Metabolic dysfunction–associated steatotic liver disease, previously known as non-alcoholic fatty liver disease, is a type of chronic liver disease. This condition is diagnosed when there is excessive fat build-up in the liver

1. 

2. NAFLD
BY
EMAD FAWZI,MD.
PROFESSOR OF INTERNAL MEDICINE &
GASTROENTEROLOGY AND HEPATOLOGY

3. Fatty Liver Diseases(FLD)
• Subdivided into:
 Alcoholic FLD.
 Nonalcoholic FLD.

4. Nonalcoholic fatty liver disease (NAFLD) refers to
the presence of hepatic steatosis when no other
causes for secondary hepatic fat accumulation (e.g.
heavy alcohol consumption) are present. NAFLD may
progress to cirrhosis

5. • NAFLD is subdivided into:
 Nonalcoholic fatty liver (NAFL) or simple steatosis.
 Nonalcoholic steatohepatitis (NASH) which may
progress to liver cirrhosis and hepatocellular
carcinoma.

6. Nonalcoholic Fatty Liver (
Nonalcoholic Fatty Liver (NAFL
NAFL)
)
•Evidence of Hepatic steatosis: either by imaging
or
or Histology (> 5% of hepatocytes) without any
other cause for secondary Fat accumulation, no
evidence of hepatocellular injury in the form of
ballooning of the hepatocytes and no evidence of
fibrosis.
•The risk of progression to cirrhosis and liver
failure is minimal.

7. Nonalcoholic steatohepatitis
Nonalcoholic steatohepatitis
(
(NASH
NASH)
)
•Presence of hepatic steatosis and inflammation
with hepatocyte injury (ballooning) with or
without fibrosis.
•This can progress to cirrhosis, liver failure and
rarely hepatocellular carcinoma (HCC).

8. Other terms that have been used to describe
NASH include:
 Pseudoalcoholic hepatitis
 Alcohol-like hepatitis
 Fatty liver hepatitis
 Steatonecrosis
 Diabetic hepatitis.

9. Natural history
• Simple steatosis: relatively benign “liver” prognosis
with a risk of developing clinical evidence of cirrhosis
over 15–20 years in the order of 1%–2%.
• NASH and fibrosis: risk of progress to cirrhosis
between 0% at 5 years to 12% over 8 years.
• Cirrhotic patients have high risk of developing
hepatic decompensation and HCC.

10. EPIDIMIOLOGY
• In the US, studies report a prevalence of NAFLD
of 20-45%.
• Estimates of prevalence of NAFLD in Asia-
Pacific regions range from 5 to 30 %.
• Worldwide, NAFLD has a reported prevalence
of 6-35%.

11. RISK FACORS
A- Common Conditions With Established
Association:
• Obesity
• T2DM
• Dyslipidemia
• Metabolic syndrome (Insulin resistance).
• Polycystic ovary syndrome
• Genetic factors.

12. RISK FACORS
B-Other Conditions Associated With NAFLD:
• Hypopituitarism
• Hypothyroidism
• Hypogpnadism
• Cushing syndrome
• Pancreatoduodenal resection
• Obstructive sleep apnea
• Psoriasis

13. C- Less Common Conditions Associated
With NAFLD:
1.Disorders of lipid metabolism
a.Abetalipoproteinemia
b.Hypobetalipoproteinemia
2.Total parenteral nutrition
3. HCV especially genotype 3
4.Severe weight loss
a. Jejuno ileal bypass
b.Gastric bypass
c.Severe starvation
5.Refeeding syndrome

14. 7.Exposure to toxic agents
e.g. vinyl chloride,
carbon tetrachloride,
yellow phosphorus.
8.post- cholecystectomy
9.Physical inactivity.
10. Junk food and soft drinks
consumption.
6. Iatrogenic
 Amiodarone
 Diltiazem
 Tamoxifen
 Steroids
 Tetracycline
 Oxaliplatin,
 Antiretroviral therapy
 OCPs, HRT.

15. NAFLD as a manifestation of syndrome-X
"metabolic" syndrome = obesity, hyperinsulinemia,
peripheral insulin resistance, diabetes,
hypertriglyceridaemia, hypertension.

18. Steatosis
Steatohepatitis
Cirrhosis
HCC
Spectrum of Hepatic Pathology in NAFLD

19. Fatty Liver: Macrovescicular steatosis with nucleus
positioning at cell periphery
NASH: Ballooning degeneration,
lobular neutrophil inflammation
and perisinusoidal fibrosis
NAFLD

20. NASH
Steatosis Cirrhosis

21. Grading and Staging of NAFLD

22. Grading and Staging of NAFLD

23. DIAGNOSIS
A. Symptoms and Signs
B. Laboratory Findings
C. Imaging
D. Liver Biopsy

24. Clinical Findings
A. Symptoms and Signs (History & Examination)
• Most patients with NAFLD are asymptomatic or
have mild right upper quadrant discomfort.
• Hepatomegaly is present in up to 75% of patients.
• Rare instances of subacute liver failure caused by
previously unrecognized NASH have been
described. Signs of portal hypertension generally
signify advanced liver fibrosis or cirrhosis.

