Hepatic venous outflow obstruction after adult living donor liver transplantation.

Hepatic venous outflow obstruction (HVOO) is a rare but critical vascular complication after adult living donor liver transplantation. We categorized HVOOs according to their morphology (anastomotic stenosis, kinking, and intrahepatic stenosis) and onset (early-onset < 3 mo vs. late-onset ≥ 3 mo). Overall, 16/324 (4.9%) patients developed HVOO between 2000 and 2020. Fifteen patients underwent interventional radiology. Of the 16 hepatic venous anastomoses within these 15 patients, 12 were anastomotic stenosis, 2 were kinking, and 2 were intrahepatic stenoses. All of the kinking and intrahepatic stenoses required stent placement, but most of the anastomotic stenoses (11/12, 92%) were successfully managed with balloon angioplasty, which avoided stent placement. Graft survival tended to be worse for patients with late-onset HVOO than early-onset HVOO (40% vs. 69.3% at 5 y, p = 0.162) despite successful interventional radiology. In conclusion, repeat balloon angioplasty can be considered for simple anastomotic stenosis, but stent placement is recommended for kinking or intrahepatic stenosis. Close follow-up is recommended in patients with late-onset HVOO even after successful treatment.

Seasonal variation in vitamin D status of Japanese infants starts to emerge at 2 months of age: a retrospective cohort study.

Vitamin D seasonality has been reported in adults and children, suggesting that sunlight exposure has effects on 25(OH)D production. While vitamin D deficiency among infants has received significant attention, little is known about the extent to which vitamin D status during early infancy is affected by sunlight exposure. Here, we retrospectively analysed serum 25(OH)D levels of 692 samples obtained from healthy infants aged 1-2 months born at Saitama City Hospital, Japan (latitude 35·9° North) between August 2017 and September 2021. Data regarding the frequency of outdoor activities, formula intake and BMI were also collected and analysed. Month-to-month comparisons of vitamin D levels revealed significant variation in 25(OH)D levels in breastfed infants starting at 2 months, with maximal and minimal levels in September and January, respectively. An outdoor activity score of 0 was most common at 1 month (83·9 %) and a score of 3 was most common at 2 months (81·2 %), suggesting an increased amount of sunlight exposure at 2 months. Multiple linear regression analysis revealed the amount of formula intake to be significantly associated with vitamin D status at both 1 (t = 17·96) and 2 months (t = 16·30). Our results comprise the first evidence that seasonal variation of vitamin D begins at 2 months among breastfed infants from East Asia, though dietary intake appears to be the major determinant of vitamin D status. These findings provide new insights into the influence of dietary and non-dietary factors on vitamin D status during early infancy.

CDKN1C hyperexpression in two patients with severe growth failure and microdeletions affecting the paternally inherited KCNQ1OT1:TSS-DMR.

BACKGROUND: Two imprinting control centres, H19/IGF2:IG-differentialy methylated region (DMR) and KCNQ1OT1:TSS-DMR, reside on chromosome 11p15.5. Paternal deletions involving the KCNQ1OT1:TSS-DMR result in variable phenotypes, namely, normal phenotype, Silver-Russel syndrome (SRS) and fetal demise. However, expression analyses for CDKN1C in these patients are very limited. CASES: Patient 1 (adult woman) and patient 2 (boy in early childhood) showed prenatal and postnatal growth failure and clinical suspicion of SRS. MOLECULAR ANALYSES: Both patients showed hypermethylation of the KCNQ1OT1:TSS-DMR caused by the paternal heterozygous de novo deletions involving the KCNQ1OT1:TSS-DMR, but not including CDKN1C enhancers. The deletion sizes were 5 kb and 12 kb for patients 1 and 2, respectively. CDKN1C gene expressions in immortalised leucocytes of both patients were increased compared with those of controls. CONCLUSION: Paternal deletions involving the KCNQ1OT1:TSS-DMR, but not including CDKN1C enhancers, disrupt KCNQ1OT1 expression, strongly activate CDKN1C expression and consequently cause severe growth failure.

Incidence and clinical risk factors of Bednar's aphthae in Japanese newborns.

