Weiqiang Ju

Can immune cell function assay identify patients at risk of infection or rejection? A meta-analysis.

Background. The Cylex ImmuKnow cell function assay (CICFA) is being considered as a possible tool for identification of infection and rejection in transplant recipients. However, the predictive capability of CICFA is still unclear. Methods. Herein, we performed a meta-analysis to assess the efficacy of CICFA in identifying risks of infection and rejection posttransplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of CICFA were pooled. Summary receiver operating characteristic curves were used to represent the overall test performance. Results. Nine studies met the inclusion criteria. The pooled estimates for CICFA in identification of infection risk were poor, with a sensitivity of 0.58 (95% confidence interval [CI]: 0.52–0.64), a specificity of 0.69 (95% CI: 0.66–0.70), a positive likelihood ratio of 2.37 (95% CI: 1.90–2.94), a negative likelihood ratio of 0.39 (95% CI: 0.16–0.70), and a diagnostic odds ratio of 7.41 (95% CI: 3.36–16.34). The pooled estimates for CICFA in identifying risk of rejection were also fairly poor with a sensitivity of 0.43 (95% CI: 0.34–0.52), a specificity of 0.75 (95% CI: 0.72–0.78), a positive likelihood ratio of 1.30 (95% CI: 0.74–2.28), a negative likelihood ratio of 0.96 (95% CI: 0.85–1.07), and a diagnostic odds ratio of 1.19 (95% CI: 0.65–2.20). Conclusion. The current evidence suggests that CICFA is not able to identify individuals at risk of infection or rejection. Additional studies are still needed to clarify the usefulness of this test for identifying risks of infection and rejection in transplant recipients.

Down-Regulation of microRNA-26a Promotes Mouse Hepatocyte Proliferation during Liver Regeneration

Background Inadequate liver regeneration (LR) is still an unsolved problem in major liver resection and small-for-size syndrome post-living donor liver transplantation. A number of microRNAs have been shown to play important roles in cell proliferation. Herein, we investigated the role of miR-26a as a pivotal regulator of hepatocyte proliferation in LR. Methodology/Principal Findings Adult male C57BL/6J mice, undergoing 70% partial hepatectomy (PH), were treated with Ad5-anti-miR-26a-LUC or Ad5-miR-26a-LUC or Ad5-LUC vector via portal vein. The animals were subjected to in vivo bioluminescence imaging. Serum and liver samples were collected to test liver function, calculate liver-to-body weight ratio (LBWR), document hepatocyte proliferation (Ki-67 staining), and investigate potential targeted gene expression of miR-26a by quantitative real-time PCR and Western blot. The miR-26a level declined during LR after 70% PH. Down-regulation of miR-26a by anti-miR-26a expression led to enhanced proliferation of hepatocytes, and both LBWR and hepatocyte proliferation (Ki-67+ cells %) showed an increased tendency, while liver damage, indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (T-Bil), was reduced. Furthermore, CCND2 and CCNE2, as possible targeted genes of miR-26a, were up-regulated. In addition, miR-26a over-expression showed converse results. Conclusions/Significance MiR-26a plays crucial role in regulating the proliferative phase of LR, probably by repressing expressions of cell cycle proteins CCND2 and CCNE2. The current study reveals a novel miRNA-mediated regulation pattern during the proliferative phase of LR.

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: A meta-analysis†

Because of the severe organ shortage, living donor liver transplantation (LDLT) offers a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatocellular carcinoma (HCC). However, the higher recurrence rate of HCC after LDLT and the indication criteria remain controversial. By conducting a quantitative meta‐analysis, we sought to compare the survival outcomes and recurrence rates with LDLT and DDLT for patients with HCC. Comparative studies of LDLT and DDLT for HCC, which were identified by a comprehensive literature search, were included in this study. The evaluated outcomes included patient survival, recurrence‐free survival (RFS), and recurrence rates at defined time points. Seven studies with a total of 1310 participants were included in this study. For LDLT and DDLT recipients, we found comparable patient survival rates [1 year, odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.62‐1.73; 3 years, OR = 1.07, 95% CI = 0.77‐1.48; and 5 years, OR = 0.64, 95% CI = 0.33‐1.24] and RFS rates (1 year, OR = 0.86, 95% CI = 0.54‐1.38; 3 years, OR = 1.04, 95% CI = 0.69‐1.58; and 5 years, OR = 1.11, 95% CI = 0.70‐1.77). Moreover, we found no significant differences in the 1‐, 3‐, or 5‐year recurrence rates between LDLT and DDLT recipients (1 year, OR = 1.55, 95% CI = 0.36‐6.58; 3 years, OR = 2.57, 95% CI = 0.53‐12.41; and 5 years, OR = 1.21, 95% CI = 0.44‐3.32). A subgroup analysis revealed similar outcomes for patients with HCC meeting the Milan criteria. These findings demonstrate that for HCC patients (especially those within the Milan criteria), LDLT represents an acceptable option that does not compromise patient survival or increase HCC recurrence in comparison with DDLT. Liver Transpl 18:1226–1236, 2012.

