Clinical symptoms, biochemistry, and liver histology during the native liver period of progressive familial intrahepatic cholestasis type 2.

BACKGROUND: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an ultra-rare disease caused by mutations in the ABCB11 gene. This study aimed to understand the course of PFIC2 during the native liver period. METHODS: From November 2014 to October 2015, a survey to identify PFIC2 patients was conducted in 207 hospitals registered with the Japanese Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Investigators retrospectively collected clinical data at each facility in November 2018 using pre-specified forms. RESULTS: Based on the biallelic pathogenic variants in ABCB11 and/or no hepatic immunohistochemical detection of BSEP, 14 Japanese PFIC2 patients were enrolled at seven facilities. The median follow-up was 63.2 [47.7-123.3] months. The median age of disease onset was 2.5 [1-4] months. Twelve patients underwent living donor liver transplantation (LDLT), with a median age at LDLT of 9 [4-57] months. Two other patients received sodium 4-phenylbutyrate (NaPB) therapy and survived over 60 months with the native liver. No patients received biliary diversion. The cases that resulted in LDLT had gradually deteriorated growth retardation, biochemical tests, and liver histology since the initial visit. In the other two patients, jaundice, growth retardation, and most of the biochemical tests improved after NaPB therapy was started, but pruritus and liver fibrosis did not. CONCLUSIONS: Japanese PFIC2 patients had gradually worsening clinical findings since the initial visit, resulting in LDLT during infancy. NaPB therapy improved jaundice and growth retardation but was insufficient to treat pruritus and liver fibrosis.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P ＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Efficacy of compliance with ventilator-associated pneumonia care bundle: A 24-month longitudinal study at Bach Mai Hospital, Vietnam.

Introduction: To decrease the risk of complications from ventilator-associated pneumonia, it is essential to implement preventative measures in all ICU patients. Since 2018, with the help of Japanese experts, we have applied a ventilator-associated pneumonia care bundle with 10 basic standards in patient care and monitoring. Therefore, we conducted a study to evaluate the results of applying 10 solutions to prevent ventilator-associated pneumonia over 24 months. Methods: A cross-sectional descriptive study with longitudinal follow-up for 24 months on 170 mechanically ventilated patients at the Center for Critical Care Medicine, Bach Mai Hospital. According to the Centers for Disease Control (CDC, 2021), the diagnosis of ventilator-associated pneumonia is when pneumonia appears 48 h after intubation by confirmation by at least two doctors. Evaluate compliance with each solution in the care bundle through camera monitoring, medical records, and directly on patients daily. Results: The rate of ventilator-associated pneumonia is 12.9%, the frequency of occurrence is 16.54 of 1000 days. The compliance rate for complete compliance with a 10-item ventilator-associated pneumonia was only 1.8%, while the average value was 84.1%. Average values of compliance with each solution for hand hygiene, head elevation 30-45 degrees, oral hygiene, stopping sedation, breathing circuit management, cuff pressure management, hypoplastic suction, Spontaneous breathing trial (SBT) daily and assessed extubation, mobilization and early leaving bed, ulcer and thrombosis prevention were 96.9%, 97.3%, 99.4%, 81.5%, 99.9%, 99.9%, 86.3%, 83.5%, 49.3%, and 46.4%, respectively. The time to appear ventilator-associated pneumonia in the high compliance group was 46.7 ± 5.0 days, higher than in the low compliance group, 10.3 ± 0.7 days, p < 0.001. Conclusions: A 10-item ventilator-associated pneumonia care bundle has helped reduce the incidence of ventilator-associated pneumonia. To reduce the risk of ventilator-associated pneumonia and shorten ICU and hospital stays, it is essential to fully adhere to subglottic secretion suction, daily SBT, and early mobilization and leaving the bed.

The protective association of HLA-C*12:02 and HLA-DQB1*06:01 with severe acute hepatitis of unknown origin in the Japanese population.

