Alcoholic Hepatitis: A Multicenter, Observational Study by the TREAT Consortium

NCT02172898 | Completed DMC

• 2 other identifiers: TREAT ObservationalU01AA021840-01
• Study Type: observational
• Target: 454
• Locations: 1 country
• Sites: 2

Brief Summary

To conduct a prospective, multicenter, observational study of patients with well-characterized alcoholic hepatitis (AH) and frequency matched individuals (by age, gender, and race) with comparable history of alcohol consumption but no clinical evidence of liver disease (controls). At the end of the study, a robust clinical information, central bio-repository will be developed from both cases and controls.

Conditions

Alcoholic Hepatitis

Outcome Measures

Primary Outcomes (1)

• Developing a repository of biological samples from AH patients and heavy drinking controls.

  To conduct a prospective, multicenter, observational study of patients with well-characterized AH and frequency matched individuals (by age, gender, and race) with comparable history of alcohol consumption but no clinical evidence of liver disease (controls). At the end of the study, a robust clinical information, central bio-repository of serum/plasma, peripheral mononuclear cells, genomic DNA, stool samples, urine, and liver tissue (where available) will be developed from both cases and controls.

  Up to 1 year

Secondary Outcomes (1)

• Characterizing AH subjects and controls to serve as the foundation for novel mechanistic and therapeutic studies.

  Up to 1 year

Study Arms (2)

Heavily Drinking Controls

Heavy alcohol drinking will be defined as \> 40 grams per day on average in women and \> 60 grams per day on average in men for a minimum of 6 months and within the 6 weeks prior to study enrollment. Heavy drinkers, who have just become abstinent within prior 2 weeks, including those we convince to seek treatment as part of the recruiting process, are eligible for enrollment. Control subjects must meet the following criteria: (1) AST, ALT, and total bilirubin levels must be within normal range; (2) no prior history of known alcoholic liver disease; and (3) absence of hepatosplenomegaly (from physical examination or radiographic imaging) or stigmata of liver disease.

Subjects with AH

Diagnosis of AH will be established on published criteria based on history of heavy alcohol consumption (defined as \> 40 grams per day on average in women and \> 60 grams per day on average for men for a minimum of 6 months and within the 6 weeks prior to study enrollment), clinical evaluation and appropriate laboratory testing (as defined as total bilirubin \> 2 mg/dL and AST \> 50 U/L). When diagnosis of AH remains in question, a liver biopsy (if clinically feasible and subject has no contraindications) will be required. We plan to enroll patients with AH in special population infected with hepatitis B (HBV), hepatitis C (HCV), or HIV.

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals with AH and suitable controls will be enrolled at Indiana University and affiliated hospitals. In addition, the enrollment will be conducted simultaneously at Mayo Clinic and Virginia Commonwealth University with the same target enrollment.

You may qualify if:

• \. The diagnosis of AH will be established on published criteria this is based on:
• Average daily ethanol consumption of \> 40 grams/day for women and \> 60 grams/day for men for a minimum of 6 months and within the 6 weeks prior to study enrolment. Judgment regarding daily and yearly alcohol use will be made by the site investigator
• Clinical evaluation and appropriate laboratory testing as defined by total bilirubin \> 2 mg/dL and AST \> 50 U/L. When the diagnosis of AH remains in question, a liver biopsy (if clinically feasible and that subject has no contra-indications) will be required.
• Subjects with HBV, HCV and/or HIV will be eligible for enrollment

You may not qualify if:

• Evidence of other liver diseases such as autoimmune or drug-induced
• Significant concomitant medical illnesses such as uncontrolled congestive heart failure or COPD, or multiorgan failure
• Abstinence of alcohol use \> 6 weeks immediately preceding enrollment
• Hemochromatosis
• Wilson Disease
• Active intravenous drug use
• CONTROLS: Heavy drinkers without alcoholic hepatitis
• Average daily ethanol consumption of \> 40 grams /day for women and \> 60 grams/day for males for a minimum of 6 months and within the 6 weeks prior to study enrollment. In addition, heavy drinkers who have just become abstinent within prior 2 weeks are eligible to be enrolled. Judgment regarding daily and yearly alcohol use will be made by the site investigator
• AST and ALT ≤ 50 and total bilirubin levels within normal range. If bilirubin is increased due to a suspected Gilbert's Syndrome, patient may be enrolled if the direct bilirubin is within normal limits
• Evidence of liver disease
• Significant concomitant medical illnesses such as uncontrolled congestive heart failure or COPD, or multiorgan failure
• Abstinence of alcohol use \> 2 weeks immediately preceding enrollment
• Hemochromatosis
• Wilson Disease
• Active intravenous drug use

Sponsors & Collaborators

• Indiana University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (3)

• Madathanapalli A, Tang Q, Lammert C, Samala N, Shah VH, Sanyal A, Chalasani N, Desai AP. Health-related quality of life is dynamic in alcoholic hepatitis and responds to improvement in liver disease and reduced alcohol consumption. Alcohol Clin Exp Res. 2022 Feb;46(2):252-261. doi: 10.1111/acer.14756. Epub 2021 Dec 16.

  PMID: 34862610 DERIVED

• Mathur K, Vilar-Gomez E, Connelly MA, He H, Sanyal AJ, Chalasani N, Jiang ZG. Circulating high density lipoprotein distinguishes alcoholic hepatitis from heavy drinkers and predicts 90-day outcome: lipoproteins in alcoholic hepatitis. J Clin Lipidol. 2021 Nov-Dec;15(6):805-813. doi: 10.1016/j.jacl.2021.10.002. Epub 2021 Oct 20.

  PMID: 34756674 DERIVED

• Shamseddeen H, Madathanapalli A, Are VS, Shah VH, Sanyal AJ, Tang Q, Liang T, Gelow K, Zimmers TA, Chalasani N, Desai AP. Changes in Serum Myostatin Levels in Alcoholic Hepatitis Correlate with Improvement in MELD. Dig Dis Sci. 2021 Sep;66(9):3062-3073. doi: 10.1007/s10620-020-06632-5. Epub 2020 Oct 19.

  PMID: 33074470 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

serum/plasma, peripheral mononuclear cells, genomic DNA, stool samples, urine, and liver tissue (where available)

MeSH Terms

Conditions

Hepatitis, Alcoholic

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Naga Chalasani, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Naga Chalasani, MD, FACG

Study Record Dates

• First Submitted: June 9, 2014
• First Posted: June 24, 2014
• Study Start: June 1, 2013
• Primary Completion: June 29, 2018
• Study Completion: July 1, 2019
• Last Updated: February 11, 2020

Record last verified: 2020-02

Locations

US (2)