Obeticholic Acid Among Chronic HBV Patients with Hepatic Steatosis : Clinical and Portal Doppler Outcomes
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Degree of hepatic steatosis before and after six months of obeticholic acid use
研究概览
简要总结
In this study, the investigators aimed to evaluate the hepatoprotective effect of OCA against HBV-induced liver injury by comparing patients demographic , laboratory date ( liver function , viremia ) , degree of hepatic steatosis and fibrosis and portal doppler at the beginning and after six months .
详细描述
Background :Obeticholic acid (OCA) is an agonist of the farnesoid X receptor (FXR), which plays an important role in the maintenance of bile acid homeostasis . OCA lessens liver exposure to the impact of bile acids . In addition, it binds and activates FXRs in the intestine and liver, leading to anti-inflammatory and anti-fibrotic impacts with modulation of metabolic profiles. It also inhibits the production of bile acids and increases their transport outside the hepatocytes . Activation of FXRs by OCA is 100 times higher than that exerted by chenodeoxycholic acid in attenuating intestinal and hepatic inflammation and/or fibrosis . Through modulation of bile acid homeostasis, OCA effectively reduces cholestasis-induced liver inflammation/injury.
Hepatitis B virus (HBV) is a hepatotropic virus and an important human pathogen. There are an estimated 296 million people in the world that are chronically infected by this virus, and many of them will develop severe liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC).
A recent study displayed that FXR agonists potentially affect the proliferation of the hepatitis B virus (HBV). FXR agonists interact with HBV viral proteins preventing their transcription and triggering off the reduction of HBV viral protein . These findings may explain the role of OCA to antagonize HBV infection. In addition, in cirrhotic animals, OCA restored intrahepatic endothelial nitric oxide(NO) synthase levels and enhances dimethylarginine dimethylaminohydrolase 1 (DDAH1)-regulated NO production, which ultimately led to a reduction of portal pressure .
Study tools :
- All patients will be included within certain inclusion criteria after informed consent from patients and permission from the hospital board to review patients' medical records.
- Patients will be randomly divided into two groups , the first will receive obeticholic acid at a dose of 5 mg once daily and antiviral drug ,and the other will receive the antiviral drug only for six months
- All patients at the beginning of the study and at the end of six months will be subjected to:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 18 years of age or older who had diagnosed as chronic HBV on treatment with with Controlled Attenuation Parameter (CAP) value more than 238 dB/m .
排除标准
- •patients under the age of
- •patients with other viral hepatitis infection .
- •Hepatocellular carcinoma .
- •portal vein thrombosis.
- •Subjects with risk of 2nd hepatic steatosis liver disease (excessive alcohol consumption and medications).
- •history of liver disease such as (α-1 antitrypsin deficiency, autoimmune hepatitis, drug-induced liver injury, 1ry biliary cirrhosis, 1ry sclerosing cholangitis).
- •Body Mass Index (BMI) > 35 (to avoid the possibility of Fibroscan failure).
- •Patient with end organ disease.
研究组 & 干预措施
the group will receive obeticholic acid
The first group that will receive obeticholic acid for six months
干预措施: Obeticholic Acid 5 mg (Drug)
结局指标
主要结局
Degree of hepatic steatosis before and after six months of obeticholic acid use
时间窗: 6 months
comparing result of fibroscan regarding degree of steatosis ,controlled attenuation parameter (CAP) which assess amount of steatosis, before and after six months of using obeticholic acid
次要结局
- portal vein doppler assesment(6 months)
研究者
Michael Melad Fekry Endrawes
Assistant lecturer of internal medicine
Assiut University