慢性活动性肝炎（Chronic active hepatitis简称CAH）是一种严重危害人类健康的疾病,且预后较差。CAH的病因主要有乙型肝炎病毒（HBV）,在我国以HBV相关的CAH约占90％左右,其次非甲非乙型肝炎病毒（NANB）及某些药物,如α—甲基多巴、...慢性活动性肝炎（Chronic active hepatitis简称CAH）是一种严重危害人类健康的疾病,且预后较差。CAH的病因主要有乙型肝炎病毒（HBV）,在我国以HBV相关的CAH约占90％左右,其次非甲非乙型肝炎病毒（NANB）及某些药物,如α—甲基多巴、异烟肼、双醋酚酊和酒精中毒,α<sub>1</sub>—抗胰蛋白酶缺乏、肝豆状核变性等也可引起类似CAH的病变。本文仅就CAH的发病机理的几个因素加以叙述。展开更多
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in pati...Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse- transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention.展开更多
Background/Aims: Inherited dysfunction of the bile salt export pump BSEP (ABCB11) causes a progressive and a benign form of familial intrahepatic cholestasis, denominated as PFIC2 and BRIC2, respectively. We functiona...Background/Aims: Inherited dysfunction of the bile salt export pump BSEP (ABCB11) causes a progressive and a benign form of familial intrahepatic cholestasis, denominated as PFIC2 and BRIC2, respectively. We functionally characterized novel ABCB11 mutations encountered in two patients with a PFIC2 and a BRIC2 phenotype, respectively. Methods: BSEP expression was determined in liver biopsies by immunohistochemistry. ABCB11 mutations were functionally characterized by taurocholate transport in SF9 cells transfected with human ABCB11. Results: The PFIC2 patient was compound heterozygous for a splicingmutation in intron 4 ((+ 3)A >C) combined with an early stop codon at position 930 (R930X), while the BRIC2 patient was compound heterozygous for two nonsynonymous mutations in exon 9 (E297G) and exon 12 (R432T), respectively. Hepatic BSEP expression was absent in PFIC2 and preserved in BRIC2. In BRIC2, taurocholate transport was decreased to 13% and 20% of reference levels for R432T and E297G, respectively. Conclusions: The intron 4 (+ 3)A >C, R930X and R432T represent previously undescribed mutations of the ABCB11 gene that confer a PFIC2 and a BRIC2 phenotype, respectively. By combining functional in-vitro characterization with immunohistochemical detection of variant BSEP we provide direct evidence for the role of ABCB11 mutations in the pathogenesis of different forms of intrahepatic cholestasis.展开更多
Liver disease in patients coinfected with HIV and hepatitis C virus (HCV) has received increasing attention in recent years. Steatosis is accepted as an important contributor to liver disease in patients with HCV, but...Liver disease in patients coinfected with HIV and hepatitis C virus (HCV) has received increasing attention in recent years. Steatosis is accepted as an important contributor to liver disease in patients with HCV, but despite coinfected patients having several reasons to have steatosis, the prevalence and significance of such changes has received scant attention. We examined steatosis in an unselected cohort of coinfected patients and compared its prevalence and predictors with findings in monoinfected patients, where these relationships have been established. We studied 92 coinfected and 372 monoinfected patients undergoing staging liver biopsy. Baseline characteristics of the two groups differed significantly, pointing at different contributors to steatosis in each. Histological inflammation and fibrosis were very similar in the two groups, but steatosis was less in coinfected patients. Steatosis had a univariate association with fibrosis in both groups, but retained a multivariate association only in monoinfected patients. Other multivariate predictors of steatosis in monoinfected patients were the accepted variables of elevated body mass index, male sex, and genotype 3a infection, as well as age. In coinfected patients, however, age was the only multivariate predictor. Undetectable HIV viral load was associated with steatosis in coinfected patients in univariate analysis, but highly active antiretroviral therapy or its individual components could not be initially linked to steatosis. In conclusion, steatosis is less common in HIV/HCV coinfected patients than similar HCV monoinfected patients, and predictors of steatosis differ between the two groups.展开更多
Background: Isolated sinusoidal dilatation is an uncommon hepatic lesion and t he cause is largely unknown. Objective: To investigate whether prothrombotic dis orders or perisinusoidal cell changes could be involved i...Background: Isolated sinusoidal dilatation is an uncommon hepatic lesion and t he cause is largely unknown. Objective: To investigate whether prothrombotic dis orders or perisinusoidal cell changes could be involved in pure idiopathic hepat ic sinusoidal dilatation (HSD). Methods: Evaluation for associated conditions, p rothrombotic disorders, and studies of hepatic perisinusoidal cell activation in consecutive patients, seen between 1993 and 2002, with isolated sinusoidal dila tation unrelated to outflow block, sinusoidal infiltration, or hepatic granuloma s. Results: Among 11 patients, associated conditions were prothrombotic disorder s (n = 5) and oral contraceptive use (n = 3). Prothrombotic disorders were polyc ythemia vera (n = 1) and anticardiolipin antibodies combined with lupus anticoag ulant (n = 4). No genetic thrombophilia factor was found. Of four patients with lupus anticoagulant, three had antinuclear factors and high serum levels of anti cardiolipin antibodies at repeated testing. There was no evidence of intrahepati c or extrahepatic thrombosis in any of the patients. Sinusoidal dilatation was m arked in six of 11 patients (54%), including two patients with antiphospholipid antibodies. Activated perisinusoidal cells were only found around markedly dila ted sinusoids. Conclusion: Idiopathic pure HSD is frequently associated with the immunological features of the antiphospholipid syndrome. Therefore, finding pur e HSD in a liver biopsy specimen should prompt the search for antiphospholipid a ntibodies.展开更多
文摘慢性活动性肝炎（Chronic active hepatitis简称CAH）是一种严重危害人类健康的疾病,且预后较差。CAH的病因主要有乙型肝炎病毒（HBV）,在我国以HBV相关的CAH约占90％左右,其次非甲非乙型肝炎病毒（NANB）及某些药物,如α—甲基多巴、异烟肼、双醋酚酊和酒精中毒,α<sub>1</sub>—抗胰蛋白酶缺乏、肝豆状核变性等也可引起类似CAH的病变。本文仅就CAH的发病机理的几个因素加以叙述。
文摘Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH). Microarray hybridizations were performed in triplicate and the microarray expression levels of a selected group of genes were confirmed using real-time quantitative reverse- transcriptase polymerase chain reaction. Serum protein profiles of the same patients were determined by SELDI-TOF mass spectrometry. Of 98 obese patients, 91 were diagnosed with NAFLD (12 steatosis alone, 52 steatosis with nonspecific inflammation, and 27 NASH), and 7 patients without NAFLD served as obese controls. Each group of NAFLD patients was compared with the obese controls, and 22 genes with more than twofold differences in expression levels were revealed. Proteomics analyses were performed for the same group comparisons and revealed twelve significantly different protein peaks. In conclusion, this genomic/proteomic analysis suggests differential expression of several genes and protein peaks in patients within and across the forms of NAFLD. These findings may help clarify the pathogenesis of NAFLD and identify potential targets for therapeutic intervention.
