Role of Bilirubin Molecular Species in Hepatic Encephalopathy and Acute-on-chronic Liver Failure

Recruiting

• Conditions: Hepatic Encephalopathy; Acute-On-Chronic Liver Failure
• Interventions: Diagnostic Test: Liquid Chromatography-Mass Spectrometry Method to identify bilirubin molecular species

• Registration Number: NCT05566548
• Lead Sponsor: Medica Sur Clinic & Foundation

Brief Summary

It has been identified that impaired liver function, as occurs in patients with liver cirrhosis, prevents proper conjugation of glucuronic acid with bilirubin; as a result, unconjugated bilirubin accumulates in the blood, and conjugated bilirubin is markedly altered to form diglucuronides or monoglucuronides. However, in the development and progress of acute-on-chronic liver failure (ACLF) there is not enough information about these processes and the possible concentration levels that they can take.

Also Hepatic encephalopathy (HE) is a reversible complication, but with a high mortality rate in patients with acute or chronic liver failure, as well as a consequence of the formation of portosystemic shunts.

Detailed Description

Liver cirrhosis is a pathological diagnosis characterized by diffuse fibrosis, severe alteration of intrahepatic arterial and venous flow, portal hypertension, and, ultimately, liver failure. The prevalence of liver cirrhosis in the Mexican population depends on various factors, including gender, ethnic groups, and geographic regions, in addition to the nature, frequency, and time of acquisition of the main risk factors for cirrhosis, such as the hepatitis B virus, hepatitis C virus (HCV) in addition to non-alcoholic steatohepatitis, non-alcoholic fatty liver or alcoholic liver disease. Liver cirrhosis has been classified as decompensated or compensated. Decompensated liver cirrhosis occurs when there is gradual progression over months causing liver and extrahepatic organ failure. On the other hand, if it appears suddenly, in a short-term deterioration for days or several weeks after the defined triggering disease, it is known as Acute-on-chronic liver failure (ACLF). ACLF is a syndrome characterized by acute and severe liver abnormalities as a result of different types of lesions present in patients with underlying chronic liver disease or cirrhosis, but unlike decompensated cirrhosis, it has a high short-term mortality.

It is important to determine the prognosis of patients with ACLF, in a short period of time, in order to act appropriately and reduce the use of temporary liver support or liver transplantation, an important variable that is included in various scores that assess liver function in different scenarios such as the Child-Pugh score and Model for End-stage Liver Disease (MELD) systems.

Among liver cirrhosis complications, there is the Hepatic encephalopathy (HE) involves a wide range of neurocognitive and psychiatric abnormalities that can range from subclinical neurological deficits and disturbances in attention to coma. Diagnosis of hepatic encephalopathy can be made using the West Haven (WH) criteria, which are clinical criteria that evaluate the degree of neurological deterioration and divide hepatic encephalopathy into 5 grades (from grade 0 to grade 4), with grades 3 and 4 having a worse prognosis. In addition to these criteria, it can be diagnose based on psychometric tests such as the Portosystemic- Encephalopathy- Syndrome test (PSE) and psychophysiological tests, such as the Critical flicker frequency (CFF). Despite the existence of this evidence and the WH criteria, there is no quantitative parameter that can be used to diagnose the hepatic encephalopathy. In addition, although the quantification of ammonia levels is carried out in multiple centers as part of the protocol for diagnosing HE, there are numerous studies showing that ammonia levels cannot be used to diagnose or rule out the presence of HE.

Study Timeline

• Study Start: 2022-08-01
• Study First Submitted: 2022-09-30
• Study First Submitted QC: 2022-09-30
• Status Verified: 2022-10
• Study First Posted: 2022-10-04
• Last Update Submitted: 2022-10-05
• Last Update Posted: 2022-10-07
• Primary Completion: 2023-07-31
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patients with Acute-on-chronic liver failure (ACLF)
• Patients hepatic encephalopathy (HE)
• Any etiology of liver cirrhosis alcoholic liver disease (ALD), HCV, liver disease fatty liver associated with metabolism dysfunction (MAFLD) and diseases autoimmune liver
• With or without the existence of any precipitating event or medical complication: infection acute bacterial, consumption hepatitis severe alcoholic, variceal bleeding, drug-induced encephalopathy, ascites, coagulopathy, sepsis
• Any ACLF grade
• Any HE grade

Exclusion Criteria

• Immunodeficiency virus infection human (HIV)
• Cholestatic liver disease,
• Past or current extrahepatic malignant tumor,
• Liver transplant,
• Other serious concomitant diseases heart, lung, kidney, or other organs
• Patients with metastatic hepatocellular carcinoma (HCC)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group of patients with liver cirrhosis and ACLF	Liquid Chromatography-Mass Spectrometry Method to identify bilirubin molecular species	This group will include patients with diagnosed liver cirrhosis regardless of the cause hospitalized and/or presenting to the emergency department for possible ACLF. With any etiology of liver cirrhosis including alcoholic liver disease (ALD), chronic hepatitis C virus (HCV), metabolism associated fatty liver disease (MAFLD) and autoimmune liver diseases.
Group of patients with liver cirrhosis and hepatic encephalopathy	Liquid Chromatography-Mass Spectrometry Method to identify bilirubin molecular species	This group will include patients with diagnosed liver cirrhosis who develop hepatic encephalopathy graded according to West Haven.
Group of patients with liver cirrhosis compensated	Liquid Chromatography-Mass Spectrometry Method to identify bilirubin molecular species	This group will include patients with diagnosed liver cirrhosis, any etiology of liver cirrhosis including alcoholic liver disease (ALD), chronic hepatitis C virus (HCV), metabolism associated fatty liver disease (MAFLD) and autoimmune liver diseases. No previous episodes of ACLF and at the time of admission.
Group of healthy people	Liquid Chromatography-Mass Spectrometry Method to identify bilirubin molecular species	People who do not have any acute or chronic degenerative disease. Participation on a voluntary basis.

Primary Outcome Measures

Name	Time	Method
Identify levels of Conjugated Bilirubin as Bilirubin monoglucuronide (BMG), bilirubin diglucuronide (BDG) and unconjugated bilirubin (UCB) in patients with acute-on-chronic liver failure	The serum sample will be taken at the moment of the first patient physician contact (admission, medical visit). The bilirubin measure will be done 24 hours after	Identification and measured concentration of bilirubin molecular species through liquid chromatography-mass spectrometry (LC-MS)

Secondary Outcome Measures

Name	Time	Method
Comparison of the bilirubin levels of the different groups	It will be analyzed when all the results from the LC-MS are done. Approximately 5 months.	The results of the groups will be compared among them to evaluate whether or not there is a change in the concentration.

Trial Locations

Locations (1)

Medica Sur Clinic & Foundation Organization; 🇲🇽 Mexico City, Mexico