The risk factors and clinical outcomes in hepatitis B seropositive and seronegative renal transplant patients.

INTRODUCTION: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients. METHODS: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. RESULTS: We identified 337 patients (47.5 ± 12 years) were enrolled in our final cohort. Fifty-two (15.4%) had HBsAg positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pre-transplant anti-HBV medication [hazard ratio (HR), 5.95; 95% confidence interval (CI), 1.31-27.02; P = 0.021 or an absence of lifelong antiviral therapy [HR, 3.14; 95% CI, 1.01-9.74; P = 0.047] Conclusion: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pre-transplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.

Risk Factors for Fractures in Renal Transplantation: A Population-Based Cohort Study.

INTRODUCTION: Kidney transplant recipients are at an increased risk of fractures, and targeted preventive strategies are needed. Therefore, in this retrospective cohort study, we investigated a large population-based cohort to identify the transplant recipient-specific risk factors for fractures in Taiwanese kidney transplant recipients. METHODS: We conducted a retrospective cohort study using the National Health Insurance Research Database. Patients who underwent renal transplantation between 2003 and 2015 were identified and followed until December 31, 2015, to observe the development of fractures. Variables associated with the development of post-transplant fractures were identified by calculating hazard ratios in a Cox regression model. RESULTS: 5,309 renal transplant recipients were identified, of whom 553 (10.4%) were diagnosed with post-transplant fractures. Independent predictors of post-transplant fractures included an age at transplant ≥65 years (p < 0.001), female sex (p < 0.001), fractures within 3 years prior to transplantation (p < 0.001), and diabetes mellitus (p < 0.001). In addition, daily prednisolone doses >2.9­5.3 mg/day (p < 0.001), >5.3­8.7 mg/day (p < 0.001), and >8.7 mg/day (p < 0.001) were also independent predictors of post-transplant fractures. Conversely, the use of peritoneal dialysis before renal transplantation (p = 0.021), hypertension (p = 0.005), and the use of tacrolimus (p < 0.001), azathioprine (p = 0.006), mycophenolate mofetil/mycophenolic acid (p = 0.002), mTOR inhibitors (p = 0.004), and calcium supplements (p = 0.009) were inversely correlated with post-transplant fractures. CONCLUSION: We recommend minimizing daily glucocorticoids as early and as far as possible in conjunction with immunosuppressive regimens such as tacrolimus, azathioprine, mycophenolate mofetil/mycophenolic acid, mTOR inhibitors, and calcium supplements, especially in older female recipients and in recipients with diabetes and a history of prior fractures.

Hybrid Method for Peritoneal Dialysis Catheter Insertion: A New Technique for Improved Outcomes and Reduced Costs.

INTRODUCTION: Peritoneal dialysis (PD) is a well-established treatment choice for end-stage kidney disease (ESKD). While there are several methods for PD catheter insertion, they each have limitations. In this study, we present a new hybrid method for PD catheter insertion and compare it to the conventional laparoscopic method. METHODS: This retrospective study included 171 patients who were undergoing their first PD catheter insertion, and a total of 20% of the enrolled patients had a past medical history of abdominal surgery. Out of these, 101 patients underwent the laparoscopic method and 70 underwent a new invented hybrid method. The study aimed to compare the surgical outcomes, incidence of early and late complications, hospital stay, and medical expenses between the two groups. RESULTS: There were no notable differences in basic demographic features and comorbid conditions between the two groups. The results of our data revealed that the hybrid group had a significantly shorter break-in period and did not require temporary hemodialysis. Additionally, length of hospital stay and medical costs were significantly lower in the hybrid group (all p < 0.05). The incidence of early complications was lower in the hybrid group, while the incidence of late complications was comparable between the two groups. CONCLUSION: Our study demonstrates that the hybrid method of PD catheter insertion provides a safe and efficient alternative to the traditional laparoscopic method, enabling urgent-start PD and reducing hospital stays and medical expenses. Our findings support the use of the hybrid method as a new standard of care for ESKD patients undergoing PD catheter insertion.

Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Safety and long-term outcomes of early liver transplantation for pediatric methylmalonic acidemia patients.

BACKGROUND: LT is a treatment option for MMA patients, but renal function impairment is one of the long-term concerns. The aim of this study was to evaluate the outcomes of early LT in these patients. METHODS: A total of 11 MMA mut-type patients (including 10 mut0 cases and 1 mut-case) who received LT in our institute were reviewed. Their metabolic profiles were compared between the pre/post-transplant periods. Their immunosuppressant and renal function changes after transplantation were assessed. RESULTS: After a mean follow-up of 97.5 ± 38.4 months, there were two deaths, and the actual survival rate was 81.8%. Their metabolic profiles had improved (mean blood ammonia level 366.8 ± 105.5 vs. 53.1 ± 17.4 µg/dl, p < .001; C3/C2 ratio 2.68 ± 0.87 vs. 0.73 ± 0.22, p = .003; mean urine MMA level 920.5 ± 376.6 vs. 196.2 ± 85.4, p = .067), and hospital stays were decreased (78.8 ± 74.5 vs. 7.4 ± 7.0 days/year, p = .009) after transplantation. The mean age at transplant was 1.81 ± 2.02 years old, and nine of these patients received LT before the age of 1.5 years old (early LT). Under prospective immunosuppressant dose reduction, three of these early LT patients discontinued the drug and were sustained for more than 5 years. Most of the patients had a preserved renal function, and no patient is currently on dialysis. CONCLUSIONS: In addition to the improvement in the metabolic parameters, early LT in MMA patients may allow for a dose reduction of the immunosuppressant, and the patient's renal function could be preserved in the long term.

Safe Strategy to Initiate Total Laparoscopic Donor Right Hepatectomy: A Stepwise Approach From a Laparoscopy-Assisted Method.

BACKGROUND: Total laparoscopic donor right hepatectomy (TLDRH) for adult living liver donors has been reported by a few experienced centers, but with limited cases, its safety and feasibility remain controversial. We report our experience initiating TLDRH using a stepwise approach to gradually convert laparoscopy-assisted donor right hepatectomy (LADRH) to TLDRH. METHODS: We retrospectively analyzed the data of 61 LADRHs, 56 conventional open donor right hepatectomies (CODRHs), and 3 TLDRHs performed between March 2014 and June 2018. RESULTS: There were no significant differences in perioperative outcomes between donors undergoing LADRH and CODRH, except for a slight elevations in the operative time (436.5 vs 392.9 min, p < 0.001) and the graft warm ischemic time (5.4 vs 4.0 min, p < 0.001) in the LADRH group. The recipients' posttransplant one-year survival rates in the LADRH and CODRH groups were also similar (93.2% and 94.6%, p = 0.384). For three donors in whom TLDRH was converted from LADRH in a stepwise manner, the average operative time and blood loss were 570 min and 316.7 ml, respectively. Donors were discharged on postoperative day 10 without any surgical complications. CONCLUSIONS: LADRH can be performed routinely on liver living donors. A stepwise approach could be adopted to "covert" suitable donors from LADRH to a total laparoscopic procedure to maximize donor safety. This strategy is reliable and could be reproduced in most LDLT centers.

Mesenchymal stem cells prolong survival and prevent lethal complications in a porcine model of fulminant liver failure.

BACKGROUND: Fulminant liver failure (FLF) is a life-threatening disease. METHODS: Lethal FLF was induced by ischemia-reperfusion (I-R) injury in mini-pigs, and MSCs were infused via splenic vein after reperfusion. RESULTS: Accumulated survival within 28 days was significantly improved by MSCs (P = 0.0348). Notably, MSCs maintained blood-gas homeostasis in the first 24 hours and prevented FLF-induced elevation of prothrombin time, international normalized ratio, and creatinine and ammonia levels in the first 3 days. With MSCs, serum levels of liver enzymes gradually decreased after 3 days, and platelet count was back to normal at 1 week of FLF. MSCs promoted liver regeneration within 2 weeks and differentiated into functional hepatocytes at 2-4 weeks after transplantation, evidenced by increase in Ki67-positive cells, detectable human hepatocyte growth factor, human vascular endothelial growth factor, human hepatocyte-specific antigen, and human albumin-expressing cells in the liver at different time points. Reactive oxidative species (ROS) were accumulated after FLF and eliminated at 4 weeks after MSC transplantation. CONCLUSIONS: Together, MSCs prolong the survival and prevent lethal sequelae of I-R injury-induced FLF by maintenance of liver-function homeostasis and rescue of ROS in the acute stage and by homing and differentiation into hepatocytes in the subacute stage.

