Changes in Liver Fibrosis, Lipid Profile and Insulin Resistance in HCV Patients Who Received Antiviral Therapy

Sponsor

Assiut University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03612973

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hepatitis C virus (HCV) is one of the major globally cause of death and morbidity.Chronic hepatitis C is the leading cause of end-stage liver disease, hepatocellular carcinoma and liver-related death in Egypt.It could be considered a special type of metabolic diseases involving insulin resistance (IR) which accelerates fibrosis and modulation of lipid-cholesterol biosynthesis with increased risk for ischemic heart diseases.It could be considered a special type of metabolic diseases involving insulin resistance (IR) which accelerates fibrosis and modulation of lipid-cholesterol biosynthesis with increased risk for ischemic heart diseases .Increased prevalence of IR and type 2 diabetes mellitus extensively reported in HCV infections

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis c	Diagnostic Test: lipid profile Diagnostic Test: fasting insulin Diagnostic Test: fibro scan	N/A

Detailed Description

Hepatitis C virus (HCV) is one of the major globally cause of death and morbidity and recent estimates showed increase in its prevalence over the last decade to > 185 million infections worldwide. Prevalence HCV infection in Egypt is the highest in the world.Chronic viral hepatitis infection increases liver fibrosis and stiffness and is an important cause of liver cirrhosis. Chronic hepatitis C is the leading cause of end-stage liver disease, hepatocellular carcinoma and liver-related death in Egypt.It could be considered a special type of metabolic diseases involving insulin resistance (IR) which accelerates fibrosis and modulation of lipid-cholesterol biosynthesis with increased risk for ischemic heart diseases .Increased prevalence of IR and type 2 diabetes mellitus extensively reported in HCV infections.Interferon (INF) based therapy was used in chronic HCV patient and investigators reported that it's effective in eradicating HCV RNA and improving liver fibrosis. However, It's associated with several side effects.Novel direct antiviral agents (DAA) for chronic hepatitis C have entered clinical practice. This therapeutics has minimal side effects and achieves sustained virological response (SVR) rates of above 90% of patients and they are shorter and simpler regimens.Liver fibrosis severity assessment is important when staging chronic HCV and it reflects impact of serological viral eradication on hepatic damage and fibrosis. Although liver biopsy is the gold standard procedure for fibrosis assessment, but non-invasive new approaches have been strongly recommended for evaluation of fibrosis, mainly in HCV. They have no complications and have good diagnostic accuracy. One of the most used non-invasive mechanical methods based on ultrasound is transient elastography (Fibro Scan). Although association of baseline metabolic characteristics with treatment outcome has not been fully assessed for DAAs, this group was reported to result in improved rates of SVR and to reduce the predictive ability of these factors except for the baseline low density lipoprotein. The highest prevalence of HCV was reported in Egypt, where genotype 4 is responsible for 91% of infections and DAAs represented main line of treatment in most centers.Although the changes in lipid metabolism after treatment with DAAs were reported for other genotypes. It was not fully studied in genotype 4 infected patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

both study groups will be investigated at same timeboth study groups will be investigated at same time

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Assessment of Changes in Liver Fibrosis and Stiffness, Lipid Profile and Insulin Resistance in Patients With Chronic Hepatitis C Viral Infection Who Received Direct Acting Antiviral Therapy

Actual Study Start Date :

Jun 1, 2019

Anticipated Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: non cirrhotic HCV patients complete blood picture Liver and renal function tests Prothrombin time and concentration HCV quantitative polymerase chain reaction Hepatitis B surface Ag lipid profile fasting blood glucose level fasting insulin level homeostasis model for the assessment of insulin resistance (HOMA-IR) fibrosis (FIB- 4) index Aspartate aminotransferase (AST)/platelet ratio index (APRI) Abdominal ultrasound to assess liver and spleen Fibroscan/transient elastography to grade hepatic fibrosis all these investigations will be done before and after receiving direct acting antiviral therapy (sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily) for 12 weeks	Diagnostic Test: lipid profile Serum samples will be withdrawn after fasting 12 hours then performed on Siemens Dimension Max: Total cholesterol and triglyceride concentrations will be estimated using enzymatic methods ( Roche Diagnostics, Mannheim, Germany). High density lipoprotein cholesterol will be determined after precipitation with phosphotungstic acid/magnesium chloride. Low density lipoprotein(LDL) cholesterol will be measured directly with a commercially available direct LDL-C assay (LDL-C Plus assay; Roche Diagnostics) Diagnostic Test: fasting insulin serum samples used for doing the test by ELISA after fasting for 8 h Diagnostic Test: fibro scan liver stiffness by fibro scan before and after treatment
Active Comparator: cirrhotic HCV patients complete blood picture Liver and renal function tests Prothrombin time and concentration HCV quantitative polymerase chain reaction Hepatitis B surface Ag lipid profile fasting blood glucose level fasting insulin level homeostasis model for the assessment of insulin resistance (HOMA-IR) Fibrosis (FIB- 4) index Aspartate aminotransferase (AST)/platelet ratio index (APRI) Abdominal ultrasound to assess liver and spleen Fibroscan/transient elastography to grade hepatic fibrosis all these investigations will be done before and after receiving direct acting antiviral therapy (sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily) for 12 weeks	Diagnostic Test: lipid profile Serum samples will be withdrawn after fasting 12 hours then performed on Siemens Dimension Max: Total cholesterol and triglyceride concentrations will be estimated using enzymatic methods ( Roche Diagnostics, Mannheim, Germany). High density lipoprotein cholesterol will be determined after precipitation with phosphotungstic acid/magnesium chloride. Low density lipoprotein(LDL) cholesterol will be measured directly with a commercially available direct LDL-C assay (LDL-C Plus assay; Roche Diagnostics) Diagnostic Test: fasting insulin serum samples used for doing the test by ELISA after fasting for 8 h Diagnostic Test: fibro scan liver stiffness by fibro scan before and after treatment

