Validation of the IWATE criteria as a laparoscopic liver resection difficulty score in a single North American cohort.

BACKGROUND: Laparoscopic liver resection (LLR) involves a difficult learning curve, for which multiple difficulty scores have been proposed to assist with safe adaptation. The IWATE Criteria is a 4-level difficulty score shown to correlate with conversion to open surgery, estimated blood loss (EBL), and operative time in Japanese and French cohorts. We set out to validate the IWATE Criteria in a North American cohort, describe the evolution of our LLR program, and analyze the IWATE Criteria's ability to predict conversion to open surgery. METHODS: Patients that underwent LLR between January 2006 and December 2019 were selected from a prospectively maintained database. Difficulty outcomes, including conversion to open surgery, EBL, operative time, and post-operative complications were analyzed according to IWATE difficulty level, both overall and between chronological eras. The IWATE Criteria's ability to predict conversion to open surgery was assessed with a receiver operating characteristic (ROC) analysis. RESULTS: A total of 426 patients met inclusion criteria. Operative time, EBL, and conversion to open surgery increased in concordance with low to advanced IWATE difficulty. ROC analysis for conversion to open surgery demonstrated an overall area under the curve (AUC) of 0.694. Predictive performance was superior during the first two eras, with AUCs of 0.771 and 0.775; predictive value decreased as the LLR program gained experience, with AUCs of 0.708 and 0.551 for eras three and four. CONCLUSIONS: This study validated the IWATE Criteria in a North American population distinct from previous Japanese and French cohorts, based on its correlation with operative time, EBL, and conversion to open surgery. The IWATE Criteria may be of utility for identification of LLR cases appropriate for surgeon experience, as well as determination of laparoscopic feasibility. Interval difficulty score recalibration may be warranted as surgeon perception of difficulty evolves.

Conditional probability of graft survival in liver transplantation using donation after circulatory death grafts - a retrospective study.

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.

Should We Be Utilizing More Liver Grafts From Pediatric Donation After Circulatory Death Donors? A National Analysis of the SRTR from 2002 to 2017.

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.

Sufficient hepatic artery flow compensates for poor portal vein flow after liver transplantation in patients with portal vein thrombosis.

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.

Risk of Post-transplant Hepatocellular Carcinoma Recurrence Is Higher in Recipients of Livers From Male Than Female Living Donors.

OBJECTIVE: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. BACKGROUND: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. METHODS: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. RESULTS: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15-3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20-3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05-3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05-3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05-3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11-3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. CONCLUSIONS: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Laparoscopic Liver Resection of Hepatocellular Carcinoma with a Tumor Size Larger Than 5 cm: Review of 45 Cases in a Tertiary Institution.

INTRODUCTION: Although laparoscopic liver resection (LLR) has developed rapidly, its usefulness for the treatment of large tumors is less clear, due to concerns about compromising oncological principles and patient safety. The purpose of this study was to explore the feasibility and safety of LLR for the treatment of hepatocellular carcinoma (HCC) with a tumor size larger than 5 cm. PATIENTS AND METHODS: From January 2007 to December 2014, we performed LLR in 45 patients with HCC with a tumor size ≥5 cm. Perioperative outcome, tumor recurrence, and overall patient survival were analyzed. RESULTS: Median age was 60 years (interquartile range [IQR] 52-68) and 64.4% (29/45) were male. Seven patients (15.6%) had larger than 10 cm of HCC. No operative deaths occurred and six of the laparoscopic procedures were converted to open resection (conversion rate 13.3%). Median operation time was 365 minutes (IQR 277-443) and median estimated blood loss (EBL) was 400.0 mL (IQR 275-600). There was no R1 or R2 resection and median resection margin was 19.0 mm (IQR 8.0-33.0). Complications above Clavien-Dindo classification grade III occurred in four patients (8.9%). The median overall follow-up time was 10.7 month (range 1.1-62.1). One-year recurrence free survival (RFS) and overall survival (OS) were 86.0% and 95.5%, and 3-year RFS and OS were 70.7% and 86.0%. CONCLUSION: LLR appears safe and feasible in patients with HCC with a tumor size larger than 5 cm. Expansion of indication for LLR in patients with HCC may be considered.

Sustained linear growth and preserved renal function in 10-year survivors of pediatric liver transplantation.