Laparoscopic major hepatectomy: a systematic literature review and comparison of 3 techniques.

OBJECTIVE: This review assesses the current status of laparoscopic liver resection. BACKGROUND: The trend in laparoscopic liver resection has been moving from limited resections toward major hepatectomy. The surgical techniques for laparoscopic major hepatectomy include pure laparoscopic, hand-assisted laparoscopic, and laparoscopy-assisted methods. We performed a literature search and systematic review to assess the current status of laparoscopic major hepatectomy. METHODS: Our literature review was conducted in Medline using the keywords "laparoscopy" or "laparoscopic" combined with "liver resection" or "hepatectomy." Articles written in English containing more than 10 cases of laparoscopic major hepatectomy were selected. RESULTS AND CONCLUSIONS: Twenty-nine articles were selected for this review. The laparoscopic major hepatectomies achieved similar patient and economic outcomes compared with open liver resections in selected (noncirrhotic) patients. Surgeon experience with the techniques affected the results; thus, a learning period is mandatory. Of these 3 techniques, the pure laparoscopic method is suitable for experienced surgeons to achieve better cosmetic outcomes, whereas the hand-assisted laparoscopic method was associated with better perioperative outcomes; the laparoscopy-assisted method is used by surgeons for unique resections such as resection of cirrhotic livers, laparoscopic resection of tumors in unfavorable locations, and living donor hepatectomies. In addition, the laparoscopic major hepatectomy-specific, long-term oncologic outcomes remain to be addressed in future publications.

A bidirectional approach for portal vein stent placement in a child with complete portal vein occlusion after living donor liver transplantation.

Delayed PV complications are not rare in pediatric liver transplantation. Although PTPV offers a treatment and minimizes surgical revision, in case of complete PV thrombosis (PVT), the failure rate of PTPV is high. Herein, we report a successful technique of PTPV in a case of complete PVT with a stent placement using a bidirectional approach in a child with living donor liver transplantation.

Single-Center Experience in Managing Right Liver Grafts From Trifurcation or Independent Right Posterior Portal Vein in Adult Living Donor Liver Transplantation.

BACKGROUND: The right liver graft has sometimes been from the trifurcation portal vein (TPV) or independent right posterior portal vein (IRPPV). Managing these PV anatomies to increase the recipient's survival rate remains challenging. Many published techniques could overcome this problem, such as simple unification venoplasty (SUV), autologous portal Y-graft interposition, conjoined unification venoplasty (CUV) with a baseball-like conduit, and SUV plus circumferential fence-like vein extension. This study reviewed our strategy for managing the right liver grafts from TPV or IRPPV in adult living donor liver transplantation (aLDLT). METHODS: We enrolled the study population who underwent aLDLT using the grafts with TPV or IRPPV at our institute from October 2004 to October 2022. We analyzed the reconstruction methods for these grafts and postoperative PV complications in donors and recipients. RESULTS: During the study period, of 528 aLDLT recipients, we identified 26 donors with TPV (n = 10) or IRPPV (n = 16). Eight grafts from TPV had a single PV orifice. The other 18 grafts had dual right PVs that underwent initial PV management, including SUV (n = 13), recipient's right and left portal veins to graft's dual PVs (n = 2), Y-graft interposition (n = 1), CUV (n = 1) and SUV with fence-like vein extension (n = 1). One SUV graft changed to fence venoplasty due to significant tension for PV anastomosis. The acute right posterior PV thrombus and anterior PV stenosis happened in 2 cases with Y-graft interposition and native PVs direct anastomosis. One donor with TPV had portal vein thrombosis and needed thrombectomy with vein patch repair. CONCLUSIONS: The graft from TPV should be carefully planned. A single PV orifice may be feasible but not always possible. An SUV could cover most IRPPVs, but if the distance between the right anterior and posterior PVs is a problem, CUV would be an alternative method. In addition, SUVs with fence venoplasty could relieve PV anastomosis tension.

