Donor sex and donor-recipient sex disparity do not affect hepatocellular carcinoma recurrence after living donor liver transplantation.

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion: Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

CT-based visual grading system for assessment of hepatic steatosis: diagnostic performance and interobserver agreement.

BACKGROUND: Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS. METHODS: In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics. RESULTS: Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%. CONCLUSION: VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment.

Assessment of pathogens and risk factors associated with bloodstream infection in the year after pediatric liver transplantation.

BACKGROUND: Bloodstream infection (BSI) is one of the most significantly adverse events that can occur after liver transplantation (LT) in children. AIM: To analyze the profile of BSI according to the postoperative periods and assess the risk factors after pediatric LT. METHODS: Clinical data, collected from medical charts of children (n = 378) who underwent primary LT, were retrospectively reviewed. The primary outcome considered was BSI in the first year after LT. Univariate and multivariate analyses were performed to identify risk factors for BSI and respective odds ratios (ORs). RESULTS: Of the examined patients, 106 (28%) experienced 162 episodes of pathogen-confirmed BSI during the first year after LT. There were 1.53 ± 0.95 episodes per children (mean ± SD) among BSI-complicated patients with a median onset of 0.4 mo post-LT. The most common pathogenic organisms identified were Coagulase-negative staphylococci, followed by Enterococcus spp. and Streptococcus spp. About half (53%) of the BSIs were of unknown origin. Multivariate analysis demonstrated that young age (≤ 1.3 year; OR = 2.1, P = 0.011), growth failure (OR = 2.1, P = 0.045), liver support system (OR = 4.2, P = 0.008), and hospital stay of > 44 d (OR = 2.3, P = 0.002) were independently associated with BSI in the year after LT. CONCLUSION: BSI was frequently observed in patients after pediatric LT, affecting survival outcomes. The profile of BSI may inform clinical treatment and management in high-risk children after LT.

Controlled attenuation parameter measured using transient elastography for the noninvasive assessment of macrovesicular steatosis in potential living liver donors.

PURPOSE: This study aimed to determine the diagnostic performance of the controlled attenuation parameter (CAP) measured using transient elastography (TE) for assessing macrovesicular steatosis (MaS) in potential living liver donors using same-day biopsy as a reference standard. METHODS: This retrospective study included 204 living liver donor candidates who underwent TE and liver biopsy on the same day between July 2013 and June 2014. The histologic degree of MaS was determined. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of CAP for diagnosing MaS of >10%, and the optimal cutoff value was identified using the maximal Youden index. RESULTS: Based on liver biopsy, 185 subjects had MaS of ≤10% and 19 had MaS of >10%. The CAP value was significantly correlated with the percentage of MaS on liver biopsy (r=0.635, P<0.001), and the median CAP value was significantly higher in subjects with MaS of >10% than in those with MaS of ≤10% (300 dB/m vs. 209 dB/m, P<0.001). The AUROC for diagnosing MaS of >10% by CAP was 0.938 (95% confidence interval, 0.896 to 0.967), and a CAP of >259 dB/m yielded a sensitivity of 84.2% and a specificity of 92.4%. CONCLUSION: The CAP measured using TE was significantly correlated with MaS and accurately detected substantial MaS in potential living liver donors. The CAP is a promising tool for the noninvasive diagnosis of MaS and may be used to screen unsuitable living liver donor candidates.

Hepatocyte-Specific Magnetic Resonance Imaging-Based Assessment of Indeterminate Hepatic Nodules in the Liver Transplant Evaluation of Patients With Cirrhosis.

