Prevalence and outcomes of patients with sinusoidal obstruction syndrome after liver transplantation: A ten year's experience of a single center in Japan

BackgroundSinusoidal obstruction syndrome (SOS) after liver transplantation (LT) is a rare and potentially lethal complication. We retrospectively reviewed the outcomes of patients with post-transplant SOS.MethodsBetween May 2001 and December 2019, of 332 patients who underwent LT, 5 (1.5%) developed SOS. The median age at LT was 1.7 years (range 0.1–66.5). SOS was histopathologically diagnosed and classified as early-onset (<1 month) or late-onset.ResultsThe median time to diagnosis of SOS was one month after LT. All patients developed acute cellular rejection before SOS, and the cause of SOS was acute cellular rejection in four patients and unknown in one. The treatment of SOS included conversion to tacrolimus from cyclosporine, intrahepatic hepatic vein stent placement, strengthening of immunosuppression, and plasma exchange. The 5-year graft survival rates in patients with and without SOS were 53.0% and 92.5%, respectively (p < 0.001). Of three patients with early-onset SOS, two patients improved and are doing well, and one patient died of graft failure four months after LT.ConclusionsThe cause and treatment of post-transplant SOS are not yet defined. The poor outcomes in patients with early-onset SOS may be improved by strengthening of immunosuppression. Patients with late-onset SOS are ultimately treated by repeat LT.     

Decabromodiphenyl ether-induced PRKACA hypermethylation contributed to glycolipid metabolism disorder via regulating PKA/AMPK pathway in rat and L-02 cells

BDE-209 is the most prevalent congener of polybrominated diphenyl ethers and has high bioaccumulation in humans and animals. BDE-209 has been reported to disrupt glycolipid metabolism, but the mechanisms are still unclear. In this study, we found that BDE-209 induced liver tissue injury and hepatotoxicity, increased the glucose and total cholesterol levels in the serum of rats, and increased glucose and triglyceride levels in L-02 cells. BDE-209 exposure changed the PKA, p-PKA, AMPK, p-AMPK, ACC, and FAS expression in rats’ liver and L-02 cells. Moreover, BDE-209 induced PRKACA-1 hypermethylation in L-02 cells. AMPK activator (AICAR) inhibited the changes of p-AMPK, ACC, and FAS expression and elevation of glucose and triglyceride levels induced by BDE-209. DNA methylation inhibitor (5-Aza-CdR) reversed BDE-209 induced alters of PKA/AMPK/ACC/FAS signaling pathway. These results demonstrated that BDE-209 could disrupt the glycolipid metabolism by causing PRKACA-1 hypermethylation to regulate the PKA/AMPK signaling pathway in hepatocytes.     

Clinical characteristics and survival analysis of liver transplantation in patients with alcoholic liver disease: A single-center retrospective study

ObjectiveBy reviewing the clinical data of liver transplantation in the treatment of alcoholic liver disease in a single center and analyzing the clinical characteristics, the long-term prognosis and main risk factors for early postoperative death were investigated.MethodsThe clinical data of 98 cases of orthotopic liver transplantation performed due to alcoholic liver disease were collected to explore the effect on survival following liver transplants. The patients had been treated in the Organ Transplantation Center of the Tianjin First Central Hospital from November 2011 to November 2020.ResultsThe follow-up duration was 1–108 months. Nine cases died; among these cases, three died during the perioperative period. Univariate analysis revealed that daily ethanol intake, Model for End-Stage Liver Disease (MELD) scores, and preoperative liver failure were associated with perioperative death, and multivariate analysis revealed that daily ethanol intake was an independent risk factor for perioperative death (P = 0.048 < 0.05); the daily intake of ethanol in the death group was significantly higher than that in the survival group (293 ± 11.5 g vs. 178.3 ± 66.8 g, P = 0.004 < 0.05). Six patients died during long-term follow-up. The one-, five-, and nine-year cumulative survival rates were 96.8%, 92.0%, and 92.0%, respectively. Preoperative liver cancer was the main risk factor for long-term survival (ORR = 2884.3, P = 0.041 < 0.05). The primary cause of death was recurrence of malignant liver tumors, followed by new lung malignancies, intracerebral hemorrhage, and hepatic allograft dysfunction.ConclusionAlcoholic liver disease is a good indication for liver transplantation. Heavy daily drinking before an operation increases the risk of perioperative death. Recurrence of malignant liver tumors is the main risk factor affecting long-term survival.     

Highlighting the interaction between immunomodulatory properties of mesenchymal stem cells and signaling pathways contribute to Graft Versus Host Disease management

BackgroundAllogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been increasingly used as a therapeutic approach for hematological malignancies. Several potential strategies have been developed for treating or preventing allo-HSCT complications, specifically graft-versus-host disease (GVHD). GVHD could significantly affect the morbidity and mortality of patients after allo-HSCT. Curative treatment and prophylaxis regimens for GVHD could reduce GVHD incidence and improve survival rate. Among these therapeutic strategies, mesenchymal stem cell (MSCs) mediated immunomodulation has been explored widely in clinical trials. MSCs immunomodulation ability in GVHD correlates with the interactions of MSCs with innate and adaptive immune cells. However, signaling pathways responsible for MSCs' impact on GVHD regulation, like JAK/STAT, NOTCH, MAPK/ERK, and NFκβ signaling pathways, have not been clearly described yet. This review aims to illuminate the effect of MSCs-mediated immunomodulation in GVHD management after allo-HSCT representing the role of MSCs therapy on signaling pathways in GVHD.ConclusionMSCs could potentially modulate immune responses, prevent GVHD, and improve survival after allo-HSCT. Previous studies have investigated different signaling pathways' contributions to MSCs immunoregulatory ability. Accordingly, targeting signaling pathways components involved in MSCs related GVHD regulation is proven to be beneficial.     

