NAFLD

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NAFLD

• Dr Allister J Grant
• Consultant Hepatologist

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How common is NAFLD?

• The most common cause of abnormal liver function
  tests in the United States.
• Estimated 30.1 million with NAFLD and 8.6 million
  with NASH
• Affects 10-24 of the population
• 58-74 of the obese population
• Affects 2.6 of children
• 23-53 of obese children

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Age Adjusted Prevalence () of Overweight and
Obese Americans Aged 20-74y
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Dallas Heart Study Results
Healthy
Fatty
Liver fat lt 5.5
Liver fat gt 5.5
Steatosis 31
Mean BMI 29
Liver enzymes NORMAL in most (79) with steatosis
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LEICESTER
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Fatty Liver

• Better detected by abdominal imaging than blood
  tests
• Common in individuals who are
• Overweight/obese
• Type 2 diabetic
• Dyslipidaemic
• Regular alcohol consumers

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Hepatic SteatosisGender Disparities in Whites
45
42
FLD
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24
M
M
F
M
F
F
Hispanics
Whites
Blacks
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Non Alcoholic Fatty Liver Disease
(NAFLD) Spectrum of Hepatic Pathology
Steatohepatitis
Steatosis
Cirrhosis
Hepatocellular carcinoma
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NAFLD
Fatty Liver Macrovescicular steatosis with
nucleus positioning at cell periphery NASH
Mallory bodies, ballooning degeneration, lobula
r neutrophil inflammation and perisinusoidal
fibrosis AGA Technical Review on Nonalcoholic
Fatty Liver Disease Gastroenterology
20021231705-1725
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NASH
Steatosis
Cirrhosis
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NASH- Peri-sinusiodal fibrosis
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Grading and Staging of NAFLD
Brunt et al Am J Gastro 1999
Grading NAFLD 1.Macrovescicular steatosis Grade
0 None Grade 1 Up to 33 Grade 2 33-66 Grade
3 gt66 2. Necroinflammatory activity Mild,
Mod, Severe
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NAFLD Diagnosis Role for Liver Biopsy?
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Role for Liver Biopsy?

• Confirmatory test
• Resolves diagnostic confusion
• (e.g. AIH, HH)
• Refines staging
• Sensitive for subclinical fibrosis
• Imperfect (sampling error)
• Invasive procedure
• Significant mortality.

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Diseases associated with Steatohepatitis

• 1.Alcoholism
• 2.Insulin resistance
• a.Metabolic Syndrome
• i.Obesity
• ii.Diabetes
• iii.Hypertriglyceridemia
• iv.Hypertension
• b.Lipoatrophy
• c.Mauriac Syndrome
• d.PCOS
• 3.Disorders of lipid metabolism
• a.Abetalipoproteinemia
• b.Hypobetalipoproteinemia
• c.Andersens disease
• d.Weber-Christian syndrome
• 4.Total parenteral nutrition
• 5. HCV

• 6.Severe weight loss
• a.Jejuno-ileal bypass
• b.Gastric bypass
• c.Severe starvation
• 7.Iatrogenic
• a.Amiodarone
• b.Diltiazem
• c.Tamoxifen
• d.Steroids
• e.HAART
• f. tetracycline
• g.glucosamine
• 8.Refeeding syndrome
• 9.Exposure to toxic agents
• a.Environment
• b.Workplace Sb,Th,Ba

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NAFLD

• NAFLD is a spectrum of disease which includes
  Fatty liver disease and NASH, but only NASH is
  known to progress to cirrhosis.

Fatty Liver Obese BMIgt28 Centipetal
(apple) Bright liver on USS Insulin
Resistance Normal ALT
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High Fat/CHO Diet Lack of Exercise
Pathogenesis of NASH
Hepatic Steatosis
?FFA oxidation ?Lipogenesis ?Lipid Export
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High Fat/CHO Diet Lack of Exercise
Pathogenesis of NASH
Hepatic Steatosis
?FFA oxidation ?Lipogenesis ?Lipid Export
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High Fat/CHO Diet Lack of Exercise
Pathogenesis of NASH
Hepatic Steatosis
?FFA oxidation ?Lipogenesis ?Lipid Export
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High Fat/CHO Diet Lack of Exercise
Treatment Strategies In NASH
Hepatic Steatosis
?FFA oxidation ?Lipogenesis ?Lipid Export
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Natural history

• Simple steatosis relatively benign liver
  prognosis with a risk of developing clinical
  evidence of cirrhosis over 1520 years in the
  order of 12.
• NASH and fibrosis risk of progress to cirrhosis
  between 0 at 5 years to 12 over 8 years.
• Cirrhotic high risk of developing hepatic
  decompensation and of dying from a liver-related
  cause including HCC.

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NASH

• Affects 3.5-5 of the population
• The rates of progression to cirrhosis have been
  estimated at between 5 and 20 over 10 years.
• There aren't any non-invasive means of
  predicting which patients are at risk of
  progression, and there are no agreed guidelines
  on how to monitor progression.

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Current Management of NAFLD and NASH. APT.
Younossi Z 2008
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Initial Investigation

• Look for risk factors
• BMI, DM, HBP, Lipids,FHx, Drugs, Alcohol
• Liver screen
• Including Glc/GTT/HbA1c/Lipids/AST
• Pl, Alb, INR
• USS
• Spleen size, fatty liver, collaterals

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Managemant of NASH

• The patient should lose weight and exercise
• Pharmacological treatment of Insulin-resistance
• Treatment of Hyperlipidaemia
• Hepatocyte-Protective treatment

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NASH Management

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• 1) All patients should be encouraged to
  exercise, as there is good evidence that even in
  the absence of weight loss exercise improves
  NASH.
• Obese Patients
• Weight reducing diet (aim for 10, 1-2lb per
  week)
• In patients with BMIgt28 with risk factors, or
  gt30 without risk factors, consider treatment with
  Orlistat.
• 2) Diabetic Patients
• Good diabetic control (HbA1c lt6.5)
• Metformin
• Thiazolidinediones (rosiglitazone and
  pioglitazone)
• Dietician for re-education.
• Diabetologist if glucose control is difficult. 

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NASH Management

• 3) Patients with Hyperlipidaemia and abnormal
  LFTs
• Dyslipidaemia should be aggressively addressed
• Dietician Review
• Hypercholesterolaemia -Statins
• Hypertriglycerideaemia -Fibrate.
• Lipid Clinic
•   Avoid Drugs
• amiodarone, glucocorticoids, methotrexate,
  nifedipine, synthetic estrogens, tamoxifen
• Antioxidants?

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Thank you
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