A Non-Linear Relationship between Preoperative Total Bilirubin Level and Postoperative Delirium Incidence after Liver Transplantation.

This study aimed to explore the correlation between preoperative total bilirubin (TBil) level and postoperative delirium (POD) in orthotopic liver transplantation (OLT). All the OLT consecutively performed between April 2019 and March 2021 were retrospectively reviewed with data retrieved from a prospectively collected database. Logistic regression model and generalized additive model were used to identify both linear and non-linear relationships between TBil and POD. A two-piecewise regression model was performed to calculate the saturation effect. Subgroup analyses were performed using stratified logistic regression models. A total of 402 recipients were enrolled. After fully adjusted for covariates, TBil was indicated to have a non-linear relationship with POD. The two-piecewise regression model showed the inflection point was 20 mg/dL. On the left side of the inflection point, the incidence of POD increased by 5% per 1 mg/dL increment of TBil (p = 0.026). On the right side of the inflection point, the effect size had no statistical significance (OR, 0.97; 95% CI, 0.90-1.05; p = 0.482). The relationship between preoperative TBil level and POD incidence is non-linear in OLT recipients. The incidence of POD is positively correlated with TBil level when it is below 20 mg/dL. A saturation effect is observed when TBil level reaches 20 mg/dL.

Safety and efficacy of an integrated endovascular treatment strategy for early hepatic artery occlusion after liver transplantation.

BACKGROUND: Hepatic artery occlusion (HAO) after liver transplantation (LT) is typically comprised of hepatic artery thrombosis (HAT) and stenosis (HAS), both of which are severe complications that coexist and interdependent. This study aimed to evaluate an integrated endovascular treatment (EVT) strategy for the resolution of early HAO and identify the risk factors associated with early HAO as well as the procedural challenge encountered in the treatment strategy. METHODS: Consecutive orthotopic LT recipients (n = 366) who underwent transplantation between June 2017 and December 2018 were retrospectively investigated. EVT was performed using an integrated strategy that involved thrombolytic therapy, shunt artery embolization plus vasodilator therapy, percutaneous transluminal angioplasty, and/or stent placement. Simple EVT was defined as the clinical resolution of HAO by one round of EVT with thrombolytic therapy and/or shunt artery embolization plus vasodilator therapy. Otherwise, it was defined as complex EVT. RESULTS: Twenty-six patients (median age 52 years) underwent EVT for early HAO that occurred within 30 days post-LT. The median interval from LT to EVT was 7 (6-16) days. Revascularization time (OR = 1.027; 95% CI: 1.005-1.050; P = 0.018) and the need for conduit (OR = 3.558; 95% CI: 1.241-10.203, P = 0.018) were independent predictors for early HAO. HAT was diagnosed in eight patients, and four out of those presented with concomitant HAS. We achieved 100% technical success and recanalization by performing simple EVT in 19 patients (3 HAT+/HAS- and 16 HAT-/HAS+) and by performing complex EVT in seven patients (1 HAT+/HAS-, 4 HAT+/HAS+, and 2 HAT-/HAS+), without major complications. The primary assisted patency rates at 1, 6, and 12 months were all 100%. The cumulative overall survival rates at 1, 6, and 12 months were 88.5%, 88.5%, and 80.8%, respectively. Autologous transfusion < 600 mL (94.74% vs. 42.86%, P = 0.010) and interrupted suture for hepatic artery anastomosis (78.95% vs. 14.29%, P = 0.005) were more prevalent in simple EVT. CONCLUSIONS: The integrated EVT strategy was a feasible approach providing effective resolution with excellent safety for early HAO after LT. Appropriate autologous transfusion and interrupted suture technique helped simplify EVT.

Lower tacrolimus trough levels in the late period after living donor liver transplantation contribute to improvements in long-term clinical outcomes.

