Xiaogang Zhang

Mycobacterium tuberculosis Infection in Solid Organ Transplant Recipients : Experience From a Single Center in China

OBJECTIVE We sought to explore the prevalence, clinical manifestations, diagnostic procedures, and treatment of tuberculosis (TB) after solid organ transplantation. PATIENTS AND METHODS In this study, we retrospectively analyzed data of 1947 renal transplant recipients and 85 liver transplant recipients. RESULTS TB developed in 28 organ transplant recipients with a prevalence of 1.38% (28/2032). The median interval between transplantation and development of TB was 32 months (range, 1-142 months). Mycobacterium tuberculosis isolation, histologic signs of caseating granulomas, and TB-DNA detection directly supported the diagnosis in 10 (35.71%), 7 (25.00%), and 5 (17.86%) patients, respectively. In addition, 6 patients (21.43%) highly suspected of TB infection received tentative antituberculosis treatment with favorable responses. Most renal transplant recipients (22/25; 78.57%) received isoniazid, rifampicin (or rifabutin), and ethambutal (or pyrazinamide) for a mean duration of 10 months (range, 6-14 months). Three liver transplant recipients received a different protocol: isoniazid, rifabutin, ethambutal, and ofloxacin for 3 months; then isoniazid and rifabutin for 6 months. Upon follow-up, 8 subjects (28.57%) died; 5 of the deaths were related to TB. During the antituberculosis therapy, toxic hepatitis was seen in 12 patients (42.86%); cyclosporine levels decreased in 15 patients (53.57%); and allograft rejection developed in 6 of them. CONCLUSIONS The peak incidences of TB in liver and kidney transplantations are in the first year and after the first year posttransplantation, respectively. Response to antituberculosis treatment should be considered to make a diagnosis among patients highly suspected of TB infections. Except in special circumstances, antituberculosis treatment protocols including isoniazid and rifampicin for about 10 months seem significantly effective and tolerable for non-liver transplant patients. Fluoroquinolones should be emphasized in posttransplantation TB treatment.

Prognosis evaluation in alpha-fetoprotein negative hepatocellular carcinoma after hepatectomy: Comparison of five staging systems

AIMS Alpha-fetoprotein (AFP) loses its potentials in treatment evaluation and prognosis prediction in patients with AFP negative (<or=20 ng/ml) hepatocellular carcinoma (HCC). The present study was to identify the risk factors affecting postoperative survival of AFP negative patients and to determine the optimal staging system in predicting the survival of these patients. METHODS The data of 306 in total and 98 AFP negative patients amongst were retrospectively reviewed. The risk factors affecting survivals of the patients were identified. And various staging systems were compared, including the sixth tumor node metastasis (TNM) system, Okuda staging, Cancer of the Liver Italian Program (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, and the Japan Integrated Staging (JIS) score. RESULTS AFP negative patients tended to have intact tumor capsule and earlier staged tumor by TNM, CLIP and BCLC. The independent risk factors worsening overall survival of AFP negative patients were absence of tumor capsule, Child-Pugh classification B, hepatitis B surface antigen positive and BCLC stage B-C. The risk factors promoting tumor recurrence were tumor size of >3 cm, distribution in two lobes, Okuda stage B-C and BCLC stage B-C. CONCLUSION Normal AFP level implies earlier staged tumors. BCLC has the strongest potential in prognosis evaluation in AFP negative patients.

Therapeutic liver repopulation for metabolic liver diseases: Advances from bench to bedside

Metabolic liver diseases are characterized by inherited defects in hepatic enzymes or other proteins with metabolic functions. Therapeutic liver repopulation (TLR), an approach of massive liver replacement by transplanted normal hepatocytes, could be used to provide the missing metabolic function elegantly. However, partial and transient correction of the underlying metabolic defects due to very few integrated donor cell mass remains the major obstacle for the effective and widespread use of this approach. Little engraftment and proliferation insufficiency lead to the poor outcome. This article reviews the advances in the mechanisms of initial engraftment and selective proliferation and suggests some effective treatment strategies, from pharmacological preconditioning to stem cell transplantation, to optimize liver repopulation with liver cell transplantation. Enhancing cell viability and plating efficiency, increasing sinusoidal spaces, regulation of sinusoidal endothelial cell barrier and controlling inflammatory reaction may promote initial cell engraftment. Liver‐directed irradiation, reversible portal vein embolization and fetal liver stem/progenitor cell transplantation induce preferential proliferation of donor cells substantially without severe side‐effects. Furthermore, it seems better to use combined approaches to achieve a high level of liver repopulation for the management of metabolic liver diseases.

