Proteomic and transcriptomic analysis to understand the biology of alcoholic hepatitis

Recruiting

Conditions: Fibrosis and cirrhosis of liver,

Registration Number: CTRI/2023/01/048844

Lead Sponsor: ICMR

Brief Summary: - **Background:** Alcoholic liver disease (ALD) portends significant burden with 21.5 million life years lost every year. Alcoholic hepatitis (AH), a severe form of ALD, confers a high mortality (33-77% in 3 months). Aberrations in metabolism, immune response and gut bacterial translocation are major drivers of disease and its outcomes. Neutrophil dysfunction plays a key role in shaping organ failures and mortality in AH patients. However, literature is limited to biased and cross-sectional reporting of neutrophil dysfunction viz. impaired phenotype, phagocytosis, and extracellular traps in AH. And the trajectories of neutrophil dysfunction remain unclear. Therapies for AH are limited to abstinence, nutrition and steroids or liver transplant (selected cases), but are often in-effective or in-feasible in providing a long-term survival benefit.

- **Novelty:** We propose that unbiased and dynamic understanding of disease pathobiology hold a strong chance in improving outcomes of AH patients.

- **Objectives:** We aim to conduct extensive, unbiased and dynamic profiling of neutrophils at transcriptional and translational level employing high throughput multi-omics and machine learning strategies.

- **Methods:** First in the discovery phase, enrolled AH patients will be followed till 90days. Transcriptomic and proteomics of isolated neutrophils will be performed at baseline and at day-7. Differentially expressed genes and proteins associated with diseased condition and 90-day outcomes will be analyzed. Second, in the validation phase, relevant genes and proteins will be validated through qRT-PCR and ELISA in another cohort of AH patients.

- **Expected outcome:** We will ascertain AH and its mortality specific biologic signatures. These will be leveraged for novel therapeutics.

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: All

Target Recruitment: 150

Inclusion Criteria

Patients age 18 to 80 years 2.
Patients with probable or definite alcoholic hepatitis (AH) (as per AASLD guidelines) will be enrolled from consecutive patients presenting first time to the department.
The diagnosis of AH will be made as per the NIAAA consensus, i.e., â€¢ onset of jaundice within the prior eight weeks, â€¢ ongoing consumption of >40g (female) or >60 (male)g of alcohol/day for 6 months or more, with less than 60 days of abstinence before the onset of jaundice â€¢ aspartate aminotransferase >50, aspartate aminotransferase/alanine aminotransferase >1.5, and both values <400IU/L â€¢ serum bilirubin (total) >3.0 mg/dL â€¢ liver biopsy confirmation in patients with confounding factors.

Exclusion Criteria

Patients having: i.
HIV infection ii.
Prior organ transplantation iii.
Hepatic or extra-hepatic malignancy iv.
Receiving any experimental therapies v.
Pregnant or lactating women, will be excluded.

Study & Design

Study Type: Observational

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Impact of GH along with standard medical therapy (SMT) as compared to SMT-alone on overall survival (Time frame 30 days)	30 days and 90 days

Secondary Outcome Measures

Name	Time	Method
Transcriptomic analysis of neutrophils to define molecular signatures linked to	pathophysiology and outcomes in alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7]
Proteomic analysis of neutrophils towards unravelling parameters influencing the	pathophysiology and outcomes in alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7]
Validation of identified transcriptomic and proteomic signatures associated with prognosis in	alcoholic hepatitis (AH) patients. [Time frame: day-0 and day-7]

Trial Locations

Locations (1): PGIMER, Chandigarh
🇮🇳
Chandigarh, CHANDIGARH, India
PGIMER, Chandigarh
🇮🇳Chandigarh, CHANDIGARH, India
Dr Nipun Verma
Principal investigator
9914208562
nipun29j@gmail.com