Background: Diabetes has been associated with an increa- sed risk of hepatocellular carcinoma (HCC) in studies of referred patients. Th is is the first population based case control study in the USA to examine this a ...Background: Diabetes has been associated with an increa- sed risk of hepatocellular carcinoma (HCC) in studies of referred patients. Th is is the first population based case control study in the USA to examine this a ssociation while adjusting for other major risk factors related to HCC. Methods: We used the Surveillance Epidemiology and End-Results Program (SEER)Medicare l inked database to identify patients aged 65 years and older diagnosed with HCC a nd randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index d ate were examined. Inpatient and outpatient claims files were searched for diagn ostic codes indicative of diabetes,hepatitis C virus (HCV), hepatitis B virus (H BV), alcoholic liver disease, and haemochromatosis. HCC patients without these c onditions were categorised as idiopathic. Unadjusted and adjusted odds ratios we re calculated in logistic regression analyses. Results: We identified 2061 HCC p atients and 6183 non-cancer controls. Compared with non-cancer controls, patie nts with HCC were male (66%v 36%) and non-White (34%v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demo graphics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis),diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjus ted odds ratio for diabetes declined but remained significant (adjusted odds rat io 2.87 (95%con-fidence interval 2.49-3.30)). A significant positive interact ion between HCV and diabetes was detected (p< 0.0001). Similar findings persiste d in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. Conclusions:Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk fac展开更多
目的构建抑制人乙醛脱氢酶2(ALDH2)基因表达的shALDH2-PLKO.1重组慢病毒质粒,并将重组质粒转染HepG2细胞株,为构建ALDH2基因沉默细胞株及研究ALDH2在酒精致HepG2细胞毒性中的作用奠定基础。方法设计3对ALDH2 sh RNA序列并插入到PLKO.1-...目的构建抑制人乙醛脱氢酶2(ALDH2)基因表达的shALDH2-PLKO.1重组慢病毒质粒,并将重组质粒转染HepG2细胞株,为构建ALDH2基因沉默细胞株及研究ALDH2在酒精致HepG2细胞毒性中的作用奠定基础。方法设计3对ALDH2 sh RNA序列并插入到PLKO.1-GFP载体中,通过测序鉴定。将ALDH2 sh RNA和包装质粒共转染293FT细胞,收集24、48和72 h病毒液进行浓缩,通过梯度稀释法测定病毒液滴度。Western blot和qRTPCR检测转染sh RNA的HepG2细胞ALDH2蛋白和mRNA表达量。MTS比色法检测转染sh RNA的HepG2细胞在酒精染毒后的增殖能力。结果测序结果显示shALDH2-PLKO.1质粒构建成功;滴度测定结果显示包装系统成功包装出病毒颗粒,病毒滴度为:4×107TU/ml;Western blot及qRT-PCR结果显示,与对照组比较,转染了shALDH2-1和shALDH2-3的HepG2细胞蛋白和mRNA表达量明显下调,其中shALDH2-1组抑制率为51%(P=0.046),shALDH2-3组抑制率为72%(P=0.008),差异有统计学意义;MTS结果显示转染sh RNA的HepG2细胞株酒精染毒后细胞增殖能力明显下降。结论成功构建了靶向ALDH2基因的重组慢病毒表达质粒,而且shALDH2-PLKO.1可以有效抑制He PG2细胞中ALDH2基因的表达,为研究ALDH2基因在酒精性肝病和肝癌中的作用机制奠定了基础。展开更多
Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complication...Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.展开更多
文摘Background: Diabetes has been associated with an increa- sed risk of hepatocellular carcinoma (HCC) in studies of referred patients. Th is is the first population based case control study in the USA to examine this a ssociation while adjusting for other major risk factors related to HCC. Methods: We used the Surveillance Epidemiology and End-Results Program (SEER)Medicare l inked database to identify patients aged 65 years and older diagnosed with HCC a nd randomly selected non-cancer controls between 1994 and 1999. Only cases and controls with continuous Medicare enrolment for three years prior to the index d ate were examined. Inpatient and outpatient claims files were searched for diagn ostic codes indicative of diabetes,hepatitis C virus (HCV), hepatitis B virus (H BV), alcoholic liver disease, and haemochromatosis. HCC patients without these c onditions were categorised as idiopathic. Unadjusted and adjusted odds ratios we re calculated in logistic regression analyses. Results: We identified 2061 HCC p atients and 6183 non-cancer controls. Compared with non-cancer controls, patie nts with HCC were male (66%v 36%) and non-White (34%v 18%). The proportion of HCC patients with diabetes (43%) was significantly greater than non-cancer controls (19%). In multiple logistic regression analyses that adjusted for demo graphics features and other HCC risk factors (HCV, HBV, alcoholic liver disease, and haemochromatosis),diabetes was associated with a threefold increase in the risk of HCC. In a subset of patients without these major risk factors, the adjus ted odds ratio for diabetes declined but remained significant (adjusted odds rat io 2.87 (95%con-fidence interval 2.49-3.30)). A significant positive interact ion between HCV and diabetes was detected (p< 0.0001). Similar findings persiste d in analyses restricted to diabetes recorded between two and three years prior to HCC diagnosis. Conclusions:Diabetes is associated with a 2-3-fold increase in the risk of HCC, regardless of the presence of other major HCC risk fac
基金Supported by An unrestricted grant from Roche-Italia
文摘Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.
