6Fatty liver disease (Steatosis) Fatty liver is excessive accumulation of fat insite the liver cell (Hepatocyte)
7Fatty liver disease Fatty liver is reversible if the patient stops drinking, other causesFatty liver can lead to steatohepatitisSteatohepatitis is fatty liver accompanied byinflammationSteatohepatitis can lead scarring of the liver anddeveloped cirrhosis
8Symptoms and Signs Usually asymptomatic Right upper quadrant pain or discomfortFatigue or maliaseSymptoms of associated conditionHepatomegaly with or without tendernessSigns of chronic liver disease
9Diagnosis for NAFLD by noninvasive method 1. Ultrasonography4 sonographic finding by diffuse fatty change in liver- Diffuse hyperechoice echotexture (Bright liver)- Increased liver echotexture compared with kidney- Vascular blurring- Deep attenuation2. Computerized tomography3. Magnetic resonance imaging
10Diagnosis for NASH Histologic picture of steatohepatitis Convincing evidence of minimal or no alcoholconsumption (< 40 gm/wk)3. Absence of serologic evidence of viral hepatitisPowell et al. Hepatology 1990;11:74-80.
11Prevalence of NAFLD The most common liver disease in developed countries20 – 40% in western industrial countries5 – 30% in Asia – Pacific regionAge 40 – 60 yrs, common in menAlcohol consumption less than 20 gm/week
13Natural History of NAFLD NormalFatty liverSteatohepatitisSteatohepatitis with fibrosisCirrhosis( Fat , Fibrosis)
14Natural history of NASH CirrhosisLiver related death9 - 20%%Subacute failureHCCPost OLTxRecurrence2%8%?
15Clinical course and prognosis Clinically stable disorderMarkedly better prognosis than alcoholic steatohepatitisNAFLD had slightly lower overall survival than expectedfor general populationHigh mortality was associated withadvancing ageimpaired fasting glucosecirrhosisImportant cause of cryptogenic cirrhosis especially inolderdiabetic woman
16Causes of fatty liver disease Alcoholic fatty liver diseaseNon-alcoholic fatty liver disease (NAFLD)Characterized histologically by mainly macrovesicular hepatic steatosisDo not consume alcohol more than 20 gm/weekNAFLD + Inflammation (NASH) ~ Alcoholic hepatitisMacrovesicular steatosisMallory bodiesBallooning degenerationHepatocyte necrosisFibrosis
17Conditions Associated With Fatty Liver Disease 1. AlcoholMetabolic SyndromeDisorder of lipid metabolismTotal parenteral nutritionSevere weight lossRefeeding syndromeToxic exposureIatrogenicAmiodaroneDiltiazemTamoxifenSteroidHighly active antiretroviral therapy
18Pathophysiology of NASH Insulin ResistanceHepatic Steatosis(Oxidative Stress)NASHDiabetesInflammatorycytokinesObesityLipidPeroxidationFirststepSecond
19Major risk factors for NAFLD Central obesityDiabetes mellitus type 2DyslipidemiaMetabolic syndrome
20Who is metabolic syndrome? Three Make The DiagnosisAbdominal obesityMen > 40”Women > 35”Fasting glucose > 110 mg%Triglyceride > 150 mg%HDLMen < 40 mg%Women < 50 mg%Blood pressure : > 130 / > 85 mmHg
21Prevention and Treatment Normal liverRisk factorsPreventionCausesFatty liverTreatmentSteatohepatitisLiver cirrhosis
22Management of Fatty liver disease 1. PreventionHealth promotionPrevention of causeControlled associated conditionTreatmentNo proven effective medical therapy for NAFLDModify potential risk factorsObesityDMHyperlipidemiaWeight reductionGradual weight reduction1.6 kg per weekTotal 10%Increase physical activity and diet controlled
25Therapy for Co-morbidities ObesityDiet with or without exerciseBariatric surgeryCannabinoid receptor antagonistHypertriglyceridemiaGemfibrozilClofibrateStatinHypertensionAngiotensin II receptor antagonistDiabetesRosiglitozone
26Potential medical treatment for NASH Vitamin E and CHypoglycemia agentMetforminPioglitazoneRosiglitazoneProbucalBetaineUrsodeoxycholic acidLosartanPentoxifyllineOrlistat
27Treatment trials for NASH Study typeDuration (mos)Improved outcomeAnti-oxidantLavineHasegawaHarrisonKugelmasVitamin EVitamin E & C11104516Open labelRCTVaried63ALT, AST, AlkphosALT, AST, Markers of fibrosisFibrosis (?)Not different from diet & exerciseProAnti-oxidantAbdelmalekBetaine12ALT, AST, HistologyAnti-cytokineSatapathyAdamsPentoxifylline1820ALT, AST, TNF, insulin resistance,steatosisALT, ASTLiver Disease : Postgraduate Course 2006.
28Summary of studies using insulin sensitizers reporting effects upon hepatic steatosisAuthor, YearDrugStudy DesignSubject NumberDurationHepatic SteatosisNeuschwander-Tetri, 2003RosiglitazoneOpen-label3048 weeksImprovedPromrat, 2004PioglitazoneOpen-lebel18Sanyal, 2004+ Vitamin ERCT86 monthsBelfort, ’06Diet +/-NCT55Bugianesi, 2005MetforminNair, 20041512 monthsLimited improvementRCT : Randomized Clinical Trial ; NCT : Non-Controlled Trial ; N/A : Not available;No sig difference : No significant difference
29SummaryFatty liver disease is the most common liver disease in developed countriesFatty liver disease can be lead to liver cirrhosisThe major risk factors are obesity, DM type2,dyslipidemia and metabolic syndromeNo proven effective therapyTreatment are modify risk factors and weight reduction