Clinical trial NCT03882307: Levels of Interleukin-6 andTransforming Growth Factor Beta in HCV Patients Sera
Official title: Association of Serum Interleukin -6 and Transforming Growth Factor Beta Levels With Response to Antiviral Therapy for Chronic Hepatitis c Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Hepatitis C, Chronic
Keywords: hepatitis C virus therapy
interleukin-6
transforming growth factor -beta
sustained virological response
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2019-03-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: assess serum level of interleukin-6 and transforming growth factor beta before intervention and after intervention with sofosbuvir and daclatasvir.
Primary purpose: TREATMENT

Brief summary: Hepatitis C virus (HCV) infection is associated with significant morbidity and mortality owing to progression of a high percentage (85%) of HCV infected patients to chronic hepatitis, which might lead to the development of liver cirrhosis or hepato cellular carcinoma..

Egypt has possibly the highest HCV prevalence in the world, 10-20% of the general population .

Detailed description: Currently, second-generation direct-acting antiviral agents have been used for chronic hepatitis C treatment. The association of sofosbuvir with daclatasvir or simeprevir , with or without ribavirin , directly inhibits viral replication .

Sofosbuvir (400 mg once per day) and daclatasvir (60mg once per day) or simeprevir (150 mg once per day) for 3 months treatment regimens.

Sofosbuvir-based antiviral therapy guarantees efficacy in HCV eradication in approximately 90% of cases and is associated with mild to moderate adverse effects.

Overall, studies describe an increase in serum cytokine levels in chronic hepatitis C patients, when compared with healthy individuals. ,interleukin-6(IL-6) is produced mainly by kupffer cells and induces the production of the acute phase proteins, C-reactive protein and haptoglobin .

Previous studies reported that serum Interleukin-6 levels were increased, compared with healthy individuals, in patients with some liver diseases.Previous results suggest that baseline levels of Interleukin, as well as their decrease during treatment .Transforming growth factor beta (TGF-β) is a cytokine that has been assigned a key role in epithelial repair. Injury to the liver elicits a rapid increase in its expression. HCV -infected hepatocytes produce (TGF-β) which may stimulate T-regulatory cells.

Eligibility criteria: Inclusion Criteria:

* Age from 18 to 70 years.
* HCV RNA positivity .
* Any Body Mass Index(BMI).
* Treatment-naive or treatment experienced.
* all fibrosis stages.

Exclusion criteria:

* Direct serum bilirubin greater than 2 mg/dl.
* Serum albumin less than 2.8 g/dl.
* International normalization ratio (INR) greater than or equal to 1.7
* Platelet count less than 50 000/mm3.
* Ascites or history of ascites.
* Hepatic encephalopathy or history of hepatic encephalopathy.
* Hepatocellular carcinoma.
* Serum creatinine greater than 2.5 mg/dl .
* Pregnancy.

Primary outcomes:
measure: mean difference in level of interleukin-6 and transforming growth factor beta after treatment
timeFrame: three months from the end of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut university
Study officials:
affiliation: faculty of medicine,medical microbiology department
name: hayam hamdy, master deree
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218.
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