Weihang Ma

Genetic variation within the glycoprotein B and H genes of human cytomegalovirus in solid organ transplant recipients.

Abstract: This study was performed to investigate human cytomegalovirus (HCMV) infection and genetic variations within glycoprotein B (gB) and H (gH) genes in Chinese transplant recipients. A total of 245 ethylene‐diamine tetraacetic acid (EDTA)‐treated blood samples were obtained from 79 transplant recipients in southeast China. Based on the sequences of highly variable regions of the gB endoprotease cleavage site (gBclv), N‐terminus of gp116 (gBn), and the gH N‐terminus (gH), nested polymerase chain reaction assays for the detection of HCMV were established. Nucleotide sequencing was employed to differentiate gB and gH genotypes. Twenty‐six of 79 (32.9%) transplant recipients were proved HCMV positive. The distribution of genotypes was gBclv1, 12/25; gBclv2, 3/25; gBclv3, 4/25; gBn1, 6/23; gBn2, 2/23; gBn3, 11/23; and no gBclv/n 4‐related genotypes were presented. The distribution of gH genotypes was gH1, 11/26; gH2, 9/26; and co‐infected with both gH1/2 in 6/26. These data show that genetic variability within the gB genes occurs frequently. Mixtures of gB and gH genotypes infection were common in Chinese solid organ transplant recipients.

Monitoring of human cytomegalovirus glycoprotein B genotypes using real-time quantitative PCR in immunocompromised Chinese patients

Based on sequence variation in the N-terminus of glycoprotein B (gB), human cytomegalovirus (HCMV) can be classified into four gBn genotypes, and these genotypes are associated with different clinical outcomes. The distribution of gBn genotypes and the level of gBn DNA load were examined in immunocompromised Chinese patients using real-time quantitative PCR. In addition, the PCR and pp65 antigenemia results were compared. In 1480 specimens, 81.4% were antigen-positive, 12.6% were PCR-positive. The gB genotype distribution was as follows among PCR-positive samples: gBn1, 63.1%; gBn2, 13.4%; gBn3, 8.6%; gBn4, not detected; mixed genotypes, 14.9% (gBn1 and gBn3, 14.4%; gBn2 and gBn3, 0.5%). The gBn3 and gBn1 genotypes had the highest and lowest copy numbers, respectively (p<0.05). The quantity of gBn DNA found in PCR-positive, pp65-negative samples was significantly lower than that found in PCR-positive, pp65-positive samples (p<0.05). The PCR and antigenemia results did not differ among bone marrow transplant patients, solid organ transplant patients, and immunocompromised patients without transplantation (p>0.05). HCMV gBn genotyping using real-time quantitative PCR was established successfully, and the distribution of gBn genotypes in immunocompromised Chinese patients was investigated. This method may help to understand better the relationship between gBn genotype and clinical outcome and aid in clinical detection.

Correlations between Clinical Features and Mortality in Patients with Vibrio vulnificus Infection.

Vibrio vulnificus is a common gram-negative bacterium, which might cause morbidity and mortality in patients following consumption of seafood or exposure to seawater in Southeast China. We retrospectively analyzed clinical data of patients with laboratory confirmed V. vulnificus infection. Twenty one patients were divided into a survival group and a non-surviving (or death) group according to their clinical outcome. Clinical data and measurements were statistically analyzed. Four patients (19.05%) died and five patients gave positive cultures from bile fluid, and 16 other patients gave positive culture from blood or blisters. Ten patients (47.62%) had an underlying liver disease and marine-related events were found in sixteen patients (76.2%). Patients with heavy drinking habits might be at increased mortality (p = 0.028). Clinical manifestations of cellulitis (47.6%), septic shock (42.9%) and multiple organ failure (28.6%) were statistically significant when comparing survivors and non-survivors (p = 0.035, p = 0.021 and p = 0.003, respectively). The laboratory results, including hemoglobin < 9.0 g/L (p = 0.012), platelets < 2.0×109 /L, prothrombin time activity (PTA) <20%, decreased serum creatinine and increased urea nitrogen were statistically significant (p = 0.012, p = 0.003, p = 0.028 and p = 0.028, respectively). Patients may be at a higher risk of mortality under situations where they have a history of habitual heavy alcoholic drink consumption (p = 0.028, OR = 22.5, 95%CI 1.5–335.3), accompanied with cellulitis, shock, multiple organ failure, and laboratory examinations that are complicated by decreased platelets, hemoglobin and significantly prolonged prothrombin time (PT).