Cigarette smoking increases risk of early morbidity after hepatic resection in patients with hepatocellular carcinoma

AIMS Cigarette smoking is an important risk factor for the development of postoperative pulmonary complications after major surgical procedures. The objective of this study was to investigate whether preoperative smoking has any impact on early morbidity after liver resection for hepatocellular carcinoma (HCC). METHODS Data of 425 consecutive patients undergoing partial hepatectomy for HCC was retrospectively reviewed. Smoking and drinking habits, biochemical tests, tumor status, operation data, and any postoperative complications occurring before discharge from the hospital were documented. The risk factors promoting postoperative complications were analyzed by univariate and multivariate methods. RESULTS The overall morbidity rate was 40% (170 of 425). 166 patients were current smokers (39%). By multivariate analysis, liver cirrhosis (Risk Ratio (RR) 4.0, 95% confidence interval (CI) 2.0-8.0), smoking status (RR 3.0, 95% CI 1.7-5.1), PY of smoking (RR 1.3, 95% CI 1.1-1.9), preoperative platelet count (RR 1.6, 95% CI 1.4-2.0) and major hepatectomy (RR 1.4, 95% CI 1.1-1.8) were independent risk factors of postoperative morbidity (all p < 0.05). Liver failure, bile leakage, intractable ascites, chest and wound infection were more frequently occurred in smokers than non-smokers. Current smokers had higher postoperative morbidity than non- & former smokers in patients with normal liver and those with liver cirrhosis (p = 0.047 and p < 0.001, respectively). CONCLUSIONS Cigarette smoking is an independent risk factor for the development of liver-related and infectious complications in patients undergoing partial hepatectomy for HCC, especially in those with liver cirrhosis.

The FIB-4 score predicts postoperative short-term outcomes of hepatocellular carcinoma fulfilling the milan criteria.

BACKGROUND The fibrosis score 4 (FIB-4) score is a useful tool to determine the degree of hepatic fibrosis. Liver fibrosis and cirrhosis are well-known predictors of postoperative complications after hepatectomy. This study examined the impact of FIB-4 on postoperative short-term outcomes of patients with hepatocellular carcinoma (HCC). METHODS Three hundred and fifty patients undergoing hepatectomy for HCC between 2008 and 2013 were enrolled. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the FIB-4. Univariate and multivariate analysis was performed to identify the risk factors. The correlation of the preoperative FIB-4 value with clinicopathological parameters was examined. RESULTS Postoperative complications were observed in 202 (57.7%) patients. The optimal cutoff value of the FIB-4 was set at 2.88 and 3.85 for postoperative complications and intraoperative blood loss respectively. It was also an independent prognostic factor for postoperative complications (hazard ratio [HR], 1.202; 95% CI, 1.076-1.344; P = 0.001) and intraoperative blood loss (HR, 1.196; 95% CI, 1.091-1.343; P < 0.001) by multivariate analysis. The FIB-4 was significantly correlated with age, liver function, coagulation function, blood loss, intraoperative blood transfusion (all P < 0.05). CONCLUSION Preoperative FIB-4 is a useful index to predict postoperative outcomes in patients with HCC. The FIB-4 should be assessed routinely for hepatocellular carcinoma patients.

Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors: Three Case Reports.

AbstractDevelopment of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately.Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation.Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well.DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed.

Characteristics of fecal microbial communities in patients with non-anastomotic biliary strictures after liver transplantation

AIM To explore the possible relationship between fecal microbial communities and non-anastomotic stricture (NAS) after liver transplantation (LT). METHODS A total of 30 subjects including 10 patients with NAS, 10 patients with no complications after LT, and 10 non-LT healthy individuals were enrolled. Fecal microbial communities were assessed by the 16S rRNA gene sequencing technology. RESULTS Different from the uncomplicated and healthy groups, unbalanced fecal bacterium ratio existed in patients with NAS after LT. The results showed that NAS patients were associated with a decrease of Firmicutes and Bacteroidetes and an increase of Proteobacteria at the phylum level, with the proportion-ratio imbalance between potential pathogenic families including Enterococcaceae, Streptococcaceae, Enterobacteriaceae, Pseudomonadaceae and dominant families including Bacteroidaceae. CONCLUSION The compositional shifts of the increase of potential pathogenic bacteria as well as the decrease of dominant bacteria might contribute to the incidence of NAS.