Risk factors of early liver dysfunction after liver transplantation using grafts from donation after citizen death donors

BackgroundAs an early complication after liver transplantation, early allograft dysfunction (EAD) indicates a poor prognosis. This study analyzes the risk factors related to early allograft dysfunction (EAD) after liver transplantation using grafts from donation after citizen death (DCD) to provide a reference for the prevention of EAD after DCD liver transplantation.MethodsA total of 32 patients who underwent DCD liver transplantation in the organ transplantation center of our hospital from September 2013 to January 2021 were enrolled in this study. The patients were divided into the EAD group and non-EAD group according to whether they developed EAD after transplantation. The general data of the donors and recipients before transplantation, intraoperative conditions, and clinical data within one week after transplantation were compared between the two groups, and related complications were statistically analyzed. The follow-up time was one week postoperatively or, if they died within the first week postoperatively, until the patient died.ResultsThe subjects included 10 females and 22 males, and the incidence of postoperative EAD was 25% (8/32). Four patients (12%) had primary malignant tumors (primary liver cancer and cholangiocarcinoma), and five donors (15%) had fatty liver. The univariate analysis revealed that the donor BMI (P = 0.005), degree of fatty liver (P = 0.025), aspartate aminotransferase (P = 0.001), alanine aminotransferase (P < 0.001), and total bilirubin (P = 0.009) were related to the occurrence of EAD after DCD liver transplantation. By analyzing the correlation between the incidence EAD and postoperative complications after liver transplantation using grafts from DCD donors, it was shown that the incidence of primary nonfunction (PNF) is related to EAD (P = 0.024).ConclusionDonor BMI, the degree of fatty liver, and preoperative liver function are risk factors for EAD after DCD liver transplantation, and the occurrence of EAD after DCD liver transplantation significantly increases the probability of PNF.     

Evanescing renal allograft cortical necrosis from living donor renal transplantation: A lesson learned over two decades

BackgroundRenal graft cortical necrosis (GCN) is a catastrophic cause of graft failure. We evaluated the incidence, causes, management, and outcome of GCN across two decades from our center.MethodsThis is a retrospective analysis of transplant patients who had biopsy-proven GCN transplanted between 2000 and 2020. The clinical details, immunological workup, induction, maintenance regimen, causes of cortical necrosis, and the outcomes were compared between the first period 2000–2012, and the second period 2013–2020, when Flow cytometric and Luminex based crossmatch were included in the workup plan.ResultsAmong 2333 live ABO-compatible renal transplants, 37 (0.015%) patients (36 patients between 2000 and 2012 and 1 between 2013 and 2020) developed GCN (60% had diffuse and 40% patchy GCN) at a median of 8 days after transplantation.Twenty-six (60%) received ATG, 4 received plasmapheresis and ATG (10.8%) as antirejection therapy. The cyclosporine-based regimen was associated with a higher risk of GCN (RR 2.54; 95% CI 1.26 to 5.12, p = 0.009), whereas tacrolimus-based therapy had a lower risk (RR 0.39; 95% CI 0.19 to 0.79, p = 0.009). The introduction of flow cytometry and DSA assay has significantly decreased the incidence of acute rejection and GCN. Only one patient had GCN during the 2013–2020 period because of graft's mucormycosis. Twenty-five (67.56%) patients had no recovery, and 12 (32.43%) had partial recovery of graft function.ConclusionGCN is mainly associated with rejection, and cyclosporin-based maintenance regimen had a higher incidence. The remarkable decrease in GCN after 2012 onwards could be attributed to the use of Flowcytometry, Luminex-based DSA assays, and tacrolimus-based regimens.     

Evaluation of procalcitonin (PCT) as a marker of infection in early post living donated liver transplant period

Background and aimProcalcitonin (PCT) has been increasingly used as a biomarker of bacterial infection and as a tool to guide antimicrobial therapy. Despite its increased use, data in patients with solid organ transplants are limited.The study aimed to assess the frequency of rising PCT associated with infectious complications in immunosuppressed living donated liver transplantation.MethodsA single-center, retrospective observational study. Preoperative patients' demographic data, operative, anesthetic data, and postoperative clinical course were analyzed post-liver transplant (LT) till discharge from the intensive care unit.ResultsSixty patients were classified according to the culture results' into a positive culture group & a negative one and then followed up the sepsis variables in each group. Total leukocyte count (TLC) was elevated in the positive culture group in comparison to the negative culture one and was statistically significant (P-value <0.05) till the fourth day postoperative. Procalcitonin was higher in the positive culture group than in the negative one on days 1, 3, and 5 postoperative and was statistically significant (P-value <0.05).The cutoff values in the receiver operating characteristic curve (ROC) with >90% specificity to infection post LT were PCT of ≥9 ng/ml and TLC of ≥17.3/mm3 on day one.ConclusionsFollowing up PCT level on day one with TLC is essential and will help to detect sepsis and guide early antimicrobial initiation post-liver transplantation.Combined measurements of PCT and TLC with cutoff values of <9 ng/ml and < 17.3/mm³ respectively will help to exclude infections in 83.7% of patients, thus avoiding unnecessary usage of higher generations empiric antimicrobials.