Global surveillance has been conducted to elucidate the pathogenesis of acute hepatitis of unknown origin (AHUO), However, the factors associated with the aggravation of this serious disease are unclear. Therefore, we conducted a HLA association study to identify HLA alleles or haplotypes predisposing or protective against Japanese AHUO. The HLA 5 locus (HLA-A, HLA-B, C, DRB1, and DQB1) 4-digit genotyping results of 72 AHUO patients who underwent liver transplantation at our institution between 2000 and 2021 were compared to those of 873 healthy Japanese controls. Protective associations of HLA-B*52:01 (p-corrected (pc) = 3.15 × 10-3 ), HLA-C*12:02 (pc = 1.66 ×10-3 ), HLA-DQB1*06:01 (pc = 1.42 × 10-2 ), and HLA-DRB1*15:02 (pc = 1.36 × 10-2 ) with severe AHUO in Japanese patients were observed. The amino acid residues of tryptophan at position 156, which are located in the antigen-binding grooves of the HLA-C protein, showed a protective association with AHUO, showing a significant difference from other amino acid variations (pc = 9.0 × 10-4 ). Furthermore, 5 amino acid residues of the HLA-DQB1 protein were also protectively associated with AHUO with a significant difference from other amino acid variations (pc = 1.42 × 10-2 to 2.89 × 10-2 ). These alleles have a protective association with the aggravation of AHUO in the Japanese population.

Living donor liver transplantation for myocerebrohepatopathy spectrum due to POLG mutations.

BACKGROUND: POLG is one of several nuclear genes associated with mitochondrial DNA maintenance defects and is a group of diseases caused by mitochondrial DNA deficiency that results in impaired adenosine triphosphate production and organ dysfunction. Myocerebrohepatopathy spectrum (MCHS) is the most severe and earliest presentation of POLG mutations, and liver transplantation (LT) for MCHS has never been reported. CASE PRESENTATION: The patient was a 3-month-old boy with acute liver failure and no neurological manifestations (e.g., seizures). We performed a living donor LT using a left lateral segment graft from his father. The postoperative course was uneventful. Subsequently, a homozygous POLG mutation (c.2890C>T, p. R964C) was identified by multigene analysis of neonatal/infantile intrahepatic cholestasis. Moreover, respiratory chain complex I, II, and III enzyme activities and the ratio of mtDNA to nuclear DNA in the liver were reduced. Therefore, we considered that these clinical manifestations and examination findings met the definition for MCHS. During meticulous follow-up, the patient had shown satisfactory physical growth and mental development until the time of writing this report. CONCLUSION: We presumed that the absence of remarkable neurologic manifestations prior to LT in patients with MCHS is a good indication for LT and contributes to a better prognosis in the present case.

Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis.

Choline is an essential nutrient, and its deficiency causes steatohepatitis. Dietary phosphatidylcholine (PC) is digested into lysoPC (LPC), glycerophosphocholine, and choline in the intestinal lumen and is the primary source of systemic choline. However, the major PC metabolites absorbed in the intestinal tract remain unidentified. ATP8B1 is a P4-ATPase phospholipid flippase expressed in the apical membrane of the epithelium. Here, we use intestinal epithelial cell (IEC)-specific Atp8b1-knockout (Atp8b1IEC-KO) mice. These mice progress to steatohepatitis by 4 weeks. Metabolomic analysis and cell-based assays show that loss of Atp8b1 in IEC causes LPC malabsorption and thereby hepatic choline deficiency. Feeding choline-supplemented diets to lactating mice achieves complete recovery from steatohepatitis in Atp8b1IEC-KO mice. Analysis of samples from pediatric patients with ATP8B1 deficiency suggests its translational potential. This study indicates that Atp8b1 regulates hepatic choline levels through intestinal LPC absorption, encouraging the evaluation of choline supplementation therapy for steatohepatitis caused by ATP8B1 dysfunction.

Effects of Adding Congested Segment IV to the Left Lateral Graft on Short-term Outcomes in Pediatric Living-donor Liver-transplant Recipients.