BACKGROUND: The etiology of Bednar's aphthae remains unclear. Our aim was to investigate the incidence of, and factors associated with, Bednar's aphthae in a Japanese newborn cohort. METHODS: A retrospective cross-sectional study was conducted on neonates discharged from the well-baby nursery at Saitama City Hospital, Japan. The principal investigator carefully examined each neonate's oral cavity, up to and including the pharynx, with a light-emitting diode (LED) headlight to determine the presence of Bednar's aphthae. Maternal and neonatal clinical characteristics were first compared between neonates with and those without Bednar's aphthae by univariate analysis. Variables with significant inter-group differences upon univariate analysis were entered into a multivariable logistic-regression model. RESULTS: This study enrolled 1996 infants. We observed Bednar's aphthae in 9.3% of the Japanese newborn infants who were included. When restricted to infants who were born via vaginal delivery, 13.2% of them had aphthae. Multivariable logistic regression analysis identified vaginal delivery (odds ratio = 6.19, p < 0.0001) in Model 1, and vaginal delivery (odds ratio = 6.73, p < 0.0001) and birth weight (odds ratio = 0.9995, p = 0.034) in Model 2 as independent risk factors for the disease. CONCLUSION: This is the first report of the prevalence of Bednar's aphthae among Japanese neonates. Vaginal delivery was identified as the strongest risk factor. Although confounding between mode of delivery and mechanical stimuli associated with sucking was not found in this study, the findings pave the way for a better understanding of the etiology of Bednar's aphthae.

Surgical Outcomes of Domino Liver Transplantation Using Grafts From Living Donors With Familial Amyloid Polyneuropathy.

Domino liver transplantation (DLT) using grafts from donors with familial amyloid polyneuropathy is an acceptable procedure for expanding the donor pool. The vascular and biliary reconstructions in living donor DLT (LDDLT) are technically demanding, and data on the short-term and long-term surgical outcomes of domino donors and recipients in LDDLT are limited. In this study, we identified 25 domino recipients from our liver transplantation program (1999-2018), analyzed the vascular and biliary reconstructions performed, and evaluated the surgical outcomes, including graft survival. Piggyback technique was adopted in all 25 domino donors. The only surgical complication in domino donors was hepatic vein (HV) stenosis with an incidence rate of 4%. In 22 domino recipients, right HV and middle/left HV were reconstructed separately. A total of 10 recipients had 2 arteries anastomosed, and 18 underwent duct-to-duct biliary anastomosis. HV stenosis and biliary stricture had incidence rates of 8% and 24%, respectively, in the recipients, but none of them developed hepatic artery thrombosis. The 1-year and 5-year graft survival rates were 100% each in the domino donors, and 84.0% and 67.3% in the domino recipients, respectively. In conclusion, LDDLT has acceptable outcomes without increasing the operative risk in donors despite the demanding surgical technique involved.

Frequency and clinical characteristics of distinct etiologies in patients with Silver-Russell syndrome diagnosed based on the Netchine-Harbison clinical scoring system.

Silver-Russel syndrome (SRS) is a representative imprinting disorder (ID) characterized by growth failure and diagnosed by clinical features. Recently, international consensus has recommended using the Netchine-Harbison clinical scoring system (NH-CSS) as clinical diagnostic criteria. Loss of methylation of H19/IGF2:intergenic differentially methylated region (H19LOM) and maternal uniparental disomy chromosome 7 (UPD(7)mat) are common etiologies of SRS; however, other IDs, pathogenic variants (PVs) of genes, and pathogenic copy number variants (PCNVs) have been reported in patients meeting NH-CSS. To clarify the frequency and clinical characteristics of each etiology, we conducted (epi)genetic analysis in 173 patients satisfying NH-CSS. H19LOM and UPD(7)mat were identified in 34.1%. PCNVs, other IDs, and PVs were in 15.0%. Patients with all six NH-CSS items were most frequently observed with H19LOM and UPD(7)mat. This study confirmed the suitability of NH-CSS as clinical diagnostic criteria, the (epi)genetic heterogeneity of SRS, and showed the necessity of further discussion regarding the "SRS spectrum".

Intellectual development of patients with biliary atresia who underwent living donor liver transplantation in infancy.

