Non-alcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation, inflammation, and potential liver damage in individuals who do not abuse alcohol, often linked to obesity, diabetes, and certain metabolic disorders. Diagnosis is confirmed through clinical history, imaging, and liver biopsy, while treatment focuses on lifestyle changes such as weight loss and dietary modifications, as there is no standard medication regimen. NASH increases the risk of cirrhosis, liver failure, and cancer, emphasizing the need for preventive measures through healthy habits.

2. PRESENTATION
ON
NON ALCOHOLIC
STEATOHEPATITIS

3. INTRODUCTION
• Non-alcoholic steatohepatitis (NASH) is a liver ailment marked by
inflammation and harm caused by the build-up of fat within the liver. As
part of the non-alcoholic fatty liver disease spectrum, NASH can result
in complications when not addressed.

4. INTRODUCTION
• NASH develops when excess fat in the liver triggers inflammation and
damages liver cells. Though many people may have a fatty liver without
experiencing symptoms, some individuals may suffer from liver
dysfunction due to this fat build-up.
• Unlike liver diseases associated with alcohol abuse, NASH occurs in
individuals who do not misuse alcohol.

5. DEFINITION
A type of liver disease in which fat builds up in the liver of people who
drink little or no alcohol. This causes inflammation of the liver and
damage to the cells in the liver, which may lead to cirrhosis (scarring of
the liver) and liver failure. Also called NASH.
-NCI(National cancer institute).

6. CAUSES AND RISK FACTORS
People with non-alcoholic steatohepatitis are at increased risk of
developing liver cancer. It is more common in middle-aged adults,
especially in those who are overweight or obese or who have diabetes or
high levels of cholesterol and triglycerides (a type of fat) in the blood.

7. CAUSES AND RISK FACTORS
An immune system reaction to excessive fatty liver tissue.The release of
toxic inflammatory chemicals (cytokines) by liver cells or fat cells, Self-
destruction (apoptosis) of liver cells, Oxidative stress, the effect of
unstable molecules called free radicals

8. CAUSES AND RISK FACTORS
1. Drugs or Toxins
Metals: Antimony, Carbon disulphide, Barium salts, Thallium compounds
Antibiotics: Bleomycin, Tetracycline
Other drugs: Amiodarone, Tetracycline, Coumadin, Valproic acid, Synthetic
estrogens, Methotrexate, Glucocorticosteroids, Cocaine, Perhexilene maleate,
Didanosine, Aspirin, Fialuridine
Calcium-channel blockers: Zidovudine, Tamoxifen

9. CAUSES AND RISK FACTORS
2. Metabolic disorders: Abetalipoproteinemia, Glycogen storage disease,
Lipodystrophy, Weber-Christian syndrome, Dysbetalipoproteinemia,
Wilson's disease, Hyperlipidemia, Wolman's disease, Galactosemia
3. Nutritional: Obesity, Total parenteral nutrition, Diabetes and
hyperglycemia, Rapid weight loss, Intravenous glucose therapy in the week
before death, Kwashiorkor.

10. CAUSES AND RISK FACTORS
4. Surgical: Jejuno colic bypass, Gastroplasty, Jejunoileal bypass,
Extensive small bowel resection, Biliopancreatic diversion
5. Other disorders: Inflammatory bowel disease, Hepatotoxins:
phosphorus, Jejunal diverticulosis with bacterial overgrowth,
Petrochemicals, organic solvents, Small bowel bacterial overgrowth,
Acute starvation, Human immunodeficiencyvirus infection

11. NASH: Pathogenesis
• Increased delivery of fatty acids to liver
Obesity
Starvation
• Increased synthesis of fatty acids in liver
 excess carbohydrate ( TPN )
• Decreased mitochondrial beta oxidation of fatty acids
 Carnitine deficiency
 Mitochondrial dysfunction
• Decreased incorporation of triglycerides into functional VLDL
 Impaired Apo lipoprotein synthesis

12. NASH: Pathogenesis
• Impaired cholesterol esterification
 Choline deficiency
 Protein malnutrition
• Impaired export of VLDL from hepatocyte
• Insulin resistance
 increased lipolysis
 hyperinsulinemia

13. Fibrosis Staging
• Scale ranging from FO to F4
 FO-no fibrosis
 F1-portal fibrosis without septa
 F2-portal fibrosis with few septa
 F3-bridging septa between central and portal veins
 F4 - cirrhosis
 Liver fibrosis can be expected to worsen by one class each
decade i.e. F2 will progress to cirrhosis in 20 years

14. SIGNS AND SYMPTOMS OF NASH
• Intense itching
• Abdominal swelling
• Easy bruising and bleeding
• Jaundice (yellowing of the skin and eyes)
• Spider-like blood vessels beneath the skin's
surface
• Behavior changes, confusion, and slurred speech.

