Current Status and Outcomes of Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Results From a Multicenter Retrospective Study Over Two Decades.

BACKGROUND: Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era. METHODS: We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared. RESULTS: The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002). CONCLUSIONS: The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further.

Long-Term Outcomes of Living Donor Liver Transplantation for Methylmalonic Acidemia.

BACKGROUND: Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations. METHODS: We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications. RESULTS: The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). CONCLUSIONS: LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Impact of Portal Flow on the Prognosis of Children With Congenital Portosystemic Shunt: A Multicentric Observation Study in Japan.

BACKGROUND: Although congenital portosystemic shunts (CPSSs) are increasingly being recognized, the optimal treatment strategies and natural prognosis remain unclear, as individual CPSSs show different phenotypes. METHODS: The medical records of 122 patients who were diagnosed with CPSSs at 15 participating hospitals in Japan between 2000 and 2019 were collected for a retrospective analysis based on the state of portal vein (PV) visualization on imaging. RESULTS: Among the 122 patients, 75 (61.5%) showed PV on imaging. The median age at the diagnosis was 5 months. The main complications related to CPSS were hyperammonemia (85.2%), liver masses (25.4%), hepatopulmonary shunts (13.9%), and pulmonary hypertension (11.5%). The prevalence of complications was significantly higher in patients without PV visualization than in those with PV visualization (P < 0.001). Overall, 91 patients (74.6%) received treatment, including shunt closure by surgery or interventional radiology (n = 82) and liver transplantation (LT) or liver resection (n = 9). Over the past 20 years, there has been a decrease in the number of patients undergoing LT. Although most patients showed improvement or reduced progression of symptoms, liver masses and pulmonary hypertension were less likely to improve after shunt closure. Complications related to shunt closure were more likely to occur in patients without PV visualization (P = 0.001). In 25 patients (20.5%) without treatment, those without PV visualization were significantly more likely to develop complications related to CPSS than those with PV visualization (P = 0.011). CONCLUSION: Patients without PV visualization develop CPSS-related complications and, early treatment using prophylactic approaches should be considered, even if they are asymptomatic. LEVEL OF EVIDENCE: Level III.

A case of paralytic shellfish poisoning caused by consumption of visceral balls from geoduck Panopea japonica in Japan.

In the end of March 2018, an unprecedented food poisoning incident due to ingestion of the visceral balls of geoduck Panopea japonica occurred in Japan. The patient, presented with symptoms of numbness on the lips and general weakness, was diagnosed as paralytic shellfish poisoning (PSP). The patient immediately treated with the mechanical ventilation recovered and left the hospital after 3 days treatment. Saxitoxins (STXs) in the plasma and urinary samples collected from the patient on the first and second day after hospitalization were analyzed by ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC/MS/MS) and liquid chromatography with post-column fluorescent detection (LC/FLD). The STXs levels of 499.1 and 6.0 µg/L of STX dihydrochloride equivalent (STX·2HCl eq.) were quantitated by LC/FLD in the urinary samples on the first and second day, respectively. In addition, geoducks harvested from the same areas of the PSP causative specimens after the incident were analyzed by LC/FLD, and the results showed the level of STXs in their whole bodies of the geoducks exceeding 0.8 mg STX·2HCl eq./kg which is the maximum levels of STX in CODEX STAN 292-2008. Prominent toxins in STXs that detected in urinary and geoduck samples and identified by UHPLC/MS/MS and LC/FLD were gonyautoxin-1+4 (GTX1+4). These results concluded that the incident was the food poisoning due to STXs accumulated in the geoducks. This is the first PSP case caused by consumption of geoducks in Japan. This is also the first PSP case that causative toxins are detected in urinary samples of patients involved in PSP in Japan.

Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.

New azaspiracid analogues detected as bi-charged ions in Azadinium poporum (Amphidomataceae, Dinophyceae) isolated from Japanese coastal waters.

