Clinical analysis of Wernicke encephalopathy after liver transplantation

Background:Wernicke encephalopathy(WE)is an acute neurological disease resulting from vitamin B1 deficiency,and there are only very few case reports of WE after liver transplantation.The present study aimed to investigate the clinical characteristics,etiology,magnetic resonance imaging(MRI)features,treatment and prognosis of patients with WE after liver transplantation.Methods:Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital,Zhejiang University School of Medicine and Jiangxi Provincial People’s Hospital between January 2011 and December 2021 were retrospectively analyzed.Results:Among the 23 patients diagnosed with WE after liver transplantation,6(26%)had a classic triad of impaired consciousness,oculomotor palsy and ataxia,and 17(74%)had two features.The misdiagno-sis rate was 65%.After treatment with high-dose vitamin B1,19(83%)patients showed improvement,whereas 4(17%)showed no improvement,including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia.Conclusions:The misdiagnosis rate is high in the early stage of WE,and the prognosis is closely asso-ciated with whether WE is diagnosed early and treated timely.High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment.Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.

Optimized postconditioning algorithm protects liver graft after liver transplantation in rats

Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.

Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation

Acute cellular rejection(ACR) remains a major concern after liver transplantation.Predicting and monitoring acute rejection by non-invasive methods are very important for guiding the use of immunosuppressive drugs.Many studies have shown that exosomes and their contents are potential biomarkers for various liver diseases.Here,we identify and validate the role of exosomes and galectin-9 in ACR after liver transplantation.Exosomes were isolated from three sets of paired patients,with and without ACR,and the proteins within the exosomes were isolated and identified.Candidate proteins were then validated using a tissue microarray containing resected liver samples from 73 ACR and 63 non-rejection patients.Finally,protein expression and clinical manifestations were included in KaplanMeier survival and Cox regression analyses.Circulating exosomes were isolated from ACR and non-rejection patients and characterized using transmission electron microscopy and western blotting for CD63/CD81.Western blotting experiments revealed higher levels of galectin-9 protein in circulating exosomes from ACR recipients.Immunohistochemical analysis of the tissue microarray showed that the expression of galectin-9 in resected liver was significantly higher in the ACR group than in the non-rejection group(P<0.05).Higher levels of galectin-9 expression in resected livers were associated with poorer prognosis(P<0.05).Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.

Early allograft dysfunction after liver transplantation with donation after cardiac death donors

Liver transplantation(LT)is recognized as one of theeffective approaches for end-stage liver diseases,and earlyallograft dysfunction(EAD)is a frequent complication afterLT,which is always associated with higher morbidity andmortality.