Reysginawathie

Chronic hepatitis of unknown etiologyCan progress to cirrhosisCharacteristics include: presence of autoimmune antibodyevidence of hepatitiselevation of serum globulins

Active chronic hepatitis or chronic active hepatitisChronic aggressive hepatitisLupoid hepatitisPlasma cell hepatitisAutoimmune chronic active hepatitis

First described in 1950sAccounts for 5.6% of liver transplants in the USAffects women more than men (3.6:1)If untreated approximately 40% die within 6 months40% develop cirrhosis

TYPE 1TYPE 2OVERLAP SYNDROMES

ANA or Anti-Smooth Muscle antibody positiveTiter usually > 1:10010% will have an antibody to Soluble Liver antigens (SLA)Other Antibodies: anti-DNA, ANCA, Antimitochondrial, Anti-Actin (AAA), cytoskeletal antibody, nuclear envelope proteins lamin A and C, plasma membrane sulfatides

Bimodal Age distribution (ages 10-20 and 45-70)Female:male (3.6:1)Associated with extrahepatic manifestations:Autoimmune thyroiditis, graves disease, chronic UCLess commonly with RA, pernicious anemia, systemic sclerosis, ITP, SLE40% present with acute onset of symptoms similar to toxic hepatitis or acute viral hepatitis

Presence of anti-Liver/Kidney Microsome Antibodies or anti-Liver Cytosol antibody (ALC-1)

Primary Biliary CirrhosisPrimary Sclerosing Cholangitis

5% of patients with chronic hepatitis C will have an ANA titer of >1:100 A homogeneous pattern of staining is more common in ANA positive autoimmune hepatitis compared to that of ANA positive chronic hepatitis C

HepatomegalyJaundiceStigmata of chronic liver diseaseSplenomegalyElevated AST and ALTElevated PTNon-specific symptoms: malaise, fatigue, lethargy, nausea, abdominal pain, anorexia

Elevated AST and ALTElevated IgGRule out other causes: Wilsons diseaseAlpha 1 antitrypsin deficiencyViral hepatitis (A, B, C)Drug induced liver disease (alcohol, minocycline, nitrofurantoin, INH, PTU, methyldopa, etc) NASHPBC, PSC, autoimmune cholangitisPresence of autoimmune antibodiesLiver biopsy

Chronic hepatitis with marked piecemeal necrosis and lobular involvementNumerous plasma cellsInterface hepatitis: hallmark finding

Unknown mechanism but several proposed mechanismsGenetically predisposed individual with exposure to an environmental agent triggers the autoimmune pathogenic processGenetic predisposing factors:HLA-DR3: early onset, severe formHLA-DR4: caucasian, late onset, better response to steroids, higher incidence of extrahepatic manifestationsIgG: part of the IgG molecule (mainly the heavy chain)T-Cell receptors

Environmental Triggers: presumed to be certain viruses, toxins, drugsDrugs:OxyphenisatinMethyldopaNitrofurantoinDiclofenacMinocyclinestatins

Should be based on:Severity of symptomsDegree of elevation in transaminases and IgGHistologic findingsPotential side effects of treatment

Treat if serum aminotransferases are greater than 10 times normalTreat if serum aminotransferases are greater than 5 times normal and IgG is elevated to greater than 2 times normalIn 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)

CorticosteroidsAzathioprineChildren: azathioprine or 6MP

Prednisone 60mg PO daily with a taper down to 30mg at the 4th week into treatment and then maintenance of 20mg daily until reach endpointReasons for Prednisone only: CytopeniaTPMT deficiencyMalignancypregnancy

Prednisone + AzathioprinePrednisone: start at 30mg daily and taper down to 15mg at week 4, then maintain on 10mg daily until therapy endpointAzathioprine 50mg daily

Disappearance of symptomsNormal serum bilirubin and IgGSerum aminotransferases normal or less than twice normalNormal hepatic tissue or minimal inflammation and no interface hepatitis.Action: d/c azathioprine and taper prednisone

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

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

Some or no improvement in clinical, laboratory or histologic featuresFailure to achieve remission after 3 yearsAction: indefinite treatment

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)

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.

40% of all pts with AIH develop cirrhosis54% develop esophageal varices within 2 yearsPoor prognosis if has presence of ascites or hepatic encephalopathy13-20% of patients can have spontaneous resolutionOf 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.

Czaja AJ, Freese DK. Diagnosis and Treatment of Autoimmune Hepatitis. Hepatology 2002; 479-497Feldman, Mark and Lawrence Friedman. Sleisenger & Fordtrans Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, and Management. Autoimmune Hepatitis. Elsevier Health Sciences. 1869-1882. July 2006. Czaja, Albert J. Current Concepts in Autoimmune Hepatitis. Annals of Hepatology 2005. 4(1) Jan-Mar: 6-24. www.uptodate.com

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