We aimed to determine the identities in explants of indeterminate hepatic nodules (IDNs) that had been scanned by dynamic magnetic resonance imaging (MRI) to establish clinicoradiological parameters predicting which IDNs were hepatocellular carcinomas (HCCs). This study included 88 patients with cirrhosis who underwent gadoxetic acid-enhanced MRI in pre-liver transplantation (LT) workup followed within 90 days by primary LT. The MRI detected 168 hepatic nodules that were classified into 6 benign tumors, 49 HCCs, and 113 IDNs, in 5, 34, and 72 patients, respectively. We compared these pre-LT radiologic diagnoses and stagings with explant pathology on a per-lesion basis to enable us to identify features of IDNs related to malignancy. Of the 168 nodules seen on MRI, 119 that were classified radiologically as consisting of 1 benign nodule (33.3%), 46 HCCs (93.9%), and 72 IDNs (63.7%) all turned out to be pathological HCCs. Of 32 patients inside Milan and 54 without HCC staged by MRI, 11 progressed beyond the criteria after LT. High serum alpha-fetoprotein level (≥20 ng/mL) was the only per-patient factor significantly associated with malignant IDNs. Per-tumor analysis of the MRI signals revealed that arterial hyperintensity, hepatobiliary hypointensity, T2 -weighted mild-to-moderate intensity, and restricted diffusion-weighted images were significantly correlated with malignant IDN. A model combining these 4 MRI factors with alpha-fetoprotein level had the best performance in predicting the identification of IDNs as HCCs in explanted livers. Over 60% of the IDNs seen on dynamic images of cirrhotic livers proved to be HCCs when explanted livers were examined. It may therefore be possible to identify HCCs with reasonable accuracy by means of their hepatocyte-specific MRI features when patients are being assessed for LT.

Assessment of patient safety and the efficiency of facility utilization following simplified ultra-rapid intravenous infusion of hepatitis B immunoglobulin in a high-volume liver transplantation center.

BACKGROUNDS/AIMS: This study intended to evaluate patient safety and efficiency of facility utilization following simplified ultra-rapid intravenous infusion of hepatitis B immunoglobulin (HBIG) in recipients of hepatitis B virus-associated adult liver transplantation (LT), who visited our outpatient clinic. METHODS: Our simplified ultra-rapid infusion protocol was to directly infuse 50 ml volume of 10,000 IU HBIG for 20-25 minutes on an ambulatory basis. The incidence of adverse side-effects and the efficiency of facility utilization were assessed retrospectively. RESULTS: A total of 1,513 patients received 12,472 sessions of HBIG infusion according to simplified ultra-rapid infusion method. Of these, 1,172 patients were converted from conventional ultra-rapid infusion method, and received 8,352 sessions of HBIG infusion for 18 months (mean 7.1 times; 4.8 times per year). The remaining 341 de novo patients received 4,120 sessions of HBIG infusion for 18 months (mean 12.1 times; 8.1 times per year). None of these patients experienced any adverse side-effects following the simplified ultra-rapid infusion. The maximal capacity of HBIG infusion sessions at the injection facility of our outpatient clinic was increased from 65-70 sessions to 80 sessions, after introduction of simplified ultra-rapid infusion method. Mean trough anti-HBs titer was lower, and mean interval of HBIG infusion was longer in the combination therapy group compared with HBIG monotherapy group. CONCLUSIONS: Our high-volume study indicates that in nearly all LT recipients, rapid infusion of highly purified HBIG within 30 minutes was well-tolerated. This suggests that it would be reasonable to perform simplified ultra-rapid infusion protocol widely for patient convenience.

Quantified Risk Assessment for Major Hepatectomy via the Indocyanine Green Clearance Rate and Liver Volumetry Combined with Standard Liver Volume.

BACKGROUND: Preoperative risk assessment for post-hepatectomy liver failure (PHLF) is essential for major hepatectomy. We intended to establish a standard liver volume (SLV) formula for Korean patients and validate the predictive power of the indocyanine green clearance rate constant (ICG-K) fraction of future remnant liver (FRL) (FRL-kICG) to total liver volume (TLV). METHODS: This study comprised 2 retrospective studies. Part I established SLV formula and acquired ICG pharmacokinetic data from 2155 living donors. In part II, FRL-kICG cutoff was determined using 723 patients who underwent right liver resection for hepatocellular carcinoma. RESULTS: In part I, the formula SLV (mL) = -456.3 + 969.8 × BSA (m(2)) (r = 0.707, r (2) = 0.500, p = 0.000) was derived with mean volume error of 10.5%. There was no correlation between TLV and ICG retention rate at 15 min. With a cutoff of 0.04 with hepatic parenchymal resection rate (PHRR) limit of 70%, 99.0% of our living donors were permissible for left or right hepatectomy. In part II, 25 hepatocellular carcinoma patients (3.5%) showed an FRL-kICG or SLV-corrected FRL-kICG <0.05. Of these, 4 (16 %) died of PHLF, whereas only 2 (0.3%) died in the other patient group with both an FRL-kICG and SLV-corrected FRL-kICG ≥ 0.05 (P = 0.000). CONCLUSIONS: The FRL-kICG appears to reliably predict PHLF risk quantitatively. We suggest FRL-kICG cutoffs of 0.04 and 0.05 with PHRR limits of 70% and 65% for normal and diseased livers, respectively. Further validation with large patient population in multicenter studies is necessary to improve FRL-kICG predictability.

