optimizing nonalcoholic fatty liver disease care using mac2 binding protein glycosylation isomer and correlations with advanced diagnostics

Optimizing non-alcoholic fatty liver disease care using mac-2 binding protein glycosylation isomer and correlations with... Global burden of cirrhosis and liver cancer due to NASH from 1

Optimizing non-alcoholic fatty liver disease care using mac-2 binding protein glycosylation isomer and correlations with

Global rates of NAFLD increasing over time

Zobair M Younossi et al THE GLOBAL EPIDEMIOLOGY OF NAFLD AND NASH Hepatology 2023;77:1335–1347

I Background.

Prevalence of NAFLD According to Global Regions Data Collected 1990–2019

Zobair M Younossi et al THE GLOBAL EPIDEMIOLOGY OF NAFLD AND NASH Hepatology 2023;77:1335–1347

Natural history of NAFLD: from liver steatosis to HCC

Desjonqueres et al Hepatoma Res 2022;7:16

Global burden of cirrhosis and liver cancer due to NASH from 1990 to 2050

(A) Incidence number of cirrhosis due to NASH; (B) Prevalence number of cirrhosis due to NASH; (C) Death number of cirrhosis due to NASH; (D) DALYs number of cirrhosis due to NASH; (E) Incidence number of liver cancer due to NASH; (F) Prevalence number of liver cancer due to NASH; (G) Death number of liver cancer due to NASH; (H) DALYs number of liver cancer due to NASH.

NASH: nonalcoholic steatohepatitis; DALYs: disability-adjusted life years Dash line: forecasted NASH burden from 2018 towards 2050 through ARIMA model.

Tianyue Zhang et al Journal of Cancer 2021, Vol 12 (10): 2855-2865

Global burden of cirrhosis and liver cancer due to NASH by age in 2017

(A) Prevalence number of cirrhosis due to NASH; (B) DALYs number of cirrhosis due to NASH; (C) Prevalence number of liver cancer due to NASH; (B) DALYs number of liver cancer due to NASH.

NASH: nonalcoholic steatohepatitis; DALYs: disability-adjusted life years Tianyue Zhang et al Journal of Cancer 2021, Vol 12 (10): 2855-2865

M2BPGi is a new Direct Biomarker to diagnostic Liver Fibrosis

Summary table for the value of conventional and elastographic imaging modalities in non-alcoholic fatty liver disease stratification.

Li Q, Dhyani M, Grajo JR, Sirlin C, Samir AE Current status of imaging in nonalcoholic fatty liver disease.World J Hepatol2018; 10(8): 530-542

• - Investigate M2BPGi levels according to age groups and genders, and diabetes.

II Objectives and Method.

Hepatology department: Screening and Recruitment

Inclusion: - ≥ 18 yo

- Diagnosed fatty liver by imaging: abdominal US or CAP on fibroscan - Nạve treatment for NAFLD or cease treating more than 6 months - Appropriate to perform MRE

Exclusion:

- Co-infection HBV & HCV - Pregnant

- Any underlying cancers

- Alcohol intake: >30g/day (male) and > 20 g/day (female) - End-stage renal disease (ESRD)

- Inapproriate samples, such as severe hemolysis, high turbidity

F0/1 (n=90)F2 (n= 73)F3 (n=95)F4 (n=43)

Enrollment

Routine lab tests

- CTC- LFTs- FIB-4- M2BPGi

Imaging diagnostic: MRE

Major analysis

- Define cut-off values of M2BPGi of each stage

- Perform correlation between M2BPGi and MRE, Fibroscan, and FIB-4- Sub-population analysis: age groups, diabetes, and genders

Objectives and study diagram

Statistic: Graphpad Prism version 10.1

Descriptive statistics of M2BPGi according stratified fibrosis stages

Diagnostic efficacy of serum

M2BPGi and other serum markers for different liver fibrosis stages

Jang SY, et al Ann Lab Med 2021;41:302-309

Abbreviations: AUC, area under the curve; APRI, aspartate aminotransfer ase to platelet ratio index; F, fibrosis; FIB-4, fibrosis index based on four fac tors; NAFLD, non-alcoholic fatty liver disease; NFS, NAFLD fibrosis score; M2BPGi, Mac-2 binding protein glycosylation isomer

Median of M2BPGi levels across fibrosis stages in overall and by genders

Tobari M and Hashimoto E Gut and Liver, Published online January 3, 2020

Distribution of patients with nonalcoholic fatty liver disease by mild or advanced fibrosis status with respect to age and sex

In the older generation, advanced fibrosis was more common than mild fibrosis in both sexes Data was obtained from Tokyo Women’s Medical University in 1991 to 2018 (n=811: 406 men and 359 women)

The percentage of cirrhotic NAFLD was higher in women than in men (56% vs 44%), while the percentage of HCC was higher in men than in women (69% vs 31%)

Percentage of male and female patients with a diagnosis of nonalcoholic fatty liver disease (NAFLD), cirrhosis, or hepatocellular carcinoma (HCC)

Tobari M and Hashimoto E Gut and Liver, Published online January 3, 2020

Median of M2BPGi levels across fibrosis stages by ages and w/wo diabetes

The percentages of fibrosis stages compared between elderly and non-elderly NAFLD patients

Elderly NAFLD patients had significantly more patients with advanced fibrosis (F3–4; 35.4% vs 13.4%; P < 0.01)

Panyavee Pitisuttithum et al BMC Gastroenterology (2020) 20:88

Type 2 diabetes and obesity aggravate the progression of NAFLD/NASH to HCC

Hyunmi Kim et al Int J Mol Sci 2021, 22, 4495

Correlation between MRE and other parameters

Diagnostic performance of M2BPGi and FIB-4 in significant fibrosis

Diagnostic performance of M2BPGi and Fib-4 in cirrhosis

Liver fibrosis marker values at each liver fibrosis stage in NAFLD patients

Jang SY, et al Ann Lab Med 2021;41:302-309

Spearman’s rank correlation analysis showed that the serum M2BPGi level (ρ=0.653, P<0.001) and FIB-4 (ρ=0.689, P<0.001) increased with the liver fibrosis stage There were moderate correlations between APRI (ρ=0.515, P<0.001) and NFS (ρ=0.628, P<0.001) and fibrosis stage, respectively However, the median APRI score decreased in F4 than in F3, and median NFS decreased in F1 than in F0

(A) Serum M2BPGi level, (B) APRI, (C) FIB-4, and (D) NFS The box height represents the

interquartile range, and the line across each box represents the median

Abbreviations: APRI, aspartate transaminase to platelet ratio index; FIB-4, fibrosis index based on four factors; M2BPGi, Mac-2 binding protein glycosylation isomer; NAFLD, non-alcoholic fatty liver disease; NFS, NAFLD fibrosis score; ns, not significant

IV Conclusion.

In early NAFLD cases (F0-1), the mean cutoff for M2BPGi was 0.69 with a standard error of the mean (SEM) of 0.039 Similarly, for F2-3 cases, the mean cutoff was 0.77 with SEM 0.031, while F4 cirrhotic cases exhibited a mean cutoff of 1.0 with SEM 0.121 The observed results demonstrated statistical significance between early liver disease

and cirrhotic study groups

This study in Vietnam aims to define precise M2BPGi cut-offs for NAFLD fibrosis stages, improving early detection.

Results show significant M2BPGi differences between early NAFLD and cirrhotic groups, with notable gender and age variations.

These findings emphasize M2BPGi's potential for nuanced NAFLD characterization and early detection in diverse demographics.