Impact of Preformed Donor-specific Antibodies in Comparison to ABO Incompatibility in Living Donor Liver Transplantation: A Propensity Score-Matched Analysis.

BACKGROUND: Immunological factors play a pivotal role in the outcomes of solid organ transplantation. We aimed to elucidate the effects of donor-specific antibodies (DSAs) and ABO compatibility on living donor liver transplantation (LDLT) outcomes. METHODS: A retrospective analysis was conducted on 584 LDLT recipients from 2015 to 2020. The recipients were stratified into 3 groups: ABO-compatible recipients without DSAs (group 1), ABO-compatible recipients with DSAs (group 2), and ABO-incompatible recipients without DSAs (group 3). Propensity score matching was used for balanced comparisons. RESULTS: In the matched comparisons, group 2 exhibited a higher incidence of T cell-mediated rejection compared with group 1 (22.7% versus 4.5%, P = 0.030). Despite this, the 5-y survival rates were similar between groups 1 and 2 (81.6% versus 95.5%, P = 0.085). Group 3, in comparison with group 1, showed elevated rates of cytomegalovirus infection (23.2% versus 7.3%, P = 0.008), T cell-mediated rejection (28.0% versus 7.3%, P = 0.001), and antibody-mediated rejection (13.4% versus 0%, P = 0.001). However, the survival rates were comparable between group 3 and group 1 (82.0% versus 86.5%, P = 0.220, respectively). Comparisons between group 2 and group 3 did not reveal significant differences in postoperative outcomes or survival rates (P > 0.05). CONCLUSIONS: DSA positivity and ABO incompatibility contribute to distinct posttransplant complications in LDLT. The integrated consideration of both factors in pretransplant assessment may enhance risk stratification and inform tailored interventions. Further research is required to corroborate these findings and provide mechanistic insights.

Risk factors for incisional hernia after liver transplantation in the era of mammalian target of rapamycin inhibitors use: a retrospective study of living donor liver transplantation dominant center in Korea.

Purpose: Incisional hernia (IH) is a common complication after liver transplantation (LT) with an incidence rate of 5% to 46%. This retrospective study aimed to evaluate the risk factors for IH development after LT in the era of mammalian target of rapamycin (mTOR) inhibitors use. Methods: Data on patients who underwent LT between 2015 and 2021 were retrospectively reviewed. The patients were divided into 2 groups (IH group and non-IH group) according to the postoperative occurrence of IH. Results: We analyzed data from 878 patients during the study period, with 28 patients (3.2%) developing IH. According to multivariate analysis, body mass index exceeding 25 kg/m2 and the use of mTOR inhibitors within the first month after LT were the sole significant factors for both IH occurrence and the subsequent need for repair operations. Notably, a history of wound complications, a Model for End-stage Liver Disease score, and the timing of LT-whether conducted during regular hours or at night-did not emerge as significant risk factors for IH after LT. Conclusion: Our study reveals a higher incidence of IH among obese patients following LT, often requiring surgical repair, particularly in cases involving mTOR inhibitor usage within the initial month after LT. Consequently, it is crucial to exercise increased vigilance, especially in obese patients, and exercise caution when considering early mTOR inhibitor administration after LT.

Pure laparoscopic donor hepatectomy: Experience of 556 cases at Seoul National University Hospital.

Pure laparoscopic donor hepatectomy (PLDH) has become a routine procedure at Seoul National University Hospital, and the pure laparoscopic method is now being applied to liver recipients as well. This study aimed to review the procedure and outcomes of PLDH to identify any areas that required improvement. Data from 556 donors who underwent PLDH between November 2015 and December 2021 and their recipients were retrospectively reviewed. Among these, 541 patients underwent pure laparoscopic donor right hepatectomy (PLDRH). The mean hospital stay of the donor was 7.2 days, and the rate of grade I, II, IIIa, and IIIb complications was 2.2%, 2.7%, 1.3%, and 0.9%, respectively, without any irreversible disabilities or mortalities. The most common early and late major complications in the recipient were intraabdominal bleeding (n = 47, 8.5%) and biliary problems (n = 198, 35.6%), respectively. Analysis of the PLDRH procedure showed that operative time, liver removal time, warm ischemic time, Δhemoglobin%, Δtotal bilirubin%, and postoperative hospital stay decreased significantly as the number of cases accumulated. In conclusion, the operative outcomes of PLDRH improved as the number of cases increased. However, continuous caution is needed because major complications still occur in donors and recipients even after hundreds of cases.

Evaluation of the efficacy and safety of conversion from the tacrolimus capsule to tablet in stable liver transplant recipients with maintenance therapy: a 24-week, open-label, single-center, phase IV exploratory clinical study.

