia duration was 14 (interquartile range: 11-17.8) min. Thirty-three patients (51.6%) were transfused with a median of 2 (1.5-3) units of packed red blood cells. Tumor-free margins were achieved in 90.6% of cases (n = 58). The overall morbidity rate was 18.8% with a 4.7% mortality rate. Our technique allowed for excellent identification and safe dissection and preservation, or ligation of major liver vessels. CONCLUSIONS: The proposed technique is simple, fast, safe and with low cost. It is associated with limited postoperative complications while from an oncologic standpoint it enables the surgeon to achieve a high percentage of tumor-free margins while protecting major vascular structures.


Subject(s)
Blood Loss, Surgical/prevention & control , Hepatectomy/instrumentation , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Surgical Instruments , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Bile Ducts, Intrahepatic/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Cholangiocarcinoma/surgery , Cohort Studies , Female , Follow-Up Studies , Hepatectomy/methods , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Operative Time , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Rate , Treatment Outcome
13.
Transplantation ; 107(4): 933-940, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36397734

ABSTRACT

BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.


Subject(s)
Coronary Artery Disease , Liver Transplantation , Non-alcoholic Fatty Liver Disease , Adult , Humans , Male , Female , Middle Aged , Coronary Artery Disease/complications , Coronary Artery Disease/surgery , Liver Transplantation/adverse effects , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/surgery , Liver Cirrhosis/surgery , Risk Factors , Retrospective Studies
14.
Transplantation ; 106(5): 997-1003, 2022 05 01.
Article in English | MEDLINE | ID: mdl-34319926

ABSTRACT

BACKGROUND: Calcineurin inhibitor (CNI)-based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit antithymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. METHODS: This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (d 10) against upfront CNI commencement (standard of care [SOC]) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary endpoint was change in (delta) creatinine from baseline to month 12. RESULTS: Fifty-five patients were enrolled in each study arm. Mean tacrolimus levels remained comparable in both groups from day 10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9 mo (P = 0.03) but not at month 12 (P = 0.05). Estimated glomerular filtration rate levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1 y were similar between groups (16.3 versus 12.7%, P = 0.58). rATG showed no significant adverse effects. Survival at 12 mo was comparable between groups (P = 0.48). CONCLUSIONS: Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 y, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 d or lower target tacrolimus levels, with acceptable safety and treatment efficacy.


Subject(s)
Kidney Transplantation , Liver Transplantation , Antilymphocyte Serum/therapeutic use , Calcineurin Inhibitors/adverse effects , Creatinine , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Induction Chemotherapy , Kidney , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Tacrolimus/therapeutic use
15.
Liver Transpl ; 17(6): 668-73, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21618687

ABSTRACT

Refractory ascites (RA) is a challenging complication after orthotopic liver transplantation. Its treatment consists of the removal of the precipitating factors. When the etiology is unknown, supportive treatment can be attempted. In severe cases, transjugular intrahepatic portosystemic shunts, portocaval shunts, and liver retransplantation have been used with marginal results. Recently, splenic artery embolization (SAE) has been described as an effective procedure for reducing portal hyperperfusion in patients undergoing partial or whole liver transplantation. Here we describe our experience with SAE for the treatment of RA. Between June 2004 and June 2010, 6 patients underwent proximal SAE for RA. Intraoperative flow measurements, graft characteristics, embolization portal vein (PV) velocities before and after SAE, and spleen/liver volume ratios were collected and analyzed. The response to treatment was assessed with imaging (ultrasound/computed tomography) and on the basis of clinical outcomes (weight changes, diuretic requirements, and the time to ascites resolution). The PV velocity decreased significantly for each patient after the embolization (median = 66.5 cm/second before SAE and median = 27.5 cm/second after SAE, P < 0.01). All patients experienced a significant postprocedural weight loss (mean = 88.1 ± 28.4 kg before SAE and mean = 75.8 ± 28.4 kg after SAE, P < 0.01) and a dramatic decrease in their diuretic requirements. All but 1 of the patients experienced a complete resolution of ascites after a median time of 49.5 days (range = 12-295 days). No patient presented with postembolization complications. In conclusion, SAE was effective in reducing the PV velocity immediately after the procedure. Clinically, this translated into a dramatic weight loss, a reduction of diuretic use, and a resolution of ascites. SAE appears to be a safe and effective treatment for RA.


