Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A.

Acute hepatitis A (AHA) involves severe CD8+ T cell-mediated liver injury. Here we showed during AHA, CD8+ T cells specific to unrelated viruses became activated. Hepatitis A virus (HAV)-infected cells produced IL-15 that induced T cell receptor (TCR)-independent activation of memory CD8+ T cells. TCR-independent activation of non-HAV-specific CD8+ T cells were detected in patients, as indicated by NKG2D upregulation, a marker of TCR-independent T cell activation by IL-15. CD8+ T cells derived from AHA patients exerted innate-like cytotoxicity triggered by activating receptors NKG2D and NKp30 without TCR engagement. We demonstrated that the severity of liver injury in AHA patients correlated with the activation of HAV-unrelated virus-specific CD8+ T cells and the innate-like cytolytic activity of CD8+ T cells, but not the activation of HAV-specific T cells. Thus, host injury in AHA is associated with innate-like cytotoxicity of bystander-activated CD8+ T cells, a result with implications for acute viral diseases.

Urinary microbiome-based metagenomic signature for the noninvasive diagnosis of hepatocellular carcinoma.

BACKGROUND: Gut microbial dysbiosis is implicated in chronic liver disease and hepatocellular carcinoma (HCC), but the role of microbiomes from various body sites remains unexplored. We assessed disease-specific alterations in the urinary microbiome in HCC patients, investigating their potential as diagnostic biomarkers. METHODS: We performed cross-sectional analyses of urine samples from 471 HCC patients and 397 healthy controls and validated the results in an independent cohort of 164 HCC patients and 164 healthy controls. Urinary microbiomes were analyzed by 16S rRNA gene sequencing. A microbial marker-based model distinguishing HCC from controls was built based on logistic regression, and its performance was tested. RESULTS: Microbial diversity was significantly reduced in the HCC patients compared with the controls. There were significant differences in the abundances of various bacteria correlated with HCC, thus defining a urinary microbiome-derived signature of HCC. We developed nine HCC-associated genera-based models with robust diagnostic accuracy (area under the curve [AUC], 0.89; balanced accuracy, 81.2%). In the validation, this model detected HCC with an AUC of 0.94 and an accuracy of 88.4%. CONCLUSIONS: The urinary microbiome might be a potential biomarker for the detection of HCC. Further clinical testing and validation of these results are needed in prospective studies.

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.

TEMPORARY REMOVAL: A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Comparison of postoperative ascites replacement strategies on time to first flatus after living donor liver transplantation: Albumin vs. lactated Ringer's solution.

INTRODUCTION: There is insufficient evidence regarding the optimal regimen for ascites replacement after living donor liver transplantation (LT) and its effectiveness. The aim of this study is to evaluate the impact of replacing postoperative ascites after LT with albumin on time to first flatus during recovery with early ambulation and incidence of acute kidney injury (AKI). METHODS: Adult patients who underwent elective living donor LT at Seoul National University Hospital from 2019 to 2021 were randomly assigned to either the albumin group or lactated Ringer's group, based on the ascites replacement regimen. Replacement of postoperative ascites was performed for all patients every 4 h after LT until the patient was transferred to the general ward. Seventy percent of ascites drained during the previous 4 h was replaced over the next 4 h with continuous infusion of fluids with a prescribed regimen according to the assigned group. In the albumin group, 30% of a total of 70% of drained ascites was replaced with 5% albumin solution, and remnant 40% was replaced with lactated Ringer's solution. In the lactated Ringer's group, 70% of drained ascites was replaced with only lactated Ringer's solution. The primary outcome was the time to first flatus from the end of the LT and the secondary outcome was the incidence of AKI for up to postoperative day 7. RESULTS: Among the 157 patients who were screened for eligibility, 72 patients were enrolled. The mean age was 63 ± 8.2 years, and 73.0 % (46/63) were male. Time to first flatus was similar between the two groups (66.7 ± 24.1 h vs. 68.5 ± 25.6 h, p = .778). The albumin group showed a higher glomerular filtration rate and lower incidence of AKI until postoperative day 7, compared to the lactated Ringer's group. CONCLUSIONS: Using lactated Ringer's solution alone for replacement of ascites after living donor LT did not reduce the time to first flatus and was associated with an increased risk of AKI. Further research on the optimal ascites replacement regimen and the target serum albumin level which should be corrected after LT is required.