Purpose: The tablet form of tacrolimus is more convenient for drug ingestion than the capsule form. We examined the efficacy and safety of tacrolimus tablets and a satisfaction survey after formula conversion in liver transplant (LT) recipients. Methods: This study was an open-label, prospective clinical trial for tacrolimus formula 1:1 conversion from capsule to tablet in 41 adult LT recipients with tacrolimus maintenance therapy of more than 1 month. The primary endpoint was incidence of biopsy-proven acute rejection (BPAR) within 24 weeks. Surveys 1 week before and 4 weeks after formula conversion were conducted for total daily dose of medication, number, scale of discomfort and satisfaction. Results: The overall incidence of BPAR was 0% and there was no graft loss or patient death. The incidence of adverse effects was 34.1% (n = 14) after formula conversion. The most common severe adverse effect was abnormal liver function test (n = 5): biliary complications (n = 4) and alcoholic recidivism (n = 1). Total daily dose and number of tacrolimus doses were significantly lower after formula conversion (P < 0.05) without changes in trough level. According to survey analysis, there was no significant difference in discomfort and satisfaction scales from capsule to tablet conversion (P < 0.05). Conclusion: The present study suggests that the new tablet formula can be a useful treatment option to maintain a consistent level of tacrolimus with a lower total daily dose and number in adult LT recipients.

Factors associated with rituximab-mediated B cell depletion in ABO-incompatible adult living donor liver transplantation.

Background: Pretransplant therapies such as rituximab and plasmapheresis have led to an increase in ABO-incompatible (ABOi) living donor liver transplantation (LDLT), thus helping to overcome organ shortages. This study evaluated the changes in anti-A/B titers and CD19 levels over time in patients undergoing ABOi LT and aimed to understand the effect of single-nucleotide polymorphisms (SNPs) in Fc gamma receptor (FcγR) on rituximab therapy. Methods: Two SNPs of FCGR2A (131H/R) and FCGR3A (158F/V) were identified. The clinical data on 44 patients who underwent ABOi LDLT between May 2019 and October 2021 at Seoul National University Hospital were reviewed retrospectively. Results: Following desensitization with rituximab and subsequent LDLT, the anti-A/B titer recovered within 1 week, but decreased thereafter. The CD19 level increased at 3 months after LT. The genotyping data for FCGR3A (158F/V) indicated that two patients had the V/V genotype, and 42 had the F/V genotype. In the genotyping data for FCGR2A (131H/R), 21 patients had the H/H genotype, three had the R/R genotype, and 20 had the H/R genotype. However, there were no significant differences in anti-A/B and CD19 levels, bacteremia rates, T cell-mediated rejection, antibody-mediated rejection, or the survival rate among the FCGR2A types. Conclusions: There were significant changes in the anti-A/B titers and CD19 levels over time in each patient after ABOi LDLT. The difference in outcomes following LT according to the FcγR SNP type for rituximab was unclear. Further studies with larger sample sizes are needed to confirm the effect of FcγR SNPs on rituximab therapy.

Recurrence in patients with totally necrotic nodules of hepatocellular carcinoma after liver transplantation: "totally" an inaccurate description.

Purpose: Total necrosis of hepatocellular carcinoma (HCC) achieved via locoregional treatment (LRT) is considered to indicate a lack of tumor viability. Nonetheless, there is insufficient evidence of recurrence after liver transplantation (LT) in patients with such a status. The aim of this study was to investigate the prognosis of patients diagnosed with totally necrotic nodules upon explant hepatectomy after LT. Methods: We conducted a retrospective study of patients diagnosed with totally necrotic nodules after LT for HCC. A total of 165 patients with HCC who underwent living- or deceased-donor LT from 2000 to 2020 in our hospital were included. Results: A total of 5 patients (3.0%) exhibited HCC recurrence during a median follow-up of 84 months (range, 4-243 months) after LT. The 5-year overall and recurrence-free survival rates of these patients were 92.8% and 92.2%, respectively. Four patients in the HCC-recurrence group (80.0%) died even after further treatment, including transarterial chemoembolization, surgery, and systemic treatment. Both univariate and multivariate analyses of clinicopathological factors identified a maximum diameter of the totally necrotic nodules of >5 cm as the only factor associated with tumor recurrence following LT (P = 0.005 and P = 0.009, respectively). Conclusion: Total necrosis of HCC via LRT yielded excellent survival outcomes for patients undergoing LT. Nevertheless, patients with large tumors should be considered at high risk of recurrence after LT, suggesting the need for their active surveillance during the follow-up period.

Posttransplant sequential adrenal and spine metastasis of hepatocellular carcinoma responsive to combined regorafenib and radiotherapy: a case report.

Adrenal and spinal metastases of hepatocellular carcinoma (HCC) are rare entities with significant morbidity and mortality, particularly after liver transplantation (LT). We report a case of a 49-year-old man who underwent LT for hepatitis B-related end-stage liver disease and HCC (single 4.5 cm lesion [T1N0], without vascular invasion) in 2016. Eighteen months later, adrenal metastasis and hepatitis B seropositive conversion were developed with normal serum tumor. Adrenal metastasis was treated with radiation therapy (RT) and hepatitis B showed spontaneous seronegative conversion. However, 35 months later, spinal metastasis occurred with elevation of the protein induced by vitamin K absence or antagonist-II (PIVKA-II) level (197 mAU/mL), along with hepatitis B seropositive conversion. After sorafenib, sequential regorafenib with RT led to partial response of the spinal lesions, along with hepatitis B seronegative conversion and normal PIVKA-II levels. After 9 months of regorafenib combined with RT, two recurrent lesions were found, as well as hepatitis B seropositive conversion and lesions were treated with transarterial chemoembolization. The patient survived for more than 71 months after LT and 53 months after recurrence under various combinations of therapy. Combined systemic and locoregional therapies can be a treatment option for HCC recurrence, even in LT patients.

