Non alcoholic Fatty Liver disease .pptx

Nafld

1. NAFLD | MAFLD Nonalcoholic Fatty liver disease | Metabolic dysfunction associated Fatty liver disease

2. CONTENTS Introduction Pathogenesis Clinical Features Diagnosis Treatment Health considerations Take home message References

3. Introduction It is the most common chronic liver disease globally Associated with obesity and insulin resistance it encompasses a spectrum of liver pathology with different clinical prognosis as a consequence of lipid accumulation in the hepatocyte Hispanic > Caucasians > Asians > African Americans

4. NAFL | NASH | Cirrhosis | HCC The risk for advanced liver fibrosis is highest in individuals with NASH who are aged >45–50 years and overweight/obese or afflicted with type 2 diabetes. Hereditary Factors : PNPLA3 Polymorphism ( Adiponutrin Lipase in hepatic stellate cells ) helps in intracellular trafficking of lipids IL28 Mutation leads to lipid deposition in Liver and Cardiovascular system

5. TM6SF2 and MBOAT7 Polymorphism : probability of NAFLD increases Most common cause of mortality in NAFLD is Cardiovascular disease

6. 2. Pathogenesis Increased triglycerides synthesis + Decreased triglycerides removal Intestinal dysbiosis : increased harvest of lipids and increased intestinal permeability therein decreased barrier leading to toxins exposure to liver and liver cytokines play a role in Insulin resistance. Adipokines from obese cells increase insulin resistance Hyperinsulinemia promotes fat uptake synthesis and storage

7. NAFLD : morphological manifestation of lipotoxicity Precursors of triglycerides such as Fatty acids and diacylglycerols are hepatotoxic Reactive oxygen species : byproducts of metabolism Hepatocyte death ; wound healing responses recruit other cells ( myofibroblasts Stellate cells )

8. 3. Clinical Features Majority asymptomatic 50-90 % are obese Metabolic syndrome Chronic fatigue Mood alterations , obstructive sleep apnea , thyroid dysfunction Clubbing Vague right upper quadrant pain with hepatomegaly Spleenomegaly Stigmata of chronic liver disease ( palmar erythema , spider angiomata ) Complications of endstage liver disease i.e Jaundice, portal hypertension

9. 4. Diagnosis Increased liver fat >5% in the absence of hazardous levels of alcohol consumption 1 standard drink per day in Females , 2 Standard drink per day in Males 1 standard drink = 10gm of Ethanol Exclude other causes eg. Autoimmune hepatitis , Wilson disease , Viral hepatitis , medications associated with hepatitis USG finding of fatty liver is when > 30% Fat deposition Transient elastography ( Firboscan)

10. Noninvasive: History / Physical Examination / Blood tests Invasive : Liver biopsy (gold standard ) tissue core of 2cm or longer required

11. Fibrosis staging according to metavir score NAFLD Fibrosis score : Age , BMI , Blood Glucose , AST/ALT ratio , Platelet count , Albumin Score > 0.676 Advanced Fibrosis , <1.455 No fibrosis BARD score : AST/ALT Ratio >= 0.8 BMI >= 28 Diabetes

12. APRI Score Ranges 0.5 to 1.5 < 0.5 No Cirrhosis >1.5 Advanced Cirrhosis APRI = Aspartate amino transferase to platelet ratio index

13. 5. Treatment

14. 3 Components NAFLD related liver disease treatment Treatment of NAFLD associated co morbidities Treatment of complications of advanced NAFLD

15. Currently no FDA approved pharmacological treatment Lifestyle modifications: Weightloss Of atleast 3-5% improves steatosis Greater than 7-10% improves steatohepatitis and liver fibrosis Diet : Low Fat Low Fructose diet , with Calorie restriction , 2-3 cups of black coffee Pharmacological Therapy: Several trials with various drugs have been tried eg: Metformin ( Tonic trial ) Thiazolidinediones ( Pivens trial ) , Vitamin E

16. Vitamin E ( Antioxidant ) dose of 800IU / day has shown improving in AST/ALT/Imaging/Biopsy improvement But Cardiovascular Morbidity Risk is high Not to be used in Type 2 DM with NASH Ursodeoxycholic acid , Statins , Omega 3 fatty acids , betaine ( improves aminotransferases and histology ) Saroglitazar(PPAR Agonist) 4mg once daily Resmetirom(Thyroid hormone receptor Beta selective agonist) 80-100mg once daily Bariatric surgery Liver transplantation

17. 6. Health Considerations

18. 7. Take Home Message Leading cause of chronic liver disease worldwide NAFLD is now termed as MAFLD / MASLD It is an umbrella term encompassing spectrum of liver pathology as consequence of lipid accumulation and lipotoxicity Rule out other causes of liver dysfunction Metabolic dysfunction underlying pathophysiology Diagnosis : Noninvasive | Invasive Always evaluate for any co-existing kidney disease Lifestyle modification cornerstone of treatment Newer emerging therapies with possible benefits underway

19. 8. References Harrisons 21st Edition Internal Medicine Online references https://main.mohfw.gov.in/sites/default/files/OG%20print%20ready%20version%20_0.pdf

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