Predictive Utility of DASIMAR as a Prognostic Biomarker in Acute-on-chronic Liver Failure (ACLF)

NCT ID: NCT01071746

Last Updated: 2010-02-19

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 700 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2010-11-30

Brief Summary

Patients with acute on chronic liver failure have a risk of developing multiorgan failure and a high mortality. The current scoring systems defining the outcome of patients with acute decompensation of cirrhosis fail to identify patients that progress to Acute-on-chronic liver failure (ACLF).

The aim of the study is to evaluate if one can identify these patients early on with the proposed biomarkers: dimethylarginines and ischemia modified albumin.

Detailed Description

Patients with acute-on-chronic liver failure (ACLF) are at risk of multiorgan failure and high mortality. Recent data suggest that patients with decompensated liver cirrhosis have higher ADMA (asymmetrical dimethylarginine) levels compared to compensated cirrhosis and plasma ADMA levels correlate with severity of liver dysfunction and inflammation. There is also an increase in symmetric dimethylarginine (SDMA), a stereo-isomer of ADMA, which is largely excreted by the kidney. Plasma SDMA levels have been shown to be associated with patients

progressing to renal failure. In a pilot study by our group involving 52 patients with acute decompensation of chronic liver disease, we showed an increase in the summed product of ADMA and SDMA, which we termed dimethylarginine score ('DAS'): This was shown to have a good predictive utility for outcome in this small group of patients (AUROC=0.89).

Furthermore, we and others have shown that albumin of patients with advanced liver disease has widespread abnormalities. The amount of albumin that is found to have reduced metal binding capacity as a consequence of oxidative damage is termed Ischemia Modified Albumin (IMA).

Our data shows that patients with ACLF who die have a significantly increased IMA/serum albumin ratio (IMAR). The summation of these two pathologically relevant biomarkers (DAS+IMAR) we termed DASIMAR and found this score to have a better predictive utility than DAS alone (AUROC:0.91).

Primary objective : To identify the patients early on that progress to ACLF which would facilitate a goal directed therapeutic approach.

Secondary objective : Generation of this dataset will further define and enable prognostication of ACLF. If this study reveals a role for these biomarkers in patients with ACLF, commercial development of simple kits may be possible.

Conditions

Liver Cirrhosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Acute decompensation of cirrhosis

acute decompensation of liver function occuring secondary to precipitating events such as sepsis, GI bleed.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• All patients with an acute clinical decompensation of presumed cirrhosis (elevated bilirubin >85 µmol/L, or/and increasing ascites or/and hepatic encephalopathy < grade 2) related to a clear precipitating event (e.g. infection, bleeding, alcoholic hepatitis, exposure to hepatotoxin)

Exclusion Criteria

• Admission for reasons other than decompensation of cirrhosis (other co-morbid diseases, especially established cardiovascular or renal disease (U/S).
• Malignancy (extra-hepatic or a hepatocellular carcinoma).
• Patients who have undergone major surgery or have unsolved surgical problems.
• Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

University College London Hospitals

OTHER

Sponsor Role: lead

Responsible Party

University College London Hospitals

Principal Investigators

Rajeshwar P Mookerjee, BScMRCPPhD

Role: PRINCIPAL_INVESTIGATOR

University College London Hospital

Locations

University College London Hospital

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Rajeshwar P Mookerjee, BScMRCPPhD

Role: CONTACT

r.mookerjee@ucl.ac.uk

02076796516

Naina Shah, MBBSMRCP

Role: CONTACT

naina.shah@ucl.ac.uk

02076796516

Facility Contacts

Rajeshwar P Mookerjee, BScMRCPPhD

Role: primary

02076796516

Naina Shah, MBBSMRCP

Role: backup

02076796516

Other Identifiers

08/HO714/8

Identifier Type: -

Identifier Source: org_study_id