BACKGROUND: Previous studies have emphasized the need to reduce tacrolimus (TAC) trough levels in the early post-liver transplantation (LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear. METHODS: We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: < 3 ng/mL group, 3-5 ng/mL group, and  >5 ng/mL group. The complications and adverse effects of TAC were analyzed. RESULTS: Each group showed similar rejection, graft loss and mortality. Patients achieved the < 5 ng/mL state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups. CONCLUSIONS: Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.

Pyogenic liver abscess related to intrahepatic bile duct stones: Difficulties in infectious control and diagnosis of concomitant cholangiocarcinoma.

BACKGROUND AND AIM: Cholangitis, bacteremia, and pyogenic liver abscess (PLA) can be often caused by intrahepatic bile ducts stone (IBDS), which is endemic to South-East Asia. The association between IBDS and cholangiocarcinoma has been well recognized. Concomitant cholangiocarcinoma in the PLA related to IBDS is often missed. METHODS: A case-control study consisting of 64 patients with PLA related to IBDS and 256 control patients with PLA not related to IBDS was used to investigate clinical features of PLA and incidence of concomitant cholangiocarcinoma in patients with PLA related to IBDS. RESULTS: The main imaging manifestations of PLA related to IBDS was cystic-solid lesions and solid lesions. Of seven patients (10.9%) with pathology-proven cholangiocarcinoma in the same area of PLA related to IBDS among 64 patients, only two patients were initially diagnosed as having concomitant cholangiocarcinoma by biopsy, and other five patients diagnosed as acute inflammatory lesion. Within 60 days after onset, the infection-related death rate and recurrence rate in patients with PLA related to IBDS were 12.9% and 20.3%, respectively, whereas in patients with PLA not related to IBDS were 3.9% and 3.1%, respectively. Only 25% of patients with PLA related to IBDS underwent surgery after admission. The main pathogens in PLA patients related to IBDS were Escherichia coli and extended-spectrum beta-lactamase-producing Enterobacteriaceae. CONCLUSIONS: The imaging manifestations of PLA related to IBDS often present cystic-solid or solid lesions. PLA related to IBDS is characterized by high rate of recurrence and infection-related death, difficulty in diagnosis of concomitant cholangicarcinoma.

Current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation.

BACKGROUND: Liver transplantation is the optimal treatment for a selected group of patients with moderate to severe cirrhosis and hepatocellular carcinoma (HCC). Despite the strict selection of candidates, post-transplant recurrence often occurs and markedly reduces the long-term survival of patients with HCC. The present review focuses on the current strategies on preventing the recurrence of HCC after liver transplantation. DATA SOURCES: Relevant articles were identified by extensive searching of PubMed using the keywords "hepatocellular carcinoma", "recurrence" and "liver transplantation" between January 1996 and January 2014. Additional papers were searched manually from the references in key articles. RESULTS: The current theories of HCC recurrence after liver transplantation are: (i) the growth of pre-transplant occult metastases; (ii) the engraftment of circulating tumor cells released at the time of transplantation. Pre-transplant treatment aims to control local tumor by radiofrequency ablation, transarterial embolization and transarterial chemoembolization. The main objective during the operation is to prevent tumor cell dissemination. Post-transplant treatment includes systemic anticancer therapy, antiviral therapy, and most recently, immunotherapy. These strategies concentrate on the control of the tumor when the patients are waiting for transplant, to reduce the release of HCC cells during surgical procedures and to clear the occult HCC cells after transplantation. CONCLUSIONS: Much can be done to prevent HCC recurrence after liver transplantation. In future, effort is likely to be directed towards combining multidisciplinary approaches and various treatment modalities.

A modified protocol with rituximab and intravenous immunoglobulin in emergent ABO-incompatible liver transplantation for acute liver failure.