Induction of renal artery hyperresponsiveness by alpha1-adrenoceptor in hepatorenal syndrome

Objective To investigate the potential role of alpha1-adrenoceptor (α1-AR) in the pathogenesis of hepatorenal syndrome. Methods Hepatorenal syndrome was induced in male rats by intraperitoneal injection of D-galactosamine and orally treatment with α1-AR antagonist tamsulosin. Hyperresponsiveness of the renal artery contraction was evaluated by the laser-Doppler flowmetry and multimyograph system, while renal blood flow (cortical and medullary perfusion) was simultaneously measured. Renal artery ring segment tone was recorded with the myograph system, and concentration-response curves were obtained by cumulative administration of agonists. Results This model developed acute renal and liver failure without renal damage in pathology, accompanied by significant hyperresponsiveness of renal artery contraction. After hepatorenal syndrome, plasma concentrations of tumor necrosis factor-α increased by two-fold, and α1-AR was significantly activated in the renal artery. Concentration-dependent vasoconstriction induced by noradrenaline was significantly decreased in the renal arteries of hepatorenal syndrome rat because of gradually decreased renal blood flow. Administration of tamsulosin prevented renal failure when given before the onset of liver injury, but it had no effect on liver injury by itself. Conclusion α1-AR expression is positively associated with renal vasoconstriction induced by renal artery hyperresponsiveness in HRS. Therefore, α1-AR may be a potential target in the treatment of HRS.

Choledochoduodenostomy as an Alternative to Choledochojejunostomy for Biliary Reconstruction in Liver Transplantation

We read with interest the article by Bennet et al., who advocated the use of choledochoduodenostomy (CDD) as an alternative method of achieving biliary drainage of the transplanted liver [1]. Although Wigmore had written a commentary for this article [2], we still have the following concerns. First, the criteria for entry in this study were not clear, particularly concerning the selection for those patients who underwent CDD or choledochoenterostomy. From the context of the article, the subjects for this study were not selected for CDD or choledochoenterostomy randomly. We think the selected criteria may influence the effects of the operations. The authors noted that no patient during followup had any anastomotic strictures or significant reflux and subsequent cholangitis. Were there any symptoms or signs suggesting partial reflux or stricture of the anastomosis during the postoperative period? Did the authors provide some interference? Second, a previous study showed that the postoperative recurrent cholangitis caused by CDD was observed mainly in patients with a narrow common bile duct (CBD) [3]. However, most CBDs in liver donors are in physiological condition, the diameters of which are less than those stated in the criteria. In their article, Bennett et al. noted that no patient during follow-up had subsequent cholangitis after the CDD. Just as the authors declaimed their brief followup may be a reason, we want to know whether they made some modification in the operative procedure that might lower the incidence of cholangitis. Third, we discovered that the line drawings of the CDD may be not precise. The remaining biliary tract of the donor was too long, which may cause necrosis of the proximal biliary tract due to a limited blood supply. Although these problems are minor, they may cause misconceptions by the readers.

Response of the xenograft endothelium in the concordant xenotransplantation

Abstract Objective To investigate the response of the xenograft endothelium in the concordant hamster to rat cardiac xenotransplantation and the mechanism of acute vascular rejection. Methods The animals were divided into 5 groups randomly: control group. CsA group, splenectomy group, D0 splenectomy+CsA group and D3 splenectomy+CsA group. Hamster heart was heterotopicaly transplanted to rat abdominal cavity. The graft survival was monitored by palpation of the rat abdominal wall. The histological and ultrastructural changes of the xenogafts were investigated. NF-κB and P-selectin expression in the xenograft were detected. Heme Oxigenase-1 and Bcl-2 expression were also detected in the xenografts of different groups. Results The mean survival time of the xenografts in control group, CsA group, splenectomy group, D0 splenectomy+CsA group and D3 splenectomy+CsA group was 3.4 ± 0.55, 3.8 ± 0.45, 6.4 ± 1.52, 30 and 7.4 ± 1.14 days. The rejected graft showed typical acute vascular rejection in control group, CsA group, splenectomy group and D3 splenectomy+CsA group. Fndothelial cells of the rejected xenograft showed dramatic assembly of ribosomes and expansion of the rough endoplasmic reticulum. However, the endothelium of the long-term survived grafts in D0 splenectomy+CsA group showed normal architecture. NF-κB and P-selectin expression were detected in the rejected xenografts. HO-1 expression was observed in the long-term survived xenografts in D0 splenectomy+CsA group. Conclusion The endothelial cells of the xenograft might be activated during the acute vascular rejection. Expression of HO-1 might inhibit the upregulation of NF-κB and adhesion molecular which decreases the activation of the endothelium of the graft.