Hepatitis C virus(HCV)affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma.Globally,at least one third of hepatocellular carcinoma cases are attributed to HCV infe...Hepatitis C virus(HCV)affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma.Globally,at least one third of hepatocellular carcinoma cases are attributed to HCV infection,and 350000 people died from HCV related diseases per year.There is a great geographical variation of HCV infection globally,with risk factors for the HCV infection differing in various countries.The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations.A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma,and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma.However,prospective cohorts comprising individuals with HCV infection are still uncommon.The risk evaluation of viral load elevation and associated liver disease/cancer in HCV(REVEAL-HCV)study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years.Most of them have acquired HCV infection through iatrogenic transmission routes.As the participants in the REVEALHCV study rarely receive antiviral therapies,it provides a unique opportunity to study the natural history of chronic HCV infection.In this review,the prevalence,risk factors and natural history of HCV infection are comprehensively reviewed.The study cohort,data collection,and findings on liver disease progression of the REVEAL-HCV study are described.展开更多
Risk calculators are widely used in many clinical fields,and integrate several important risk factors through the conversion of a risk function into a single measure of risk.Several studies have been carried out to cr...Risk calculators are widely used in many clinical fields,and integrate several important risk factors through the conversion of a risk function into a single measure of risk.Several studies have been carried out to create risk calculators for the prediction of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB).Most of them were hospital-based,with limited sample sizes and insufficient external validation.These study groups collaborated to establish the REACH-B risk score,which incorporated five clinical variables to predict HCC risk.This risk score was then validated ininternational clinical cohorts.Evidence suggests that quantitative serum HBsAg level provides additional predictability of HCC,especially in patients with low levels of hepatitis B virus DNA.This novel marker was incorporated into a risk calculator and was internally validated.This tool will hopefully be externally validated in the near future.Risk calculators can be used to support clinical practice,and to establish preventive measures;several"off-label"extension usages have also been implemented.Albeit beneficial,several precautions and discussions should be noted in using the risk calculators.The future development of risk calculators for CHB patients can be extended by applying them to additional CHB-related outcomes,and by incorporating emerging risk parameters.展开更多
AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles...AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicated in additional prospective studies.展开更多
文摘Hepatitis C virus(HCV)affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma.Globally,at least one third of hepatocellular carcinoma cases are attributed to HCV infection,and 350000 people died from HCV related diseases per year.There is a great geographical variation of HCV infection globally,with risk factors for the HCV infection differing in various countries.The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations.A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma,and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma.However,prospective cohorts comprising individuals with HCV infection are still uncommon.The risk evaluation of viral load elevation and associated liver disease/cancer in HCV(REVEAL-HCV)study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years.Most of them have acquired HCV infection through iatrogenic transmission routes.As the participants in the REVEALHCV study rarely receive antiviral therapies,it provides a unique opportunity to study the natural history of chronic HCV infection.In this review,the prevalence,risk factors and natural history of HCV infection are comprehensively reviewed.The study cohort,data collection,and findings on liver disease progression of the REVEAL-HCV study are described.
基金Supported by The Department of Health,Executive Yuan,Taipei,Taiwan,Bristol-Myers Squibb Co.,United StatesAcademia Sinica,Taipei,Taiwan+1 种基金the National Science Council No.NSC101-2314-B-039-029-MY3,Taipei,Taiwanthe National Health Research Institutes(NHRI-EX98-9806PI),Chunan,Taiwan
文摘Risk calculators are widely used in many clinical fields,and integrate several important risk factors through the conversion of a risk function into a single measure of risk.Several studies have been carried out to create risk calculators for the prediction of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB).Most of them were hospital-based,with limited sample sizes and insufficient external validation.These study groups collaborated to establish the REACH-B risk score,which incorporated five clinical variables to predict HCC risk.This risk score was then validated ininternational clinical cohorts.Evidence suggests that quantitative serum HBsAg level provides additional predictability of HCC,especially in patients with low levels of hepatitis B virus DNA.This novel marker was incorporated into a risk calculator and was internally validated.This tool will hopefully be externally validated in the near future.Risk calculators can be used to support clinical practice,and to establish preventive measures;several"off-label"extension usages have also been implemented.Albeit beneficial,several precautions and discussions should be noted in using the risk calculators.The future development of risk calculators for CHB patients can be extended by applying them to additional CHB-related outcomes,and by incorporating emerging risk parameters.
基金Supported by the Grant NSC 2000-2314-B-002-373, NSC 2001-2320-B-002-123 and NSC 2002-2320-B-002-121 from the National Science Council, Taipei, Taiwan, China
基金Supported by National Institutes of Health grants,RO1ES005116(Santella RM)and P30ES009089(Santella RM)
文摘AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicated in additional prospective studies.