文摘Background/Aims: Inherited dysfunction of the bile salt export pump BSEP (ABCB11) causes a progressive and a benign form of familial intrahepatic cholestasis, denominated as PFIC2 and BRIC2, respectively. We functionally characterized novel ABCB11 mutations encountered in two patients with a PFIC2 and a BRIC2 phenotype, respectively. Methods: BSEP expression was determined in liver biopsies by immunohistochemistry. ABCB11 mutations were functionally characterized by taurocholate transport in SF9 cells transfected with human ABCB11. Results: The PFIC2 patient was compound heterozygous for a splicingmutation in intron 4 ((+ 3)A >C) combined with an early stop codon at position 930 (R930X), while the BRIC2 patient was compound heterozygous for two nonsynonymous mutations in exon 9 (E297G) and exon 12 (R432T), respectively. Hepatic BSEP expression was absent in PFIC2 and preserved in BRIC2. In BRIC2, taurocholate transport was decreased to 13% and 20% of reference levels for R432T and E297G, respectively. Conclusions: The intron 4 (+ 3)A >C, R930X and R432T represent previously undescribed mutations of the ABCB11 gene that confer a PFIC2 and a BRIC2 phenotype, respectively. By combining functional in-vitro characterization with immunohistochemical detection of variant BSEP we provide direct evidence for the role of ABCB11 mutations in the pathogenesis of different forms of intrahepatic cholestasis.
文摘Liver disease in patients coinfected with HIV and hepatitis C virus (HCV) has received increasing attention in recent years. Steatosis is accepted as an important contributor to liver disease in patients with HCV, but despite coinfected patients having several reasons to have steatosis, the prevalence and significance of such changes has received scant attention. We examined steatosis in an unselected cohort of coinfected patients and compared its prevalence and predictors with findings in monoinfected patients, where these relationships have been established. We studied 92 coinfected and 372 monoinfected patients undergoing staging liver biopsy. Baseline characteristics of the two groups differed significantly, pointing at different contributors to steatosis in each. Histological inflammation and fibrosis were very similar in the two groups, but steatosis was less in coinfected patients. Steatosis had a univariate association with fibrosis in both groups, but retained a multivariate association only in monoinfected patients. Other multivariate predictors of steatosis in monoinfected patients were the accepted variables of elevated body mass index, male sex, and genotype 3a infection, as well as age. In coinfected patients, however, age was the only multivariate predictor. Undetectable HIV viral load was associated with steatosis in coinfected patients in univariate analysis, but highly active antiretroviral therapy or its individual components could not be initially linked to steatosis. In conclusion, steatosis is less common in HIV/HCV coinfected patients than similar HCV monoinfected patients, and predictors of steatosis differ between the two groups.
文摘Background: Isolated sinusoidal dilatation is an uncommon hepatic lesion and t he cause is largely unknown. Objective: To investigate whether prothrombotic dis orders or perisinusoidal cell changes could be involved in pure idiopathic hepat ic sinusoidal dilatation (HSD). Methods: Evaluation for associated conditions, p rothrombotic disorders, and studies of hepatic perisinusoidal cell activation in consecutive patients, seen between 1993 and 2002, with isolated sinusoidal dila tation unrelated to outflow block, sinusoidal infiltration, or hepatic granuloma s. Results: Among 11 patients, associated conditions were prothrombotic disorder s (n = 5) and oral contraceptive use (n = 3). Prothrombotic disorders were polyc ythemia vera (n = 1) and anticardiolipin antibodies combined with lupus anticoag ulant (n = 4). No genetic thrombophilia factor was found. Of four patients with lupus anticoagulant, three had antinuclear factors and high serum levels of anti cardiolipin antibodies at repeated testing. There was no evidence of intrahepati c or extrahepatic thrombosis in any of the patients. Sinusoidal dilatation was m arked in six of 11 patients (54%), including two patients with antiphospholipid antibodies. Activated perisinusoidal cells were only found around markedly dila ted sinusoids. Conclusion: Idiopathic pure HSD is frequently associated with the immunological features of the antiphospholipid syndrome. Therefore, finding pur e HSD in a liver biopsy specimen should prompt the search for antiphospholipid a ntibodies.
