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Autoimmune Hepatitis

Autoimmune Hepatitis. Is a liver disease of unknown aetiology characterized by a strong association with other autoimmune diseases, high levels of serum immunoglobulin ( Hypergammaglobulinaemia ) & auto antibodies in the serum.

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Autoimmune Hepatitis

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  1. Autoimmune Hepatitis

  2. Is a liver disease of unknown aetiology characterized by a strong association with other autoimmune diseases, high levels of serum immunoglobulin ( Hypergammaglobulinaemia ) & auto antibodies in the serum. It occur most often in young women particularly in the second & third decades of life.

  3. Conditions associated with autoimmune hepatitis 1-Migratory polyarthritis 2-Urticarial rash 3-Lymphadenopathy 4-Hashimatos thyroiditis 5-Throtoxicosis 6-Hypothyroidism 7-Coombs +ve hemolytic anemia 8-Pleurisy 9-Transient pulmonary infiltrates 10-Ulcerative colitis 11-Glomerulonephritis 12-Nephrotic syndrome

  4. Types: Classical (Type 1): • Increased incidence of autoimmune diseases like Graves disease. • Associated with HLA-DR3 & DR4. • Increased titer of ANF & Anti smooth muscle Abs. Type 2: • Characterized by the presence of Anti-LKM (Liver,kidney,microsomal )Abs . • Lack of ANF & Anti smooth muscle Abs. Type 3 • Serum immunoglobulines are elevated • ANF& Antismooth muscle & other antibodies are absent • Antibodies against soluble liver antigen are present

  5. Clinical features: • Insidious onset with fatigue, anorexia & jaundice. • 25% present with acute hepatitis but no resolution occur. • Fever, arthralgia ,vitiligo & pruritis. • Amenorrhea is the role. • Sings of chronic liver disease. • Some patients have cushingoid face with acne,hirsutisim & pink striae.

  6. Investigations: • Liver functions tests: Increase transaminases (10 folds),Hypoalbuminmia,Markd hyperglobulinemia,increase TSB& S.alkaline phosphetase • Serological tests for specific Abs. ANF+ve in > 80%,Anti smooth muscle AB +ve in 70%,Antimitochondrial AB in 15%. • Anti microsomal (anti LKM )occur in children & adolescent. • Liver biopsy: Interface Hepatitis with or without cirrhosis.

  7. Management: • Steroid: Pridnisolon 40 mg /d decrease with improvement in LFTs to maintenance dose of 10mg/d for 2 y & withdrawn when liver biopsy become normal. • Azothioprine:1-1.5mg/kg/d with Pridnisolon to decrease the dose & side effect of steroid. • Prognosis:50% die within 5 years withouttreatment. decrease to 10% with treatment.

  8. Haemochromatosis

  9. Causes of Haemochromatosis A-Primary Haemochromatosis: 1-Heriditory Hemochromatosis. 2-Congenital acaeruloplasminaemia 3-congental atrransferrinaemia B-Secondary iron overload: 1-Paranteral iron loading (e.g repeated blood transfusion ). 2-Liver disease. 3-dietary iron overload ( prolonged oral iron therapy ) 4-Iron-loading anaemia ( Thalaseamia ,sideroplastic anaemia ) C-Complex iron overload: 1-Juvenile haemochromatosis. 2-Neonatal haemochromatosis. 3-Alcoholic liver disease. 4-Porphyria cutania tarda 5-African iron overload.

  10. Heriditory (Primary Haemochromatosis) • Caused by increased absorption of dietary iron. • Autosomal recessive disease (defect in chromosome 6). • 90% male. Clinical features: • Signs of liver cirrhosis. • Heart failure. • DM. • Leaden skin pigmentation. • Impotence. • Arthritis,chondrocalcinosis. • Tiredness, fatigue& arthropathy.

  11. Investigations • Increase serum iron. • Increase serum ferritin. • Increased total Serum Iron Binding Capacity. • CT scan of the abdomen: Increase hepatic iron. • Liver biopsy: confirm the diagnosis. • Gene detection.

