AUTOIMMUNE HEPATITIS

Reysginawathie

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
Active chronic hepatitis or chronic active hepatitis Chronic aggressive hepatitis Lupoid hepatitis Plasma cell hepatitis Autoimmune chronic active hepatitis

BACKGROUND

First described in 1950s 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

CLASSIFICATION
TYPE 1 TYPE 2 OVERLAP SYNDROMES

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, Antimitochondrial, Anti-Actin (AAA), cytoskeletal antibody, nuclear envelope proteins lamin A and C, plasma membrane sulfatides

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

TYPE 2

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

OVERLAP SYNDROMES
Primary Biliary Cirrhosis Primary 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

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

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

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

HISTOLOGY

INTERFACE HEPATITIS

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

PATHOGENESIS
Environmental Triggers: presumed to be certain viruses, toxins, drugs Drugs:

Oxyphenisatin

Methyldopa
Nitrofurantoin Diclofenac Minocycline statins

TREATMENT

Should be based on:

Severity

of symptoms Degree of elevation in transaminases and IgG Histologic findings Potential side effects of treatment

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)

TREATMENT
Corticosteroids Azathioprine Children: azathioprine or 6MP

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

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

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

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

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

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

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)

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.

PROGNOSIS

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.

REFERENCES

Czaja AJ, Freese DK. Diagnosis and Treatment of Autoimmune Hepatitis. Hepatology 2002; 479-497 Feldman, 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) JanMar: 6-24. www.uptodate.com