No abstract

Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.

Acetaminophen (APAP) overdose is a common cause of drug-induced acute liver failure. Although hepatocyte cell death is considered to be the critical event in APAP-induced hepatotoxicity, the underlying mechanism remains unclear. Ferroptosis is a newly discovered type of cell death that is caused by a loss of cellular redox homeostasis. As glutathione (GSH) depletion triggers APAP-induced hepatotoxicity, we investigated the role of ferroptosis in a murine model of APAP-induced acute liver failure. APAP-induced hepatotoxicity (evaluated in terms of ALT, AST, and the histopathological score), lipid peroxidation (4-HNE and MDA), and upregulation of the ferroptosis maker PTGS2 mRNA were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1). Fer-1 treatment also completely prevented mortality induced by high-dose APAP. Similarly, APAP-induced hepatotoxicity and lipid peroxidation were prevented by the iron chelator deferoxamine. Using mass spectrometry, we found that lipid peroxides derived from n-6 fatty acids, mainly arachidonic acid, were elevated by APAP, and that auto-oxidation is the predominant mechanism of APAP-derived lipid oxidation. APAP-induced hepatotoxicity was also prevented by genetic inhibition of acyl-CoA synthetase long-chain family member 4 or α-tocopherol supplementation. We found that ferroptosis is responsible for APAP-induced hepatocyte cell death. Our findings provide new insights into the mechanism of APAP-induced hepatotoxicity and suggest that ferroptosis is a potential therapeutic target for APAP-induced acute liver failure.

No abstract

Biliary complications remain a major concern after living donor liver transplantation. We describe a pediatric case who underwent a successful endoscopic balloon dilatation of biliary-enteric stricture following living donor liver transplantation using a newly developed method of enteroscopy. The 7-year-old boy with late biliary stricture of choledochojejunostomy was admitted 6 years after transplantation. Since percutaneous transhepatic cholangiography was technically difficult in this case, endoscopic retrograde cholangiography was performed using a double-balloon enteroscope under general anesthesia. The enteroscope was advanced retrograde through the duodenum, jejunum, and the leg of Roux-Y by the doubleballoon method, and anastomotic stricture of choledochojejunostomy was clearly confirmed by endoscopic retrograde cholangiography and endoscopic direct vision. Balloon dilatation was performed and the anastomosis was expanded. Restenosis was not noted as of 2 years after the treatment. In conclusion, endoscopic balloon dilation of biliary-enteric anastomotic stricture using a new enteroscopic method can be regarded as an alternative choice to percutaneous transhepatic management and surgical re-anatomists. (Liver Transpl 2005;11:1608-1610.)

PLB at two years after LT is an unnecessary examination, because the serum ALT level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding.

LDLT is indicated for a variety of metabolic disorders, primarily in Asian countries due to the absolute scarcity of deceased donor LT. We analyzed data for all pediatric LDLTs performed between November 1989 and December 2010, during which 2224 pediatric patients underwent LDLT in Japan. Of these patients, 194 (8.7%) underwent LDLT for metabolic disorders. Wilson's disease (n = 59; 30.4%) was the most common indication in the patients with metabolic disorders, followed by OTCD (n = 40; 20.6%), MMA (n = 20; 10.3%), and GSD (n = 15; 7.7%). The one-, five-, 10-, and 15-yr patient and graft survival rates were 91.2%, 87.9%, 87.0%, and 79.3%, and 91.2%, 87.9%, 86.1%, and 74.4%, respectively. Wilson's disease and urea cycle deficiency were associated with better patient survival. The use of heterozygous donors demonstrated no negative impact on either the donors or recipients. With regard to X-linked OTCD, symptomatic heterozygote maternal donors should not be considered potential donor candidates. Improving the understanding of the long-term suitability of this treatment modality will require the registration and ongoing evaluation of all patients with inherited metabolic disease considered for LT.

Summary Portal vein stenosis (PVS) after living donor liver transplantation (LDLT) is a serious complication that can lead to graft failure. Few studies of the diagnosis and treatment of late‐onset (≥3 months after liver transplantation) PVS have been reported. One hundred thirty‐three pediatric (median age 7.6 years, range 1.3–26.8 years) LDLT recipients were studied. The patients were followed by Doppler ultrasound (every 3 months) and multidetector helical computed tomography (once a year). Twelve patients were diagnosed with late‐onset PVS 0.5–6.9 years after LDLT. All cases were successfully treated with balloon dilatation. Five cases required multiple treatments. Early diagnosis of late‐onset PVS and interventional radiology therapy treatment may prevent graft loss.