Subject(s)
Ascites/etiology , Ascites/therapy , Embolization, Therapeutic , Liver Transplantation/adverse effects , Splenic Artery , Fatty Liver/surgery , Hepatitis C/surgery , Humans , Liver/diagnostic imaging , Liver Cirrhosis/surgery , Non-alcoholic Fatty Liver Disease , Portal Vein/physiopathology , Regional Blood Flow/physiology , Retrospective Studies , Treatment Outcome , Ultrasonography
16.
World J Transplant ; 11(10): 421-431, 2021 Oct 18.
Article in English | MEDLINE | ID: mdl-34722171

ABSTRACT

BACKGROUND: As the population of the United States ages, there has been an increasing number of elderly patients with cirrhosis listed for transplant. Previous studies have shown variable results in terms of the relative survival benefit for elderly liver transplant (LT) recipients. There may be factors that are associated with a poor post-transplant outcome which may help determine which elderly patients should and should not be listed for LT. AIM: To identify factors associated with futility of transplant in elderly patients. METHODS: This was a retrospective study of all patients above the age of 45 who underwent liver transplantation at our tertiary care center between January 2010 and March 2020 (n = 1019). "Elderly" was defined as all patients aged 65 years and older. Futile outcome was defined as death within 90 d of transplant. Logistic regression analysis was performed to determine what variables, if any were associated with futile outcome in elderly patients. Secondary outcomes such as one year mortality and discharge to facility (such as skilled nursing facility or long-term acute care hospital) were analyzed in the entire sample, compared across three age groups (45-54, 55-64, and 65 + years). RESULTS: There was a total of 260 elderly patients who received LT in the designated time period. A total of 20 patients met the definition of "futile" outcome. The mean Model of End-Stage Liver Disease scores in the futile and non-futile group were not significantly different (21.78 in the futile group vs 19.66 in the "non-futile" group). Of the variables tested, only congestive heart failure was found to have a statistically significant association with futile outcome in LT recipients over the age of 65 (P = 0.001). Of these patients, all had diastolic heart failure with normal ejection fraction and at least grade I diastolic dysfunction as measured on echocardiogram. Patients aged 65 years and older were more likely to have the outcomes of death within 1 year of LT [hazard ratio: 1.937, confidence interval (CI): 1.24-3.02, P = 0.003] and discharge to facility (odds ratio: 1.94, CI: 1.4-2.8, P < 0.001) compared to patients in younger age groups. CONCLUSION: Diastolic heart failure in the elderly may be a predictor of futility post liver transplant in elderly patients. Elderly LT recipients may have worse outcomes as compared to younger patients.

17.
Transplant Rev (Orlando) ; 35(2): 100595, 2021 04.
Article in English | MEDLINE | ID: mdl-33548685

ABSTRACT

PURPOSE OF REVIEW: Neuroendocrine tumor (NET) metastasis localized to the liver is an accepted indication for liver transplantation as such tumors have a low biological aggressiveness in terms of malignancy and are slow growing. RECENT FINDINGS: The long-term results are comparable with and in some cases even better than those of transplantations performed for primary liver cancer. However, compared with nonmalignant conditions, neuroendocrine liver metastasis (NELM) may result in an inferior outcome of transplantation. In the face of the scarcity of donated organs and recent improved results of non-surgical treatment for NELM, controversy over patient selection and timing for liver transplantation continues. SUMMARY: In this review, we provide an overview of the diagnostic work-up and selection criteria of patients with NELM being considered for liver transplantation. Thereafter, we provide a critical analysis of the reported outcomes of OLT.