Machine Perfusion versus Cold Storage of Kidneys Derived from Donation after Cardiac Death: A Meta-Analysis

Background In response to the increased organ shortage, organs derived from donation after cardiac death (DCD) donors are becoming an acceptable option once again for clinical use in transplantation. However, transplant outcomes in cases where DCD organs are used are not as favorable as those from donation after brain death or living donors. Different methods of organ preservation are a key factor that may influence the outcomes of DCD kidney transplantation. Methods We compared the transplant outcomes in patients receiving DCD kidneys preserved by machine perfusion (MP) or by static cold storage (CS) preservation by conducting a meta-analysis. The MEDLINE, EMBASE and Cochrane Library databases were searched. All studies reporting outcomes for MP versus CS preserved DCD kidneys were further considered for inclusion in this meta-analysis. Odds ratios and 95% confidence intervals (CI) were calculated to compare the pooled data between groups that were transplanted with kidneys that were preserved by MP or CS. Results Four prospective, randomized, controlled trials, involving 175 MP and 176 CS preserved DCD kidney transplant recipients, were included. MP preserved DCD kidney transplant recipients had a decreased incidence of delayed graft function (DGF) with an odd ration of 0.56 (95% CI = 0.36–0.86, P = 0.008) compared to CS. However, no significant differences were seen between the two technologies in incidence of primary non-function, one year graft survival, or one year patient survival. Conclusions MP preservation of DCD kidneys is superior to CS in terms of reducing DGF rate post-transplant. However, primary non-function, one year graft survival, and one year patient survival were not affected by the use of MP or CS for preservation.

The development and function of follicular helper T cells in immune responses

Follicular helper T cells (Tfh) have been referred as a lineage that provides a help for B cells to proliferate and undergo antibody affinity maturation in the germinal center. Evidence has supported that Tfh subset development, like other lineages, is dependent on microenvironment where a particular transcriptional program is initiated. It has been shown that Bcl-6 and IL-21 act as master regulators for the development and function of Tfh cells. Tfh dysregulation is involved in the development of autoimmune pathologies, such as systemic lupus erythematosus, rheumatoid arthritis and other autoimmune diseases. The present review highlights the recent advances in the field of Tfh cells and focus on their development and function.

The first case of ischemia-free organ transplantation in humans: A proof of concept

Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post‐transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia‐free organ transplantation (IFOT) for patients with end‐stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25‐year‐old man. The recipient was a 51‐year‐old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved, and implanted under continuous normothermic machine perfusion. The recipient did not suffer post‐reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post‐transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, or vascular or biliary complications occurred. The patient was discharged on day 18 post‐transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization.

Adjuvant chemotherapy for patients with primary hepatocellular carcinoma: a meta-analysis.

Numerous studies have investigated the effects of adjuvant chemotherapy for primary hepatocellular carcinoma (HCC) patients. We conducted this analysis to evaluate the efficacy of adjuvant chemotherapy in HCC patients after hepatectomy. PubMed/MEDLINE, EMBASE, Cochrane, and other databases were searched for eligible studies. The major endpoints were overall survival (OS) and disease‐free survival (DFS). The pooled odds ratio (OR) was calculated using a random‐effects model to summarize the results. In the meta‐analysis of 13 randomized control trials (RCTs) and 35 observational studies with 4747 patients, hepatectomy plus adjuvant chemotherapy showed superiority over hepatectomy alone in 1‐year DFS (OR = 1.86, 1.38–2.51, p < 0.001), 3‐year DFS (OR = 2.37, 1.73–3.24, p < 0.001) and 5‐year DFS (OR = 1.99, 1.55–2.55, p < 0.001), as well as 1‐year OS (OR = 2.16, 95% confidence interval 1.75–2.68, p < 0.001), 3‐year OS (OR = 1.77, 1.48–2.13, p < 0.001) and 5‐year OS (OR = 1.92, 1.44–2.56, p < 0.001). Subgroup and sensitivity analysis revealed that only adjuvant TACE had significant survival benefits. The meta‐analysis of studies involving patients with portal vein tumor thrombus (PVTT), but not other factors related to recurrence risk, revealed favorable outcomes of the Treatment arm over the Control arm. The present study shows that adjuvant chemotherapy can improve outcomes for HCC patients. The benefits of adjuvant TACE have been confirmed whereas the effects of other adjuvant chemotherapy modalities remain uncertain. Adjuvant chemotherapy is likely to be more applicable to certain patient populations for instance those with PVTT, but further research in identifying these patient factors is of importance for tailoring adjuvant therapies to individual patients in the future.