Feasible living donor liver transplantation for patients on chronic hemodialysis: a multicenter study in East Asian countries.

PURPOSES: End-stage liver and kidney disease is an indication for simultaneous liver and kidney transplantation. However, in countries where deceased donor transplantation is not well established, living donor liver transplantation (LDLT) is a realistic option for patients on hemodialysis (HD). We investigated the outcomes of LDLT for patients on HD. METHODS: We conducted a retrospective multicenter survey of patients on chronic HD who underwent LDLT in East Asian countries. The characteristics of donors and recipients and the short and long-term outcomes were analyzed. RESULTS: Between 2001 and 2021, 45 patients on HD underwent LDLT and 11 of these patients also underwent kidney transplantation (KT). The overall survival rate at 5 years of the 34 patients who underwent only LDLT was 44.5%. Multivariate analysis identified a low graft recipient weight ratio (< 1%) (p = 0.048) and long HD duration (≥ 10 years) (p = 0.046) as independent predictors of poor overall survival. The major complication was posttransplant bleeding, which occurred in12 patients (35%). CONCLUSION: It is important to establish the indications for LDLT, taking into consideration graft size and HD duration in candidate patients on HD.

A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma.

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) test's sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.

Donor Safety and Risk Factors of Pure Laparoscopic Living Donor Right Hepatectomy: A Korean Multicenter Study.

OBJECTIVE: The aim of this study was to identify safety and risk factors of living donor after pure laparoscopic donor right hepatectomy in a Korean multicenter cohort study. BACKGROUND: Pure laparoscopic donor right hepatectomy is not yet a standardized surgical procedure due to lack of data. METHODS: This retrospective study included 543 patients undergoing PLRDH between 2010 and 2018 in 5 Korean transplantation centers. Complication rates were assessed and multivariate logistic regression analyses were performed to identify risk factors of open conversion, overall complications, major complications, and biliary complications. RESULTS: Regarding open conversion, the incidence was 1.7% and the risk factor was body mass index >30 kg/m 2 [ P =0.001, odds ratio (OR)=22.72, 95% CI=3.56-146.39]. Rates of overall, major (Clavien-Dindo classification III-IV), and biliary complications were 9.2%, 4.4%, and 3.5%, respectively. For overall complications, risk factors were graft weight >700 g ( P =0.007, OR=2.66, 95% CI=1.31-5.41), estimated blood loss ( P <0.001, OR=4.84, 95% CI=2.50-9.38), and operation time >400 minutes ( P =0.01, OR=2.46, 95% CI=1.25-4.88). For major complications, risk factors were graft weight >700 g ( P =0.002, OR=4.01, 95% CI=1.67-9.62) and operation time >400 minutes ( P =0.003, OR=3.84, 95% CI=1.60-9.21). For biliary complications, risk factors were graft weight >700 g ( P =0.01, OR=4.34, 95% CI=1.40-13.45) and operation time >400 minutes ( P =0.01, OR=4.16, 95% CI=1.34-12.88). CONCLUSION: Careful donor selection for PLRDH considering body mass index, graft weight, estimated blood loss, and operation time combined with skilled procedure can improve donor safety.

Initial outcome of external biliary drainage in living donor liver transplantation with pure laparoscopic donor hepatectomy.