Portal vein reconstruction in pediatric liver transplantation using end-to-side jump graft: A case report.

Attenuated portal vein (PV) flow is challenging in pediatric liver transplantation (LT) because it is unsuitable for classic end-to-end jump graft reconstruction from a small superior mesenteric vein (SMV). We thus introduce a novel technique of an end-to-side jump graft from SMV during pediatric LT using an adult partial liver graft. We successfully performed two cases of end-to-side retropancreatic jump graft using an iliac vein graft for PV reconstruction. One patient was a 2-year-old boy with hepatoblastoma and a Yerdel grade 3 PV thrombosis who underwent split LT. Another patient was an 8-month-old girl who had biliary atresia and PV hypoplasia with stenosis on the confluence level of the SMV; she underwent retransplantation because of graft failure related to PV thrombosis. After native PV was resected at the SMV confluence level, an end-to-side reconstruction was done from the proximal SMV to an interposition iliac vein. The interposition vein graft through posterior to the pancreas was obliquely anastomosed to the graft PV. There was no PV related complication during the follow-up period. Using a jump vascular graft in an end-to-side manner to connect the small native SMV and the large graft PV is a feasible treatment option in pediatric recipients with inadequate portal flow due to thrombosis or hypoplasia of the PV.

Risk factors of recurrence following common bile duct exploration for choledocholithiasis.

Purpose: The purpose of this study was to investigate the recurrence factors of choledocholithiasis after common bile duct (CBD) exploration. Methods: From January 2000 to December 2018, we retrospectively reviewed 253 patients who underwent CBD exploration surgery. We excluded 100 cases who had residual stone, combined major surgery, or follow-up loss after surgery. Total of 153 patients were included, and we investigated the recurrence factors of choledocholithiasis. Various variables such as patients' demographics, gallstones, preoperative endoscopic treatment, and laboratory data were analyzed to find factors related to recurrent choledocholithiasis. Results: The median follow-up period was 20.6 months (range 4.7-219 months), and 27 patients (17.6%) had experienced recurrent choledocholithiasis. Univariate analysis showed that the following variables were associated with recurrence of choledocholithiasis; preoperative leukocytosis (white blood cell ≥ 11,000/µL), open procedure, T tube insertion, long hospital duration, and long operation time. Logistic regression multivariate analysis identified preoperative leukocytosis (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.21-9.73; p = 0.021), open procedure (OR, 5.54; 95% CI, 4.73-6.35; p = 0.037), and T-tube insertion (OR, 2.82; 95% CI, 1.04-7.65; p = 0.042) as independent predictors of recurrent choledocholithiasis. Conclusion: Because of delayed recurrence of choledocholithiasis, it is recommended to continue follow-up of patients after CBD exploration surgery. Laparoscopic surgery was observed to be associated with a reduction in recurrence. The preoperative leukocytosis and clinical conditions in which open surgery is performed could be associated with recurrence of choledocholithiasis. However, further study is necessary to validate the result.

Nutritional risk factors are associated with postoperative complications after pancreaticoduodenectomy.

PURPOSE: The purpose of this study was to investigate whether the indicators of nutritional risk screening tool are associated with postoperative complications following pancreaticoduodenectomy (PD). METHODS: We investigated whether nutritional risk is associated with postoperative complications based on the medical records of 128 patients who underwent PD from 2010. The tool was composed of 6 risk factors: albumin, total lymphocyte count, body mass index, weight loss, dietary intake loss, and nutritional symptoms. The patients were divided into 2 groups: a nutritional risk group and a nonrisk group. The rates of general complications and postoperative pancreatic fistula (POPF) were investigated according to this nutritional status. RESULTS: There were 65 patients who did not have any risk factors. However, 63 patients had one risk factor or more. In the nonrisk group, the overall complication rate and serious complication rate were 30.8% and 15.4%, respectively. If there were one or more risk factors, the overall and serious complication rates were 59.5% and 41.3%, respectively (P = 0.001 and P = 0.001, respectively). The rate of clinically relevant POPF (grade B or C) was 9.2% in the nonrisk group. However, this rate was 23.8% in the NRS risk group (P = 0.029). In multivariate analysis, the NRS risk group was a significant factor of clinically relevant POPF (odds ratio, 9.878; 95% confidence interval, 1.527-63.914; P = 0.016). CONCLUSION: There were statistically significant associations between complications and nutritional indicators. A comprehensive analysis of nutritional parameters will help predict postoperative complications.