Assessment of right liver graft perfusion effectiveness between one and two-catheter infusion methods.

BACKGROUNDS/AIMS: Conventional graft perfusion method using one small-caliber catheter takes a relatively long time for right liver graft perfusion, thus some modification is needed. In this study, we intended to assess the effectiveness of right liver graft perfusion methods through comparison of different infusion catheters. METHODS: The study consisted of two parts including one bench experiment to obtain data of hydraulic infusion and one clinical trial of 40 cases on graft perfusion with one- versus two-catheter infusion methods. These two graft infusion methods were compared in terms of the perfusion time and washing-out efficiency. RESULTS: At bench experiment, the infusion flow rate and infusion pressure were 3.3 ml/sec and 1.9 cmH20 in one blood transfusion catheter group, and 11.7 ml/sec and 3.1 cmH20 in single transurethral resection of prostate irrigation catheter group, and 6.6 ml/sec and 2.0 cmH20 in two blood transfusion catheters group, respectively. In clinical trial with 40 right liver grafts, two-catheter group had a shorter graft portal perfusion time for the first 2 L of histidine-tryptophan-ketoglutarate (HTK) solution than the conventional one-catheter group (375±25 seconds vs. 662±34 seconds; p=0.001) and a lower rate of incomplete blood washing-out after the initial 2 L portal perfusion (40% vs. 85%; p=0.03). CONCLUSIONS: The two-catheter infusion method appears to be more effective than the conventional one-catheter infusion method for right liver graft perfusion at the back table. Large size of right liver grafts seems to be its good indication.

A clinical assessment of mycophenolate drug monitoring after liver transplantation.

BACKGROUND: Recent findings have suggested the clinical utility of therapeutic drug monitoring (TDM) in patients treated with mycophenolate mofetil (MMF). AIM: To assess whether routine mycophenolic acid (MPA) TDM is beneficial and how to utilize it. METHODS: A series of short-term prospective studies on TDM for MPA and/or tacrolimus was performed at a large-volume center. RESULTS: The 673 adult liver transplants were divided into four groups based on immunosuppressive regimens as tacrolimus monotherapy (n = 369), tacrolimus-MMF therapy (n = 270), MMF-minimal tacrolimus therapy (n = 17), and MMF monotherapy (n = 17). There was a significant difference of tacrolimus concentration between the groups receiving tacrolimus monotherapy and tacrolimus-MMF therapy during the first two yr (at two yr: 8.4 +/- 2.7 vs. 6.3 +/- 2.6 ng/mL; p < or = 0.002). MMF-minimal tacrolimus therapy and MMF monotherapy were applied after first three months and MPA levels ranged from 1.8 to 5.3 microg/mL. Correlation between MMF dosage and MPA concentration showed wide interindividual variations (n = 304, r(2) = 0.271, p < 0.001), in which r(2) was fluctuating from 0.056 to 0.213 according to the post-transplant period over five yr; wide intraindividual variation was also observed during the first two months (n = 12, r(2) < 0.2, p > 0.195). About 10% of patients were classified as poor MMF absorber and excluded from MMF usage. Mean MPA level leading to successful MMF monotherapy or MMF-minimal tacrolimus therapy was > or =1.0 microg/mL in 87% and >2.0 microg/mL in 56.5%. CONCLUSION: MPA TDM-based MMF dosage adjustment enabled us to administer MMF more confidently than categorical dosing. MPA TDM appears to be a useful tool to cope with the wide pharmacokinetic variability of MMF after liver transplantation.

Continuous peritransplant assessment of consciousness using bispectral index monitoring for patients with fulminant hepatic failure undergoing urgent liver transplantation.