BACKGROUND: The established procedure for ABO-incompatible liver transplantation (ABO-I LT) was too complicated to be used in case of emergency. We developed a protocol consisting of rituximab and intravenous immunoglobulin (IVIG) for ABO-I LT in patients with acute liver failure (ALF). METHODS: The data from 101 patients who had undergone liver transplantation (LT) for ALF were retrospectively analyzed. The patients were divided into two groups: ABO-compatible liver transplantation group (ABO-C LT, n=66) and ABO-I LT group (n=35). All the patients in the ABO-I LT group received a single dose of rituximab (375 mg/m2) and IVIG (0.4 g/kg per day) at the beginning of the operation. IVIG was administered for 10 consecutive days after LT. Plasma exchange, splenectomy and graft local infusion were omitted in the protocol. Quadruple immunosuppressive therapy including basiliximab, corticosteroids, tacrolimus and mycophenolatemofetil was used to reinforce immunosuppression. RESULTS: The 3-year cumulative patient survival rates in the ABO-I LT and ABO-C LT groups were 83.1% and 86.3%, respectively (P>0.05), and the graft survival rates were 80.0% and 86.3%, respectively (P>0.05). Two patients (5.7%) suffered from antibody-mediated rejection in the ABO-I LT group. Other complications such as acute cellular rejection, biliary complication and infection displayed no significant differences between the two groups. CONCLUSIONS: The simplified treatment consisting of rituximab and IVIG prevented antibody-mediated rejection for LT of blood-type incompatible patients. With this treatment, the patients did not need plasma exchange, splenectomy and graft local infusion. This treatment was safe and efficient for LT of the patients with ALF.

Neuroprotective compounds from the bulbs of Lycoris radiata.

Three new alkaloids (1-3) and one new phenolic glycoside (4), together with twenty five known alkaloids (5-29), were isolated from the bulbs of Lycoris radiata collected from Huaihua county of Hunan province, China. Their structures were elucidated on the basis of comprehensive NMR and MS spectroscopic analysis. The isolated alkaloids were evaluated for their neuroprotective activities against CoCl2, H2O2 and Aß(25-35)-induced SH-SY5Y cell injuries. Compounds 1-3 showed significant neuroprotective effects against H2O2 or CoCl2-induced SH-SY5Y cell death, while compound 3 exhibited significant neuroprotective effects against Aß(25-35)-induced SH-SY5Y cell injury. The known alkaloids 5-29 also exhibited similar bioactivities of different degrees. These findings highlight the fact that the over 100 Amaryllidaceae alkaloids may have a big potential to neuroprotective activity.

[The study on the relationship between expression of B7-H1 on HBV transgenic mice and immune tolerance to HBV].

OBJECTIVE: To investigate whether there is an association between the expression of B7-H1 in HBV transgenic mice and the immune tolerance to HBV. METHODS: T cells stimulatory capacity of DC was analyzed using mixed lymphocyte reaction. Expression of MHC-II, CD80, CD86, B7-H1 on DC was detected by Flow Cytometry. IL-2, IFNgamma, IL-10 production of T cells were determined by using ELISA. B7-H1 mRNA and protein expression in liver tissue were detected by RT-PCR and Western blotting respectively. RESULTS: The ability of DC cells from HBV transgenic mice to stimulate T cell proliferation was significantly impaired compared with DC cells from control mice (t = 16.674, 19.674, 21.712, P less than 0.01). Expression of MHC-II, CD80 on DC was markedly decreased in transgenic mice (t = 7.910, 6.413, P less than 0.05). Meanwhile, the expression of CD86 and B7-H1 on DC cells in HBV transgenic mice were not significantly different from that in control mice. The levels of IL-2, IFNgamma, IL-10 in supernatant of T cells was significantly lower compared with controls (t = 18.712, 18.712 and 11.683, P less than 0.05). There was no significant difference in B7-H1 expression at mRNA and protein levels in liver tissue compared with controls. CONCLUSIONS: Functional defect of DC, partly due to decreased expression of MHC-II, CD80, but not related to B7-H1 expression, is the cause for immune tolerance to HBV in HBV transgenic mice.