Sangbin Han

Association Between Intraoperative Platelet Transfusion and Early Graft Regeneration in Living Donor Liver Transplantation.

Objective: To evaluate the association between anesthetic management before and after graft reperfusion and early graft regeneration in living donor liver transplantation (LDLT). Background: Sufficient graft regeneration is essential for the success of LDLT. Diverse signals start to trigger liver regeneration immediately after graft reperfusion. Methods: Graft volume at 14 ± 2 days after LDLT was measured in 379 consecutive recipients using computed tomography images with 3-dimensional reconstruction. The association between anesthetic variables and the degree of graft regeneration for 2 weeks was analyzed using simple and multiple linear regressions. The anesthetic variables included hemodynamics, laboratory measurements, vasoactive drugs, and blood products transfusion. Results: The degree of graft regeneration for 2 weeks was 52% in median and ranged from 5% to 123%. Platelet transfusion was identified as the sole independent anesthetic factor contributing to graft regeneration. Platelet concentrate transfusion of 1 to 6 units vs none was correlated with a 6.5% increase in graft regeneration (P = 0.012). Platelet concentrate transfusion of more than 6 units vs none was further correlated with an 18.4% increase in regeneration (P < 0.001). In the subgroup of recipients without intraoperative platelet transfusion, mean platelet count measured during the intraoperative reperfusion phase was positively associated with graft regeneration (P = 0.033). Conclusions: Graft regeneration after LDLT increased in relation to a graded increase in the amount of transfused platelets and higher postreperfusion platelet counts during surgery. These results offer additional evidence regarding the important role of platelets in initiating liver regeneration and, furthermore, the indications for and the benefits vs risks of platelet transfusion during LDLT.

Safety of the Use of Blood Salvage and Autotransfusion During Liver Transplantation for Hepatocellular Carcinoma.

Objective: To determine whether autotransfusion of red blood cells (RBCs) salvaged during liver transplantation is associated with the recurrence of hepatocellular carcinoma (HCC). Background: Blood salvage is widely used during liver transplantation to reinfuse salvaged autologous RBCs and reduce allogeneic transfusion. However, the reintroduction of cancer cells via autotransfusion is a major concern in HCC patients. Methods: Among 397 patients who underwent living-donor liver transplantation for HCC, 97 of 114 recipients without intraoperative autotransfusion were matched with 222 of 283 recipients with intraoperative autotransfusion with unfixed matching ratio using the propensity score based on age, sex, allogeneic transfusion, immunosuppression, tumor biology, and others. Competing risks Cox regression was used to compare HCC recurrence risk of the 2 paired groups. Results: Recipients in autotransfusion group received 1177 ± 1318 mL of salvaged RBCs during surgery. A leukocyte depletion filter was used for all autotransfused RBCs. Cumulative HCC recurrence rate at 1, 2, and 5 years after transplantation were 10.4% (5.3%–17.6%), 19.1% (11.6%–28.0%), and 24.1% (15.2%–34.0%) for nonautotransfusion group and 10.8% (7.2%–15.4%), 14.9% (10.5%–20.0%), and 20.3% (14.9%–26.4%) for autotransfusion group, respectively. Autotransfusion versus nonautotransfusion group was not significantly different in overall recurrence [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.47–1.53, P = 0.579] and intrahepatic recurrence (HR 0.75, 95% CI 0.36–1.56) or extrahepatic recurrence (HR 1.00, 95% CI 0.49–2.04). Conclusions: We found no evidence of a significant impact of autotransfusion on posttransplant HCC recurrence. Thus, salvaged and filtered RBCs could be used in HCC patients undergoing liver transplantation with potential benefits from avoiding allogeneic RBCs transfusion and its complications.

Microsteatosis may not interact with macrosteatosis in living donor liver transplantation

BACKGROUND & AIMS The insignificance of pure microsteatosis (MiS) was reported in living donor liver transplantation (LDLT). However, since steatosis is mostly found in a mixed form of microsteatosis (MiS) and macrosteatosis (MaS), we aimed to determine the importance of MiS mixed with MaS in LDLT. METHODS Donor matching and recipient matching were independently performed with unfixed matching ratios. In donor matching, 51 donors with high (⩾30%) MiS mixed with MaS (H-MiS) were matched with 160 donors with low (⩽10%) MiS mixed with MaS (L-MiS), based on MaS degree, remnant liver volume, and others. In recipient matching, 50 recipients who received H-MiS grafts were matched with 176 recipients who received L-MiS grafts, based on MaS degree, graft volume, MELD score, and others. RESULTS The median MiS degree was 10% (range 0%-10%) vs. 35% (range 30%-80%) in L-MiS livers vs. H-MiS livers after both matching. L-MiS and H-MiS donors were not significantly different regarding postoperative biochemical liver function (e.g. peak AST 232 vs. 246 IU/L, p=0.931). L-MiS and H-MiS recipients were not significantly different regarding 2-week graft regeneration (51% for both) and 5-year survival (HR 0.87, 95% CI 0.43-1.76, p=0.699). Post-transplant donor/recipient complication rates were not significantly different, either. CONCLUSIONS There were no evidences of a significant impact of MiS mixed with MaS on post-LDLT outcomes. The results suggest less importance of MiS, and further indicate that there is no interaction between MiS and MaS. Thus, the risk of steatosis may be determined by the relative composition of MiS and MaS, rather than the total quantitative degree.

