Epigenetic Changes in Hepatocellular Carcinoma Developed After Direct Acting Antiviral Therapy for Chronic Hepatitis C

NCT ID: NCT04220151

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-03-01
• Study Completion Date: 2021-01-01

Brief Summary

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.

Detailed Description

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Hepatocellular carcinoma

Sixty patients with HCC

DNA methylation

Intervention Type: GENETIC

DNA methylation will be measured by real time polymerase chain reaction

Hepatic cirrhosis

Thirty patients with hepatic cirrhosis

DNA methylation

Intervention Type: GENETIC

DNA methylation will be measured by real time polymerase chain reaction

Healthy controls

Ten healthy controls.

DNA methylation

Intervention Type: GENETIC

DNA methylation will be measured by real time polymerase chain reaction

Interventions

DNA methylation

DNA methylation will be measured by real time polymerase chain reaction

Intervention Type: GENETIC

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Reham I El-mahdy

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

reham elmahdy

Role: CONTACT

reham.elmahdy@aun.edu.eg

+201002714637

References

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Reference Type: BACKGROUND

PMID: 31057614 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31546948 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26319021 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31216276 (View on PubMed)

Other Identifiers

Hepatocellular carcinoma

Identifier Type: -

Identifier Source: org_study_id