  12. Management: • Venesection. weekly removal of 500ml(250mg of iron) until serum iron is normal . • Liver & cardiac problems improve after iron removal but DM doesn't resolve after venisection. • Treatment of diabetes mellitus. • Liver biopsy is only indicated in asymptomatic relatives if liver function tests are abnormal and/or the serum ferritin is greater than 1000Mg/l. • First degree members screening & asymptomatic should be treated. • Prognosis:3/4 of patients survive 5 ys.

  13. Wilson's disease (Hepatolenticular degeneration) • AR • Due to abnormality in chromosome 13. • Total body cupper is increased with excess cupper deposited in & causing damage to several organs • Liver ,basal ganglia of the brain , eyes , kidneys & skeleton are the organs which are most affected.

  14. There is always almost a failure of synthesis of cerialoplasmin in Wilson disease. in 5% of patients its level is normal. The amount of copper at birth is normal , but increases steadily thereafter.

  15. Clinical features: • Affect young age (5-45 years). • As mainly hepatic in childhood & early adolescence. • Neurological : in late adolescence as basal ganglion damage & dementia • Kayser-Flescher ring +Ve.

  16. Liver disease: • Acute or recurrent hepatitis. • Acute hepatic failure with liberation of excess copper in the blood leading to hemolysis & renal tubulopathy. • Chronic hepatitis which leads to cirrhosis. • Recurrent acute hepatitis of unknown cause especially when accompanied with hemolysis , or chronic liver disease of unknown cause in a patient under 40 years old suggests Wilson disease

  17. Neurological: • Extra pyramidal features. Tremor Chorioathetosis Dystonia Parkinsonism Dementia Kayser-Fleischer rings: -Can be seen in 60% of Wilson disease more in adult. -Always seen with neurological Wilson disease. -Some times seen only with slit lamp examination. -They disappear with treatment.

  18. Investigations • Decrease serum cerialoplasmin • High free serum cupper. • Increase urine copper excretion >0.6umol/24hrs is diagnostic . • >25umol/24hrs of urinary copper excretion after giving D-penicillamine is confirmatory test. • Increase hepatic cupper content

  19. Management • Penicillamine 1-4g/d for life. • SE: Protein losing nephropathy Lupus like syndrome Bone morrow suppression • Trientine dihydrochloride 1.2-2.4g/d • Zinc 50mg 8hourly. • Liver transplantation

  20. Biliary cirrhosis Primary biliary cirrhosis: • Is a chronic progressive cholestatic liver disease of unknown cause. • Predominantly affect middle aged female with female to male predominance 9:1. • Strongly associated with anti-mitochondrial antibodies which are diagnostic. • More common among smokers.

  21. Aetiology -The cause of PBC is unknown but immune mechanisms are clearly involved. -PBC is associated with other autoimmune diseases like thyroid disease. -Antimitochodrial & ANF are present in the serum -Elevation of serum immunoglobulines especially IgM. -Cellular immunity is impaired -Infectious agents such as retrovirus ,bacteria as E coli & mycobacteria could be the trigger for the disease process ??

  22. Pathology • Characterized by chronic granulomatous inflammation of the portal tract which lead to damage to small & middle size interlobular bile ducts, progressive lymphocyte mediated inflammatory damage leading to fibrosis which progress from the portal tracts to the liver parenchyma eventually lead to cirrhosis.

  23. Clinical features • Nonspecific symptoms such as lethargy & arthralgia. • Pruritus. • Jaundice. • Fever ,abdominal discomfort , rigor. • Diarrhea from malabsorption • Bone pain or fracture result from osteomalacia (fat soluble vitamin malabsorption) or from accelerated osteoporosis (Hepatic osteodystrophy )

  24. Associated diseases Sicca syndrome Systemic sclerosis Coeliac disease Thyroid disease Hypothyroidism should always considered in every patients with fatigue.

