Role of neutrophil-specific NOX2 in alcohol-induced liver injury
S
Suthat Liangpunsakul, MD
Primary Investigator
Enrolling By Invitation
18 years - 70 years
All
Phase
N/A
60 participants needed
1 Location
Brief description of study
What is the purpose of this study?
NADPH oxidase 2 (NOX2) is the isoform of NOX found in phagocytes including neutrophils, NOX2 activation generates reactive oxygen species (ROS) with antimicrobial activities. Patients with advanced alcoholic cirrhosis or alcoholic hepatitis are more susceptible to infections due to deficient ROS production by neutrophils. The primary aim of this study is to see if ROS production by neutrophils is attributed to reduced NOX2 activity in neutrophils amongst these patients which cause them to be more susceptible to infections.
NADPH oxidase 2 (NOX2) is the isoform of NOX found in phagocytes including neutrophils, NOX2 activation generates reactive oxygen species (ROS) with antimicrobial activities. Patients with advanced alcoholic cirrhosis or alcoholic hepatitis are more susceptible to infections due to deficient ROS production by neutrophils. The primary aim of this study is to see if ROS production by neutrophils is attributed to reduced NOX2 activity in neutrophils amongst these patients which cause them to be more susceptible to infections.
THIS STUDY IS ENROLLING BY INVITATION ONLY - Our recruitment process for cases consists of screening patients weekly that have appointments in the DaLD Liver Clinic at IU Hospital by reviewing their medical records to see if they fit the eligibility/ineligibility criteria listed in the protocol. If they do, it is sent to the PI for further review and if the PI confirms then the patient will be approached at their liver appointment in their exam room while waiting to see the doctor or right after they have been seen. Controls will be recruited by flyer, they will be contacting us after seeing flyer and then determined eligibility will conducted and if they are we will schedule an appointment with them to be seen in a reserved research room.
Detailed description of study
What will happen during the study?
- Controls: Collection of background/demographics, CMP panel and INR blood samples to be sent to IU Pathology Lab, and a blood sample (2 tablespoons or ~30 ml) will be collected through the intravenous catheter by experienced research coordinators.
- Cases: Collection of background/demographics, most recent (+/- 6 weeks from the enrollment date) laboratory tests (such as CBC and INR, comprehensive metabolic panel, and hepatic panel) from patient medical records, and a blood sample (2 tablespoons or ~30 ml) will be collected through the intravenous catheter by experienced research coordinators.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Healthy, Alcohol-associated liver disease, ALD
-
Age: 18 years - 70 years
-
Gender: All
Inclusion criteria
Controls:
Controls:
(1) individuals 18 to 70 years old
(2) able to provide informed consent
(3) subjects do not consume any alcohol or those who drink < 50 grams per day on average in women and < 80 grams per day on average in men and do not consume any alcohol within 3 months before the study
(4) subjects are healthy without underlying acute or chronic medical conditions.
Exclusion criteria
1) subjects with active and serious medical disease at the time of screening (such as congestive heart failure, chronic obstructive pulmonary disease, cancer, uncontrolled diabetes, and chronic renal failure
2) subjects with history of any localized or systemic infectious disease within 4 weeks prior to the study
3) subjects with history of recent major surgeries (such as abdominal surgery or thoracic surgery) within the past 3 months.
Alcohol-associated hepatitis (AH):
Alcohol-associated hepatitis (AH):
(1) History of excessive alcohol use as defined by an average consumption of more than 3 drinks (~40 g) per day for women and 4 drinks (~50–60 g) per day for men
(2) Heavy alcohol use has occurred for >6 months, with <60 days of abstinence before the onset of jaundice
(3) Serum bilirubin >3 mg/dL, AST >50 IU/mL, and AST to alanine aminotransferase (ALT) ratio of >1.5 (results +/- 1 week of enrollment date)
(4) no history of other liver diseases such as viral hepatitis or autoimmune liver disease.
Alcohol-associated cirrhosis:
Alcohol-associated cirrhosis:
(1) subjects must have had alcohol consumption averaging at least 80 grams per day (for men) or 50 grams per day (for women), for at least 10 years.
These criteria are based on epidemiological evidence of the alcohol–cirrhosis relationship, (2) evidence of cirrhosis as per clinical signs and/or noninvasive transient elastography (Fibroscan®), computed tomography, magnetic resonance imaging including MR elastography compatible with corrhosis and/or histopathology by biopsy, with the exclusion of other liver diseases such as hepatitis B or C, autoimmune liver disease, hemochromatosis, drug-induced liver injury or Wilson’s disease.
Updated on
17 Dec 2024.
Study ID: GI-NIH-NS-NOX2, 23287
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