Biliary complications after living donor liver transplantation (LDLT) are the most common and intractable complications due to both surgical and nonsurgical factors. External biliary drainage (EBD), a surgical option to prevent biliary complications, has recently been adopted in the era of pure laparoscopic donor right hepatectomy, which may result in increased bile duct problems in the recipients. This study retrospectively reviewed the patients who underwent LDLT with duct-to-duct anastomosis between July 2017 and October 2020 to analyze the initial outcomes of EBD and to compare the incidence of biliary complications in adult LDLT recipients who underwent duct-to-duct anastomosis with or without EBD. Only patients who underwent pure laparoscopic donor hepatectomy were included in this study. The patients were divided into 2 groups according to the application of EBD. The median follow-up period was 28.5 months. The overall incidence of Clavien-Dindo grade IIIa biliary complications was 35.0% (n=14) in the EBD group and 50.7% (n=76) in the non-EBD group ( p = 0.08). The incidence of biliary leakage was 0% in the EBD group and 15.3% in the non-EBD group ( p = 0.01). The EBD-related complication rate, that is, involving retraction, accidental removal, and dislocation, was 40.0%. EBD implementation is effective in preventing biliary leakage after LDLT with a graft procured using the pure laparoscopic donor right hepatectomy method with duct-to-duct biliary anastomosis. However, efforts should be made to prevent EBD-related complications. Further studies are needed to establish appropriate selection criteria for EBD.

Anatomical classification and clinical outcomes of biliary strictures in living donor liver transplantation using right liver grafts.

This study aimed to classify the anatomical types of biliary strictures, including intrahepatic biliary stricture (IHBS), after living donor liver transplantations (LDLTs) using right liver grafts and evaluate their prognosis. Among 692 adult patients who underwent right liver LDLT, 198 recipients with biliary strictures (28.6%) were retrospectively reviewed. Based on data obtained during the first cholangiography, the patients' biliary strictures were classified into the following three types according to the levels and number of branches involved: Types 1 (anastomosis), 2 (second-order branch [a, one; b, two or more; c, extended to the third-order branch]), and 3 (whole graft [a, multifocal strictures; b, diffuse necrosis]). IHBS was defined as a nonanastomotic stricture. Among the 198 recipients with biliary strictures, the IHBS incidence rates were 38.4% ( n = 76). The most common type of IHBS was 2c ( n = 43, 56.6%), whereas Type 3 ( n = 10, 13.2%) was uncommon. The intervention frequency per year significantly differed among the types (Type 1, 2.3; Type 2a, 2.3; Type 2b, 2.8; Type 2c, 4.3; and Type 3, 7.2; p < 0.001). The intervention-free period for more than 1 year, which was as follows, also differed among the types: Type 1, 84.4%; Type 2a, 87.5%; Type 2b, 86.7%; Type 2c, 72.1%; and Type 3, 50.0% ( p = 0.048). The graft survival rates of Type 3 (80.0%) were significantly lower than those of the other types ( p = 0.001). IHBSs are relatively common in right liver LDLTs. Although Type 3 IHBSs are rare, they require more intensive care and are associated with poorer graft survival rates than anastomosis strictures and Type 2 IHBS.

Early experiences with developing techniques for pure laparoscopic explant hepatectomy in living donor liver transplantation.

In recent years, laparoscopic techniques for liver resection or living donor hepatectomy have become common surgical methods. However, reports on laparoscopic surgeries for recipients are lacking. Our center has launched the minimally invasive living donor liver transplantation (LDLT) program in March 2020, which is led by two surgeons who are experienced in laparoscopic surgeries. Recently, we reported our first successful pure laparoscopic recipient explant hepatectomy and the first laparoscopic explant hepatectomy and robotic-assisted graft implantation. In this article, we introduce a series of minimally invasive surgical cases that were conducted by a single experienced surgeon to share our early experiences leading to our recent successes. We included 10 cases performed from June 2020 to May 2021 in our initial attempt at laparoscopic explant hepatectomy, graft implantation using midline incision, and robotic-assisted graft implantation surgery. The first four cases required open conversion during the liver mobilization process because of bleeding. The next two cases required open conversion to facilitate portal vein and hepatic artery division. We successfully performed pure laparoscopic explant hepatectomy in the last four cases. For the last case, we attempted to perform graft implantation using a robotic system, but bleeding required open conversion. All patients recovered without any significant acute postoperative problems and were discharged within 2 weeks. All 10 patients were followed up at outpatient clinics, and only one of the 10 patients had a late complication of LDLT. This study has shown that the minimally invasive approach in LDLT may be conducted safely without significant complications if it is performed by highly experienced surgeons working in high-volume centers.