  25. Investigations • Liver function tests. Cholestasis. • Hypercholesterolemia. • Anti mitochondrial Antibodies +ve >95% if absent diagnosis should not be made without obtaining histological evidence & considering cholangiography ( MRCP or ERCP ) • Liver biopsy is only needed if there is diagnostic uncertainty, there is poor correlation between histological & clinical features . • ANF & Anti smooth muscle Antibodies is present in 15% of patients. • U/S: No evidence of biliary obstruction

  26. Management • No specific therapy is available. • Ursodeoxycholic acid 10-15mg/kg/d: • Improve bile flow, replace toxic hydrophobic bile acids, reduces apoptosis of biliary epithelium ,clinically URSO improve LFTs , slow down histological progression & has few SE.

  27. Liver transplantation for those with liver failure , 5 y survival is 80% but recurrence in graft is about 30% in 10 years. • Pruritis: Colystyramin 4-16g/d,Rifampicin 300mg/d, naltrexone 25mg/d reaching to 300mg/d, plasmapharesis & liver support device.

  28. Malabsorption: Decrease fat intake, monthly injection of Vitamin K, Vitamin D supply. • Bone disease: Base line bone density should be measured, calcium & vitamin D3,Bisphophonates such as risedronate if there is evidence of osteopenia.

  29. Secondary Biliary Cirrhosis • Due to prolonged large bile duct obstruction by gallstone, Bile duct stricture or sclerosing cholangitis • Clinical presentation: Chronic cholestasis with ascending cholangitis or even liver abscess, digital clubbing, xanthoma& bone pain. • Cirrhosis & Portal hypertension. • Management :Cholangitis treated with antibiotic.

  30. Primary sclerosing Cholangitis • Is a cholestatic liver disease caused by diffuse inflammation & fibrosis that can involve the entire biliary tree & leads to fibrotic obliteration of intra & extrahepatic bile duct & ultimately biliary cirrhosis ,portal hypertension & hepatic failure. • Cholangiocarcinoma develops in 10-30% of patients during the coarse of the disease. • Occur mainly in young men with male: female ratio is 2:1

  31. Accepted diagnostic criteria for PSC: A-Generalized beading & stenosis of the biliary system on the cholangiography. B-Absence of choledocholithiasis ( or history of bile duct surgery ). C-Exclusion of bile duct cancer.

  32. Diseases associated with PSC 1-Ulcerative colitis 2-Crohns disease. 3-Chronic pancreatitis. 4-Retroperitoneal fibrosis 5-Reidels thyroiditis 6-Retro-orbital tumors 7-Immune deficiency state 8-Sjogrens syndrome 9-Angioimmunoplstic lymphadenopathy 10-Histocytosis X 11-Autoimmune hemolytic anemia

  33. Secondary sclerosing cholangitis Causes: 1-previous bile duct surgery with stricturing & cholangitis. 2-Bile duct stone causing cholangitis. 3-Intrahepatic infusion of 5-flurodeoxyuridine 4-Insertion of formalin into hepatic hydated cyst 5-Insertion of alcohol into hepatic tumours 6-AIDS ( probably infective due to CMV or cryptosporidium )

  34. Aetiology of Primary Sclerosing Cholangitis: - the cause of PSC remains unknown. • - There is close association with IBD especially ulcerative colitis. • - 2/3 of patients with sclerosing cholangitis have coexisting ulcerative colitis. • - Primary sclerosing cholangitis is the most common form of chronic liver disease found in ulcerative colitis. • - 3-10% of patients with ulcerative colitis ( especially total colitis ) develop PSC. • -Patients with UC & PSC have increased risk of colorectal carcinoma & those who develop colorectal carcinoma are at greater risk of cholangiocarcinoma

  35. Immunological factors: --There is abnormalities in cellular & humoral immunity in patients with PSC. --Perinuclear antineutrophil cytoplasmic antibodies (ANCA) present in 60-80% of patients with PSC with or without UC & in 30-40% in patients with UC alone.

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