Subject(s)
Liver Neoplasms , Liver Transplantation , Neuroendocrine Tumors , Humans , Liver Neoplasms/surgery , Neuroendocrine Tumors/surgery , Patient Selection , Prognosis
18.
Transplantation ; 105(9): 1998-2006, 2021 09 01.
Article in English | MEDLINE | ID: mdl-32947583

ABSTRACT

BACKGROUND: Rates of withdrawal of life-sustaining treatment are higher among critically ill pediatric patients compared to adults. Therefore, livers from pediatric donation after circulatory death (pDCD) could improve graft organ shortage and waiting time for listed patients. As knowledge on the utilization of pDCD is limited, this study used US national registry data (2002-2017) to estimate the prognostic impact of pDCD in both adult and pediatric liver transplant (LT). METHODS: In adult LT, the short-term (1-year) and long-term (overall) graft survival (GS) between pDCD and adult donation after circulatory death (aDCD) grafts was compared. In pediatric LT, the short- and long-term prognostic outcomes of pDCD were compared with other type of grafts (brain dead, split, and living donor). RESULTS: Of 80 843 LTs in the study, 8967 (11.1%) were from pediatric donors. Among these, only 443 were pDCD, which were utilized mainly in adult recipients (91.9%). In adult recipients, short- and long-term GS did not differ significantly between pDCD and aDCD grafts (hazard ratio = 0.82 in short term and 0.73 in long term, both P > 0.05, respectively). Even "very young" (≤12 y) pDCD grafts had similar GS to aDCD grafts, although the rate of graft loss from vascular complications was higher in the former (14.0% versus 3.6%, P < 0.01). In pediatric recipients, pDCD grafts showed similar GS with other graft types whereas waiting time for DCD livers was significantly shorter (36.5 d versus 53.0 d, P < 0.01). CONCLUSIONS: Given the comparable survival seen to aDCDs, this data show that there is still much scope to improve the utilization of pDCD liver grafts.


Subject(s)
Donor Selection , Graft Survival , Liver Transplantation , Tissue Donors/supply & distribution , Adolescent , Adult , Age Factors , Cause of Death , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Liver Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/epidemiology , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States/epidemiology , Waiting Lists , Young Adult
20.
Hepatogastroenterology ; 57(102-103): 1005-12, 2010.
Article in English | MEDLINE | ID: mdl-21410022

ABSTRACT

BACKGROUND/AIMS: Advanced gallbladder cancer (GC) carries dismal prognosis, due to its extent at diagnosis and the low R0 resection performance rate. METHODOLOGY: Thirty-two GC patients referred to our Department with an intention to treat between 1993 and 2005. All patients had advanced T stage (> or = T3). Pathological findings, surgical procedures and survival data were analyzed. RESULTS: Seventeen radical procedures (16 hepatectomies and 1 cholecystectomy with common bile duct resection), 4 palliative procedures (12.5%) and 11 surgical explorations (34.4%) were performed (53.1%, resectability rate). Hepatectomies were performed with 0% mortality, 11.8% morbidity and 94.1% resectability rate. The respective 1-, 3- and 5- year survival rates were 71.4%, 28.6% and 14.3%. Radical lymph node dissection (p = 0.03), absence of perineural tumor invasion (p = 0.03) and patients' age <70 years (p < 0.01) were non-independently associated with favorable prognosis in the hepatectomy-treated group of GC patients. CONCLUSIONS: GC patients with stage > or = IIA should be treated with hepatectomy combined with radical lymphadenectomy in order to achieve better staging and disease control. Incorporating the caudate lobe, more than 4 liver segments, or part of the extrahepatic biliary tree in the resection specimen in selected patients, might help eliminate perineural metastatic spread and achieve improved overall survival.


Subject(s)
Gallbladder Neoplasms/surgery , Adult , Aged , Bile Ducts/surgery , Cholecystectomy , Female , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Hepatectomy , Humans , Lymph Node Excision , Male , Middle Aged , Retrospective Studies
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