Allografts positive for hepatitis B surface antigen in liver transplant for disease related to hepatitis B virus.

OBJECTIVES Liver grafts from hepatitis B surface antigen-negative and anti-core antibody-positive donors are safe for liver transplant. However, the use of hepatitis B surface antigen-positive liver donors in liver transplants is controversial. We assessed the safety and effectiveness of liver transplants using hepatitis B surface antigen-positive liver grafts to patients with diseases related to hepatitis B virus. MATERIALS AND METHODS We retrospectively reviewed 23 patients who had a deceased-donor liver transplant using hepatitis B surface antigen-positive liver grafts. All patients had end-stage liver disease secondary to hepatitis B virus infection. Recipients had oral entecavir and intravenous or intramuscular injection of hepatitis B immune globulin for >1 year after the transplant. RESULTS Two patients died from severe perioperative pneumonia, and the other 21 patients were followed for 9 to 38 months after transplant. All 21 patients remained hepatitis B surface antigen-positive. A repeat liver transplant was performed in 1 patient at 5 months after the initial transplant because of biliary ischemia. There were 3 patients who died from recurrent liver cancer at 9, 14, and 18 months after transplant. There were 18 patients (78%) who survived and 17 grafts (74%) that survived. CONCLUSIONS Liver transplant using hepatitis B surface antigen-positive liver grafts is safe for patients with end-stage liver disease secondary to hepatitis B virus infection.

Prognostic significance of preoperative aspartate aminotransferase to neutrophil ratio index in patients with hepatocellular carcinoma after hepatic resection

Objectives Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC), and neutrophils display important roles. However, few studies have illuminated the relationship between preoperative aspartate aminotransferase (AST) to neutrophil ratio index (ANRI) and poor prognosis of HCC. We aimed to clarify the prognostic value of ANRI and evaluate the ability of different inflammation-based prognostic scores such as ANRI, AST to lymphocyte ratio index (ALRI), AST to platelet count ratio index (APRI), neutrophil-lymphocyte ratio index (NLR), and platelet-lymphocyte ratio index (PLR). Methods Data were collected retrospectively from 303 patients who underwent curative resection for HCC. Preoperative ANRI, ALRI, APRI, NLR, PLR and clinico-pathological variables were analyzed. Univariate, multivariate and Kaplan-Meier analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). Results ANRI was correlated with presence of HBsAg, AST, presence of cirrhosis, tumor size, PVTT, cancer of the liver Italian program (CLIP) score, recurrence. Univariate analysis showed ANRI, ALRI, APRI, NLR, PLR were significantly associated with DFS and OS in HCC patients with curative resection. After multivariate analysis, ANRI was demonstrated to be superior to ALRI, APRI, NLR, PLR, which were independently correlated with DFS and OS. Survival analysis showed that preoperative ANRI > 7.8 predicted poor prognosis of patients with HCC after hepatectomy. preoperative ANRI also showed different prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of ANRI and NLR. Conclusions preoperative ANRI is an independent effective predictor of prognosis for patients with HCC, higher levels of ANRI predict poorer outcomes and the combining ANRI and NLR increases the prognostic accuracy of testing.

ABO‐incompatible liver transplantation for severe hepatitis B patients

Effect of ABO‐incompatible liver transplantation on patients with severe hepatitis B (SHB) remains unclear. Herein, we summarized 22 cases with SHB in whom were performed emergency liver transplantation from ABO‐incompatible donors. The immunosuppressive protocol consisted basiliximab, tacrolimus, steroids and mycophenolate mofetil. The mean MELD score was 35.2 ± 7.1. Major complications included rejection, infections, biliary complications, hepatic artery thrombosis or stenosis and portal vein thrombosis. Patient survival rates were 40.9%, 78.9% and 82.3% in 1 year, 29.2%, 66.8% and 72.9% in 3 years, and 21.9%, 60.1% and 62.5% in 5 years for ABO‐incompatible, ABO‐compatible and ABO‐identical groups. Graft survival rates were 39%, 78.9% and 82.3% in 1 year, 27.8%, 66.4% and 71.1% in 3 years, and 20.9%, 57.9% and 61.0% in 5 years for incompatible, compatible and identical ABO graft‐recipient match. The 1‐, 3‐, 5‐year graft and patient survival rates of ABO‐incompatible were distinctly lower than that of ABO‐compatible group (P < 0.05). Our results suggested that ABO‐incompatible liver transplantation might be a life‐saving procedure for patients with SHB as a promising alternative operation when ABO‐compatible donors are not available and at least bridges the second opportunity for liver retransplantation.