Comparison of the tolerance of hepatic ischemia/reperfusion injury in living donors: macrosteatosis versus microsteatosis.

A safe use of intermittent hepatic inflow occlusion (IHIO) has been reported for living donor hepatectomy. However, it remains unclear whether the maneuver is safe in steatotic donors. In addition, the respective importance of macrosteatosis (MaS) and microsteatosis (MiS) is an important issue. Thus, we compared MiS and MaS with respect to the tolerance of hepatic ischemia/reperfusion (IR) injury induced by IHIO. One hundred forty‐four donors who underwent a right hepatectomy were grouped according to the presence of MaS and MiS: a non‐MaS group (n = 68) versus an MaS group (n = 76) and a non‐MiS group (n = 51) versus an MiS group (n = 93). The coefficients of the regression lines between the cumulative IHIO time and the peak postoperative transaminase concentrations were used as surrogate parameters indicating the tolerance of hepatic IR injury. The coefficients were significantly greater for the MaS group versus the non‐MaS group (4.12 ± 0.59 versus 2.22 ± 0.46 for alanine aminotransferase, P = 0.01). Conversely, the MiS and non‐MiS groups were comparable. A subgroup analysis of donors who underwent IHIO for >30 minutes showed that MaS significantly increased the transaminase concentrations, whereas MiS had no impact. Also, IHIO for >30 minutes significantly increased the biliary complication rate for MaS donors (12.1% for ≤ 30 minutes versus 32.6% for >30 minutes, P = 0.04), whereas MiS donors were not affected. In conclusion, the tolerance of hepatic IR injury might differ between MaS livers and MiS livers. It would be rational to assign more clinical importance to MaS versus MiS. We further recommend limiting the cumulative IHIO time to 30 minutes or less for MaS donors undergoing right hepatectomy. Liver Transpl 20:775–783, 2014.

Effect of active airway warming on body core temperature during adult liver transplantation.

INTRODUCTION Active inspired gas humidification (AH) preserves body heat and maintains normothermia intraoperatively. However, it is unclear whether AH shows comparable influences during liver transplantation (OLT), which may be affected by both large internal heat loss and external heat supply. Thus, the aim of this study was to evaluate the effect of AH compared with passive humidification (PH) on body temperature in OLT. MATERIALS AND METHODS Thirty-four adult patients undergoing living donor OLT were randomly enrolled into two groups: those given AH using a heated humidifier (HH group, n = 17) and those using a heat-and-moisture exchanger (HME group, n = 17). Both core and skin temperatures (Tc and Ts), as well as respiratory parameters, including static/dynamic lung compliances and PaO(2), were recorded at predetermined times. RESULTS Both Tc and Ts were consistently higher among the HH versus the HME group after 2 hours of anesthesia. Differences in Tc and Ts between the two groups increased gradually over time. The overall Tc during surgery was higher among the HH than the HME group (P = .023). The incidences of hypothermia were lower in the HH group at 3 hours of anesthesia, 1 and 3 hours of reperfusion, and at the end of surgery (P = .037, 0.024, 0.005, and 0.010 respectively). The duration of hypothermia was lower in the HH than the HME group (3.9 ± 3.5 hours versus 6.7 ± 3.3 hours, P = .025). Both groups showed no significant intraoperative changes in respiratory parameters; there were no postoperative respiratory complications. CONCLUSION Active humidification warms the patients body effectively, lessening the incidence and duration of hypothermia during OLT with no respiratory risks.

Development of a Prediction Rule for Estimating Postoperative Pulmonary Complications

Patient- and procedure-related factors associated with postoperative pulmonary complications (PPCs) have changed over the last decade. Therefore, we sought to identify independent risk factors of PPCs and to develop a clinically applicable scoring system. We retrospectively analyzed clinical data from 2,059 patients who received preoperative evaluations from respiratory physicians between June 2011 and October 2012. A new scoring system for estimating PPCs was developed using beta coefficients of the final multiple regression models. Of the 2,059 patients studied, 140 (6.8%) had PPCs. A multiple logistic regression model revealed seven independent risk factors (with scores in parentheses): age ≥70 years (2 points), current smoker (1 point), the presence of airflow limitation (1 point), American Society of Anesthesiologists class ≥2 (1 point), serum albumin <4 g/dL (1 point), emergency surgery (2 points), and non-laparoscopic abdominal/cardiac/aortic aneurysm repair surgery (4 points). The area under the curve was 0.79 (95% CI, 0.75–0.83) with the newly developed model. The new risk stratification including laparoscopic surgery has a good discriminative ability for estimating PPCs in our study cohort. Further research is needed to validate this new prediction rule.

