AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients wi...AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCVRNA were included. Markers of fibrosis progression were assessed. RESULTS： Median duration of infection and time between paired biopsies was 13 （95% CI： 1-28） and 4 （95% CI： 2-16） years respectively. Alaninetransaminase （ALT） activity was normal in 43.4% of cases. 50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years （95% CI： 2-16）. The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression （P = 0.03） was observed in patients with body mass index （BMI） 〉 25. Fibrosis progression correlated with the time interval between biopsies （P = 0.01）. A significant progression of activity （1.7 vs 0.4, P 〈 0.05） or fibrosis （0.9 vs 0.0, P 〈 0.01） was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression（P = 0.003）. Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI 〉 25 and the time interval between 2 biopsies. CONCLUSION： There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI 〉 25.展开更多
AIM To study the effect of hepatocyteapoptosis and necrosis induced by TNF-α on thepathogenesis of acute severe hepatitis(ASH).METHODS The model of ASH was prepared inD-galactosamine(GAIN)sensitized BALB/c miceby inj...AIM To study the effect of hepatocyteapoptosis and necrosis induced by TNF-α on thepathogenesis of acute severe hepatitis(ASH).METHODS The model of ASH was prepared inD-galactosamine(GAIN)sensitized BALB/c miceby injection of either endotoxin(ET)or tumornecrosis factor-α(TNF-α).Morphologicalchanges of apoptotic hepatocytes were studiedby both light and electron microscope and in siteend labeling method(ISEL).Molecular biologicalchanges of DNA ladder were observed byelectrophoresis of extract from liver tissues.Biochemical changes were measured by alanineaminotransferase(ALT),asparticaminotransferase(AST)and TNF-α.The relationbetween apoptosis and necrosis was evaluatedsimultaneously.RESULTS The sequence of hepatocyteapoptosis,necrosis,and final death from ASHwas observed both in GAIN/ET and GAIN/TNF-agroup.Apoptosis was prominent at 3.5 h and 5 hafter injection of inducer,while necrosis becamedominant at 9 h after challenge.The appearanceof apoptosis was earlier in GAIN/TNF-α groupthan that in GAIN/ ET group.Pretreatment ofmice with antiTNF IgG1 may completely preventthe liver injury induced by GalN/ET.CONCLUSION TNF-α can cause liver damageby inducing hepatic apoptosis and necrosis inmice with endotoxemia.展开更多
BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene...BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%)展开更多
文摘AIM： To determine factors associated with fibrosis progression in hepatitis C virus （HCV）-infected patients without significant initial pathological lesions. METHODS： Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCVRNA were included. Markers of fibrosis progression were assessed. RESULTS： Median duration of infection and time between paired biopsies was 13 （95% CI： 1-28） and 4 （95% CI： 2-16） years respectively. Alaninetransaminase （ALT） activity was normal in 43.4% of cases. 50% demonstrated progression of the necroinflammation and 34% of fibrosis after a median time evolution of 4 years （95% CI： 2-16）. The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression （P = 0.03） was observed in patients with body mass index （BMI） 〉 25. Fibrosis progression correlated with the time interval between biopsies （P = 0.01）. A significant progression of activity （1.7 vs 0.4, P 〈 0.05） or fibrosis （0.9 vs 0.0, P 〈 0.01） was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression（P = 0.003）. Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI 〉 25 and the time interval between 2 biopsies. CONCLUSION： There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI 〉 25.
文摘AIM To study the effect of hepatocyteapoptosis and necrosis induced by TNF-α on thepathogenesis of acute severe hepatitis(ASH).METHODS The model of ASH was prepared inD-galactosamine(GAIN)sensitized BALB/c miceby injection of either endotoxin(ET)or tumornecrosis factor-α(TNF-α).Morphologicalchanges of apoptotic hepatocytes were studiedby both light and electron microscope and in siteend labeling method(ISEL).Molecular biologicalchanges of DNA ladder were observed byelectrophoresis of extract from liver tissues.Biochemical changes were measured by alanineaminotransferase(ALT),asparticaminotransferase(AST)and TNF-α.The relationbetween apoptosis and necrosis was evaluatedsimultaneously.RESULTS The sequence of hepatocyteapoptosis,necrosis,and final death from ASHwas observed both in GAIN/ET and GAIN/TNF-agroup.Apoptosis was prominent at 3.5 h and 5 hafter injection of inducer,while necrosis becamedominant at 9 h after challenge.The appearanceof apoptosis was earlier in GAIN/TNF-α groupthan that in GAIN/ ET group.Pretreatment ofmice with antiTNF IgG1 may completely preventthe liver injury induced by GalN/ET.CONCLUSION TNF-α can cause liver damageby inducing hepatic apoptosis and necrosis inmice with endotoxemia.
文摘BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%)
