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รศ.นพ.กิตติ จันทร์เลิศฤทธิ์ 13 ตุลาคม 2552. จะป้องกันรักษาและช่วยเหลือผู้ป่วยที่เป็นโรคตับได้อย่างไร : โรคตับจากไขมันในตับ. Cause of death 2548 - 2550. Genetic and metabolic. Fatty liver. Normal liver. Infection. Hepatitis or Steatohepatitis. Autoimmune. Chemical. Fibrosis.
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รศ.นพ.กิตติ จันทร์เลิศฤทธิ์ 13 ตุลาคม 2552 จะป้องกันรักษาและช่วยเหลือผู้ป่วยที่เป็นโรคตับได้อย่างไร : โรคตับจากไขมันในตับ
Genetic and metabolic Fatty liver Normal liver Infection Hepatitis or Steatohepatitis Autoimmune Chemical Fibrosis Liver Cirrhosis
Cause of Liver Cirrhosis Viral hepatitis Alcoholic Metabolic Cardiac cirrhosis Cryptogenic NAFLD
Fatty liver disease (Steatosis) Fatty liver is excessive accumulation of fat insite the liver cell (Hepatocyte)
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
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
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
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.
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
Normal Natural History of NAFLD Fatty liver Steatohepatitis Steatohepatitis with fibrosis Cirrhosis ( Fat , Fibrosis)
Natural history of NASH 30 - 40% 9 - 20% NASH Cirrhosis Liver related death ? 2% 8% Subacute failure HCC Post OLTx Recurrence
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
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
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
Pathophysiology of NASH Insulin Resistance Obesity Diabetes First step Hepatic Steatosis (Oxidative Stress) Inflammatory cytokines Lipid Peroxidation Second step NASH
Major risk factors for NAFLD Central obesity Diabetes mellitus type 2 Dyslipidemia Metabolic syndrome
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
Prevention and Treatment Normal liver Causes Prevention Risk factors Fatty liver Treatment Prevention Steatohepatitis Treatment Liver cirrhosis
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
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
Potential medical treatment for NASH Vitamin E and C Hypoglycemia agent Metformin Pioglitazone Rosiglitazone Probucal Betaine Ursodeoxycholic acid Losartan Pentoxifylline Orlistat
Treatment trials for NASH Liver Disease : Postgraduate Course 2006.
Summary of studies using insulin sensitizers reporting effects upon hepatic steatosis
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