Background: In some pediatric patients undergoing living-donor liver transplantation, segment IV without the middle hepatic vein can be added to a left lateral segment graft to obtain larger graft volume. Because no clear consensus on this technique exists, this study investigated the effects of congested areas on postoperative outcomes in pediatric patients with biliary atresia undergoing living-donor liver transplantation. Methods: We retrospectively reviewed data of recipients with biliary atresia aged ≤15 y who had undergone living-donor liver transplantation at Kyoto University Hospital between 2006 and 2021 and with graft-to-recipient weight ratios (GRWR) of ≤2%. Based on the percentage of congested area in the graft, patients were classified into the noncongestion (n = 40; ≤10%) and congestion (n = 13; >10%) groups. To compare the differences between groups with similar nooncongestive GRWRs and investigate the effect of adding congested areas, patients in the noncongestion group with GRWRs of ≤1.5% were categorized into the small noncongestion group (n = 24). Results: GRWRs and backgrounds were similar between the noncongestion and congestion groups; however, patients in the congestion group demonstrated significantly longer prothrombin times, higher ascites volumes, and longer hospitalization. Further, compared with the small noncongestion group, the congestion group had significantly greater GRWR and similar noncongestive GRWR; however, the congestion group had significantly longer prothrombin time recovery (P = 0.020, postoperative d 14), higher volume of ascites (P < 0.05, consistently), and longer hospitalization (P = 0.045), requiring significantly higher albumin and gamma-globulin transfusion volumes than the small noncongestion group (P = 0.027 and P = 0.0083, respectively). Reoperation for wound dehiscence was significantly more frequent in the congestion group (P = 0.048). Conclusions: In pediatric liver-transplant recipients, adding a congested segment IV to the left lateral segment to obtain larger graft volume may negatively impact short-term postoperative outcomes.

Management and outcomes after liver transplantation for progressive familial intrahepatic cholestasis: A systematic review and meta-analysis.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous rare congenital cholestatic liver disease. Disease progression might necessitate liver transplantation (LT). The aim of this study was to describe the outcome of PFIC1-4 patients after LT. METHODS: Electronic databases were searched to identify studies on PFIC and LT. Patients were categorized according to PFIC type, genotype, graft type, age at LT, time of follow-up, and complications and treatment during follow-up. RESULTS: Seventy-nine studies with 507 patients met inclusion criteria; most patients were classified as PFIC1-3. The median age at LT was 50 months. The overall 5-year patient survival was 98.5%. PFIC1 patients with diarrhea after LT were at significant risk of developing graft steatosis ( p < 0.0001). Meta-analysis showed an efficacy of 100% [95% CI: 73.9%-100%] for surgical biliary diversion to ameliorate steatosis and 94.9% [95% CI: 53.7%-100%] to improve diarrhea (n = 8). PFIC2 patients with bile salt export pump (BSEP)2 or BSEP3-genotype were at significant risk of developing antibody-induced BSEP deficiency (AIBD) ( p < 0.0001), which was reported in 16.2% of patients at a median of 36.5 months after LT. Meta-analysis showed an efficacy of 81.1% [95% CI: 47.5%-100%] for rituximab-based treatment regimens to improve AIBD (n = 18). HCC was detected in 3.6% of PFIC2 and 13.8% of PFIC4 patients at LT. CONCLUSIONS: Fifty percent of PFIC1 patients develop diarrhea and steatosis after LT. Biliary diversion can protect the graft from injury. PFIC2 patients with BSEP2 and BSEP3 genotypes are at significant risk of developing AIBD, and rituximab-based treatment regimens effectively improve AIBD. PFIC3 patients have no PFIC-specific complications following LT.

Adrenocortical carcinoma mimicking hepatocellular carcinoma: A case report.

INTRODUCTION AND IMPORTANCE: Adrenocortical carcinoma (ACC) is a relatively rare tumor arising in the adrenal cortex. Its imaging and histopathologic findings are not well known to be similar to those of hepatocellular carcinoma (HCC). We report here a case of ACC with hepatic resection in the preoperative diagnosis of HCC. CASE PRESENTATION: A 46-year-old woman was noted to have a tumor 45 mm in size in the segment 7 of the liver on CT during a medical checkup. The tumor had consistent imaging findings as HCC on Ultrasound, CT, and MRI examinations, and the result of the liver tumor biopsy was a diagnosis of intermediate differentiated HCC. We considered the tumor to be HCC and performed a posterior segmentectomy with combined resection of the right adrenal gland, which had adhesions suspected to direct invasion. The pathology of the resected specimen confirmed the diagnosis of ACC with direct invasion into the liver. CLINICAL DISCUSSION: ACC may show a contrast pattern similar to that of HCC on imaging, and histopathology may show atypical cells with eosinophilic sporulation, similar to that of HCC. Our case serves to alert physicians that ACC should be considered a differential diagnosis in patients with suspected HCC in the posterior segment. CONCLUSION: Tumors suspected of HCC in the dorsal posterior segment of the liver should be considered as possible ACC.

