Advertisement

Topics

Cholestatic Drug-induced Liver Injury

2014-08-27 03:13:02 | BioPortfolio

Summary

Cholestatic drug-induced liver injury (DILI) is the severe form of DILI with a grave outcome. Drug-metabolizing enzymes play an important role in the metabolism of drugs. The genetic polymorphism of drug-metabolizing enzymes may influence the activities and expression of these enzymes and thereby affect the susceptibility and severity of DILI. UDP-glucuronosyltransferase (UGT) is an important phase 2 detoxification enzyme, which is related to congenital hyperbilirubinemia. Recently, the genetic polymorphism of UGT1A1 was reported to be associated with jaundice induced by some drugs, and UGT1A7 was shown to be related to the susceptibility of hepatocellular carcinoma and other cancers. Ursodeoxycholic acid (UDCA ) is a hydrophilic bile acid that is increasingly used for the treatment of various cholestatic disorders. The aims of this study are (1) to assess the association of the genetic polymorphism of UGT1A1 and 1A7, and the susceptibility and severity of drug-induced liver injury (DILI), with emphasis on the cholestatic DILI; (2) to evaluate the treatment effect of UDCA in the DILI, with special reference to the cholestatic hepatotoxicity.

Description

Cholestatic drug-induced liver injury (DILI) is the severe form of DILI with a grave outcome. Drug-metabolizing enzymes play an important role in the metabolism of drugs. The genetic polymorphism of drug-metabolizing enzymes may influence the activities and expression of these enzymes and thereby affect the susceptibility and severity of DILI. UDP-glucuronosyltransferase (UGT) is an important phase 2 detoxification enzyme, which is related to congenital hyperbilirubinemia. Recently, the genetic polymorphism of UGT1A1 was reported to be associated with jaundice induced by some drugs, and UGT1A7 was shown to be related to the susceptibility of hepatocellular carcinoma and other cancers. Ursodeoxycholic acid (UDCA ) is a hydrophilic bile acid that is increasingly used for the treatment of various cholestatic disorders. The aims of this study are (1) to assess the association of the genetic polymorphism of UGT1A1 and 1A7, and the susceptibility and severity of drug-induced liver injury (DILI), with emphasis on the cholestatic DILI; (2) to evaluate the treatment effect of UDCA in the DILI, with special reference to the cholestatic hepatotoxicity.

Owing to the limited number of DILI patients, 3 years are needed in this study. Each year, a total of 60 patients with DILI and 60 age- and sex-matched controls will be enrolled in this study. Their genetic polymorphisms of UGT1A1 and UGT1A7 will be assessed using the real time PCR, or PCR with RFLP. The DILI patients will be randomized to UDCA Treatment group and Control group. UDCA 13-15 mg/kg/day with 3 divided doses will be administered to the patients with Treatment group.

The frequencies of genotypes of UGT1A1 and 1A7 will be compared between DILI cases and controls, survival cases and non-survival cases, and cholestatic and non-cholestatic cases. Chi-square test, with or without Yates' correction, will be used to compare the categorical parameters. A paired t test will be performed to compare the continuous parameters. Odds ratios (OR) and confidence intervals (CI) will be calculated using a logistic regression analysis. The multivariate logistic regression analysis will be applied to check on the OR, adjusted with other possible risk factors. Survival rates will be estimated from survival curves based on the Kaplan-Meier method and compared with the log-rank test between the UDCA Treatment group and Control group.

We believe that this pharmacogenetic study may help us realize the pathogenesis of cholestatic DILI, and the clinical trial can elucidate the therapeutic value of UDCA in the DILI, especially in the cholestatic hepatotoxicity.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Conditions

Hepatitis, Toxic

Intervention

Ursodeoxycholic Acid, Placebo

Location

Taipei Veterans General Hospital
Taipei
Taiwan
11217

Status

Recruiting

Source

Taipei Veterans General Hospital,Taiwan

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:13:02-0400

Clinical Trials [2647 Associated Clinical Trials listed on BioPortfolio]

Efficacy and Safety Study of Ursodeoxycholic Acid to Treat Chronic Hepatitis C

This study is a 24-week multicenter, randomized, double-blind control trial with ursodeoxycholic acid (UDCA) in patients with chronic hepatitis C in Japan. The primary objectives of this s...

