Prediction model of hepatocarcinogenesis for patients with hepatitis C virus-related cirrhosis. Validation with internal and external cohorts

Ikeda, Kenji; Arase, Yasuji; Saitoh, Satoshi; Kobayashi, Masahiro; Someya, Takashi; Hosaka, Tetsuya; Akuta, Norio; Suzuki, Yoshiyuki; Suzuki, Fumitaka; Sezaki, Hitomi; Kumada, Hiromitsu; Tanaka, Akihisa; Harada, Hideharu

doi:10.1016/j.jhep.2006.02.008

Cited by 41 publications

(37 citation statements)

References 35 publications

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“…Other clinical variables supposed to be related to HCC occurrence, such as age (ref. 29; >68 or V 68 years old), gender (30), and ALT(ref. 31; >50 or V50 IU/L), could not differentiate gene expression in PBMCs.…”

Section: Resultsmentioning

confidence: 99%

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

et al. 2008

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Hepatocellular carcinoma (HCC) is frequently associated with infiltrating mononuclear inflammatory cells. We performed laser capture microdissection of HCC-infiltrating and noncancerous liver-infiltrating mononuclear inflammatory cells in patients with chronic hepatitis C (CH-C) and examined gene expression profiles. HCC-infiltrating mononuclear inflammatory cells had an expression profile distinct from noncancerous liver-infiltrating mononuclear inflammatory cells; they differed with regard to genes involved in biological processes, such as antigen presentation, ubiquitin-proteasomal proteolysis, and responses to hypoxia and oxidative stress. Immunohistochemical analysis and gene expression databases suggested that the up-regulated genes involved macrophages and Th1 and Th2 CD4 cells. We next examined the gene expression profile of peripheral blood mononuclear cells (PBMC) obtained from CH-C patients with or without HCC. The expression profiles of PBMCs from patients with HCC differed significantly from those of patients without HCC (P < 0.0005). Many of the up-regulated genes in HCCinfiltrating mononuclear inflammatory cells were also differentially expressed by PBMCs of HCC patients. Analysis of the commonly up-regulated or down-regulated genes in HCCinfiltrating mononuclear inflammatory cells and PBMCs of HCC patients showed networks of nucleophosmin, SMAD3, and proliferating cell nuclear antigen that are involved with redox status, the cell cycle, and the proteasome system, along with immunologic genes, suggesting regulation of anticancer immunity. Thus, exploring the gene expression profile of PBMCs may be a surrogate approach for the assessment of local HCC-infiltrating mononuclear inflammatory cells.

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Section: Resultsmentioning

confidence: 99%

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

et al. 2008

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“…Numerous predictive factors have been identified ranging from simple epidemiological parameters such as age or sex [21] to most sophisticated ones identified by molecular biology [22,23] . However most of the studies have assessed simultaneously a limited number of factors (sometimes only one) precluding global interpretation, and have included patients with different causes of liver diseases although risk factors might be different from a cause to another.…”

Section: Risk (Or Predictive) Factorsmentioning

confidence: 99%

“…However most of the studies have assessed simultaneously a limited number of factors (sometimes only one) precluding global interpretation, and have included patients with different causes of liver diseases although risk factors might be different from a cause to another. The more commonly identified predictive factors (most of them not specific to HCV patients) are age higher than 50, male sex, advanced cirrhosis (reflected by low platelet count or oesophageal varices), high basal alpha-fetoprotein (AFP) serum levels [21,24,25] , and more recently overweight and diabetes [26,27] . Factors can be combined in scores or indexes allowing to split patients between different categories of HCC risk.…”

Section: Risk (Or Predictive) Factorsmentioning

confidence: 99%

Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Trinchet

Ganne-Carrié²,

Nahon³

et al. 2007

WJG

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Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained.

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“…In the natural course of persistent viral infection, approximately 20-30 % of the patients develop liver cirrhosis within 20-30 years after HCV infection [32], and the estimated incidence of HCC in patients with HCV-associated liver cirrhosis is 1-8 % per year [33][34][35]. A number of studies reported the risk factors of HCV-related HCC development, including the level of fibrosis/cirrhosis present at diagnosis, alfa-fetoprotein levels, alanine aminotransferase levels, sex, age, platelet count, and HCV RNA levels [36][37][38]. Multicentric tumorigenesis, a major characteristic of HCV-associated HCC, makes curative treatment for HCC difficult, leading to high mortality.…”

Section: Introductionmentioning

confidence: 99%

Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection, inflammation, and tumorigenesis

et al. 2016

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Hepatitis virus infection is a leading cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Although anti-viral therapies against hepatitis B virus (HBV) and hepatitis C virus (HCV) have dramatically progressed during the past decade, the estimated number of people chronically infected with HBV and/or HCV is *370 million, and hepatitis virus-associated hepatocarcinogenesis is a serious health concern worldwide. Understanding the mechanism of virus-associated carcinogenesis is crucial toward both treatment and prevention, and the recently developed whole genome/exome sequencing analysis using next-generation sequencing technologies has contributed to unveiling the landscape of genetic and epigenetic aberrations in not only tumor tissues but also the background liver tissues underlying chronic liver damage caused by hepatitis virus infection. Several major mechanisms underlie the genetic and epigenetic aberrations in the hepatitis virus-infected liver, such as the generation of reactive oxidative stress, ectopic expression of DNA mutator enzymes, and dysfunction of the DNA repair system. In addition, direct oncogenic effects of hepatitis virus, represented by the integration of HBV-DNA, are observed in infected hepatocytes. Elucidating the whole picture of genetic and epigenetic alterations, as well as the mechanisms of tumorigenesis, will facilitate the development of efficient treatment and prevention strategies for hepatitis virus-associated HCC.

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Prediction model of hepatocarcinogenesis for patients with hepatitis C virus-related cirrhosis. Validation with internal and external cohorts

Cited by 41 publications

References 35 publications

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection, inflammation, and tumorigenesis

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