Evaluation of a bundle approach for the prophylaxis of ventilator-associated pneumonia: A retrospective single-center Study.

Ventilator-associated pneumonia (VAP) is defined as pneumonia occurring after the first 48 hours of intubation and mechanical ventilation and is the most frequent hospital-acquired infection associated with intensive care unit (ICU) admissions. Herein, we defined a novel VAP bundle including 10 preventive items. We analyzed compliance rates and clinical effectiveness associated with this bundle in patients undergoing intubation at our medical center. A total of 684 consecutive patients who underwent mechanical ventilation were admitted to the ICU between June 2018 and December 2020. VAP was diagnosed by at least two physicians based on the relevant United States Centers for Disease Control and Prevention criteria. We retrospectively evaluated associations between compliance and VAP incidence. The overall compliance rate was 77%, and compliance generally remained steady during the observation period. Moreover, although the number of ventilatory days remained unchanged, the incidence of VAP improved statistically significantly over time. Low compliance was identified in four categories: head-of-bed elevation of 30- 45º, avoidance of oversedation, daily assessment for extubation, and early ambulation and rehabilitation. The incidence of VAP was lower in those with an overall compliance rate of ≥ 75% than its incidence in the lower compliance group (15.8 vs. 24.1%, p = 0.018). When comparing low-compliance items between these groups, we found a statistically significant difference only for daily assessment for extubation (8.3 vs. 25.9%, p = 0.011). In conclusion, the evaluated bundle approach is effective for the prophylaxis of VAP and is thus eligible for inclusion in the Sustainable Development Goals.

Hemodynamic and Clinical Response to Liver Transplantation in Children and Young Adults POPH Patients.

Portopulmonary hypertension is an intractable form of pulmonary hypertension. Although liver transplantation is recommended for patients who respond poorly to treatments, the mechanisms by which liver transplantation improves pulmonary hypertension remain unclear. The present study investigated these mechanisms by retrospectively evaluating patients' data. This study retrospectively evaluated echocardiography and catheterization data before and after liver transplantation in 12 patients who underwent liver transplantation from 2001 to 2019. The 12 patients included one male and 11 females, of median age at liver transplantation of 10 years, 2 months. Nine patients underwent liver transplantation for congenital biliary atresia and three for portal vein aplasia or hypoplasia. Mean pulmonary arterial pressure was 44.1 ± 8.1 mmHg at the first cardiac catheter examination, 35.3 ± 7.8 mmHg before liver transplantation, and 29.5 ± 9.3 mmHg 6 months after liver transplantation. Pulmonary artery pressure was reduced by treatments of pulmonary hypertension and by liver transplantation. Pulmonary vascular resistance did not differ before and after liver transplantation, whereas the cardiac index decreased significantly, indicating that the significant reduction in mean pulmonary artery pressure was due to a decrease in cardiac index. Decreased cardiac index was thought to result from improvements in hyperdynamic conditions due to increased (normalized) systemic vascular resistance. Liver transplantation likely suppresses shear stress on pulmonary arteries, preventing further damage by hyper-circulation. A longer-term evaluation is required to determine the effect of improving pulmonary artery remodeling.

Nonsuperiority of technetium-99m-galactosyl human serum albumin scintigraphy over conventional volumetry for assessing the future liver remnant in patients undergoing hepatectomy after portal vein embolization.

