1. What exactly is a Fatty Liver?
With the prevalence of MASLD increasing from 22% in 1991 to 40% in 2023, If the term NAFLD (Non Alcoholic Fatty Liver Disease) has to be effectively retired for non-alcoholic patients in the absence of any obesity or obesity-related diseases such diabetes mellitus, then, how could we justify the term MASLD (Metabolic-Dysfunction Associated Steatotic Liver Disease), if the patient does not fall in any of the following 8 categories?
(1) BMI being greater than 23 – 25 kg/m2
(2) Waist Circumference being greater than 95 cm in Men; or, being greater than 80 cm in women
(3) Fasting serum glucose being greater than 100 mg/Dl; Or, HbA1c being greater than 5.6
(4) 2-hour post-load glucose level being greater than 140 mg/Dl; Or, HbA1c being greater than 5.7
(5) Blood pressure being greater than 130/85 mmHg
(6) Plasma Triglycerides being greater than 150 mg/dL
(7) Plasma HDL cholesterol being less than 40 mg/dL for men; or, being less than 50 mg/dL for women
(8) Undergoing specific drug treatment
2. Would it remain feasible to find out the presence of lobular inflammation and/or hepatocyte ballooning – associated with the Metabolic dysfunction-associated Steatohapatitis (MASH), at an early stage?
Are there any symptoms (in the absence of going for imaging techniques; or, biopsy; or, blood biomarkers; or, analyzing liver history) to figure out MASH, before it leads to fibrosis progression?
3. Under what circumstances, T2DM (Type 2 Diabetes Mellitus) remains to be an inevitable independent risk factor for MASH and for advanced Liver Fibrosis? In such cases, whether, Fibrosis-4 (FIB4) Index test would remain to be sufficient (in case, if we have a positive predictive value, as against the expected very good negative predictive value)?
Or
A test on Liver Stiffness Measurement (LSM) also be required?
4. In the absence of having an approved pharmacological therapy for MASH, whether its progression towards Atherosclerotic Cardiovascular disease (ASCVD) remains inevitable?
If not, then, how exactly to proceed from
(a) T2DM; or,
(b) Abdominal Adiposity; or,
(c) Increased Insulin Resistance;
(d) Pro-Inflammatory Mediators;
(e) Pro-atherogenic Dyslipidemia;
(f) oxidative stress; or,
(g) Hepatokines –
in order to reduce CVD risks associated with MASLD patients?
Since, SGLT2 inhibitors are approved only for patients in the absence of diabetes but with ischemic heart disease or heart failure; and GLP1 RAs for patients with diabetes or obesity, then, Statins Or, Ezetimibe with statins is the only solution for mitigating CVD/hcc risks in all other MASLD patients?
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