Opportunistic Posttransplantation Virus Infections in Renal Transplant Recipients

BACKGROUND Opportunistic virus infection is one of the most common complications in renal transplant (RT) recipients. Cytomegalovirus (CMV) and BK virus (BKV) are important pathogens and each of these infections affects the other. In contrast, there is only limited information on JC virus (JCV) infection and its relation to CMV infection in RT recipients. This prospective study investigated the rates of JCV and CMV infections and their risk factors and correlations. METHODS We studied 52 RT recipients. JCV and CMV were detected using nested qualitative polymerase chain reaction assays of urine. The clinical characteristics of JCV and CMV infection were compared and risk factors analyzed with the use of binary logistic regression. RESULTS JCV and CMV were detected in 40.4% and 34.6% of the RT recipients, respectively. Cyclosporine (CsA) was a risk factor for both JCV and CMV infection (odds ratio [OR] 7.187; P=.002; OR 4.182; P=.021); CMV infection was a risk factor for JCV infection (OR 3.900; P=.039). CONCLUSIONS JCV and CMV infections are common in RT recipients. CsA is a risk factor for both JCV and CMV infection. JCV infection is related to CMV infection.

Community- or Healthcare-Associated Bacterial Infections Increase Long-Term Mortality in Patients With Acute Decompensation of Cirrhosis

Background: The aim of the present study was to determine the specific role of different types of bacterial infections (BIs) on the prognosis of cirrhotic patients with acute decompensation (AD). Methods: We performed a prospective, observational cohort study consisting of 492 cirrhotic patients with AD at our center from February 2014 to March 2015. Clinical, laboratory and survival data were collected. The relationship between BIs and mortality was analyzed. Results: BIs were identified in 157 of 492 patients at the time of admission or during the hospital stay. Among the patients, 65 had community‐acquired (CA) or healthcare‐associated (HCA) BIs, 54 developed hospital‐acquired (HA) BIs, and 38 had CA/HCA with HA BIs. Patients with CA/HCA BIs had higher 90‐day, 1‐year and 2‐year mortality rates (29.2%, 44.6% and 52.3%, respectively) and CA/HCA BIs remained an independent risk factor for long‐term mortality on multivariate analysis (1 year: hazard ratio = 1.60; 95% CI: 1.07‐2.41; P = 0.023 and 2 year: hazard ratio = 1.54; 95% CI: 1.05‐2.25; P = 0.026). In contrast, patients with HA BIs had a higher 28‐day mortality rate than patients with CA/HCA BIs. Logistic regression analysis showed previous ascites and prior BIs within 3 months were independent risk factors for CA/HCA BIs, whereas invasive minor surgical procedures with acute‐on‐chronic liver failure throughout the hospital stay and high chronic liver failure‐sequential organ failure assessment scores were associated with nosocomial BIs. Conclusions: CA/HCA BIs were associated with increased long‐term mortality in cirrhotic patients with AD, whereas nosocomial BIs may be related to poor short‐term prognosis.

Nocardiosis in ectopic ACTH syndrome: A case report and review of 11 cases from the literature

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) associated with nocardiosis is rare, and little information is available regarding its clinical characteristics. In this study, the case of a 35-year-old male patient who showed significant cushingoid features and had a cough with yellow phlegm for 1 month is described. Pulmonary computed tomography (CT) scanning and 18F-fluorodeoxyglucose positron emission tomography combined with CT identified two different lesions in the mediastinum and pulmonary region, respectively. The lesion in the mediastinum was finally diagnosed as an ACTH-secreting mediastinal paraganglioma via biopsy. The sputum culture confirmed pulmonary nocardiosis. The patient was effectively treated with complete tumor resection following the treatment of nocardiosis using trimethoprim-sulfamethoxazole. Following the present case, 11 additional cases of nocardiosis in EAS were identified in the literature and their clinical characteristics were compared and evaluated. It may be concluded that, although Nocardia remains a rare opportunistic infection pathogen in EAS, it is necessary to consider nocardiosis as a diagnosis for patients with pulmonary imaging findings of cavity, consolidation or nodule, particularly when there are brain and extra-pulmonary lesions as well as a poor response to regular treatment.

Monitoring of Human Cytomegalovirus Infection in Bone Marrow and Liver Transplant Recipients by Antigenaemia Assay and Enzyme-Linked Immunosorbent Assay

Human cytomegalovirus (HCMV) infection is a common complication in transplant recipients. Sensitive, specific and timely diagnostic tests for the detection of HCMV infection remain essential for successful therapy. The results of three tests to detect HCMV in bone marrow and liver transplant recipients were compared: a pp65 antigenaemia assay, an immediate-early (IE) antigenaemia assay and an anti-HCMV immunoglobulin M (IgM) antibody enzyme-linked immunosorbent assay (ELISA). Of 1344 samples, 911 (67.8%) and 917 (68.2%) samples were positive for pp65 and IE, respectively. The coincidence level was 85.1%. There was no statistical difference after transplantation to the first positive detection of HCMV (mean first checkout time) between the pp65 and IE antigenaemia assays. Moreover, the levels of HCMV detected by the pp65 and IE antigenaemia assays were significantly correlated. The HCMV-positivity rate as detected by the anti-HCMV IgM ELISA was 11.1%, which was significantly different from the IE and pp65 antigenaemia assays. We suggest that the IE antigenaemia assay could replace the pp65 antigenaemia assay for monitoring active HCMV infection and early detection of HCMV infection.

