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.... 13 2552. Cause of death 2548 - 2550 Cause% Cerebrovascular disease Ischemic heart disease HIV / AIDS Transport accident COPD Liver Cirrhosis 11.6.

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Presentation on theme: ".... 13 2552. Cause of death 2548 - 2550 Cause% Cerebrovascular disease Ischemic heart disease HIV / AIDS Transport accident COPD Liver Cirrhosis 11.6."— Presentation transcript:

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2 Cause of death Cause% Cerebrovascular disease Ischemic heart disease HIV / AIDS Transport accident COPD Liver Cirrhosis

3 Normal liver Fatty liver 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 1.Histologic picture of steatohepatitis 2.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 NASHCirrhosisLiver related death % % Subacute failureHCCPost 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 1.Alcoholic fatty liver disease 2.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 2. Metabolic Syndrome 3. Disorder of lipid metabolism 4. Total parenteral nutrition 5. Severe weight loss 6. Refeeding syndrome 7. Toxic exposure 8. 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 step

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 PreventionCauses Fatty liverTreatment Prevention Steatohepatitis Treatment Liver cirrhosis

22 Management of Fatty liver disease 1. Prevention Health promotion Prevention of cause Controlled associated condition 2.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 TrialTreatmentnStudy type Duration (mos) Improved outcome Anti-oxidant Lavine Hasegawa Harrison Kugelmas Vitamin E Vitamin E & C Vitamin E Open label RCT Open label Varied 6 3 ALT, AST, Alkphos ALT, AST, Markers of fibrosis Fibrosis (?) Not different from diet & exercise ProAnti-oxidant AbdelmalekBetaine10Open label 12 ALT, AST, Histology Anti-cytokine Satapathy Adams Pentoxifylline Open label 6 12 ALT, AST, TNF, insulin resistance, steatosis ALT, AST Liver Disease : Postgraduate Course 2006.

28 Author, YearDrug Study Design Subject Number Duration Hepatic Steatosis Neuschwander-Tetri, 2003RosiglitazoneOpen-label3048 weeksImproved Promrat, 2004PioglitazoneOpen-lebel1848 weeksImproved Sanyal, 2004 Pioglitazone + Vitamin E RCT86 monthsImproved Belfort, 06 Diet +/- Pioglitazone NCT556 monthsImproved Bugianesi, 2005MetforminRCT556 monthsImproved Nair, 2004 MetforminOpen-label1512 months Limited improvement RCT : Randomized Clinical Trial ; NCT : Non-Controlled Trial ; N/A : Not available; No sig difference : No significant difference Summary of studies using insulin sensitizers reporting effects upon hepatic steatosis

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


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