ALCOHOLIC LIVER DISEASE

1. ALCOHOLIC LIVER DISEASE DR. SUBHAN ALI R ASSISTANT PROFESSOR PATHOLOGY

2. Introduction • Pathogenesis • Clinical features • Fatty liver • Alcoholic hepatitis • Alcoholic steatofibrosis • Nonalcoholic Fatty liver disease ( NAFLD)

3. Models of Liver Anatomy • Lobular • Acinar

5. Introduction • The leading cause of liver disease in western countries- Alcohol • It accounts 3.8% of deaths globally • 8th risk factor for death • Three distinctive and overlapping features of alcoholic liver disease-Hepatocellar steatosis –Alcoholic hepatitis- Steatofibrosis • Consumption of 80 gm/day • Cirrhosis- 10- 15 yrs

6. Pathogenesis • Mild reversible hepatic steatosis- 80gm/ day –six beers • Daily 160 gm or more for 10 to 20 yrs – severe hepatic injury • Only 10 -15% of alcoholics develop cirrhosis • Gender • Ethnic and genetic differences • Comorbid conditions

7. Metabolism of Alcohol

9. Clinical features • Symptoms-Malaise,anorexia, weight loss, upper abdominal discomfort • Signs- Hepatomegaly • Lab findings- serum bilirubin – Elevated Aminotransferanse (AST and ALT) and Alkaline phosphatase – Elevated • Chronic liver disease – ALT > AST • Alcoholic liver disease- AST> ALT (2:1) • Cirrhosis – hepatic dysfunction ( bilirubin, AST, ALT) , Hypoproteinemia ( globulins, albumin and clotting factors)

10. Complications and death • Hepatic coma • Massive gastrointestinal bleeding • Intercurrent infection • Hepatorenal syndrome • Hepatocelluar carcinoma

11. Pathological findings

12. Fatty liver • Alcoholic hepatitis • Alcoholic steatofibrosis

13. Fatty liver • Gross- Large, soft with yellow and greasy apperance • Microscopy – Lipid accumulates in hepatocytes • Micro and macrovesicles • Completely reversible – abstention from intake of alcohol

14. Microscopy

15. Alcoholic hepatitis • Hepatic swelling and necrosis • Mallory- denk bodies : Clumped, amorphous, eosinophilic material • Tangled skeins of intermediate filaments ( Keratin 8 & 18) • Neutrophilic reaction

16. Microscopy

17. Mallory- denk bodies

18. Alcoholic steatofibrosis • Activation of sinusoidal stellate cells and portal fibroblasts- fibrosis • Central veins-Sclerosis • Perisinusoidal scar-Space of Disse • Chicken wire fence pattern • Classic micronodular / Laennec cirrhosis

19. Microscopy

20. Gross

21. Microscopy

22. Nonalcoholic Fatty Liver Disease

23. Nonalcoholic Fatty Liver Disease • NAFLD/ NASH • Spectrum of disorders that have in common the presence of fatty liver in individuals who do not consume alcohol or very small quantities . ( < 20 gm/ week ) • Histologic hallmarks of NAFLD are most consistently associated with the metabolic syndrome.

24. Metabolic syndrome. • ONE of – • Diabetes mellitus or • imparied glucose tolerance or • imparied fasting glucose or • insulin resistance • TWO of • Blood pressure > 140/90 mm Hg • Dyslipidemia • Central obesity • Microalbuminuria

25. Pathogenesis • Insulin resistance- Hepatic steatosis. • Hepatocellular oxidative injury – Liver cell necrosis and inflammatory reactions.

26. Microscopy

27. Microscopy