Arm

Intervention/Treatment

Active Comparator: non cirrhotic HCV patients

complete blood picture Liver and renal function tests Prothrombin time and concentration HCV quantitative polymerase chain reaction Hepatitis B surface Ag lipid profile fasting blood glucose level fasting insulin level homeostasis model for the assessment of insulin resistance (HOMA-IR) fibrosis (FIB- 4) index Aspartate aminotransferase (AST)/platelet ratio index (APRI) Abdominal ultrasound to assess liver and spleen Fibroscan/transient elastography to grade hepatic fibrosis all these investigations will be done before and after receiving direct acting antiviral therapy (sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily) for 12 weeks

Diagnostic Test: lipid profile

Serum samples will be withdrawn after fasting 12 hours then performed on Siemens Dimension Max: Total cholesterol and triglyceride concentrations will be estimated using enzymatic methods ( Roche Diagnostics, Mannheim, Germany). High density lipoprotein cholesterol will be determined after precipitation with phosphotungstic acid/magnesium chloride. Low density lipoprotein(LDL) cholesterol will be measured directly with a commercially available direct LDL-C assay (LDL-C Plus assay; Roche Diagnostics)

Diagnostic Test: fasting insulin

serum samples used for doing the test by ELISA after fasting for 8 h

Diagnostic Test: fibro scan

liver stiffness by fibro scan before and after treatment

Active Comparator: cirrhotic HCV patients

complete blood picture Liver and renal function tests Prothrombin time and concentration HCV quantitative polymerase chain reaction Hepatitis B surface Ag lipid profile fasting blood glucose level fasting insulin level homeostasis model for the assessment of insulin resistance (HOMA-IR) Fibrosis (FIB- 4) index Aspartate aminotransferase (AST)/platelet ratio index (APRI) Abdominal ultrasound to assess liver and spleen Fibroscan/transient elastography to grade hepatic fibrosis all these investigations will be done before and after receiving direct acting antiviral therapy (sofosbuvir 400 mg once daily + daclatasvir 60 mg once daily) for 12 weeks

Diagnostic Test: lipid profile

Diagnostic Test: fasting insulin

serum samples used for doing the test by ELISA after fasting for 8 h

Diagnostic Test: fibro scan

liver stiffness by fibro scan before and after treatment

Outcome Measures

Primary Outcome Measures

Changes in liver fibrosis in HCV patients after receiving direct acting antiviral therapy [1 year]
by using non-invasive measures (fibro scan) before and after end of treatment (12 weeks0

Secondary Outcome Measures

Effect of HCV treatment by direct acting antiviral therapy on lipid profile of chronic HCV patients [1 year]
changes in values of total cholesterol, triglycerides, LDL and HDL at the baseline and end of treatment (12 weeks)
Changes and degree of improvement in insulin resistance in HCV patients after receiving direct acting antiviral therapy [1 year]
measuring fasting insulin and glucose level with calculation of homeostasis model for the assessment of insulin resistance at the baseline and end of treatment (12 weeks)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 ys.
Disease status: patients with chronic hepatitis C infection, based on the presence of anti-HCV and detectable serum HCV-RNA for 6 months or more who had different grades of fibrosis (F) as estimated by fibroscan
Treatment: treatment naïve patients who will receive direct acting antiviral drugs (Sofosbuvir and Daclatasvir ± ribavirin) for 12 weeks
Negative hepatitis B virus surface Ag and HIV antibodies
No history of hepatocellular carcinoma or development of hepatocellular carcinoma during the treatment period
No other causes of chronic liver disease (alcohol consumption more than 80 g/day, hepatotoxic drugs, autoimmune hepatitis, primary biliary cholangitis, hemochromatosis and Wilson's disease).

Exclusion Criteria:

Diabetic patients.
Patients using lipid lowering agents.
HCV co-infection with hepatitis B virus(HBV) or human immunodeficiency virus(HIV)
Presence of other causes of chronic liver disease (alcohol consumption more than 80 g/day, hepatotoxic drugs, autoimmune hepatitis, primary biliary cholangitis, hemochromatosis and Wilson's disease).
Patients with hepatocellular carcinoma