Mathematical Model for early Diagnosis of - PowerPoint Presentation

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Mathematical Model for early Diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD)/ Non-Alcoholic Steatohepatitis (NASH)

Dr.

Ranjitsinh

Devkar

Asst

Professor Department of Zoology,

The

M.S.University

of Baroda, Vadodara, India

.

rv.devkar-zoo@msubaroda.ac.in

Liver is a metabolic hub that regulates complex processes, such as digestion of sugars and fats, synthesis of bile acids, detoxification of blood, etc.

Liver is prone to injury and damage due to such wide range of metabolite processing.

Liver diseases such as Alcoholic Liver Disease (ALD), Non-Fatty Liver Disease (NAFLD), Hepatic Steatohepatitis, Non-alcoholic Steatohepatitis (NASH), are major disorders culminating due to altered metabolic processes.

NAFLD/NASHNAFLD is a multifactorial metabolic ailment often seen in patients with obesity, insulin resistance, hypertension and hyperlipidemia

but is not limited to the said disease cohort.

Non-alcoholic steatohepatitis (NASH) is the progressive form of NAFLD which carries the risk of progressive fibrosis, cirrhosis, and end-stage liver disease.

NASH etiology can be characterized by excessive triglycerides (TGs) and free fatty acid (FFA) accumulation in the liver which subsequently leads to inflammation, apoptosis, and ballooning degeneration.

Western Lifestyle/Night Shifts/Long Working hours

High Fat High Sugar Diets

Disturbed Light/Dark Cycles and sleep

longer exposure to light, irregular sleeping patternNAFLD/NASH

Western Lifestyle

Night Shift

Long Working Hours

Liver

Dysbiosis

, Hyperlipidemia

Chronodisruption

Circadian misalignment

Junk Food /High Fat Diet

INCREASES GUT PERMEABILITY/INCREASED ABSORPTION OF LIPIDS

INCREASED SHORT CHAIN FATTY ACIDS AND TRIGLYCERIDES IN BLOOD

NAFLDLIPID ACCUMULATION AND BLOONINGNASH

Apoptosis, Necrosis, inflammation

ETIOLOGY OF NASH

Rationale Behind development of Mathematical Model for DiagnosisLiver biopsy continues to be the gold standard for confirming NAFLD/NASH along with PET scans and MRI scans also being effective at advanced stages of the disease.A cohort of markers in blood and urine for an early prediction of NAFLD/NASH is the need of the hour. Hence, a metabolomic approach for an early detection of NAFLD/NASH can be effective.

Hence an early detection of NAFLD/NASH and to monitor its onset and progression are the major challenges for clinicians today.

MetabolomicsQuantification of each and every molecule or metabolite present in a given sample is termed as metabolomics.Metabolomics of serum and urine samples has been studied in patients of NAFLD/NASH.Mathematical Index scores have been created from patient serum samples but correlates with urine metabolomics data is a research lacunae.

Metabolites undergoing change in metabolome profile of NAFLD patients

0

SERUM

URINE

Hypoxanthine

Xanthine

Citrulline

Agrinine

Valine

Glucose

Gluconic

acid

7

methylxanthine

2

methylguanosine

Indoxysulfuric

acid

Acetylcarnitine

Deoxycholic

acid

Ursodeoxycholic

acid

Indole

acetic acid

Insulin

Triacylglycerols

Phosphocholine

Lysophosphatidylcholine

Tryptophan

Phenylalanine

Lysine

Carnitine

+2

-2

0

Metabolites suggested as diagnostic markers

HEALTHY LEVELS

0

Lysine

Valine

CitrullineArginineThreonine

Hippuric

acid

3-indoleacetic acid

Gluconic

acid

Carnitine

Indole

acetic acid

5-hydroxyl

indole

acetic acid

Indole

acetic acid

2-methylguanosine

Indoxysulfuric

acid

Indole

acetic acid

Acetylcarnitine

Leucine

Isoleucine

Tyrosine

Insulin

Triglycerides

Sphingomyelins

Lysophospatidylcholine

glutamate

Glycine

Serine

acylcarnitine

Metabolites undergoing change in metabolome profile of NASH patients

0

Metabolites suggested as diagnostic markers

+2

-2

SERUM

URINE

HEALTHY LEVELS

0

Gluconic

acid

carnitinePyroglutamic acid

Acetylcarnitine

Methylxanthine

Xanthine

Tryptophan

Glucose

3

indole

acetic acid

Indole acetic acid

Tyrosine

Cysteine

Alanine

phenylalanine

Valine

SERUM

URINE

Metabolites undergoing change in metabolome profile of NASH vs NAFLD patients

0

Metabolites suggested as diagnostic markers

+2

-2

NAFLD

AimTo design a mathematical model that shall be helpful ina. Early detectionb. Severity of the diseasec. Stage of transition of NAFLD to NASH

Crux of the studyA Mathematical model that can provide an index score by including metabolomic profiles of serum and urine can be a novel approach for early detection of NAFLD/NASH.

My Lab: Circadian Biology and regulation of NAFLD/NASHOngoing Studies:Circadian Basis of miR122 and liver adipocyte crosstalk in NASHRegulatory Clock genes in Immunomodulation of NASHNeurobehavioral alterations in NASH: Role of Bile acids

Atherogenic intimal modelling and role of miR34a-5p

Epigenetic regulation of NASH progression: Role of miR192

My Team:Aliasgar VohraHitarthi VyasShruti KulshresthaNilay DalviRhydham Karnik

Noninvasive detection of nonalcoholic steatohepatitis using clinical markers and circulating levels of lipids and metabolites. Link:

https://www.cghjournal.org/article/S1542-3565(16)30315-9/fulltext

Study

of the serum metabolomic profile in nonalcoholic fatty liver disease: research and clinical perspectives. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876006/Distinguishing NASH histological severity using a multiplatform metabolomics approach. Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240949/

Urinary

metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease. 

Link

:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403757/

Metabolic

analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry. 

Link

:

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02820-7

Links for the research content used herein