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AUTOIMMUNE HEPATITIS

AUTOIMMUNE HEPATITIS. Dr.mousavi Abadan- Khordad 1397. Liver. Immunity. AUTOIMMUNE HEPATITIS. Chronic hepatitis of unknown etiology Can progress to cirrhosis Characteristics include: presence of autoimmune antibody evidence of hepatitis elevation of serum globulins. OTHER NAMES.

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AUTOIMMUNE HEPATITIS

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  1. AUTOIMMUNE HEPATITIS Dr.mousavi Abadan-Khordad 1397

  2. Liver Immunity

  3. AUTOIMMUNE HEPATITIS • Chronic hepatitis of unknown etiology • Can progress to cirrhosis • Characteristics include: • presence of autoimmune antibody • evidence of hepatitis • elevation of serum globulins

  4. OTHER NAMES • Active chronic hepatitis or chronic active hepatitis • Chronic aggressive hepatitis • Lupoid hepatitis • Plasma cell hepatitis • Autoimmune chronic active hepatitis

  5. BACKGROUND • First described in 1950’s • Accounts for 5.6% of liver transplants in the US • Affects women more than men (3.6:1) • If untreated approximately 40% die within 6 months • 40% develop cirrhosis

  6. PATHOGENESIS • Unknown mechanism but several proposed mechanisms • Genetically predisposed individual with exposure to an environmental agent triggers the autoimmune pathogenic process • Genetic predisposing factors: • HLA-DR3: early onset, severe form • HLA-DR4: caucasian, late onset, better response to steroids, higher incidence of extrahepatic manifestations • IgG: part of the IgG molecule (mainly the heavy chain) • T-Cell receptors

  7. PATHOGENESIS • Environmental Triggers: presumed to be certain viruses & drugs • Drugs: • Oxyphenisatin • Methyldopa • Nitrofurantoin • Diclofenac • Minocycline • statins

  8. CLASSIFICATION • TYPE 1 • TYPE 2 • OVERLAP SYNDROMES

  9. TYPE 1 • ANA or Anti-Smooth Muscle antibody positive • Titer usually > 1:100 • 10% will have an antibody to Soluble Liver antigens (SLA) • Other Antibodies: anti-DNA, ANCA, Anti-mitochondrial, Anti-Actin (AAA), cytoskeletal antibody, nuclear envelope proteins lamin A and C, plasma membrane sulfatides

  10. TYPE 1 • Bimodal Age distribution (ages 10-20 and 45-70) • Female:male (3.6:1) • Associated with extrahepatic manifestations: • Autoimmune thyroiditis, graves disease, chronic UC • Less commonly with RA, pernicious anemia, systemic sclerosis, ITP, SLE • 40% present with acute onset of symptoms similar to toxic hepatitis or acute viral hepatitis

  11. TYPE 2 • Presence of anti-Liver/Kidney Microsome Antibodies or anti-Liver Cytosol antibody (ALC-1)

  12. OVERLAP SYNDROMES • Primary Biliary Cholangitis • Primary Sclerosing Cholangitis

  13. CLINICAL PRESENTATION • Hepatomegaly • Jaundice • Stigmata of chronic liver disease • Splenomegaly • Elevated AST and ALT • Elevated PT • Non-specific symptoms: malaise, fatigue, lethargy, nausea, abdominal pain, anorexia

  14. Symptoms

  15. palmar erythema Spider angiomas

  16. DIAGNOSIS • Elevated AST and ALT • Elevated IgG • Rule out other causes: • Wilsons disease • Alpha 1 antitrypsin deficiency • Viral hepatitis (A, B, C) • Drug induced liver disease (alcohol, minocycline, nitrofurantoin, INH, PTU, methyldopa, etc) • NASH • PBC, PSC, autoimmune cholangitis • Presence of autoimmune antibodies • Liver biopsy

  17. Liver biopsy? • Establish diagnosis • Disease severity • Need for treatment • Therapeutic monitoring

  18. HISTOLOGY • Chronic hepatitis with marked piecemeal necrosis and lobular involvement • Numerous plasma cells • Interface hepatitis: hallmark finding

  19. HISTOLOGY

  20. INTERFACE HEPATITIS

  21. Diagnostic criteria Laboratory features

  22. Diagnostic criteria Auto antibodies Laboratory features

  23. Diagnostic criteria Histological findings Auto antibodies Laboratory features

  24. Diagnostic criteria No toxic or alcohol injury Histological findings Auto antibodies Laboratory features

  25. Diagnostic criteria No genetic liver disease No active viral infection No toxic or alcohol injury Histological findings Auto antibodies Laboratory features

  26. TREATMENT • Should be based on: • Severity of symptoms • Degree of elevation in transaminases and IgG • Histologic findings • Potential side effects of treatment

  27. Liver Immunity

  28. Liver Drugs Immunity

  29. AASLD RECOMMENDATIONS • Treat if serum aminotransferases are greater than 10 times normal • Treat if serum aminotransferases are greater than 5 times normal and IgG is elevated to greater than 2 times normal • In patients with inactive cirrhosis evaluate for preexisting comorbidities (hep C), pregnancy, and drug intolerances (increased risk of steroid side effects in pts with DM, osteoporosis, HTN)

  30. TREATMENT • Corticosteroids • Azathioprine • Children: azathioprine or 6MP

  31. PREDNISONE ONLY • Prednisone 60mg PO daily with a taper down to 30mg at the 4th week into treatment and then maintenance of 20mg daily until reach endpoint • Reasons for Prednisone only: • Cytopenia • TPMT deficiency • Malignancy • pregnancy

  32. COMBINATION THERAPY • Prednisone + Azathioprine • Prednisone: start at 30mg daily and taper down to 15mg at week 4, then maintain on 10mg daily until therapy endpoint • Azathioprine 50mg daily

  33. TREATMENT REMISSION • Disappearance of symptoms • Normal serum bilirubin and IgG • Serum aminotransferases normal or less than twice normal • Normal hepatic tissue or minimal inflammation and no interface hepatitis. • Action: d/c azathioprine and taper prednisone

  34. TREATMENT FAILURE • Worsening clinical, laboratory and histologic findins despite compliance with therapy • Increase in aminotransferases by >60% • Action: increase prednisone to 60mg daily and azathioprine to 150mg daily for one month

  35. TREATMENT FAILURE • Treatment failures are frequent in patients with established cirrhosis, HLA-DR3 or in patients who present with disease at a younger age and with a longer duration of symptoms

  36. INCOMPLETE RESPONSE • Some or no improvement in clinical, laboratory or histologic features • Failure to achieve remission after 3 years • Action: indefinite treatment

  37. LIVER TRANSPLANT • Patients with ascites and hepatic encephalopathy (generally will have a poor prognosis) but consider liver transplant if they have failed glucocorticoid therapy. • Considered in patients with multilobar necrosis and have at least one laboratory parameter which does not normalize within 2 weeks of treatment (theses patients have a high immediate mortality rate)

  38. LIVER TRANSPLANTATION • Considered in pts who worsen while on glucocorticoid therapy. • Recurrence of disease after transplant is common in those with AIH but has only been described in patients who are not adequately immunosuppressed.

  39. PROGNOSIS • 40% of all pts with AIH develop cirrhosis • 54% develop esophageal varices within 2 years • Poor prognosis if has presence of ascites or hepatic encephalopathy • 13-20% of patients can have spontaneous resolution • Of patients who survive the most early and active stage of disease, approximately 41% of them develop inactive cirrhosis. • Of patients who have severe initial disease and survive the first 2 years, typically survive long term.

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