BACKGROUND: Rapid deterioration of consciousness is a critical situation for patients with fulminant hepatic failure (FHF). Bispectral (BIS) index was derived from electroencephalography parameters, primarily to monitor the depth of unconsciousness. AIM: To assess the usability of peritransplant BIS monitoring in patients with FHF. METHODS: A prospective study using peritransplant BIS monitoring was performed in 26 patients with FHF undergoing urgent liver transplantation (LT). RESULTS: Pre-transplant Child-Pugh score was 12.2 +/- 1.0; model for end-stage liver disease score was 32.4 +/- 4.4; Glasgow coma score (GCS) was 9.9 +/- 1.3; and BIS index was 44.0 +/- 6.7. Pre-transplant sedation significantly decreased BIS index. After LT, all patients having endotracheal intubation recovered consciousness within one to three d and showed progressive increase in BIS index, which appeared slightly earlier and was more evident than the increase in derived GCS score. There was a significant correlation between BIS index and derived GCS scores (r(2) = 0.648). Timing of eye opening to voice was matched with BIS index of 66.3 +/- 10.4 and occurred 12.7 +/- 8.3 h after passing BIS index of 50. CONCLUSION: These results suggest that BIS monitoring is a non-invasive, simple, easy-to-interpret method, which is useful in assessing peritransplant state of consciousness. BIS monitoring may therefore be a useful tool during peritransplant intensive care for patients with FHF showing hepatic encephalopathy.

Feasibility assessment for tailoring preservation of segment VIII hepatic vein during left liver graft procurement.

BACKGROUND/AIMS: Procurement of left lobe (LL) graft occasionally induces large-sized hepatic venous congestion (HVC) at the remnant right liver. Isolated preservation of segment VIII vein (V8) could reduce this HVC, but it has been applied to only a small number of living donor operations to date. METHODOLOGY: We investigated the indication of tailoring V8 preservation through the anatomical analyses and computer simulation in a large-volume donor pool. After setting up its surgical technique in 3 donor cases, we analyzed the liver anatomy of 147 LL graft donors. RESULTS: We regarded the first anatomical condition as direct convergence of a large V8 branch on middle hepatic vein root, by which 27 livers were selected. The second was absence of complex hepatic vein branching at the graft cutting line, and 4 livers were excluded. The third was relatively large-sized HVC more than 35% of right lobe volume, and 11 livers were additionally excluded. Finally, 12 (8.2%) of 147 were left after 3-step selection processes. V8 preservation was estimated to reduce the total amount of HVC by 40%. CONCLUSIONS: We think that tailoring V8 preservation seems to be indicated for 8.2% of LL graft donor livers according to the 3 anatomical conditions.

Long-term incidence, risk factors, and management of biliary complications after adult living donor liver transplantation.

A considerable proportion of adult living donor liver transplantation (LDLT) recipients experience biliary complication (BC), but there are few reports regarding BC based on long-term studies of a large LDLT population. The present study examined BC incidence, risk factors and management using single-center data from 259 adult patients (225 right liver and 34 left liver grafts) between 2000 and 2002. The mean follow-up period was 46 +/- 14 months. Biliary reconstruction included single duct-to-duct anastomosis (DD, n = 141), double DD (n = 19), single hepaticojejunostomy (HJ, n = 67), double HJ (n = 28), and combined DD and HJ (n = 4). There were 12 episodes of anastomotic bile leak and 42 episodes of anastomotic stenosis in 50 recipients. Most leaks occurred within the first month, whereas stenosis occurred over 3 yr. Most stenoses were successfully treated using radiological intervention. Cumulative 1-, 3-, and 5-yr BC rates were 12.9%, 18.2%, and 20.2%, respectively. BC occurred much more frequently in right liver grafts compared to left liver grafts (P = 0.024). Stenosis-free survival curves for right liver graft recipients were similar for all reconstruction groups. When right liver graft recipients with single biliary reconstructions were grouped according to graft duct size and type of biliary reconstruction, DD involving a small-sized duct (less than 4 mm in diameter) was found to be a BC risk factor (P = 0.015), whereas HJ involving such duct sizes was not found to be associated with a higher risk (P = 0.471). In conclusion, close surveillance for BC appears necessary for at least the first 3 yr after LDLT. We found that most BC could be successfully controlled using radiological intervention. In terms of anastomotic stenosis risk, HJ appears a better choice than DD for right liver grafts involving ducts less than 4 mm in diameter.