BACKGROUND: The impact of pediatric liver transplantation on intellectual development has yet to be determined. We investigated the intellectual outcomes of school-aged patients after living donor liver transplantation for biliary atresia in infancy. METHODS: The Wechsler Intelligence Scale for Children-fourth edition test was administered to 20 patients who survived [Formula: see text] 5 years after living donor liver transplantation. Borderline full scale intelligence quotient was defined as ≤ 85. Pre-, peri-, and postoperative data were compared between patients with > 85 and ≤ 85 to identify predictive factors of borderline performance. RESULTS: The one-sample t test demonstrated that the mean full scale intelligence quotient of patients after transplantation for biliary atresia was significantly lower than that of the general population (91.8 vs. 100.0, p = 0.026) and 7 (35%) were classified as intellectual borderline functioning. Multivariable logistic regression models were unable to identify any factors predictive of full scale intelligence quotients of ≤ 85. CONCLUSION: This is the first study to indicate that the mean full scale intelligence quotient among school-aged patients who underwent living donor liver transplantation for biliary atresia in infancy is significantly lower than that of the general population.

Portal Vein Complications After Adult Living Donor Liver Transplantation: Time of Onset and Deformity Patterns Affect Long-Term Outcomes.

Portal vein complications (PVCs) after adult living donor liver transplantation (LDLT) are potentially lethal. We categorized PVCs by the time of onset (early versus late, <1 month versus ≥1 month, respectively) and deformity patterns (portal vein stenosis [PVS], portal vein thrombosis [PVT], and portal vein occlusion [PVO]) to establish optimal treatment strategies. Overall, 35/322 (10.9%) recipients developed PVCs between 2000 and 2019. Pretransplant PVT (odds ratio [OR], 15.20; 95% confidence interval [CI], 3.70-62.40; P < 0.001) was the only independent risk factor for PVS. In contrast, male sex (OR, 5.57; 95% CI, 1.71-18.20; P = 0.004), pretransplant PVT (OR, 4.79; 95% CI, 1.64-14.00; P = 0.004), and splenectomy (OR, 3.24; 95% CI, 1.23-8.57; P = 0.018) were independent risk factors for PVT. PVS was successfully treated with interventional radiology regardless of its time of onset. On the other hand, late PVT and PVO had significantly lower treatment success rates (2/15, 13%) compared with those that occurred in the early period (10/11, 91%) despite aggressive intervention (P < 0.001). Deformity patterns had a significant impact on the 5-year cumulative incidence of graft loss as a result of PVC (PVO + Yerdel grades 2-4 PVT group [n = 16], 41% versus PVS + Yerdel grade 1 PVT group [n = 19], 0%; P = 0.02). In conclusion, late grades 2 to 4 PVT and PVO are refractory to treatment and associated with poor prognoses, whereas PVS has a good prognosis regardless of time of onset. A tailored approach according to the time of onset and deformity patterns of PVC is essential.

A patient with Silver-Russell syndrome with multilocus imprinting disturbance, and Schimke immuno-osseous dysplasia unmasked by uniparental isodisomy of chromosome 2.

Silver-Russell syndrome (SRS) is a congenital disorder characterized by prenatal and postnatal growth failure and craniofacial features. Hypomethylation of the H19/IGF2:IG-differential methylated region (H19LOM) is observed in 50% of SRS patients, and 15% of SRS patients with H19LOM had multilocus imprinting disturbance (MLID). Schimke immuno-osseous dysplasia (SIOD), characterized by spondyloepiphyseal dysplasia and nephropathy, is an autosomal recessive disorder caused by mutations in SMARCAL1 on chromosome 2. We report a patient with typical SRS-related features, spondyloepiphyseal dysplasia, and severe nephropathy. Molecular analyses showed H19LOM, paternal uniparental isodisomy of chromosome 2 (iUPD(2)pat), and a paternally inherited homozygous frameshift variant in SMARCAL1. Genome-wide methylation analysis showed MLID in this patient, although it showed no MLID in another patient with SIOD without SRS phenotype. These results suggest that iUPD(2)pat unmasked the recessive mutation in SMARCAL1 and that the SMARCAL1 gene mutation may have no direct effect on the patient's methylation defects.

Asymptomatic hepatic artery dissection early after living-donor liver transplantation with simultaneous splenectomy: two case reports.