Bioreactance Is Not Interchangeable with Thermodilution for Measuring Cardiac Output during Adult Liver Transplantation

Background Thermodilution technique using a pulmonary artery catheter is widely used for the assessment of cardiac output (CO) in patients undergoing liver transplantation. However, the unclearness of the risk-benefit ratio of this method has led to an interest in less invasive modalities. Thus, we evaluated whether noninvasive bioreactance CO monitoring is interchangeable with thermodilution technique. Methods Nineteen recipients undergoing adult-to-adult living donor liver transplantation were enrolled in this prospective observational study. COs were recorded automatically by the two devices and compared simultaneously at 3-minute intervals. The Bland–Altman plot was used to evaluate the agreement between bioreactance and thermodilution. Clinically acceptable agreement was defined as a percentage error of limits of agreement <30%. The four quadrant plot was used to evaluate concordance between bioreactance and thermodilution. Clinically acceptable concordance was defined as a concordance rate >92%. Results A total of 2640 datasets were collected. The mean CO difference between the two techniques was 0.9 l/min, and the 95% limits of agreement were -3.5 l/min and 5.4 l/min with a percentage error of 53.9%. The percentage errors in the dissection, anhepatic, and reperfusion phase were 50.6%, 56.1%, and 53.5%, respectively. The concordance rate between the two techniques was 54.8%. Conclusion Bioreactance and thermodilution failed to show acceptable interchangeability in terms of both estimating CO and tracking CO changes in patients undergoing liver transplantation. Thus, the use of bioreactance as an alternative CO monitoring to thermodilution, in spite of its noninvasiveness, would be hard to recommend in these surgical patients.

Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation

ABO‐incompatible (ABO‐I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO‐compatible (ABO‐C) and ABO‐I LDLT. The aim was to compare the outcomes of ABO‐I LDLT with those of ABO‐C LDLT using the matched‐pairs method.

Macrosteatotic and nonmacrosteatotic grafts respond differently to intermittent hepatic inflow occlusion: Comparison of recipient survival

Intermittent hepatic inflow occlusion (IHIO) during liver graft procurement is known to confer protection against graft ischemia/reperfusion injury and thus may benefit the recipients outcome. We evaluated whether the protective effect of IHIO differs with the presence of macrosteatosis (MaS) and with an increase or decrease in the cumulative occlusion time. The subgroup of 188 recipients who received grafts with MaS was divided into 3 groups according to the number of total IHIO rounds during graft procurement: no IHIO, n = 70; 1 to 2 rounds of IHIO, n = 50; and ≥3 rounds of IHIO, n = 68. Likewise, the subgroup of 200 recipients who received grafts without MaS was divided into 3 groups: no IHIO, n = 108; 1 to 2 rounds of IHIO, n = 40; and ≥3 rounds of IHIO, n = 52. The Cox model was applied to evaluate the association between the number of total IHIO rounds and recipient survival separately in the subgroup of MaS recipients and the subgroup of non‐MaS recipients. Analyzed covariables included the etiology, Milan criteria, transfusion, immunosuppression, and others. In the subgroup of MaS recipients, 1 to 2 rounds of IHIO were favorably associated with recipient survival [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.10‐0.80; P = 0.03 after Bonferroni correction], whereas ≥3 rounds of IHIO were not associated with recipient survival (HR, 0.56; 95% CI, 0.25‐1.23). In the subgroup of non‐MaS recipients, neither 1 to 2 rounds of IHIO (HR, 0.69; 95% CI, 0.30‐1.61) nor ≥3 rounds of IHIO (HR, 0.91; 95% CI, 0.42‐1.96) were associated with recipient survival. In conclusion, 1 to 2 rounds of IHIO may be used for the procurement of MaS grafts with potential benefit for recipient survival, whereas IHIO has a limited impact on recipient survival regardless of the cumulative occlusion time when it is used for non‐MaS grafts. Liver Transpl 21:644–651, 2015.

Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109/L were matched with 97 of 119 patients who had preoperative PLT >75 × 109/L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109/L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow‐up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio [HR] = 3.09; 95% confidence interval [CI], 1.86‐5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23‐3.60; P =  0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36‐4.01; P =  0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02‐3.54; P =  0.04). Preoperative PLT had no interaction with the Milan criteria, alpha‐fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation‐based scores including neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and the inflammation‐based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation. Liver Transplantation 24 44–55 2018 AASLD.