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Wang H.,Zhejiang Peoples Provincial Hospital | Xue L.,Zhejiang Peoples Provincial Hospital | Yan R.,Zhejiang Peoples Provincial Hospital | Zhou Y.,Zhejiang Peoples Provincial Hospital | And 3 more authors.
Journal of Viral Hepatitis | Year: 2013

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT). Liver biopsy (LB) is the current gold standard for assessing hepatic inflammation and fibrosis in patients with chronic HBV. However, associated risks have led to the development of noninvasive models. Their utility in patients with normal ALT is unknown. FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) were calculated for patients with chronic HBV infection undergoing biopsy. The performance of each model and AUROC for predicting significant fibrosis (Scheuer's score ≤yen; S2) were determined for the entire cohort and stratified by elevated (≤yen;50 U/L) and normal ALT. Two-hundred and thirty-one liver biopsies were included. The number of patient with normal ALT was 140, and 22.1% had significant fibrosis. The AUROC curve for patients with normal ALT was 0.81 for FIB-4 and 0.80 for APRI, compared with 0.71 for FIB-4 and 0.72 for APRI for those with mildly elevated ALT level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FIB-4 were 0.63, 0.88, 0.61 and 0.93, for patients with normal ALT; the values for APRI were 0.40, 0.88, 0.33 and 0.93. Both FIB-4 and APRI are useful for identification of those without significant fibrosis. However, because they have poor PPV, LB will continue to be used for assessment of HBV-infected patients with normal ALT and mildly elevated ALT. © 2012 Blackwell Publishing Ltd.


Dong H.-Y.,Zhejiang Peoples Provincial Hospital | Wang Z.-F.,Zhejiang Peoples Provincial Hospital
Chinese Journal of Cancer Research | Year: 2014

Purpose: The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate (ART) action on breast cancer in vivo using tumor transplanted nude mice. Methods: The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide (CTX) or normal saline (NS). The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry (FCM). The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed. Results: The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were (24.39±10.20)%, (40.24±7.02)%, (57.01±5.84)% and (68.29±5.1)%, respectively. The cell cycle was arrested in phase G0/G1 after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation. Conclusions: ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The anti-tumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation. © Chinese Journal of Cancer Research. All rights reserved.


Wang H.,Zhejiang Peoples Provincial Hospital | Yan R.,Zhejiang Peoples Provincial Hospital | Zhou Y.,Zhejiang Peoples Provincial Hospital | Wang M.S.,Zhejiang Peoples Provincial Hospital | And 2 more authors.
Hepatology International | Year: 2014

Background/Aim: The purpose of this study was to determine the relationship between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels and liver histology in HBeAg-positive patients with chronic hepatitis B virus (CHB) infection. Methods: Serum HBsAg and HBeAg levels were analyzed, and liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6 % males; median age 31.3 years). The upper limit of normal (ULN) for ALT in this study was 30 and 19 U/L for males and females, respectively. Histologic assessment was based on Scheuer classification. Results: ALT <2 x ULN, fibrosis stage


PubMed | Zhejiang Peoples Provincial Hospital
Type: Journal Article | Journal: Journal of clinical gastroenterology | Year: 2014

We aimed to develop a clinically useful scoring system to predict the probability of significant fibrosis (the Scheuer score S2) in patients with chronic hepatitis B infection (CHB) and alanine aminotransferase (ALT) levels 2-fold lower than the upper limit of normal (ULN), in order to facilitate the clinical decision to perform a subsequent liver biopsy.Consecutive subjects who underwent percutaneous liver biopsy were examined. The predictors evaluated included demographic, clinical, and laboratory variables. A clinical scoring system was developed by rounding the estimated regression coefficients for the independent predictors in multivariate logistic models for the diagnosis of significant fibrosis.A total of 283 patients with ALT levels 2-fold lower than the ULN were divided into 2 groups to develop (n=190) and validate (n=93) the scoring system. Of the 190 subjects examined, 52 (27.4%) had significant fibrosis. Aspartate transferase levels, platelet counts, and hepatitis B surface antigen levels were independently associated with significant liver fibrosis. A fibrosis clinical scoring system comprising these 3 variables in CHB patients with ALT levels 2-fold lower than the ULN was developed to predict the probability of significant fibrosis in 4 categories (low, intermediate, high, and very high risk).The proposed fibrosis scoring system predicted the probability of significant fibrosis in CHB patients with ALT levels 2-fold lower than the ULN with sufficient accuracy. It identified individuals with a very high risk for significant fibrosis in whom liver biopsy would most likely yield a diagnostic benefit. It also identified individuals with a low risk of moderate fibrosis in whom a liver biopsy can be delayed or avoided.


PubMed | Zhejiang Peoples Provincial Hospital
Type: Comparative Study | Journal: Journal of viral hepatitis | Year: 2013

Significant liver disease has been reported in chronic hepatitis B patients with normal alanine aminotransferase (ALT). Liver biopsy (LB) is the current gold standard for assessing hepatic inflammation and fibrosis in patients with chronic HBV. However, associated risks have led to the development of noninvasive models. Their utility in patients with normal ALT is unknown. FIB-4 and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) were calculated for patients with chronic HBV infection undergoing biopsy. The performance of each model and AUROC for predicting significant fibrosis (Scheuers score S2) were determined for the entire cohort and stratified by elevated (50 U/L) and normal ALT. Two-hundred and thirty-one liver biopsies were included. The number of patient with normal ALT was 140, and 22.1% had significant fibrosis. The AUROC curve for patients with normal ALT was 0.81 for FIB-4 and 0.80 for APRI, compared with 0.71 for FIB-4 and 0.72 for APRI for those with mildly elevated ALT level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FIB-4 were 0.63, 0.88, 0.61 and 0.93, for patients with normal ALT; the values for APRI were 0.40, 0.88, 0.33 and 0.93. Both FIB-4 and APRI are useful for identification of those without significant fibrosis. However, because they have poor PPV, LB will continue to be used for assessment of HBV-infected patients with normal ALT and mildly elevated ALT.

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