Characteristics of H7N9 avian influenza pneumonia: a retrospective analysis of 17 cases.

BACKGROUND: H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. AIMS: To describe the clinical features of H7N9 avian influenza and the response to treatment. METHODS: Clinical, radiological and histopathological data, and treatment-related of H7N9-infected patients hospitalised during 2014-2017 were extracted and analysed. RESULTS: A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground-glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252-C/C interferon-induced transmembrane protein-3 (IFITM3) genotype, while the others had the C/T genotype. CONCLUSIONS: H7N9 virus infection causes human influenza-like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high-risk patients. The presence of the IFITM3 rs12252-C genotype may predict severe illness.

Prediction of hepatic necroinflammatory activity in patients with chronic hepatitis B by a simple noninvasive model.

BACKGROUND: A model was constructed using clinical and serum variables to discriminate between chronic hepatitis B (CHB) patients with and without significant necroinflammatory activity (score 4-18 vs. score 0-3). METHODS: Consecutive CHB patients who underwent liver biopsy were divided into two sequential groups: a training group (n = 401) and a validation group (n = 401). Multivariate analysis identified alanine aminotransferase, γ-glutamyltransferase, prothrombin time and albumin as independent predictors of necroinflammatory activity. RESULTS: The area under the receiver operating characteristic curve was 0.826 for the training group and 0.847 for the validation group. Using a cut-off score of H ≤ 0.375, significant necroinflammatory activity (score 4-18) was excluded with high accuracy [78.2% negative predictive value (NPV), 72% positive predictive value (PPV), and 90.8% sensitivity] in 238 (59.4%) of 401 patients in the training group and with the same certainty (88.1% NPV, 61.2% PPV, and 95.1% sensitivity) among 204 (50.9%) of 401 patients in the validation group. Similarly, applying a cut-off score of H > 0.720, significant necroinflammatory activity was correctly identified with high accuracy (90.8% PPV, 57.7% NPV, and 92.0% specificity) in 150 (37.4%) of 401 patients in the training group and with the same certainty (91.8% PPV, 64.6% NPV, and 95.4% specificity) in 188 (46.9%) of 401 patients in the validation group. CONCLUSIONS: A predictive model based on easily accessible variables identified CHB patients with and without significant necroinflammatory activity with a high degree of accuracy. This model may decrease the need for liver biopsy for necroinflammatory activity grading in 72.1% of CHB patients.

Prediction of significant fibrosis and cirrhosis in hepatitis B e-antigen negative patients with chronic hepatitis B using routine parameters.

AIM: As liver biopsy has considerable limitations in the assessment of liver fibrosis, non-invasive models have achieved great progress in the past. However, many tests consist of variables that are not readily available, and there are few data about patients with hepatitis B e-antigen (HBeAg) negative chronic hepatitis B (CHB). The aim of this study was to develop a model using routine data to predict liver fibrosis in HBeAg negative CHB patients. METHODS: We randomly divided 349 patients who underwent liver biopsy into training (n = 200) and validation (n = 149) sets. Multivariable logistic regression and receiver-operator curve (ROC) analyses were used to develop a model for predicting both significant fibrosis (stages 2-4) and cirrhosis (stage 4) in the training set. The model was validated in 149 patients in comparison to FIB-4, Forn's, S and aspartate aminotransferase-to-platelet ratio index indices using ROC. RESULTS: Multivariable logistic regression analysis showed that the parameters of the model for predicting both significant fibrosis and cirrhosis included sex, age, prothrombin time, platelet count, cholesterol and γ-glutamyltransferase. In the training set, the areas under the ROC (AUC) for predicting significant fibrosis and cirrhosis were 0.856 and 0.956, respectively. In the validation group, the AUC for predicting significant fibrosis and cirrhosis were 0.889 and 0.937, respectively. Using the best cut-off values, significant fibrosis and cirrhosis can be accurately predicted in 40.9% and 91.3% of patients, respectively. CONCLUSION: Our model can accurately predict both significant fibrosis and cirrhosis and may decrease the need of liver biopsy in a considerable proportion of patients with HBeAg negative CHB.

Mechanism and efficacy of mobilization of granulocyte colony-stimulating factor in the treatment of chronic hepatic failure.

BACKGROUND/AIMS: To explore the efficacy of G-CSF mobilization in the treatment of chronic liver failure (CLF) and the mechanism of its action. METHODOLOGY: The proportions of cluster-of-differentiation (CD)-34+ cells and their receptor-CXCR4 were detected by flow cytometry in patients with different types of chronic HBV infection. The levels of chemokines and cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: The proportion of CD34+ cells in patients with cirrhosis was significantly increased compared with the healthy controls (p<0.05) and was increased obviously after treatment by G-CSF mobilization (p<0.01). The expression levels of SDF-1, SCF and MMP-9 were significantly elevated in patients with chronic hepatitis B and liver cirrhosis (p<0.01). The expression levels of SCF and MMP-9 were significantly elevated after treatment with G-CSF (p<0.05). No significant differences were found in the levels of total bilirubin, albumin and prothrombin time between the treated and control groups; furthermore, no significant differences were observed in the cure and improvement rates between the two groups. CONCLUSIONS: The basal levels of stem cell mobilization in patients with liver cirrhosis might be associated with the repair of liver injury. G-CSF could promote hematopoietic stem cell mobilization through regulation of the expression levels of stem-cell-mobilization-related factors in patients with liver cirrhosis. No apparent effects of G-CSF therapy on both liver function and short-term prognosis in patients with liver cirrhosis were confirmed.

Changes in the proportions of CD4(+)T cell subsets defined by CD127 and CD25 expression during HBV infection.