Redo hepatic artery reconstruction for thrombosis without retransplantation in 1355 adult living donor liver transplantations.

Hepatic artery thrombosis (HAT) after liver transplantation is associated with a marked increase in morbidity, leading to graft and patient loss. We evaluated the outcomes of adult living donor liver transplantation patients with HAT under an aggressive surgical intervention. A total of 1355 recipients underwent adult living donor liver transplantation at the Seoul National University Hospital. Surgical redo reconstruction for HAT was performed in all cases except in those with graft hepatic artery injury and late detection of HAT. Postoperative HAT developed in 33 cases (2.4%) at a median time of 3.5 days. Thirty patients (90.9%) underwent redo-arterial reconstruction. The survival rates in patients with HAT were similar to the rates in those without HAT (72.7% vs. 83.8%, p = 0.115). Although graft survival rates were lower in patients with HAT (84.8%) than in those without HAT (98.0%) ( p < 0.001), the graft survival rate was comparable (92.0% vs. 98.0%, p = 0.124) in the 25 patients with successful revascularization. Biliary complication rates were higher in patients with HAT (54.5%) than in those without HAT (32.0%) ( p = 0.008). In conclusion, the successful redo reconstruction under careful selection criteria saved the graft without retransplantation in 96.0% of the cases. Surgical revascularization should be preferentially considered for the management of HAT in adult living donor liver transplantation.

p21-activated kinase 4 inhibition protects against liver ischemia/reperfusion injury: Role of nuclear factor erythroid 2-related factor 2 phosphorylation.

BACKGROUND AND AIMS: p21-activated kinase 4 (PAK4), an oncogenic protein, has emerged as a promising target for anticancer drug development. Its role in oxidative stress conditions, however, remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. APPROACH AND RESULTS: Hepatocyte- and myeloid-specific Pak4 knockout (KO) mice and their littermate controls were subjected to a partial hepatic I/R (HIR) injury. We manipulated the catalytic activity of PAK4, either through genetic engineering (gene knockout, overexpression of wild-type [WT] or dominant-negative kinase) or pharmacological inhibitor, coupled with a readout of nuclear factor erythroid 2-related factor 2 (Nrf2) activity, to test the potential function of PAK4 on HIR injury. PAK4 expression was markedly up-regulated in liver during HIR injury in mice and humans. Deletion of PAK4 in hepatocytes, but not in myeloid cells, ameliorated liver damages, as demonstrated in the decrease in hepatocellular necrosis and inflammatory responses. Conversely, the forced expression of WT PAK4 aggravated the pathological changes. PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. Nrf2 silencing in liver abolished the protective effects of PAK4 deficiency. A PAK4 inhibitor protected mice from HIR injury. CONCLUSIONS: PAK4 phosphorylates Nrf2 and suppresses its transcriptional activity. Genetic or pharmacological suppression of PAK4 alleviates HIR injury. Thus, PAK4 inhibition may represent a promising intervention against I/R-induced liver injury.

Abbreviated MRI for Secondary Surveillance of Recurrent Hepatocellular Carcinoma After Presumed Curative Treatment.