The aim of this study was to characterize the clinical outcomes of children and adolescents who achieved survival of more than 10 years following liver transplantation (LT) in a single center in Korea. From June 1996 to October 2003, 57 pediatric LTs were performed. The medical records of 44 patients who had survived more than 10 years were reviewed retrospectively. Median age of patients at LT was 0.8 years. Forty-one patients received living donor LT, and three patients received deceased donor LT. Biliary atresia was the most common indication (65.9%). Thirty-five patients were on tacrolimus monotherapy at 10 years post-LT with a mean trough level of 2.73 ng/ml, and five patients were maintaining stable graft function without any immunosuppression. There were no patients receiving antihypertensive medication and one case of diabetes mellitus. Renal dysfunction was seen in two patients (4.5%), while none required renal replacement therapy. Mean height z-score prior to LT was -1.35 and at 10 years post-transplant was 0.05. Good linear growth was sustained in this cohort throughout the 10 years, approaching the 50th percentile. Also, there were remarkably low incidences of renal dysfunction and patients requiring medications for glycemic or hypertensive control, all hallmarks of continued use of immunosuppressive agents.

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.

Antiviral treatment for hepatitis B virus recurrence following liver transplantation.

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV-related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty-seven LTs were performed for HBsAg-positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow-up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 10(5) IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV-recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre-transplant HBV viremia and an effective post-transplant HBV prophylaxis.

Clinical implications of quantitative real time-polymerase chain reaction of parvovirus B19 in kidney transplant recipients - a prospective study.

This prospective study was designed to investigate the clinically significant level of parvovirus B19 viral load using quantitative real-time (RT) polymerase-chain reaction (PCR) in kidney transplantation (KT) recipients. One hundred forty-three adult recipients who underwent their first KT between November 2003 and October 2005 were enrolled. Six blood samples (the first taken preoperatively, subsequent samples taken every 4 weeks for 20 weeks) were taken from each patient for parvovirus B19 DNA RT-PCR analysis. All recipients were diligently followed for 1 year post-transplant. One hundred sixty-eight of the 715 (23.5%) postoperative samples were positive for parvovirus B19 PCR. Eighty-four of the 143 KT recipients (58.7%) showed at least one positive PCR. Sixteen of the 143 (11.1%) KT recipients had sustained severe anemia (SSA) with hemoglobin lower than 7.0 g/dl, after 4 weeks post-transplant. The incidence of SSA in recipients with a titer higher than 1 x 10(6) copies/5 microl whole blood was significantly higher than those with a negative or low titer (P < 0.001, positive predictive value 84.6%, negative predictive value 96.2%). In conclusion, a high titer of parvovirus B19 DNA higher than 1 x 10(6) copies/5 microl whole blood in KT recipients was related with SSA after 4 weeks post-transplant.

Prolonged cold ischemic time is a risk factor for biliary strictures in duct-to-duct biliary reconstruction in living donor liver transplantation.

BACKGROUND: Duct-to-duct (DD) anastomosis is an accepted procedure for biliary reconstruction in living donor liver transplantation (LDLT). However, biliary complication rates in LDLT recipients have been reported to be as high as 20% to 30% or more. In this study, we examined various potential risk factors for biliary stricture (BS) that occurs in the context of DD reconstruction in a single-active transplant center. METHODS: Enrolled in this study were adults who underwent their first LDLT with DD reconstruction between August 2002 and May 2007 (n=283). BSs were defined as anastomotic strictures that required interventions or operative procedures to be corrected. We reviewed retrospectively the medical records of recipients, including medical history, surgical procedures, and progress, and analyzed risk factors of BS with the Kaplan-Meier method. RESULTS: BS occurred in 58 of the 283 recipients (20.5%). The mean follow-up period was 24.4 months posttransplant (SD=16.5). The univariate analysis revealed that recipient age (P=0.032), bile duct size (P=0.003), biliary reconstruction surgeon (P=0.023), perfusion solution (P=0.001), cold ischemic time (CIT) (P<0.001), and biliary leakage history (P<0.001) were significant risk factors. In the multivariable analysis, CIT (P=0.001), biliary leakage history (P=0.002), bile duct size (P=0.021), and recipient age (P=0.036) were significant risk factors for BS. And, a CIT cutoff value of 71 min was calculated using the minimum P value approach with correction by the Miller and Siegmund method (P=0.0186). CONCLUSIONS: In this study, prolonged CIT is identified as a risk factor for BS in DD biliary reconstruction in LDLT.