Epigenetic Changes in Hepatocellular Carcinoma Developed After Direct Acting Antiviral Therapy for Chronic Hepatitis C
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, its survival rate ranks only second to lung cancer and it is a severe threat to human health.
In Egypt, HCC constitutes a significant public health problem. Where it is responsible for 33.63% and 13.54% of all cancers in males and females respectively. It has a poor prognosis after discovery, which is usually at a late stage of disease. This had been strongly linked to the hepatitis C virus epidemic that affected around 10-15% of the Egyptian population during the last 3 decades, and was reported as the highest prevalence of HCV in the world. However, the pathophysiological mechanisms involved remain unclear. The occurrence of HCC is a complicated process involving multiple genes and steps. Imbalances in cellular signal transduction pathways, deficiencies in DNA repair regulating genes, activation of protooncogenes, inactivation of tumor suppressor genes and epigenetic modifications all promote the occurrence of liver cancer.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
HCC is the fourth leading cause of cancer mortality in 2018. The alarming incidence of HCC is explained by genetic and epigenetic alterations, as well as by the presence of risk factors: hepatitis C virus (HCV), hepatitis B virus (HBV) infection, alcohol consumption, smoking, diabetes, dietary exposure to aflatoxins, and obesity.
The development of direct-acting antivirals (DAAs) with cure rates of higher than 90% has been a major breakthrough in the management of patients with chronic HCV infection. However, although viral cure decreases the overall HCC risk in HCV-infected patients, it does not eliminate virus-induced HCC risk, especially in patients with advanced fibrosis. Furthermore, convenient biomarkers to robustly predict HCC risk after viral cure and strategies for HCC prevention are absent. These unexpected findings pose new challenges for patient management. Meanwhile, recent studies in patients treated with interferone-free therapy have also identified several risk factors for developing HCC after achieving sustained virological response (SVR), namely advanced hepatic fibrosis and higher levels of alpha feto protein and agglutinin-positive Mac-2 binding protein.
Epigenetics refers to inherited altered gene expression without an alteration of the DNA sequence itself. Epigenetic alterations, such as DNA hypomethylation or hypermethylation and aberrant expression of micro-RNAs have been studied and associated with HCC. Epigenetic changes may represent diagnostic and prognostic biomarkers of HCC.
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Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Bemonsteringsmethode
Studie Bevolking
Beschrijving
Inclusion Criteria:
- HCC treated with DAAs drugs for chronic hepatitis C in Assiut University Hospital.
Exclusion Criteria:
- Cases who started treatment for HCC like alcohol ablation or chemoembolization
- Hepatitis B infection
- Non-responder patients to DAAs
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
|---|---|
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Hepatocellular carcinoma
Sixty patients with HCC
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DNA methylation will be measured by real time polymerase chain reaction
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Hepatic cirrhosis
Thirty patients with hepatic cirrhosis
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DNA methylation will be measured by real time polymerase chain reaction
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Healthy controls
Ten healthy controls.
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DNA methylation will be measured by real time polymerase chain reaction
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Percentages of methylation of DNA in patients with HCC
Tijdsspanne: Baseline
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Hypermethylation is known to be associated with decreased gene expression
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Baseline
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Medewerkers en onderzoekers
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Publicaties en nuttige links
Algemene publicaties
- Aguilar-Medina M, Avendano-Felix M, Lizarraga-Verdugo E, Bermudez M, Romero-Quintana JG, Ramos-Payan R, Ruiz-Garcia E, Lopez-Camarillo C. SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer. J Oncol. 2019 Apr 1;2019:6754040. doi: 10.1155/2019/6754040. eCollection 2019.
- Cozma A, Fodor A, Vulturar R, Sitar-Taut AV, Orasan OH, Muresan F, Login C, Suharoschi R. DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma. Medicina (Kaunas). 2019 Sep 19;55(9):607. doi: 10.3390/medicina55090607.
- Saleh DA, Amr S, Jillson IA, Wang JH, Crowell N, Loffredo CA. Preventing hepatocellular carcinoma in Egypt: results of a Pilot Health Education Intervention Study. BMC Res Notes. 2015 Aug 29;8:384. doi: 10.1186/s13104-015-1351-1.
- Perez S, Kaspi A, Domovitz T, Davidovich A, Lavi-Itzkovitz A, Meirson T, Alison Holmes J, Dai CY, Huang CF, Chung RT, Nimer A, El-Osta A, Yaari G, Stemmer SM, Yu ML, Haviv I, Gal-Tanamy M. Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals. PLoS Genet. 2019 Jun 19;15(6):e1008181. doi: 10.1371/journal.pgen.1008181. eCollection 2019 Jun.
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Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het spijsverteringsstelsel
- RNA-virusinfecties
- Virusziekten
- Infecties
- Door bloed overgedragen infecties
- Overdraagbare ziekten
- Neoplasmata per histologisch type
- Neoplasmata
- Neoplasmata per site
- Adenocarcinoom
- Neoplasmata, glandulair en epitheel
- Neoplasmata van het spijsverteringsstelsel
- Lever Ziekten
- Flaviviridae-infecties
- Hepatitis, viraal, menselijk
- Lever neoplasmata
- Hepatitis, chronisch
- Hepatitis
- Carcinoom
- Carcinoom, hepatocellulair
- Hepatitis C
- Hepatitis C, chronisch
Andere studie-ID-nummers
- Hepatocellular carcinoma
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