BACKGROUND: Hepatic artery dissection after liver transplantation is an uncommon morbidity. The onset mechanism and management for this disorder remain unclear. The present report describes the cases of two patients with hepatic artery dissection after living-donor liver transplantation (LDLT) with simultaneous splenectomy and provides new insight into the onset mechanism of this disorder. CASE PRESENTATION: CASE 1: A 51-year-old man with liver cirrhosis caused by hepatitis B virus underwent LDLT with a right lobe graft and splenectomy simultaneously. The recipient's right hepatic artery had partial dissection at the anastomosis site; therefore, his left hepatic artery was anastomosed. Contrast-enhanced computed tomography (CT) on postoperative day (POD) 27 showed dissection from his celiac artery to his left hepatic artery with bleeding in the false lumen. There was a risk of rupture of the false lumen; therefore, emergency interventional radiology and coil embolization of the false lumen were performed. The patient was doing well at 6 months after LDLT. CASE 2: A 58-year-old woman with liver cirrhosis caused by primary biliary cholangitis underwent LDLT with a left lobe graft and splenectomy simultaneously. Her hepatic artery had a dissection that extended from her left hepatic artery to the proper hepatic artery. The gastroduodenal artery was anastomosed. Contrast-enhanced CT on POD 8 revealed dissection from the celiac artery to the common hepatic artery as well as a pseudoaneurysm at the celiac artery. We managed the patient with conservative treatment and performed daily follow-ups with Doppler ultrasonography examination and serial contrast-enhanced CT. At the time of writing this report, the patient was doing well at 34 months after LDLT. CONCLUSIONS: Patients who have an intimal dissection at the anastomosis site and/or simultaneous splenectomy are at a higher risk of hepatic artery dissection. Most patients with asymptomatic hepatic artery dissections can be treated conservatively. Blood flow in the intrahepatic artery should be checked frequently using Doppler ultrasonography or contrast-enhanced CT soon after diagnosis.

The duodenal tube test is more specific than hepatobiliary scintigraphy for identifying bile excretion in the differential diagnosis of biliary atresia.

PURPOSE: Confirmation of bile excretion into the gastrointestinal tract is important to exclude biliary atresia (BA). We compared the duodenal tube test (DTT) with hepatobiliary scintigraphy (HS) for their efficiency in detecting bile secretion. METHODS: The subjects of this retrospective study were 47 infants who underwent both DTT and HS to diagnose or exclude BA between January 2000 and March 2018. RESULTS: BA was diagnosed in 32 of the 47 patients, and 7 of the remaining 15 non-BA patients underwent intraoperative cholangiography. Among the various DTT parameters, the total bile acid in duodenal fluid (DF-TBA)/serum (S) gamma-glutamyl transferase (γGTP) ratio was found to be the most specific for BA, with sensitivity and specificity of 98.0-100%, respectively. One BA patient in whom cut off values were not met was a premature infant. The sensitivity and specificity of HS were 100-56.3%, respectively. The diagnostic accuracy of the DF-TBA/S-γGTP parameter was higher than that of HS (98.6% vs. 85.1%, respectively). CONCLUSIONS: The DTT could be more a specific method than HS to detect bile excretion. Thus, the DTT should be incorporated into the multidisciplinary diagnostic approach for the differential diagnosis of BA to prevent unnecessary intraoperative cholangiography in patients who do not have BA.

Intravital Imaging of Neutrophil Recruitment Reveals the Efficacy of FPR1 Blockade in Hepatic Ischemia-Reperfusion Injury.

Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R. LysM-eGFP mice were subjected to partial warm hepatic I/R. They were pretreated with an FPR1 antagonist, cyclosporine H (CsH), or formyl peptide, fMLF. Liver was imaged after hepatic laser irradiation or I/R using the TPLSM technique. CsH treatment alleviated hepatic I/R injury, as evidenced by decreased serum transaminase levels, reduced hepatocyte necrosis/apoptosis, and diminished inflammatory cytokine, chemokine, and oxidative stress. In contrast, systemic administration of fMLF showed few effects. Time-lapse TPLSM showed that FPR1 blockade inhibited the accumulation of neutrophils in the necrotic area induced by laser irradiation in vivo. In the CsH-treated I/R group, the number and crawling velocity of neutrophils in the nonperfused area were lower than those in the control group. Meanwhile, FPR1 blockade did not affect monocyte/macrophage recruitment. Hepatic I/R promoted the retention of neutrophils and their active behavior in the spleen, whereas CsH treatment prevented their changes. Intravital TPLSM revealed that formyl-peptide-FPR1 signaling is responsible for regulating neutrophil chemotaxis to allow migration into the necrotic area in hepatic I/R. Our findings suggest effective approaches for elucidating the mechanisms of immune cell responses in hepatic I/R.