BACKGROUND: Technetium-99m-galactosyl human serum albumin scintigraphy is preferred for assessing the liver functional reserve in patients undergoing hepatectomy, but its superiority over computed tomography volumetry after portal vein embolization and subsequent hepatectomy remains elusive. We aimed to compare technetium-99m-galactosyl human serum albumin scintigraphy with conventional computed tomography volumetry for predicting posthepatectomy liver failure in patients after portal vein embolization. METHODS: This retrospective study analyzed 152 consecutive patients who underwent hepatobiliary cancer resection after portal vein embolization between 2006 and 2021. Posthepatectomy liver failure was graded according to the International Study Group of Liver Surgery criteria. The predictive abilities for posthepatectomy liver failure were compared between the future remnant uptake (%) by technetium-99m-galactosyl human serum albumin scintigraphy and the future remnant volume (%) by computed tomography volumetry. RESULTS: Future remnant uptake (%) was significantly greater than future remnant volume (%) after portal vein embolization (47.9% vs 40.8%; P < .001), while the values were comparable before portal vein embolization (32.7% vs 31.2%; P = .116). Receiver operating characteristic curve analysis revealed that post-portal vein embolization future remnant volume (%) had a significantly higher area under the curve than post-portal vein embolization future remnant uptake (%) (0.709 vs 0.630; P = .046) for predicting posthepatectomy liver failure. Multivariable analysis revealed that post-portal vein embolization future remnant volume (%) independently predicted posthepatectomy liver failure, but future remnant uptake (%) did not. Although the incidence of posthepatectomy liver failure grade ≥B was 17.8% when indocyanine green-clearance of the future liver remnant based on both future remnant volume (%) and future remnant uptake (%) was ≥0.05, it was higher in other combinations: 55.6% for indocyanine green clearance of the remnant volume ≥0.05/indocyanine green clearance of the remnant uptake ≤0.05; 50.0% for indocyanine green clearance of the remnant volume ≤0.05/indocyanine green clearance of the remnant uptake ≥0.05; and 50% for indocyanine green clearance of the remnant volume ≤0.05/indocyanine green clearance of the remnant uptake ≤0.05. CONCLUSIONS: Technetium-99m-galactosyl human serum albumin scintigraphy is not superior to computed tomography volumetry for assessing the future liver remnant in patients undergoing major hepatectomy after portal vein embolization.

Clinical outcomes after tracheostomy in patients with coronavirus disease 2019: a single-center experience in Japan.

PURPOSE: Many patients with coronavirus disease 2019 require mechanical ventilation and tracheostomy. However, the timing and indications for tracheostomy are controversial. This study assessed 11 patients with coronavirus disease 2019 who underwent tracheostomy with clinical information and retrospective analyses. METHODS: A single-center retrospective observational study was performed on patients with coronavirus disease 2019 who underwent tracheostomy between 2020 and 2021. RESULTS: Failure to wean was the most common indication for tracheostomy, followed by extracorporeal membrane oxygenation decannulation and the need for secretion management. After tracheostomy, six patients (54.5%) were liberated from the ventilator. The time from intubation to tracheostomy (21.1 ± 9.14 days) was correlated with the duration of ventilator dependency (36.83 ± 20.45 days, r2 = 0.792, p = 0.018). The mean Acute Physiological and Chronic Health Evaluation II score was significantly lower in the ventilator-liberated group (23 ± 2.77) than in the non-ventilator-liberated group (31 ± 6.13, p = 0.0292). Furthermore, patients with Acute Physiological and Chronic Health Evaluation II scores of < 27 points achieved ventilator liberation and a long-term survival (p = 0.0006). CONCLUSIONS: This study describes the outcomes of a cohort of patients who underwent tracheostomy after intubation for coronavirus disease 2019. The Acute Physiological and Chronic Health Evaluation II score predicted whether or not the patient could achieve ventilator liberation.

Two Cases of Possible Exacerbation of Chronic Rejection After Anti-SARS-CoV-2 Messenger RNA Vaccination: A Case Report.

In post-liver transplant recipients, SARS-CoV-2 infection is a health threat, and novel messenger RNA vaccines such as Pfizer BioNTech BNT162b2 and Moderna mRNA-1273 are aggressively recommended. However, there are few reports on their adverse effects, some of which may be potentially fatal. We have experienced 2 post-liver transplant recipients with exacerbated chronic rejection after vaccination, one of whom had to undergo retransplant and the other who is still in the process of liver function without improvement. These alarming cases will be presented as case reports.