Risk factors for fractures following liver transplantation: a population-based cohort study.

BACKGROUND: Liver transplant recipients have an increased risk of osteoporosis and fractures. The aim of this study was to identify risk factors for fractures after liver transplant in a Taiwanese population. METHODS: We identified newly diagnosed liver transplant recipients from the National Health Insurance Research Database in Taiwan between 2003 and 2015. Risk factors of post-transplant fractures were analyzed using a Cox proportional hazards model. RESULTS: A total of 4821 patients underwent liver transplantation, of whom 419 (8.7%) had post-transplant fractures. Independent predictors of post-transplant fractures were age ≥65 years at transplantation (hazard ratio (HR): 1.566; 95% confidence interval (CI) 1.122-2.186), female sex (HR: 1.648; 95% CI 1.319-2.057), fractures within 1 year prior to transplant (HR: 3.664; 95% CI 2.503-5.364), hepatitis C carriers (HR: 1.594; 95% CI 1.289-1.970), alcoholism (HR: 1.557; 95% CI 1.087-2.230) and daily prednisolone dose >1.61-3.78 mg/day (HR: 1.354; 95% CI 1.005-1.824), >3.78-9.18 mg (HR: 4.182; 95% CI 3.155-5.544) and >9.18 mg (HR: 13.334; 95% CI 9.506-18.703). Post-transplant fractures were inversely correlated with tacrolimus (HR: 0.617; 95% CI 0.417-0.913) and sirolimus/everolimus (HR: 0.504; 95% CI 0.391-0.650) treatment. CONCLUSIONS: The liver transplant recipients, and especially those who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were associated with an increased risk of post-transplant fractures. Conversely, the use of tacrolimus and sirolimus/everolimus was associated with a decreased risk of fractures.

This study identified risk factors for fractures after liver transplant in a population-based study in an area with high prevalence of hepatitis B and hepatitis C.Recipients who were aged ≥65 years, female, hepatitis C carriers, had a history of fractures within 1 year prior to transplant, alcoholism, and higher daily prednisolone dose were independent risk factors for post-transplant fractures.Our findings highlight the importance of identifying individuals at high risk of fractures and concomitant tacrolimus and sirolimus/everolimus treatment to avoid the use of high-dose steroids and prevent post-transplant fractures.

The strategy of diminishing age gap effect on different donor-recipient combinations in living donor kidney transplantation.

BACKGROUND: The disparity between kidney donation and the number of uremic patients on the waiting list has increased the demand for older live-donor kidneys (OLK). However, the donor-recipient age gap may have an impact on the recipient's outcome. METHODS: Patients who underwent living donor kidney transplantation at our institute between 2005 and 2019 were enrolled and categorized into four donor-recipient groups according to age (≥50 years and <50 years). The Estimated Post-Transplant Survival (EPTS) score was used to quantify the recipient's condition. Adjusted models analyzed recipient outcomes and related risks among the four groups. RESULTS: Of the 154 pairs of live donors and recipients, OLK did not influence overall or death-censored graft survival. The four donor-recipient combinations had similar recipient outcomes, except it slightly worsened in the "old donor to young recipient" group. The EPTS score (adjusted HR, 1.02; 95% CI, 1.01-1.04; p = 0.014) and rejection (adjusted HR, 4.26; 95% CI, 1.36-13.37; p = 0.013) were significant risk factors for overall and death-censored graft survival, respectively. Recipients with pretransplant diabetes or prior solid organ transplantation could have amplified risk effects. The main causes of graft loss were death in older recipients and chronic rejection in younger recipients. CONCLUSION: OLK is safe for young recipients. Nevertheless, adequate immunosuppression should be maintained to prevent rejection and subsequent graft loss, especially for those receiving second kidney transplantation. In contrast, older recipients should avoid overt immunosuppression and control their comorbidities, such as diabetes-related complications to improve their long-term outcomes.

