NAFLD
BY
EMAD FAWZI,MD.
PROFESSOR OF INTERNAL MEDICINE &
GASTROENTEROLOGY AND HEPATOLOGY
Fatty Liver Diseases(FLD)
• Subdivided into:
Alcoholic FLD.
Nonalcoholic FLD.
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
• NAFLD is subdivided into:
Nonalcoholic fatty liver (NAFL) or simple
steatosis.
Nonalcoholic steatohepatitis (NASH) which may
progress to liver cirrhosis and hepatocellular
carcinoma.
Nonalcoholic Fatty Liver (NAFL)
•Evidence of Hepatic steatosis: either by
imaging 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.
Nonalcoholic steatohepatitis
(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).
Other terms that have been used to
describe NASH include:
Pseudoalcoholic hepatitis
Alcohol-like hepatitis
Fatty liver hepatitis
Steatonecrosis
Diabetic hepatitis.
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.
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%.
RISK FACORS
A- Common Conditions With Established
Association:
• Obesity
• T2DM
• Dyslipidemia
• Metabolic syndrome (Insulin resistance).
• Polycystic ovary syndrome
• Genetic factors.
RISK FACORS
B-Other Conditions Associated With NAFLD:
• Hypopituitarism
• Hypothyroidism
• Hypogpnadism
• Cushing syndrome
• Pancreatoduodenal resection
• Obstructive sleep apnea
• Psoriasis
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
6. Iatrogenic
7.Exposure to toxic agents
Amiodarone e.g. vinyl chloride,
Diltiazem carbon tetrachloride,
Tamoxifen yellow phosphorus.
Steroids 8.post- cholecystectomy
9.Physical inactivity.
Tetracycline
10. Junk food and soft
Oxaliplatin, drinks consumption.
Antiretroviral therapy
OCPs, HRT.
NAFLD as a manifestation of syndrome-X
"metabolic" syndrome = obesity, hyperinsulinemia,
peripheral insulin resistance, diabetes,
hypertriglyceridaemia, hypertension.
Spectrum of Hepatic Pathology in NAFLD
Steatohepatitis
Steatosis
Cirrhosis
HCC
NAFLD
Fatty Liver: Macrovescicular steatosis with nucleus
positioning at cell periphery
NASH: Ballooning degeneration,
lobular neutrophil inflammation
and perisinusoidal fibrosis
NASH
Steatosis Cirrhosis
Grading and Staging of NAFLD
Grading and Staging of NAFLD
DIAGNOSIS
A. Symptoms and Signs
B. Laboratory Findings
C. Imaging
D. Liver Biopsy
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
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
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
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
Ultrasonography
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
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.
• 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.
• 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.
DRUGS
• 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.
• 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
• 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.
• 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
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.
NASH Management sumery
1) All patients should be encouraged toexercise , 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.
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
Thank you
