Life-Threatening Portal Flow Steal Reappearing Under Increased Intrahepatic Vascular Resistance After Living Donor Liver Transplantation.

Maintenance of adequate portal inflow is crucial for graft regeneration in adult living donor liver transplantation (ALDLT) to allow the recipients to meet their early metabolic demands. A persistent large spontaneous portosystemic shunt can divert portal flow away from the liver graft, leading to impaired or delayed graft regeneration and subsequent graft failure. The importance of obliterating huge portosystemic shunt during liver transplantation is obvious for successful ALDLT. However, in partial liver graft with a relatively small graft-to-recipient weight ratio (GRWR) (compared with deceased donor whole graft liver transplantation), even the persisting small portosystemic shunt may result in repeated portal flow steal when a liver graft faces increased intrahepatic vascular resistance caused by rejection or graft congestion with hepatic venous outflow stenosis. We present 2 complicated cases of reappearing portal flow steal that were derived from the remaining small portosystemic shunt under the increased vascular resistance of the liver graft, even after interruption of a large portosystemic shunt during ALDLT. Because ALDLT is always a partial liver graft, even when GRWR is over 1%, it is much more vulnerable to hemodynamic changes in portal flow by rejection or graft congestion by hepatic venous outflow obstruction. Therefore, a comprehensive understanding of complex portosystemic shunt and complete reinterruption of reappearing portosystemic shunt, even though small and insignificant, during ALDLT is important for graft salvage procedures before irreversible liver graft damage.

Technical refinement of prosthetic vascular graft anastomosis to recipient inferior vena cava for secure middle hepatic vein reconstruction in living donor liver transplantation.

BACKGROUNDS/AIMS: Hemashield vascular grafts has been used for middle hepatic vein (MHV) reconstruction during living donor liver transplantation (LDLT). We occasionally encounter outflow disturbance of MHV conduit at the anastomotic stump of the middle-left hepatic vein (MLHV) trunk. To mitigate the disturbance, we carried out a series of studies regarding hemodynamics-compliant MHV reconstruction. METHODS: This study comprised of three parts: Part 1: Determining the causes of outflow disturbance; Part 2: Computational simulative analysis; and, Part 3: Clinical application of our refined technique. The types of Hemashield conduit-MLHV stump reconstruction were end-to-end anastomosis (type 1), side-to-end anastomosis (type 2), and oblique cutting of the conduit end and patch plasty (type 3). RESULTS: In Part 1 study, the reconstruction types were type 1 in 23, type 2 in 25, and type 3 in 2. Significant anastomotic stenosis was identified in 7 (30.4%) in type 1, 6 (24.0%) in type 2, and none (0%) in type 3. The size of MLHV stump was the most important factor for anastomotic stenosis. Through Part 2 study, technical knacks were developed as follows: the conduit end was cut in a dumb-bell shape and a vessel patch attached; and then sutured bidirectionally from the 9 o'clock direction. In Part 3 study, these knacks were applied to 5 patients and none of them experienced noticeable anastomotic stenosis. CONCLUSIONS: Our refined technique to perform conduit-MLHV stump anastomosis appears to reduce the risk of anastomotic outflow disturbance for relatively small MLHV stump.

Determination of Hepatitis B Immunoglobulin Infusion Interval Using Pharmacokinetic Half-life Simulation for Posttransplant Hepatitis B Prophylaxis.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL). METHODS: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients. RESULTS: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L. CONCLUSION: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration.

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.

Characteristics and prognosis of breast cancer after liver or kidney transplantation.

PURPOSE: Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. METHODS: Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age. RESULTS: After a median of 61 and 90.8 months after liver and kidney transplantation, respectively, 8 and 16 patients were diagnosed with breast cancer, respectively (p = 0.178). Mean age at breast cancer diagnosis was 51.9 (±8.7) and 45.2 (±4.5) years in liver and kidney transplantation patients, respectively. Age at diagnosis was significantly younger in kidney transplantation patients than in general breast cancer patients (45.2 ± 4.5 vs. 48.5 ± 10.1 years; p = 0.008). Cancer was detected via asymptomatic screening in 41.7% of the PTBC cohort but 30.6% of the control cohort (p = 0.241). In the PTBC cohort, 7 (29.2%) patients had stage 0 breast cancer compared with 1704 (9.7%) in the control cohort (p = 0.022); 22 (91.7%) patients had lymph node-negative cancer compared with 11,704 (66.8%) in the control cohort (p = 0.01). Estrogen receptor, progesterone receptor, and HER2 positivity did not differ between cohorts. Immunosuppressant use was not a poor prognostic factor for breast cancer patients. CONCLUSIONS: Age at breast cancer diagnosis was younger in patients who received kidney transplants; the subtype and prognosis of breast cancer were comparable with that in the general cohort. Immunosuppressants do not adversely affect breast cancer prognosis.