Optimizing the Safe Washout Period for Liver Transplantation Following Immune Checkpoint Inhibitors with Atezolizumab, Nivolumab, or Pembrolizumab.

BACKGROUND: Using immune checkpoint inhibitors (ICIs) as a downstaging therapy for liver transplantation (LT) has improved outcomes for patients with advanced hepatocellular carcinoma (HCC). However, this therapy carries a risk of post-transplant graft rejection. The washout (WO) period between the last ICI dose and LT seems critical in preventing postoperative rejection. This study aimed to optimize the WO period by balancing tumor burden suppression and rejection prevention using ICIs before LT. METHODS: We reviewed published case reports or series from March 2020 to December 2022 regarding LT for HCC after downstaging or bridge therapy with ICIs and included 4 of our cases. Most patients received atezolizumab, nivolumab, or pembrolizumab; these ICIs shared a half-life of around 28 days. Therefore, we excluded cases without definite WO period data and those using non-atezolizumab/nivolumab/pembrolizumab ICIs and ultimately enrolled 22 patients for analysis. We compared their clinical outcomes and estimated the rejection-free survival for every 0.5 half-life interval. RESULTS: Most study subjects received nivolumab (n = 25). Six patients had severe rejections (nivolumab group, n = 5) and needed rescue management. Of the 6 cases, 1 patient died after rejection, and 2 underwent re-transplantation. The median WO period in these 6 patients was 22 days (IQR: 9-35 days). In addition, we found that a 1.5 half-life (42 days) was the shortest safe WO period associated with significant rejection-free survival (P = .005). CONCLUSIONS: Our results showed that 42 days was the safest WO period before LT for HCC after ICI with atezolizumab, nivolumab, or pembrolizumab.

Long-term outcomes of liver transplantation for alcohol-related liver disease.

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

Retrograde arterial flush of the liver graft in living donor liver transplantation may ameliorate post-transplantational cholestasis--prospective randomized study.

Retrograde arterial flush (RGAF) of liver grafts, which prevents arterial intima injuries in living donor liver transplantation (LDLT), seemed to reduce post-transplantational cholestasis by our preliminary study. The aim of this study was to further confirm this effect of RGAF of grafts in LDLT by a prospective randomized study. The enrolled cases were randomly divided into two groups, RGAF (portal flush plus RGAF) and non-RGAF (portal flush only). The outcome measures included intra-operative hemodynamic changes, one-month post-transplantational liver function tests and acute cellular rejection, vascular and biliary complications, the length of postoperative hospital stay, and graft and patient survivals. The significant findings of results were lower postoperative serum bilirubin in the RGAF group until three wk after transplantation (days 1, 3, 7, 14, and 21 serum total bilirubin, mg/dL: 5.82±5.46, 3.95±4.28, 4.87±5.01, 3.62±5.32, and 3.63±6.91 vs. 8.41±5.49, 7.47±5.61, 10.0±10.1, 9.06±11.6, and 6.02±9.84, respectively, in RGAF and non-RGAF, p=0.017, 0.002, 0.014, 0.011, 0.109) and shorter postoperative hospital stay in the RGAF group (31.1±17.6 vs. 44.8±32.3 d, respectively, in RGAF and non-RGAF, p=0.035). In conclusion, the RGAF of liver grafts on a back table may ameliorate postoperative functional cholestasis in LDLT, which possibly reduces postoperative hospital stay.

Living donor liver transplantation using a graft from a donor with Dubin-Johnson syndrome.