Lipophilic marine biotoxin azaspiracids (AZAs) are produced by dinoflagellates Azadinium and Amphidoma. Recently, several strains of Azadinium poporum were isolated from Japanese coastal waters, and detailed toxin profiles of two strains (mdd421 and HM536) among them were clarified by several detection techniques on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOFMS). In our present study, AZA analogues in seven strains of A. poporum from Japanese coastal waters (including two previously reported strains) were determined by these detection techniques. The dominant AZA in the seven strains was AZA2 accompanied by small amounts of several known AZAs and twelve new AZA analogues. Eight of the twelve new AZA analogues discovered in our present study were detected as bi-charged ions on the positive mode LC/MS/MS. This is the first report describing AZA analogues detected as bi-charged ions with hexose and sulfate groups in their structures.

Corrigendum to "Expert management of congenital portosystemic shunts and their complications" [JHEP Reports 6 (2024)].

[This corrects the article DOI: 10.1016/j.jhepr.2023.100933.].

N-Desmethylmajusculamide B, a lipopeptide isolated from the Okinawan cyanobacterium Okeania hirsuta.

A new lipopeptide, N-desmethylmajusculamide B (1), was isolated from the Okinawan cyanobacterium Okeania hirsuta along with 2 known compounds majusculamide A (2) and majusculamide B (3). The planar structure of (1) was elucidated by a detailed analysis of mass spectrometry and nuclear magnetic resonance spectra. The absolute configurations of the amino acid residues were determined using Marfey's analysis. The configuration of C-16 in the α-methyl-ß-keto-decanoyl moiety was determined unambiguously to be S by conducting a semisynthesis of N-desmethylmajusculamide B from 3. The cytotoxicity against mouse L1210 leukemia cells was evaluated for majusculamides (1-3).

"Reduced Size Liver Grafts in Pediatric Liver Transplantation; Technical Considerations".

Liver transplantation (LT) has become a vital treatment option for children with end-stage liver disease. Left lateral segment (LLS) grafts are particularly common in split and living donor LT for pediatric patients. However, challenges arise in small infants receiving LLS grafts, primarily due to graft-size mismatches, resulting in "large-for-size" grafts. To overcome this issue, the practice of further reducing grafts from the LLS to diminish graft thickness has been explored. Currently, the indication for reducing the thickness of LLS grafts includes recipients with a body weight (BW) under 5.0 kg, neonates with acute liver failure, or those with metabolic liver disease. At the National Center for Child Health and Development in Tokyo, Japan, among 131 recipients of reduced-size LLS grafts, a remarkable 15-year graft survival rate of 89.9% has been achieved in small infants. This success indicates that with experience and refinement of the technique, there's a trend towards improved graft survival in recipients with reduced-thickness LLS grafts. This advancement underscores the importance of BW-appropriate methods in graft selection to ensure exceptional outcomes in vulnerable pediatric patients in need of LT. These techniques' ongoing development and refinement are crucial in enhancing the survival rates and overall outcomes for these young patients.

Okeanic acid-A, a trihydroxy fatty acid from the Okinawan cyanobacterium Okeania hirsuta.

Trihydroxy fatty acids are oxidative metabolites of polyunsaturated fatty acids isolated from plants, bacteria, fungi, and microalgae and have a variety of biological activities. In this study, a new trihydroxy fatty acid, okeanic acid-A (1), was isolated together with malyngic acid (2) and 15,16-dihydromalyngic acid (3) from the cyanobacterium Okeania hirsuta collected in Okinawa, Japan. The planar structure of 1 was elucidated by detailed analyses using high-resolution ESI-MS and 1D and 2D NMR spectroscopy. The absolute configurations of the hydroxy groups in 1 were determined unambiguously by chemical derivatisation and a modified Mosher's method. These cyanobacterial trihydroxy fatty acids (1-3) have identical configurations at their respective trihydroxy parts. Okeanic acid-A (1) showed mild growth-inhibitory activity against the marine diatom Nitzschia amabilis.

Expert management of congenital portosystemic shunts and their complications.

Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up.