1. Other causes of Cirrhosis: Genetic eg. Wilson's Disease, Hemochromatosis Autoimmune eg. Autoimmune Hepatitis, Primary Biliary Cirrhosis, Primary Sclerosing cholangitis Alcoholic Liver Disease NASH (Non-Alcoholic Steatohepatitis) Misc: eg Budd-Chiari Syndrome

2. Wilson’s Disease Autosomal recessive Abnormality in handling of copper Copper deposits in liver and basal ganglia Presentation age 5-30 years with either neurologic or hepatic disease Liver disease can vary from acute hepatitis to cirrhosis

3. Wilson’s Disease Must be ruled out in all patients < age 30 with liver disease May present as 1) ABN LFT’s 2) Fulminant Hepatic Failure 3) Chronic Active Hepatitis 4) Cirrhosis CNS Features

4. Wilson’s Disease Decreased ceruloplasmin (a copper binding protein) Increased Urinary Copper Kayser-Fleisher Rings Neurologic manifestations esp tremor and psychiatric abnormalities

7. Presentation of Wilson’s Disease

8. Wilson’s Disease Treatment: D-Penicillamine- binds copper so not absorbed from diet and copper deposits gradually decline

9. Hereditary hemochromatosis  0.4-1.0% of N European  One of the most common inherited disorders  Autosomal recessive  Leads to excess iron absorption in gut and deposition in liver,heart,joints,pancreas and other endocrine organs

10. HFe

13. Hemochromatosis genes:  85% of HFe patients are Homozygous for C282Y mutation-leads to inappropriate absorption of iron from GI tract  5% are C282Y/H63D heterozygote  C282Y predominantly northern Europe (1/300)  H63D common in all ethnic groups- 14% allelic frequency, low penetrance

14. Management of Hemochromatosis:  Gene testing  Phlebotomy/ Become Blood Donor??  Family screening esp siblings  ?MRI  Screening for hepatoma in Cirrhotics

15. Other causes of iron overload:  Metabolic syndrome Obesitas Hypertension Insulin resistance  Chronic Liver Disease Hepatitis Alcohol use NASH Porphyria Cutanea Tarda  Iron overload in sub-Saharan Africa

16. α-1 Antitrypsin Deficiency Hereditary deficiency of α-1 antitrypsin Often presents as neonatal Jaundice - 5/28 infants with neonatal hepatitis ultimately diagnosed as α- 1 at deficiency. - 9/13 patients with α-1 antitrypsin deficiency presented as jaundice < age 1 year. Usually develop cirrhosis in childhood Liver disease associated with Pizz Phenotype

18. Autoimmune Chronic Hepatitis Disease of young women and menopausal women C/O fatigue high AST, high ALT-may be markedly elevated High IgG levels ANA +VE in 80% Anti-smooth muscle antibody most specific test (80%) Liver biopsy shows chronic hepatitis with plasma cells and more damage than anticipated Treatment = Corticosteroids

20. Primary Biliary Cirrhosis (PBC) Disease of Middle-aged women Presents with fatigue, hepatomegaly, +- pruritus (itch) Increased Alkaline phosphate Cell-mediated damage to intrahepatic ductules +ve antimitochondrial antibodiesin 95%

23. Primary Biliary Cirrhosis Was major cause of liver transplant URSO (Ursodeoxycholic Acid) treatment since 1986.. Few progress Itch can be debilitating: Rx cholystyramine which binds bile salts in GI tract

24. Primary Sclerosing Cholangitis: PSC 70% have Ulcerative colitis Either can present first PSC can develop after colectomy Autoimmune damage of medium size intra and extra- hepatic bile ducts Presents as abnormal cholestatic liver enzymes and occasionally recurrent cholangitis

27. Primary Sclerosing Cholangitis Frequently progresses to Liver transplant- but age varies No Known treatment ERCP dilatation of tight strictures Risk of cholangiocarcinoma ( and hepatoma)

28. Budd-Chiari Syndrome: Blockage of Hepatic veins Usually secondary to Hypercoagulable state Often presents with ascites Diagnosed with US/doppler of hepatic veins Rx: anticoagulation +/- Tipps +/- Liver transplant Rare

29. Medication Induced Liver Disease Several medications/herbal products can cause severe liver disease Nitrofurantoin and Minocycline –Autoimmune hepatitis Methotrexate and Amiodarone- NASH/cirrhosis Hydroxycut/Tylenol –fulminant liver failure

30. Summary: The main function of the liver is NOT to metabolize alcohol!! Important to recognize TREATABLE causes of liver disease eg Wilson’s Disease, hemochromatosis, autoimmune hepatitis Patient may have > 1 cause Medications can mimic other liver conditions