Clinical trial NCT04220151: Epigenetic Changes in Hepatocellular Carcinoma Developed After Direct Acting Antiviral Therapy for Chronic Hepatitis C
Official title: Epigenetic Changes in Hepatocellular Carcinoma Developed After Direct Acting Antiviral Therapy for Chronic Hepatitis C
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Epigenetics
DNA methylation
Direct-acting antivirals
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-01-07
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Hepatocellular carcinoma patients

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.

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

Primary outcomes:
measure: Percentages of methylation of DNA in patients with HCC
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
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citation: 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.
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