1 / 105

nonalcoholic fatty liver diseases Alcoholic liver diseases Acute liver failure

nonalcoholic fatty liver diseases Alcoholic liver diseases Acute liver failure. Yasar Kucukardali MD Professor / I nternal Medicine. Non-Alcoholic Steatohepatitis. Represents only a part of wide spectrum of non alcoholic fatty liver Prevalence – 2 to 3 %

Télécharger la présentation

nonalcoholic fatty liver diseases Alcoholic liver diseases Acute liver failure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.


Presentation Transcript

  1. nonalcoholicfattyliverdiseasesAlcoholicliverdiseasesAcuteliverfailurenonalcoholicfattyliverdiseasesAlcoholicliverdiseasesAcuteliverfailure Yasar Kucukardali MD Professor / InternalMedicine

  2. Non-Alcoholic Steatohepatitis • Represents only a part of wide spectrum of non alcoholic fatty liver • Prevalence – 2 to 3 % • NASH – 3rd most common cause of CLD in North America after alcoholic liver disease & Hepatitis C • The most common cause of raised transaminases more than 6 months.

  3. NASH was coined by Ludwig et al while describing a series of patients of non-alcoholic, diabetic patients, mostly females, in whom liver histology was consistent with alcoholic liver disease but did not have a history of alcohol consumption.

  4. Prevalence • Steatosis is the most common cause of raised transaminases & affects 10-24 % of gen.population while only 2-3 % of gen.population have steatohepatitis. • In pts undergoing liver biopsy, the prevalence of NAFLD & steatohepatitis ranges from 15-39% &1.2-4.8% respectively.

  5. Risk Factors for NAFLD • Obesity • Diabetes • Hyperlipidemia • Female sex

  6. etiology • Drugs / Toxins • Metals – Antimony Barium salts Carbon disulfide Thallium compounds • Cytotoxic/cytostatic drugs • Antibiotics – Bleomycin Tetracycline • Others – Amiodarone Estrogen Glucocorticoids

  7. etiology • Inborn errors of metabolism – • Abetalipoproteinemia • Galactosemia • Glycogen storage disease • Weber-Christian syndrome • Wilson’s Disease • Nutritional – • Obesity • Rapid weight loss • Kwashiorkor

  8. etiology • Surgical – • Jejuno colic bypass • Jejunoileal bypass • Gastroplasty • Extensive bowel resection

  9. Pathogenesis • Increased delivery of fatty acids to liver Obesity Starvation • Increased synthesis of fatty acids in liver excess carbohydrate ( TPN ) • Decreased mitochondrial beta oxidation of fatty acids Carnitine deficiency Mitochondrial dysfunction • Decreased incorporation of triglycerides into functional VLDL Impaired apolipoprotein synthesis

  10. Pathogenesis • Impaired cholesterol esterification Choline deficiency Protein malnutrition • Impaired export of VLDL from hepatocyte • Insulin resistance increased lipolysis hyperinsulinemia

  11. Pathology • Diagnosis of NASH depends on histopathological features & exclusion of alcohol as the cause of disease. • Liver biopsy features : steatosispolymorphonuclear and / mononuclear hepatocyte ballooning and necrosi, malloryhyaline,glycogenatednuclei,metamitochondria and fibrosis indistinguishable from alcoholic liver disease

  12. Pathology • Steatosis in NASH – macrovesicular • Inflammation of steatohepatitis is predominantly lobular, whereas intense portal inflammation with interface activity is seen in chronic viral, autoimmune & drug indued hepatitis • But in children , NASH may have portal infiltrate. • Neutrophilic cells in lobular inflammatory infiltrate • Balloon degeneration – recognized form & characteristic finding in NASH. • Mallory hyaline may be +/- . It is characteristic of alcoholic hepatitis

  13. Pathology • Pattern of fibrosis is initial collagen deposition in perivenular & peri sinusoidal spaces of Zone 3 . • Chicken wire fibrosis • Fibrosis – in 66% pts • While 25% have severe fibrosis • And 14% have well established cirrhosis

  14. Histological Differential Diagnosis • Hepatitis C • Primary Biliary Cirrhosis • Autoimmune hepatitis • Alpha 1 anti trypsin deficiency • Hemochromatosis

  15. Clinical features Symptoms & Signs • Most of the patients are asymptomatic • 1/3rd present with nonspecific constitutional symptoms like weakness, fatigue & malaise. • Rapid onset of Fulminant hepatic failure – NASH d//t drugs like nucleoside analogues, tetracyclines • Hepatomegaly , splenomegaly • Presence of ascites, spider angiomata – indicate development of cirrhosis

  16. Clinical featuresLaboratory findings • Mild – moderate elevations of S.Transaminases, typically less than 4 times the upper normal limit. • ALT level greater than AST in absence of cirrhosis. • Liver biopsy