25. INVESTIGATIONS
B. Laboratory Findings: (LFTS,FBG,2HPPBG, HbA1C,LIPID
PROFILE)
• Laboratory values may be normal in up to 80% of
persons with hepatic steatosis.
• Mildly elevated aminotransferase and alkaline
phosphatase levels

26. INVESTIGATIONS
C. Imaging:
 Macrovascular steatosis may be demonstrated on
ultrasonography, CT, or MRI. However, imaging does
not distinguish steatosis from steatohepatitis or detect
fibrosis.
Fibroscan

27. ultrasonography
There are 4-sonographic findings of diffuse fatty
change in the liver:
1- A diffuse hyperechoic echotexture (bright
liver)
2- Increased liver echotexture compared with
the kidneys
3- Vascular blurring
4- Deep attenuation

28. Ultrasonography

29. INVESTIGATIONS
D. Liver Biopsy:
• Percutaneous liver biopsy is diagnostic and is
the standard approach to assessing the degree
of inflammation and fibrosis.
• Is risky.
• Not recommended in asymptomatic persons
with unsuspected hepatic steatosis detected on
imaging but normal liver biochemistry test
results

30. MANAGEMENT OF NAFLD
• Lifestyle changes to remove or modify the
offending factors.
• Weight loss, dietary fat restriction, and even
moderate exercise (through reduction of
abdominal obesity) often lead to
improvement in liver biochemical tests and
steatosis in obese patients with NAFLD.

31. • A Mediterranean diet can reduce liver fat
without weight loss and is often
recommended. Loss of 3–5% of body weight
appears necessary to improve steatosis, but
loss of at least 10% may be needed to improve
necroinflammation and fibrosis.

32. • Exercise may reduce liver fat with minimal or
no weight loss and no reduction in ALT levels.
Resistance training and aerobic exercise are
equally effective in reducing hepatic fat
content in patients with NAFLD and type 2
diabetes mellitus.

33. • Vitamin E 800 international units/day (to
reduce oxidative stress) appears to be of
benefit in patients with NASH who do not
have diabetes mellitus.
DRUGS

34. • Thiazolidinediones (TZDs) (PIOGLITAZONE)
reverse insulin resistance and, in most relevant
studies, have improved both serum
aminotransferase levels and histologic features
of steatohepatitis but lead to weight gain (C.I.
IN HF, Osteoporosis)
• Metformin, which reduces insulin resistance,
improves abnormal liver chemistries but may
not reliably improve liver histology.

35. • Pentoxifylline improves liver biochemical test
levels but is associated with a high rate of side
effects, particularly nausea,pruritus.
• Ursodeoxycholic acid, 12–15 mg/kg/day, has
not consistently resulted in biochemical and
histologic improvement in patients with NASH
but may be effective when given in
combination with vitamin E.

36. • Hepatic steatosis due to total parenteral
nutrition may be ameliorated—and perhaps
prevented— with supplemental choline.
• Other approaches under study include
obeticholic acid, a semisynthetic bile acid
analog that has been approved for the
treatment

37. Obeticholic acid
• FDA accepts NDA for obeticholic acid for the
treatment of NASH November 26, 2019.
• Obeticholic acid is a farnesoid-X receptor (FXR)
agonist and is used to treat a number of liver
diseases.
• Obeticholic acid increases bile flow from the
liver and suppresses bile acid production in the
liver, thus reducing the exposure of the liver to
toxic levels of bile acids.

38. NASH Management sumery
1) All patients should be encouraged to exercise
exercise, and change life style.
Obese Patients
Weight reducing diet (aim for 10%)
In patients with BMI>28 with risk factors, or >30 without risk factors,
consider medical treatment with Orlistat .
2) Diabetic Patients
Good diabetic control (HbA1c <6.5%)
Metformin
Thiazolidinediones (pioglitazone)
Dietician for re-education.

39. NASH Management sumery
3) Patients with Hyperlipidaemia and abnormal LFT’s
Dyslipidaemia should be aggressively addressed
 Dietician Review
 Hypercholesterolaemia -Statins
 Hypertriglycerideaemia -Fibrate.
Avoid Drugs
amiodarone, glucocorticoids, methotrexate, nifedipine,
synthetic estrogens, tamoxifen

41. Thank you