CD4(+)T cell counts are closely related to the progression of HBV infection. Here, we investigated how the proportions of three CD4(+)T cell subsets - CD127(-)CD25(-), CD127(+)CD25(low/-) and CD127(low)CD25(high) - changed during HBV infection, as is little known. Compared with healthy controls, the proportions of CD127(-)CD25(-) in chronic hepatitis B (CHB) patients and HBV carriers significantly increased, while that of CD127(+)CD25(low/-) significantly decreased. The proportion of CD127(low)CD25(high) in CHB patients was significantly higher than those in HBV carriers or healthy controls. Compared with HBV-DNA negative group, the proportion of CD127(-)CD25(-) in positive group significantly decreased and that of CD127(+)CD25(low/-) significantly increased. In the follow-up study for CHB patients treated with interferon-α2b for 12 weeks or 24 weeks, the proportions of CD127(-)CD25(-) significantly decreased, while that of CD127(low/-)CD25(high) significantly increased. The results suggested that specific changes in the fraction of CD4(+)T cell subsets expressing CD127 and/or CD25 were associated with hepatitis B progression.

[Liver histological changes in chronic hepatitis B patients with elevated ALT less than 2 x ULN].

OBJECTIVE: To investigate the relevant factors of liver histological changes in chronic hepatitis B (CHB) patients with mildly elevated ALT and to explore the clinical values of these factors on anti-viral treatment. METHODS: A total of 152 CHB patients with mildly elevated ALT (less than 2 x ULN) who underwent liver biopsy were included in the study. Correlations between routine laboratory markers, liver histological inflammation grade and fibrosis stage were statistically assessed by Spearman correlation analysis, one-way ANOVA, area under the curve (AUC) of the receiver operating characteristic curves (ROC) and Logistic regression statistical analysis. RESULTS: All patients in the study showed various hepatic histological damages. Among the 152 patients 50 (32.9%) were found with inflammation grade 1 (G1), 42 (27.6%) with G2, 46 (30.3%) with G3 and 14 (9.2%) with G4. 16 patients (10.5%) were found with fibrosis stage 2 (S2), 25 (16.5%) with S3 and 41 (27.0%) with S4. Routine laboratory markers Alb, BPC and WBC were significantly correlated with hepatic histological inflammation grade and fibrosis stage. Marked liver fibrosis and moderate to severe liver damage were significantly higher in patients aged more than 40 years as compared to those less than 40 years of age (P = 0.002, P = 0.010). The regression equation P = 1/[1+e-(9.36250-1625Alb-0.0234BPC)] was established with sensitivity and specificity of 83.3% and 65.0%, respectively. CONCLUSION: 67.8% of CHB patients with mildly elevated ALT have significant injury to the liver tissue. CHB patients aged more than 40 years have a significant increase of marked liver fibrosis and moderate to severe liver damage. The regression equation is valuable to predict whether CHB patients need antiviral therapy or not.

Simpler score of routine laboratory tests predicts liver fibrosis in patients with chronic hepatitis B.

BACKGROUND AND AIM: In recent years, a great interest has been dedicated to the development of noninvasive predictive models to substitute liver biopsy for fibrosis assessment and follow-up. Our aim was to provide a simpler model consisting of routine laboratory markers for predicting liver fibrosis in patients chronically infected with hepatitis B virus (HBV) in order to optimize their clinical management. METHODS: Liver fibrosis was staged in 386 chronic HBV carriers who underwent liver biopsy and routine laboratory testing. Correlations between routine laboratory markers and fibrosis stage were statistically assessed. After logistic regression analysis, a novel predictive model was constructed. This S index was validated in an independent cohort of 146 chronic HBV carriers in comparison to the SLFG model, Fibrometer, Hepascore, Hui model, Forns score and APRI using receiver operating characteristic (ROC) curves. RESULTS: The diagnostic values of each marker panels were better than single routine laboratory markers. The S index consisting of gamma-glutamyltransferase (GGT), platelets (PLT) and albumin (ALB) (S-index: 1000 x GGT/(PLT x ALB(2))) had a higher diagnostic accuracy in predicting degree of fibrosis than any other mathematical model tested. The areas under the ROC curves (AUROC) were 0.812 and 0.890 for predicting significant fibrosis and cirrhosis in the validation cohort, respectively. CONCLUSIONS: The S index, a simpler mathematical model consisting of routine laboratory markers predicts significant fibrosis and cirrhosis in patients with chronic HBV infection with a high degree of accuracy, potentially decreasing the need for liver biopsy.

[Clinical significance and detection of the expression of CD25- CD127- on CD4+ T cells in peripheral blood in patients with hepatitis B].

OBJECTIVE: To investigate the clinical significance and detection of the expression of CD25- CD127- on CD4+ T cells in peripheral blood in patients with hepatitis B. METHODS: The expression of CD25- CD127- on CD4+ T cells were measured by using flow cytometry in 53 patients with chronic hepatitis B, 53 carrier with hepatitis B virus and 26 healthy blood donors, and follow up 20 patients with HBV-DNA positive treated with interferon. RESULTS: (1) Compared with healthy controls, the expression of CD25- CD127- on CD4+ T cells in patients and carrier with hepatitis B virus were lower (Q = 4.559, P < 0.05; Q = 6.230, P < 0.05). (2) The expression of CD25- CD127- on CD4+ T cells in patients with HBV-DNA positive (n = 77) was lower than that of negative (n = 29) (t = 2.290, P = 0.024). (3) Compared with the prior treatment,the expression of CD25- CD127- on CD4+ T cells in patients with B hepatitis were lower after interferon treated with 12 weeks (t = 2.469, P = 0.024). CONCLUSION: It suggested that the CD25- CD127- expression on CD4+ T cells correlated with viral infections and cleared,exogenous interferon could decrease CD25- CD127- expression on CD4+ T cells.