DJS is an autosomal recessive disorder that causes an increase in conjugated bilirubin without elevation of liver enzymes. Most patients are asymptomatic and have normal life spans, but to the best of our knowledge, their livers have never been reported to be grafts in liver transplantation. Herein, we report an infant patient with MMA that received a partial liver graft from his mother, who had DJS. A biliary anastomosis stricture was noted five months after transplantation and was successfully treated with radiological interventions. Otherwise, the patient's liver functions were normal, and a liver biopsy showed a pathognomonic picture of DJS nine months after the transplantation. The patient was followed for one yr, and the results were satisfactory for an increase in oral intake and protein uptake, no recurrence of metabolic stroke and there was a gradual catch-up with regard to physical development despite having a persistently abnormal profile of amino acid analysis. From the experience of our case, we suggest that a liver from a donor with DJS can be used as a graft for liver transplantation, although long-term follow-up is mandatory to examine the grafted liver under the use of immunosuppressive medications.

Liver transplantation for a patient with homocystinuria.

A 24-yr-old man was diagnosed with HCU during neonatal screening and remained on a pyridoxine, vitamin B12, folic acid, and betaine regimen with dietary methionine restriction for more than 10 yr. He had normal mental development, marfanoid appearance, myopia because of lens dislocation, and recurrent ankle subluxation during adolescence. Thereafter, he was a poor adherent to the conventional diet-restrictive therapy, and LT was considered when he developed hypertension and multiple infarctions over the right cerebellum early in the second decade of his life despite taking aspirin as a prophylaxis from 17 yr of age. In November 2009, he received a deceased whole LT from a blood group compatible donor. Along with the success of the transplantation, he was completely disease free without dietary or nutritional control. To the best of our knowledge, this is the first case of LT intended to cure HCU, and with promising results. This case provides an insight into the role of LT for this congenital metabolic disease, for which the decision should be made by judging between the severity of the disease and the risk of the operation, as well as the life quality of the patient.

Advanced preoperative three-dimensional planning decreases the surgical complications of using large-for-size grafts in pediatric living donor liver transplantation.

BACKGROUND: Using "large-for-size" liver graft, graft-to-recipient weight ratio (GRWR) ≥4%, has been debated in pediatric liver transplantation due to possible graft compartment after abdomen closure. Meticulous preoperative evaluation with three-dimensional (3D) techniques may prevent these problems. This study compared the safety of large-for-size grafts in pediatric living donor liver transplantation (PLDLT) during the eras with or without 3D planning. METHODS: We defined the 3D era was after November 2017 due to our first implication of 3D printing for surgical planning and subsequently developing a 3D simulation implanting model. From November 2004 to July 2021, we enrolled 30 PLDLT patients with body weight (BW) < 10 kg and categorized them into conventional group: GRWR ≥4% before the 3D era (n = 9), 3D group: GRWR ≥4% in the 3D era (n = 8), and control group: GRWR <4% (n = 13). We followed and compared their clinical outcomes. RESULTS: The 3D group had the lowest BW and the highest graft volume reduction rate, with all receiving modified left lateral segments (LLS), such as reduced LLS (n = 2), hyperreduced LLS (n = 5), and segment 2 monosegment (n = 1). Overall postoperative complications were similar in conventional and control groups but significantly lower in the 3D group (OR 0.06, 95% CI 0.006-0.70, p = 0.025). However, all groups had similar graft and patient survival at 1, 2, and 4 years. CONCLUSION: Advanced preoperative 3D planning can decrease post-transplant complications and increase the safety of large-for-size grafts in PLDLT. LEVEL OF EVIDENCE: Type of study: Retrospective comparative study; Evidence level: Level III.

High-Throughput Sequencing of Complementarity Determining Region 3 in the Heavy Chain of B-Cell Receptor in Renal Transplant Recipients: A Preliminary Report.

BACKGROUND: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients' immune status for detecting a rejection/graft failure early on. METHODS: We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (IGH) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation. BCR-IGH-CDR3 in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server. RESULTS: Datasets covering VDJ regions of BCR-IGH-CDR3 indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one's D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients. CONCLUSIONS: Clonal diversity in BCR-IGH-CDR3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of BCR iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.