Risk of HCC in Cirrhotic Patients Post DAAs Ttt

January 29, 2018 updated by: Alshaimaa Mohammed Rafat Ali, Assiut University

Risk of Hepatocellular Carcinoma in HCV Cirrhotic Patients Treated With Direct Acting Antiviral Drugs.

Direct acting antivirals (DAAs) are a novel and completely oral hepatitis C therapy . DAAs are used in most patients being treated for hepatitis C, including those with decompensated cirrhosis. This type of treatment has now completely replaced interferon-based therapy .Therapy of chronic hepatitis C with direct-acting antivirals (DAAs) is able to induce a sustained virological response (SVR) in over 85% of patients, even if liver cirrhosis is present. Cirrhotic patients should be closely monitored after treatment.HCC is thought to develop over time as the liver is exposed to inflammation and develops fibrosis. Thus, if DAAs can eliminate inflammation mediated by HCV, the risk of HCC should decrease. However, several centers have observed that this actually may not be the case. Tumor genesis occurs through a multistep, multifactorial process. Eliminating HCV-induced inflammation may not be enough to decrease risk of HCC.DAAs have provided an effective, well tolerated treatment for hepatitis C in patents with cirrhosis . However, several studies have shown unexpectedly high rates of recurrence of HCC in the early post DAAs treatment time period.

  1. Evalution of occurrence and risk factors for hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis after direct acting antiviral drugs (DAAs) therapy.
  2. To asses diagnostic value of novel markers in patients who developed hepatocellular carcinoma (HCC) after (DAAs)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

HCV is a worldwide infection, it is estimated that about at about 3.0% (170-200 million people) of the world's population are infected. HCV is associated with an increased disease burden due to liver cirrhosis and considerable mortality . More than 350,000 people dying each year from hepatitis C-related liver disease. Adding to the problem of HCV infection is the presence of occult HCV infection.

Egypt has the highest prevalence worldwide, it is estimated to be 14.7% among a representative sample of Egyptian population, aged 15-59 year . Egypt is among countries responsible for 80.0% of global infections. Further, prevalence is higher among hospitalized patients and special clinical populations.

Hepatitis C virus (HCV) has great genetic variability, with 6 major genotypes (GTs); GT-1 to 6. In Egypt, HCV is almost exclusive GT-4 distribution. HCV has significant differences in their global distribution and prevalence.

Worldwide, Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and one of the leading causes of death among patients with cirrhosis. In Egypt, HCC is the second most common cancer in men and the sixth most common cancer in women.

Direct acting antivirals (DAAs) are a novel and completely oral hepatitis C therapy . DAAs are used in most patients being treated for hepatitis C, including those with decompensated cirrhosis. This type of treatment has now completely replaced interferon-based therapy .Therapy of chronic hepatitis C with direct-acting antivirals (DAAs) is able to induce a sustained virological response (SVR) in over 85% of patients, even if liver cirrhosis is present. Cirrhotic patients should be closely monitored after treatment.

HCC is thought to develop over time as the liver is exposed to inflammation and develops fibrosis. Thus, if DAAs can eliminate inflammation mediated by HCV, the risk of HCC should decrease. However, several centers have observed that this actually may not be the case. Tumor genesis occurs through a multistep, multifactorial process. Eliminating HCV-induced inflammation may not be enough to decrease risk of HCC.

DAAs have provided an effective, well tolerated treatment for hepatitis C in patents with cirrhosis. However, several studies have shown unexpectedly high rates of recurrence of HCC in the early post DAAs treatment time period.

MicroRNAs (miRNAs) are a set of small, single-stranded, non-coding RNA molecules (21-30 nucleotides) that negatively regulate gene expression at the posttranscriptional level by translational inhibition or degradation of target mRNA, depending on the degree of complementary base pairing. Aberrant expression of miRNA is common in various human malignancies and modulates cancer-associated genomic regions or fragile sites. As for the relationship between miRNA and HCC several studies have demonstrated that the aberrant expression of specific miRNA can be detected in HCC cells and tissues. However, little is known about the mechanisms of miRNA-related cell proliferation and development.ref

Aim of work:

  1. Evalution of occurrence and risk factors for hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis after direct acting antiviral drugs (DAAs) therapy.
  2. To asses diagnostic value of novel markers in patients who developed hepatocellular carcinoma (HCC) after direct acting antiviral drugs -DAAs -therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

This study is a prospective study that will be carried out on patients with HCV-related liver cirrhosis treated with direct acting antiviral drugs at ALRAJHI Liver hospital, Assiut university from February 2018 to December 2019.

Description

Inclusion Criteria:

  • Patients with HCV-related liver cirrhosis (eligible for treatment) who developed (HCC) after DAAs therapy within one year follow up.
  • Age and sex matched group of patients with HCV- related liver cirrhosis who didn't develop HCC after DAAs therapy within one year follow up(as control group)
  • Patients with chronic HCV related liver cirrhosis complicated by hepatocellular carcinoma not eligible for treatment.(discovered during enrollment in HCV treatment program)

Exclusion Criteria:

  • Patients who refuse to participate in the study.
  • Patients with hepatitis B virus, any other causes of cirrhosis.(Alcohol consumpation, Biliary, Cardiac…..etc)
  • Patients with cancers other than HCC or metastatic liver cancer.
  • Patients who developed HCC on transplanted liver.
  • Patients who previously treated for HCC.
  • Patients who receive any immunosuppression drugs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
HCV patients receiving DAAs
Patients with HCV-related liver cirrhosis (eligible for treatment) who will recieve DAAs therapy with one year follow up.markers: miR121, miR122, miR124will be assessed in both groups before and after DAAs

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Occurrence and risk factors for HCC post DAAs
Time Frame: One year
Perecentage of occurrence of hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis after direct acting antiviral drugs (DAAs) therapy.
One year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Diagnostic value of miRNA in patients who developed HCC post DAAs
Time Frame: One Year
Measuring miRNA in patients who developed HCC post DAAs in mmol/L
One Year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assiut University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alshaimaa Rafat, MD, Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2018

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 23, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 30, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 30, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HCCDAAs

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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