Low Friction of Graphene Oxide Aggregates in Lubricant Oil between a Steel Ball and Glass Disk under Boundary Lubrication.

Previously, isolated nanocarbons in lubricating oils were considered essential for good lubrication. However, we observed that graphene oxide (GO) aggregates in lubricating oil have lower frictional properties than isolated dispersed GO. The GO was dispersed in polyα-olefin (PAO) using alkylamine at different ratios of GO and alkylamine, or it was heated at different temperatures to synthesize high- and low-dispersible GO-dispersed PAO. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy measurements showed that low-dispersible modified GOs retained many of the original GO chemical and structural features. Macrotribological tests between a steel ball and glass disk in GO-dispersed oil were conducted with a load of 5 N under boundary lubrication. The friction interface was observed in situ using an optical microscope. In the low-dispersible GO-dispersed PAO, many GO aggregates were observed through optical microscopy. Surprisingly, the friction coefficients decreased when the GO aggregates entered the friction interface and covered the contact area. The low-dispersible GO-dispersed PAO using alkylamine had the lowest friction coefficient of 0.05, as the GO aggregates covered the contact area. From microtribological tests with a load of 0.8 mN as well, it is assumed that the low friction of the GO aggregates originates due to the sliding between the weakest shear layers in the aligned multiple GO layers.

The New Challenge in Pediatric Liver Transplantation: Chronic Antibody-Mediated Rejection.

Antibody-mediated rejection (AMR) of liver allograft transplantation was considered as anecdotal for many decades. However recently, AMR has gained clinical awareness as a potential cause of chronic liver injury, leading to liver allograft fibrosis and eventual graft failure. (1) Methods: Literature on chronic AMR (cAMR) in pediatric post-liver transplant patients was reviewed for epidemiologic data, physiopathology, diagnosis, and treatment approaches. (2) Results: Accurate incidence of cAMR in pediatric liver transplantation remains unknown. Diagnostic criteria of cAMR were suggested by the Banff Working Group in 2016 and are based on standardized histopathological findings, C4d staining pattern, associated with the presence of donor-specific antibodies (DSA). Physio-pathological mechanisms are not clear for the technically difficult-to-obtain animal models reproducing cAMR. Treatment protocols are not established, being limited to case reports and case series, based on experience in ABO incompatible transplantation and kidney transplantation. Immunosuppression compliance with adequate dose adjustment may prevent cAMR. Conversion of Cyclosporine to Tacrolimus may improve pathological findings if treated in early phase. The association of steroids, Mycophenolate Mofetil (MMF) and mTOR inhibitors have shown some synergistic effects. Second-line treatments such as intravenous immunoglobulin (IVIG) and plasma exchange may decrease antibody titers based on ABO incompatible transplant protocols. The use of anti-CD20 (Rituximab) and proteasome inhibitors (Bortezomib) is controversial due to the lack of qualified studies. Therefore, multicenter randomized trials are needed to establish the best therapeutic strategy. In refractory cases, re-transplantation is the only treatment for allograft failure. (3) Conclusions: This literature review collects recent clinical, histopathological, and therapeutical advances of cAMR in liver allograft transplantation of pediatric patients. There are many physio-pathological aspects of cAMR to be clarified. Further efforts with multicenter prospective protocols to manage patients with cAMR are needed to improve its outcome.

The impact of human leukocyte antigen mismatch on recipient outcomes in living-donor liver transplantation.

Donor-recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living-donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990-2020). The primary and secondary endpoints were recipient survival and the incidence of T cell-mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ. Subgroup analyses were also performed in between-siblings that characteristically have widely distributed 0-10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult-to-adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p = 0.03, 0.01, 0.03, 0.001, and <0.001 for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA-B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21-5.87; p = 0.02) and recipient survival (HR 2.44, 95% CI 1.11-5.35; p = 0.03) in between-siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor-recipient relationships are parent-to-child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.

Application of laparoscopic distal pancreatectomy for normal anatomy after hiatal hernia repair: A case report.

We describe a case of pancreatic tumor associated with a giant type IV hiatal hernia that had prolapsed into the posterior mediastinum. Hiatal hernia repair should be performed first because it enables laparoscopic distal pancreatectomy to be performed in the normal anatomical position.