Risk factors for the recurrence of perineal canal.

PURPOSE: The aim of this study was to investigate risk factors for recurrence in the perineal canal (PC). METHODS: Patients with PC who underwent operations were enrolled in this study and were divided into recurrence and non-recurrence groups. Preoperative infection, the age at the operation, the presence of colostomy and the treatment procedure for fistula were retrospectively investigated. Regarding the treatment procedure for fistula, either closure of the rectal wall with stitches or ligation of fistula in the rectum was performed. These factors were compared between the two groups. RESULTS: Six of 17 patients with PC who underwent surgical treatment had recurrence. There were no significant differences in the incidence of preoperative infection, age at operation or presence of colostomy (p = 0.60, 0.38, 1.00, respectively). In the recurrence group, all patients were treated by closure of the rectal wall. In the non-recurrence group, five were treated by the closure of the rectal wall with stitches and six by ligation of the fistula. There was a significant association between recurrence and the treatment procedure for fistula (p = 0.04). CONCLUSION: Closure of the rectal wall with stitches is a risk factor for the recurrence of PC.

Repair of type IV laryngotracheoesophageal cleft (LTEC) on ECMO.

PURPOSE: A type IV laryngotracheoesophageal cleft (LTEC) is a very rare congenital malformation. Type IV LTEC that extends to the carina have poor prognosis and are difficult to manage. We present our experience with surgical repair in such a case using extracorporeal membranous oxygenation (ECMO). METHODS: A male infant, who was diagnosed with Goldenhar syndrome, showed severe dyspnea and dysphagia. Laryngoscopy indicated the presence of LTEC. The patient was transferred to our institute for radical operation 26 days after birth. Prior to surgery, a balloon catheter was inserted in the cardiac region of stomach through the lower esophagus to block air leakage, to maintain positive pressure ventilation. We also performed observations with a rigid bronchoscope to assess extent of the cleft, and diagnosed the patient with type IV LTEC. After bronchoscopy, we could intubate the tracheal tube just above the carina. Under ECMO, repair of the cleft was performed by an anterior approach via median sternotomy. RESULTS: The patient was intubated via nasotracheal tube and paralysis was maintained for 2 weeks, using a muscle relaxant for the first 3 days. Two weeks after surgery, rigid bronchoscopy showed that the repair had been completed, and the tracheal tube was successfully extubated without tracheotomy. CONCLUSIONS: Although insertion of a balloon catheter is a very simple method, it can separate the respiratory and digestive tracts. This method allowed for positive pressure ventilation and prevented displacement of the endotracheal tube until ECMO was established. As a result, we safely performed the operation and the post-operative course was excellent.

Pretransplant trends in α-fetoprotein levels as a predictor of recurrence after living donor liver transplantation for unresectable hepatoblastoma: A single-institution experience.

LT is a practical therapeutic alternative for unresectable hepatoblastoma; however, deciding when to perform LT is difficult. The aim of this study was to optimize the timing of LT for hepatoblastoma using pretransplant trends in AFP levels. Trends in pretransplant AFP levels and their influence on post-transplant outcomes were retrospectively evaluated. All patients who underwent living donor LT for hepatoblastoma in our institution since 2002 were included. Variables analyzed included history of prior tumor resection, pretransplant AFP responses to chemotherapy, metastatic disease at diagnosis, and post-transplant chemotherapy. Eight patients (seven boys and one girl; median age, 35 months; range, 15 months-12 years) were transplanted. The overall post-transplant recurrence-free survival rate was 62.5% (5/8) with a mean follow-up of 77 months. Patients with post-transplant recurrence showed a 0.573 log increase in AFP levels after the last chemotherapy session before LT. This was significantly higher than the 0.279 log decrease observed in patients without post-transplant recurrence (P = .024). Because the AFP response cannot be accurately predicted before each cycle of chemotherapy, it may be appropriate to perform LT when AFP levels do not decrease after the last cycle and before they are found to be elevated again.