BACKGROUND: Little is known about the performance of abbreviated MRI (AMRI) for secondary surveillance of recurrent hepatocellular carcinoma (HCC) after curative treatment. PURPOSE: To evaluate the detection performance of AMRI for secondary surveillance of HCC after curative treatment. STUDY TYPE: Retrospective. POPULATION: A total of 243 patients (183 men and 60 women; median age, 65 years) who underwent secondary surveillance for HCC using gadoxetic acid-enhanced MRI after more than 2 year of disease-free period following curative treatment, including surgical resection or radiofrequency ablation (RFA). FIELD STRENGTH/SEQUENCE: A 3.0 T/noncontrast AMRI (NC-AMRI) (T2-weighted fast spin-echo, T1-weighted gradient echo, and diffusion-weighted images), hepatobiliary phase AMRI (HBP-AMRI) (T2-weighted fast spin-echo, diffusion-weighted, and HBP images), and full-sequence MRI ASSESSMENT: Four board-certified radiologists independently reviewed NC-AMRI, HBP-AMRI, and full-sequence MRI sets of each patient for detecting recurrent HCC. STATISTICAL TESTS: Per-lesion sensitivity, per-patient sensitivity and specificity for HCC detection at each set were compared using generalized estimating equation. RESULTS: A total of 42 recurred HCCs were confirmed in the 39 patients. The per-lesion and per-patient sensitivities did not show significant differences among the three image sets for either reviewer (P ≥ 0.358): per-lesion sensitivity: 59.5%-83.3%, 59.5%-85.7%, and 59.5%-83.3%, and per-patient sensitivity: 53.9%-83.3%, 56.4%-85.7%, and 53.9%-83.3% for NC-AMRI, HBP-AMRI, and full-sequence MRI, respectively. Per-lesion pooled sensitivities of NC-AMRI, HBP-AMRI, and full-sequence MRI were 72.6%, 73.2%, and 73.2%, with difference of -0.6% (95% confidence interval: -6.7, 5.5) between NC-AMRI and full-sequence MRI and 0.0% (-6.1, 6.1) between HBP-AMRI and full-sequence MRI. Per-patient specificity was not significantly different among the three image sets for both reviewers (95.6%-97.1%, 95.6%-97.1%, and 97.6%-98.5% for NC-AMRI and HBP-AMRI, respectively; P ≥ 0.117). DATA CONCLUSION: NC-AMRI and HBP-AMRI showed no significant difference in detection performance to that of full-sequence gadoxetic acid-enhanced MRI during secondary surveillance for HCC after more than 2-year disease free interval following curative treatment. Based on its good detection performance, short scan time, and lack of contrast agent-associated risks, NC-AMRI is a promising option for the secondary surveillance of HCC. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Pure laparoscopic donor right hepatectomy in patients over 50 years old: Why age should not be a barrier.

INTRODUCTION: Given the global aging population, the average age of liver donors is increasing. This study aimed to evaluate the surgical outcomes of grafts from pure laparoscopic donor right hepatectomy (PLDRH) in liver donors aged > 50 years. METHODS: The medical records of liver donors were retrospectively reviewed. The donors underwent conventional donor right hepatectomy (CDRH) from January 2011 to May 2019 or PLDRH from March 2016 to May 2019. We divided the donors into three groups: PLDRH donors aged ≥50 (n = 26; Group 1) and aged < 50 (n = 257; Group 2), and CDRH donors aged ≥50 years (n = 66; Group 3). RESULTS: Operation time (p < .01) and hospital stay (p < .01) were significantly lower in Group 1 than in Group 3. Other postoperative outcomes of donors including graft anatomical variation, graft weight, graft-to-recipient weight ratio, and hepatic steatosis were similar among the three groups. Although no postoperative complications occurred in Groups 1 and 3, they were detected in 17 cases (6.6%) in Group 2. No postoperative complications were detected among the recipients. CONCLUSIONS: PLDRH was feasible and safe in donors aged over 50 years, with outcomes similar to those for donors aged <50 years. PLDRH should not be avoided solely based on the donor's age ≥50 years.

Posttransplant renal replacement therapy is an alarm signal for survival outcomes in pediatric liver transplantation.