15. DIAGNOSIS
• Clinical history
• Exclusion of significant alcohol intake
• Pursue dietary history, medication,
occupational exposure to organic solvents
• Family history of liver disease
• Other causes of CLD - infections, metabolic,
hereditary & autoimmune causes to be ruled
out

16. • Magnetic resonance imaging (MRI), or ultrasound may also be used to help.
• Liver biopsy - confirm diagnosis & for prognostic information
• Fatty Liver Program also uses special MRI technology, called MR-EFF
(elastography fat fraction), to determine the percentage of fat and scarring
present. This non-invasive diagnostic tool may eliminate the need for a liver
biopsy.
DIAGNOSIS

17. TREATMENT
• There is no standard treatment for patients NASH
• Lifestyle changes have been shown to affect its progression. This may include
 losing weight,
 maintaining a healthy diet, or
 addressing underlying conditions such as hypothyroidism and
diabetes.
• It is important for patients with NASH to avoid consuming excessive alcohol
as this can contribute to the condition.

18. TREATMENT
WEIGHT REDUCTION:
• wt. loss - normalization of s.aminotransferases.
• Means of wt. loss is important not the amount of wt. loss
• Recommended wt. loss - 230 g/day or 1.6 kg/week
• Diet : 45 -100 g high quality animal protein
<100g carbohydrates
<10 g fat per day providing
600 -800 kcal

19. TREATMENT
Ursodeoxycholic acid :
• Has membrane stabilizing / cytoprotective / immunological
effect 10-15 mg/kg/day for 6-12 months
• Significant improvement in transaminases levels and degree
of steatohepatitis

20. TREATMENT
Liver Transplantation :
• NASH - A relative contraindication
• Many of pts with NASH with CLD who underwent
• Liver Transplant - redeveloped NASH in the new donor liver
( 2/3 cases ) & 1/3rd cases - liver transplantation is unsuccessful

21. NEWER TREATMENT MODALITIES
Inhibition of macrophage activation:
• Anti oxidant ( Vit E ) glutathione prodrugs
• Antibiotics, preprobiotics
• Anti cytokines ( anti TNF alpha antibodies, pentoxiphylline )

22. • Protect hepatocyte ATP stores
 PARP inhibitors
• Minimize CYP2F activity
 Dietary modification ( avoid fats )
• Insulin sensitizers : pioglitazone
• Anti obesity drugs : sibutramine, orlistat
• Anti lipid drugs : Simvastatin, Procusol
NEWER TREATMENT MODALITIES

23. • NASH increases the risk of cirrhosis-related liver failure and liver
cancer, which could require a liver transplant.
• The average life expectancy for someone with cirrhosis of advanced
liver disease is about nine to 12 years.
• However, NAFLD greatly increases the risk of cardiovascular disease
and decreases life expectancy in adults.
NASH Complications

24. • Unlike inherent NASH risk factors such as genetics, age, and race,
some can be reduced through healthy diet and lifestyle choices that
can help protect the liver.
NASH PREVENTION

25. REFERENCES
o https://www.nejm.org/doi/full/10.1056/NEJMra1503519
 Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis
 Anna M. Diehl, M.D., and Christopher Day, M.D.
 N Engl J Med 2017; 377:2063-2072 DOI: 10.1056/NEJMra1503519
o https://www.nejm.org/doi/full/10.1056/NEJMc1716786
o https://resident360.nejm.org/contentitems/nonalcoholic-steatohepatitis/
o https://www.pathpedia.com/education/eatlas/histology/liver and bile ducts/
o https://www.uptodate.com/contents/natural-history-and-management-of-nonalcoholic-fatty-liver-disease-in
adults?search=nash%20statin&source=search result&selectedTitle=1~150&usag e type=default&display
rank=1#H2027876431