1. รศ.นพ.กิตติ จันทร์เลิศฤทธิ์ 13 ตุลาคม 2552
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รศ.นพ.กิตติ จันทร์เลิศฤทธิ์
13 ตุลาคม 2552

2. Cause of death 2548 - 2550 Cause % Cerebrovascular disease
Ischemic heart disease
HIV / AIDS
Transport accident
COPD
Liver Cirrhosis
11.6
8.1
7.7
6.4
4.8
4.3

3. Normal liver Fatty liver Infection Hepatitis or Steatohepatitis
Genetic and metabolic
Hepatitis or
Steatohepatitis
Fibrosis
Infection
Autoimmune
Chemical
Liver Cirrhosis

4. Cause of Liver Cirrhosis
Viral hepatitis
Alcoholic
Metabolic
Cardiac cirrhosis
Cryptogenic
NAFLD

5. Non-alcoholic Fatty Liver Disease

6. Fatty liver disease (Steatosis)
Fatty liver is excessive accumulation of fat insite the liver cell (Hepatocyte)

7. Fatty liver disease Fatty liver is reversible if the patient stops
drinking, other causes
Fatty liver can lead to steatohepatitis
Steatohepatitis is fatty liver accompanied by
inflammation
Steatohepatitis can lead scarring of the liver and
developed cirrhosis

8. Symptoms and Signs Usually asymptomatic
Right upper quadrant pain or discomfort
Fatigue or maliase
Symptoms of associated condition
Hepatomegaly with or without tenderness
Signs of chronic liver disease

9. Diagnosis for NAFLD by noninvasive method
1. Ultrasonography
4 sonographic finding by diffuse fatty change in liver
- Diffuse hyperechoice echotexture (Bright liver)
- Increased liver echotexture compared with kidney
- Vascular blurring
- Deep attenuation
2. Computerized tomography
3. Magnetic resonance imaging

10. Diagnosis for NASH Histologic picture of steatohepatitis
Convincing evidence of minimal or no alcohol
consumption (< 40 gm/wk)
3. Absence of serologic evidence of viral hepatitis
Powell et al. Hepatology 1990;11:74-80.

11. Prevalence of NAFLD The most common liver disease in developed
countries
20 – 40% in western industrial countries
5 – 30% in Asia – Pacific region
Age 40 – 60 yrs, common in men
Alcohol consumption less than 20 gm/week

12. Prevalence of NASH

13. Natural History of NAFLD
Normal
Fatty liver
Steatohepatitis
Steatohepatitis with fibrosis
Cirrhosis
( Fat , Fibrosis)

14. Natural history of NASH
Cirrhosis
Liver related death
9 - 20% %
Subacute failure
HCC
Post OLTx
Recurrence 2% 8% ?

15. Clinical course and prognosis
Clinically stable disorder
Markedly better prognosis than alcoholic steatohepatitis
NAFLD had slightly lower overall survival than expected
for general population
High mortality was associated with
advancing age
impaired fasting glucose
cirrhosis
Important cause of cryptogenic cirrhosis especially in
older
diabetic woman

16. Causes of fatty liver disease
Alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD)
Characterized histologically by mainly macrovesicular hepatic steatosis
Do not consume alcohol more than 20 gm/week
NAFLD + Inflammation (NASH) ~ Alcoholic hepatitis
Macrovesicular steatosis
Mallory bodies
Ballooning degeneration
Hepatocyte necrosis
Fibrosis

17. Conditions Associated With Fatty Liver Disease
1. Alcohol
Metabolic Syndrome
Disorder of lipid metabolism
Total parenteral nutrition
Severe weight loss
Refeeding syndrome
Toxic exposure
Iatrogenic
Amiodarone
Diltiazem
Tamoxifen
Steroid
Highly active antiretroviral therapy

18. Pathophysiology of NASH
Insulin Resistance
Hepatic Steatosis
(Oxidative Stress)
NASH
Diabetes
Inflammatory
cytokines
Obesity
Lipid
Peroxidation
First
step
Second

19. Major risk factors for NAFLD
Central obesity
Diabetes mellitus type 2
Dyslipidemia
Metabolic syndrome

20. Who is metabolic syndrome?
Three Make The Diagnosis
Abdominal obesity
Men > 40”
Women > 35”
Fasting glucose > 110 mg%
Triglyceride > 150 mg%
HDL
Men < 40 mg%
Women < 50 mg%
Blood pressure : > 130 / > 85 mmHg

21. Prevention and Treatment
Normal liver
Risk factors
Prevention
Causes
Fatty liver
Treatment
Steatohepatitis
Liver cirrhosis

22. Management of Fatty liver disease
1. Prevention
Health promotion
Prevention of cause
Controlled associated condition
Treatment
No proven effective medical therapy for NAFLD
Modify potential risk factors
Obesity DM
Hyperlipidemia
Weight reduction
Gradual weight reduction
1.6 kg per week
Total 10%
Increase physical activity and diet controlled

23. Diet for NAFLD

24. None

25. Therapy for Co-morbidities
Obesity
Diet with or without exercise
Bariatric surgery
Cannabinoid receptor antagonist
Hypertriglyceridemia
Gemfibrozil
Clofibrate
Statin
Hypertension
Angiotensin II receptor antagonist
Diabetes
Rosiglitozone

26. Potential medical treatment for NASH
Vitamin E and C
Hypoglycemia agent
Metformin
Pioglitazone
Rosiglitazone
Probucal
Betaine
Ursodeoxycholic acid
Losartan
Pentoxifylline
Orlistat

27. Treatment trials for NASH
Study type
Duration (mos)
Improved outcome
Anti-oxidant
Lavine
Hasegawa
Harrison
Kugelmas
Vitamin E
Vitamin E & C 11 10 45 16
Open label
RCT
Varied 6 3
ALT, AST, Alkphos
ALT, AST, Markers of fibrosis
Fibrosis (?)
Not different from diet & exercise
ProAnti-oxidant
Abdelmalek
Betaine 12
ALT, AST, Histology
Anti-cytokine
Satapathy
Adams
Pentoxifylline 18 20
ALT, AST, TNF, insulin resistance,
steatosis
ALT, AST
Liver Disease : Postgraduate Course 2006.

28. Summary of studies using insulin sensitizers reporting effects upon
hepatic steatosis
Author, Year
Drug
Study Design
Subject Number
Duration
Hepatic Steatosis
Neuschwander-Tetri, 2003
Rosiglitazone
Open-label 30
48 weeks
Improved
Promrat, 2004
Pioglitazone
Open-lebel 18
Sanyal, 2004
+ Vitamin E
RCT 8
6 months
Belfort, ’06
Diet +/-
NCT 55
Bugianesi, 2005
Metformin
Nair, 2004 15
12 months
Limited improvement
RCT : Randomized Clinical Trial ; NCT : Non-Controlled Trial ; N/A : Not available;
No sig difference : No significant difference

29. Summary
Fatty liver disease is the most common liver disease in developed countries
Fatty liver disease can be lead to liver cirrhosis
The major risk factors are obesity, DM type2,
dyslipidemia and metabolic syndrome
No proven effective therapy
Treatment are modify risk factors and weight reduction