Clinical features and risk factors of bile duct perforation associated with pediatric congenital biliary dilatation.

PURPOSE: This study aimed to investigate the clinical features and risk factors of bile duct perforation in pediatric congenital biliary dilatation (CBD) patients. METHODS: CBD patients, whose initial symptom was abdominal pain, were enrolled in this study and were divided into perforated and non-perforated groups. The clinical features of the perforated group were investigated. Moreover, the age at operation, sex, and morphologic features of the extrahepatic bile duct were compared between the groups. RESULTS: Fifteen cases of bile duct perforation (10.4%) were identified among the 144 CBD patients who had abdominal pain. Majority of bile duct perforation occurred in patients aged < 4 years. The median duration from onset of abdominal pain to bile duct perforation was 6 (4-14) days. Age at onset [< 4 years old; P = 0.02, OR 13.9, (1.663, 115.3)], shape of extrahepatic bile duct [non-cystic type; P = 0.009, OR 8.36, (1.683, 41.5)], and dilatation of the common channel [P = 0.02, OR 13.6, (1.651, 111.5)] were risk factors of bile duct perforation. CONCLUSIONS: Emergent bile duct drainage might be planned to prevent bile duct perforation if CBD patients have the abovementioned risk factors and experience persistent abdominal pain lasting for a few days from onset.

A Case Report of Living Donor Liver Transplantation for Fulminant Hepatitis Related to Hepatitis E Virus Infection.

Hepatitis E virus (HEV) infection which may become fulminant, especially in elderly people is more common than previously recognized in develop countries. Here we report successful living-donor liver transplantation (LDLT) in a case of acute liver failure due to HEV. A 63-year-old Japanese man with no previous history of liver disease was admitted for severe acute hepatitis. Detection of anti-HEV immunoglobulin A established a diagnosis of this virus-related liver failure. The patient suffered from hepatic encephalopathy 10 days after symptom onset and underwent LDLT. The patient had an uneventful course. The HEV RNA showed spontaneous negative conversion 10 weeks after LDLT. LDLT led to a successful outcome in a patient with acute liver failure due to HEV infection and regular testing for HEV RNA should be performed until HEV RNA is undetectable.

Outcomes of treatment with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation.

AIM: The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT). METHODS: A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis. RESULTS: Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12 weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4 months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment. CONCLUSIONS: The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12 weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection.

Recipient aging accelerates acquired transthyretin amyloidosis after domino liver transplantation.

Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n = 19], Y114C [n = 1], L55P [n = 1], and S50I [n = 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan-Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow-up for early amyloidosis detection and new treatments, including TTR stabilizers and gene-silencing therapies, are required. Liver Transplantation 22 656-664 2016 AASLD.

Antibody-mediated rejection after ABO-incompatible pediatric living donor liver transplantation for propionic acidemia: A case report.

We herein present the case of a four-yr-old boy with PA who developed AMR after ABO-incompatible LDLT despite undergoing B cell desensitization using rituximab. Although the CD19+ lymphocyte count decreased to 0.1% nine days after the administration of rituximab, he developed a high fever which was accompanied by arthralgia due to a streptococcal infection 13 days after rituximab prophylaxis. After the clearance of the infection, he underwent ABO-incompatible LDLT 36 days after the administration of rituximab. The CD19+ lymphocyte count just prior to LDLT was 1.2%. He developed AMR five days after LDLT, and the antidonor-type IgM and IgG antibody titers increased to 1:1024 and 1:1024, respectively. He was treated by plasma exchange, IVIG, steroid pulse therapy, and rituximab re-administration; however, his liver dysfunction continued. Despite intensive treatment, he died due to complicated abdominal hernia, acute renal failure, and ARDS. This case suggests that a streptococcal infection may induce the activation of innate immune responses; thus, additional desensitization therapy should be considered prior to ABO-incompatible LDLT if B cell reactivation is suspected.