  17. Diagnosis • Clinical history • Exclusion of significant alcohol intake • Pursue dietary history, medication, occupational exposure to organic solvents • Family history of liver disease • Other causes of CLD – infections, metabolic heriditary & autoimmune causes to be ruled out • Liver biopsy – confirm diagnosis & for prognostic information

  18. Natural course • Steatosis • Steatohepatitis • Cirrhosis • Steatosis – good prognosis • Steatohepatitis , cirrhosis – bad prognosis

  19. Treatment • Treatment options are limited • Weight Reduction: • wt loss – normalization of s.aminotransferases. • Means of wt loss is important not the amount of wt loss • Recommended wt loss – 230 g/day or 1.6 kg/week • Diet : 45 -100 g high quality animal protein less than 100g carbohydrates less than 10 g fat per day providing 600 -800 kcal

  20. Treatment • Ursodeoxycholic acid : • Has membrane stabilizing / cytoprotective / immunological effect • 10-15 mg/kg/day for 6-12 months – significant improvement in transaminases levels and degree of steatohepatitis

  21. Treatment • Liver Transplantation : • NASH – A relative contraindication • Many of pts with NASH with CLD who underwent Liver Transplant – redeveloped NASH in the new donor liver ( 2/3 cases ) & • 1/3rd cases – liver transplantation is unsuccessful.

  22. Newer treatment modalities • Inhibition of macrophage activation: • Anti oxidant ( Vit E ) glutathione prodrugs • Antibiotics, preprobiotics • Anti cytokines ( anti TNF alpha antibodies, pentoxiphylline )

  23. Protect hepatocyte ATP stores • PARP inhibitors • Minimize CYP2F activity • Dietary modification ( avoid fats ) • Insulin sensitizers : pioglitazone • Antiobesity drugs : sibutramine, orlistat • Antilipid drugs : Simvastatin, Procusol

  24. Alcoholic liver diseases

  25. INTRODUCTION  • There is a spectrum of clinicalandlaboratoryfindings in patientswithalcoholicliverdisease, rangingfromasymptomaticfattylivertoalcoholichepatitistoend-stageliverfailurewithjaundice, coagulopathy, andencephalopathy • Unfortunately, manyalcoholicsfirstbecomesymptomaticonlywhen severe, life threateningliverdisease is alreadypresent. • Even at thisstage, abstinence can result in significantreversal in somepatients.

  26. Patientswithalcoholicliverdiseaseoftenhavecoexistingdysfunction in otherorgans. cardiomyopathy, skeletalmusclewasting, neuropathies, pancreaticdysfunction. • The presence of feverandabdominalpainshouldnot be takenlightly in a patientwithalcoholichepatitiswithcirrhosisandascites, and can mimicthepresentation of spontaneousbacterialperitonitis. • Thedistinctionbetweenthesedisordersshould be madebyasciticfluidanalysis. A polymorphonuclearleukocytecountthat is ≥250/mm3 is presumptiveevidence of spontaneousbacterialperitonitis since it does not occurwithalcoholichepatitisalone.

  27. Excessive alcohol consumption is the leading cause of liver disease. • Alcoholic liver disease comprises of three main stages • Hepatic steatosis • Alcoholic hepatitis • Cirrhosis

  28. Hepatic steatosis • Pathogenesis : • Fatty change is an acute, reversible manifestation of ethanol ingestion. • Ethanol causes • Increased fatty acid synthesis by causing catabolism of fat in the peripheral tissues • Acetaldehyde which is metabolite of ethanol converts NAD+ to NADH. An excess NADH stimulates lipid biosynthesis. • Oxidation of fatty acid by mitochondria is decreased • Acetaldehyde impairs the function of microtubules, resulting in decreased transport of lipoproteins from liver • Collectively these metabolic consequences produce fatty liver.

  29. Pathology: • Gross: • The liver becomes yellow, greasy and is enlarged (up to 4 to 6 kg) • The increase in weight is because of accumulation of fat, protein and water

  30. Microscopy: • Following even moderate intake of alcohol, small (microvesicular) lipid droplets accumulates in the liver • With chronic intake of alcohol, more lipid accumulates, creating a large macrovesicular globules, compressing the nucleus the periphery.

  31. Steatosis in Alcoholism

  32. Clinical features of alcoholic steatosis • Hepatomegaly • Mild elevation of serum bilirubin, alkaline phasphatase and gamma GT

  33. Alcoholic hepatitis • Is characterized by • Hepatocyte swelling and necrosis • Mallory bodies • Neutrophilic inflammatory response • Perivenular fibrosis

  34. Hepatocyte swelling and necrosis: • Single or scattered foci of cells undergo swelling (ballooning degeneration) and necrosis

  35. Mallory bodies: • Scattered hepatocytes accumulate cytokeratin intermediate filaments and other proteins • Visible as eosinophilic cytoplasmic inclusions in degenerating hepatocytes

  36. Neutrophilic reaction: • Neutrophils accumulate around the degenerating hepatocytes, particularly those having Mallory bodies. • Lymphocytes and macrophages also enter portal tracts and spill into parenchyma

More Related