Effectiveness of Ursodeoxycholic Acid Use in the Prevention of Gallstone Formation After Sleeve Gastrectomy

This is a randomized double-blind placebo-controlled trial with a total of 100 patients who are free of gallstones at baseline. The study involves taking an oral drug (Ursodeoxycholic Acid...

Remission Induction of Primary Biliary Cholangitis-autoimmune Hepatitis Overlap Syndrome

Biochemical response of primary biliary cholangitis-autoimmune hepatitis overlap syndrome induced by ursodeoxycholic acid only or combination therapy of immunosuppressive agents

Ursodeoxycholic Acid for Rhegmatogenous Retinal Detachment

20 patients presenting a rhegmatogenous retinal detachment with more than 4 days of duration will be prospectively included. A single dose of ursodeoxycholic acid will be administered ora...

Ursodeoxycholic Acid in the Treatment of Duodenal Adenomas in Familial Adenomatous Polyposis (FAP) Patients

Malignant transformation of adenomas of the duodenum is now the leading cause of death in familial adenomatous polyposis (FAP) patients who had a restorative proctocolectomy. Ursodeoxychol...

PubMed Articles [10658 Associated PubMed Articles listed on BioPortfolio]

Increased prescribing of ursodeoxycholic acid in Norway.

Background Ursodeoxycholic acid is a hydrophilic bile acid prescribed for a variety of cholestatic liver disorders, although with variable clinical evidence with regards to efficacy. Objective The aim...

A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis.

Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome prol...

Cost effectiveness of using ursodeoxycholic acid to treat primary biliary cholangitis.

Primary biliary cholangitis is a chronic inflammatory, autoimmune cholestatic liver disease, which untreated will usually progress to end-stage biliary cirrhosis. The aims of treatment and management ...

Adherence to ursodeoxycholic acid therapy in patients with cholestatic and autoimmune liver disease.

Ursodeoxycholic acid (UDCA) is used for treatment of cholestatic liver diseases and may improve long-term outcome. Although treatment with this hydrophilic bile acid is virtually without side effects,...

Influence factors and a predictive scoring model for measuring the biochemical response of primary biliary cholangitis to ursodeoxycholic acid treatment.

The biochemical response after ursodeoxycholic acid (UDCA) treatment contributes toward predicting the prognosis for primary biliary cholangitis (PBC) patients. This study aimed to establish a score m...

Medical and Biotech [MESH] Definitions

An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.

INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D).

A family of hepatotropic DNA viruses which contains double-stranded DNA genomes and causes hepatitis in humans and animals. There are two genera: AVIHEPADNAVIRUS and ORTHOHEPADNAVIRUS. Hepadnaviruses include HEPATITIS B VIRUS, duck hepatitis B virus (HEPATITIS B VIRUS, DUCK), heron hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis B virus (HEPATITIS B VIRUS, WOODCHUCK).

A species in the genus HEPATOVIRUS containing one serotype and two strains: HUMAN HEPATITIS A VIRUS and Simian hepatitis A virus causing hepatitis in humans (HEPATITIS A) and primates, respectively.

INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS, a defective RNA virus that can only infect HEPATITIS B patients. For its viral coating, hepatitis delta virus requires the HEPATITIS B SURFACE ANTIGENS produced by these patients. Hepatitis D can occur either concomitantly with (coinfection) or subsequent to (superinfection) hepatitis B infection. Similar to hepatitis B, it is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.

More From BioPortfolio on "Cholestatic Drug-induced Liver Injury"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Hepatology
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...


Searches Linking to this Trial