Bacterial Infection and Predictors of Mortality in Patients with Autoimmune Liver Disease-Associated Acute-On-Chronic Liver Failure

Objective To date, few studies are available on autoimmune liver disease-associated acute-on-chronic liver failure (ACLF). The aim of this study is to investigate bacterial infection and predictors of mortality in these patients. Methods We retrospectively studied patients with autoimmune liver disease from August 2012 to August 2017. Clinical data of the patients were retrieved for analysis. Results There were 53 ACLF patients and 53 patients without ACLF in this study. The ACLF group had a higher prevalence of complications (P < 0.05). The 28-day and 90-day mortality rates were also obviously high in patients with ACLF (38.3% and 74.5%, resp.) (P < 0.05). No predictor was significantly associated with 28-day and 90-day transplant-free mortality. In 53ACLF patients, 40 (75.5%) patients showed bacterial infection. ACLF patients with bacterial infection showed high Child-Pugh score, MELD score, CLIF-SOFA score, 28-day mortality, and 90-day mortality (P > 0.05). Moreover, C-reactive protein (CRP) using 12.15 mg/L cut-off value proved to be more accurate than procalcitonin in identifying patients with infection. Conclusions Autoimmune liver disease-associated ACLF showed more complications and high mortality. Bacterial infection patients displayed a more severe condition than those without infection. Elevated CRP is an accurate marker for diagnosing bacterial infection in autoimmune liver disease-associated ACLF patients.

Herpesvirus infections in hematopoietic stem cell transplant recipients seropositive for human cytomegalovirus before transplantation

BACKGROUND Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The effect of herpesvirus infections in human cytomegalovirus (HCMV)-seropositive (IgG-positive/IgM-negative) HSCT recipients remains poorly understood. The risk factors associated with Epstein-Barr virus (EBV), HCMV, and human herpes virus type 6 (HHV-6) infections after HSCT, both alone and in combination, were investigated in this study. METHODS Peripheral blood specimens were collected from 44 HSCT recipients and examined for viral DNA using quantitative fluorescence PCR assays. Risk factors for EBV, HCMV, and HHV-6 infections were analyzed by binary logistic regression, and relationships between these viruses were analyzed using the Chi-square test. RESULTS EBV, HCMV, and HHV-6 were detected in 50%, 45.45%, and 25% of HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients, respectively. Male sex (p=0.007) and conditioning regimens including anti-thymocyte globulin (ATG) (p=0.034) were strongly associated with an increased risk of EBV infection. Graft-versus-host disease (GVHD) prophylaxis with corticosteroids was a risk factor for both EBV (p=0.013) and HCMV (p=0.040) infections, while EBV infection (p=0.029) was found to be an independent risk factor for HHV-6 infection. Pre-existing HHV-6 infection was associated with lower rates of HCMV infection (p=0.002); similarly, pre-existing HCMV infection was protective against HHV-6 infection (p=0.036). CONCLUSIONS HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients exhibited a high rate of herpesvirus infections, particularly EBV. ATG and male sex were strongly associated with an increased risk of EBV infection. GVHD prophylaxis with prednisone was found to affect both EBV and HCMV infections. Prior infection with EBV was shown to promote HHV-6 infection. Taken together, these data highlight the need for active monitoring of herpesvirus infections in patients undergoing HSCT.

Active cytomegalovirus infection in autologous stem cell transplant recipients: Incidence and clinical impact

Cytomegalovirus (CMV) infection in patients after autologous stem cell transplant (ASCT) has become a major medical concern. However, few studies have reported active CMV infection before the transplantation. In this study, we retrospectively analyzed the incidence, clinical impact, risk factors, and outcome of CMV pp65 antigenemia in 44 consecutive patients who underwent ASCT between January 2005 and June 2011. CMV pp65 antigenemia assay was performed weekly, from 7 days before stem cell infusion until the patient was discharged. All patients were CMV seropositive before ASCT. Pre-transplantation antigenemia was detected in 19 patients (43.2%) and post-transplantation antigenemia in 17 patients (38.6%). Multivariate analysis could not identify any pre-transplantation risk factors for CMV antigenemia. When patients with and without pre-transplantation antigenemia were compared, we found that pre-transplantation active CMV infection had significant effects on posttransplantation platelet and neutrophil recovery, although the time of hospitalization and amount of blood transfusion were similar in both groups. CMV antigenemia was asymptomatic in all cases, and cleared spontaneously in 86.7% of patients who did not receive antiviral treatment. In conclusion, CMV reactivation before ASCT might occur frequently and even an asymptomatic infection could significantly delay engraftment. Therefore, ASCT candidates should be routinely evaluated for active CMV infection.