BACKGROUND: The impact of renal replacement therapy (RRT) on the long-term survival outcomes of pediatric liver recipients remains controversial. METHODS: A total of 224 patients aged <18 years, who underwent liver transplantation (LT), were divided into two groups: patients who underwent renal replacement therapy (RRT) (group R, n = 25, 11.2%) and those who did not (group N, n = 199, 88.8%). The posttransplant patient survival outcomes according to RRT use constituted the primary end-point. RRT was initiated preoperatively in 12 patients (48.0%) and postoperatively in 13 [early: <6 months after LT (n = 5, 20.0%) and late: ≥6 months after LT (n = 8, 32.0%)]. The indications for RRT included liver disease involving the kidney (44.0%) and hepatorenal syndrome (56.0%). RESULTS: The age at the time of LT (71.6 vs. 19.1 months) was higher, the pediatric end-stage liver disease score was lower (9.9 vs. 21.2), and the duration of hospitalization posttransplantation (41.0 vs. 27.0 days) was longer, while the rates of hepatic artery thrombosis (8.0% vs. 3.5%) were higher in group R (p < .05). The number of patients (60.0% vs. 93.0%; p < .001) and graft survival rates (68.0% vs. 93.0%; p < .001) were significantly lower in group R. Multivariate analysis revealed that posttransplant RRT and hepatic artery complications were risk factors for patient survival outcomes. Renal function was recovered in 7 patients (28.0%) in group R, and 9 (36.0%) eventually underwent kidney transplantation. CONCLUSION: The survival outcomes of children requiring posttransplant RRT were significantly worse than those of children, who did not undergo RRT. Physicians should pay meticulous attention to patients requiring post-LT RRT.

The Clinical Course and Prognosis of Patients With Nontuberculous Mycobacterial Pulmonary Disease After Solid Organ Transplantation.

BACKGROUND: Due to impaired cell-mediated immunity, solid organ transplantation (SOT) recipients are at increased risk of developing nontuberculous mycobacterial pulmonary disease (NTM-PD). However, the clinical course of NTM-PD in SOT patients and the impact of SOT on the prognosis of NTM-PD remain unclear. METHODS: We analyzed patients who developed NTM-PD after receiving SOT between January 2001 and December 2020, at a tertiary referral hospital in South Korea. Baseline characteristics, clinical course, and prognosis were evaluated. Propensity score-matched analysis was performed to assess the impact of SOT on long-term survival in patients with NTM-PD. RESULTS: Among 4,685 SOT recipients over 20 years, 12 patients (median age, 64 years; interquartile range [IQR], 59-67 years; men, 66.7%) developed NTM-PD. Seven (58.3%) and five (41.7%) patients underwent kidney and liver transplantation, respectively, before the diagnosis of NTM-PD. The incidence of NTM-PD was 35.6 cases per 100,000 person-years among kidney transplant recipients and 28.7 cases per 100,000 person-years among liver transplant recipients. The median time between transplantation and the diagnosis of NTM-PD was 3.3 (IQR, 1.5-10.8) years. The most common mycobacterial species was Mycobacterium avium (50.0%). Antibiotic treatment was initiated in five (41.7%) patients, and two patients (40.0%) achieved microbiological cure. Two patients died during a median follow-up of 4.2 (IQR, 2.3-8.8) years and NTM-PD was assumed to be the cause of death in one patient. When matched to patients without a history of SOT, patients with a history of SOT did not show worse survival (P value for log-rank test = 0.62). CONCLUSION: The clinical course of NTM-PD in SOT recipients was comparable to that of patients without SOT, and SOT did not increase the risk of all-cause mortality in patients with NTM-PD.

Laparoscopic donor and recipient hepatectomy followed by robot-assisted liver graft implantation in living donor liver transplantation.

Minimally invasive surgery has been introduced for liver transplantations. Although laparoscopic or robot-assisted living donor hepatectomy is being used, minimally invasive surgery is rarely performed in recipients during liver transplantation. A 63-year-old patient (body mass index: 21.9 kg/m2 ) with primary biliary cirrhosis underwent total laparoscopic explant hepatectomy, followed by robot-assisted liver engraftment using advanced technological innovations. The total operation time for the recipient was 12 h 20 min, including laparoscopic explant hepatectomy (140 min) and robot-assisted engraftment (220 min). Achieving hepatic and portal vein anastomoses consumed 35 and 28 min, respectively. The hepatic artery anastomosis and bile duct reconstruction took 83 and 66 min, respectively. The estimated blood loss was 3600 ml. The warm and cold ischemic times were 87 and 220 min, respectively. The patient received 10 units each of red blood cells and fresh frozen plasma during the surgery and recovered from early allograft dysfunction after liver transplantation. This case study suggests that laparoscopic explant hepatectomy followed by robot-assisted engraftment is feasible in selected recipients only. We obtained informed consent for this innovative procedure from the patient and from her living donor.