|
Autoimmune Hepatitis
By Howard J. Worman, MD
Autoimmune hepatitis is a condition in which the patient's own immune systems
attacks the liver causing inflammation and liver cell death. The condition is
chronic and progressive. Although the disease is chronic, many patients with
autoimmune hepatitis present acutely ill with jaundice, fever and sometimes
symptoms of severe hepatic dysfunction, a picture that resembles acute hepatitis.
Autoimmune hepatitis usually occurs in women (70 %) between the ages of 15
and 40. Although the term "lupoid" hepatitis was originally used to describe
this disease, patients with systemic lupus erythematosus do not have an increased
incidence of autoimmune hepatitis and the two diseases are distint entities.
Patients usually present with evidence of moderate to severe hepatitis with
elevated serum ALT and AST activities in the setting of normal to marginally
elevated alkaline phosphatase and gamma-glutamyltranspeptidase activities. The
patient will sometimes present with jaundice, fever and right upper quadrant
pain and occasionally systemic symptoms such as arthralgias, myalgias, polyserositits
and thrombocytopenia. Some patients will present with mild liver dysfunction
and have only laboratory abnormalities as their initial presentation. Others
will present with severe hepatic dysfunction.
Autoimmune hepatitis should be suspected in any young patient with hepatitis,
especially those without risk factors for alcoholic, drug, metabolic or viral
etiologies. Serum protein electrophoresis and testing for autoantibodies are
of central importance in the diagnosis of autoimmune hepatitis. Patients with
one subtype of autoimmune hepatitis have serum gamma-globulin concentrations
more than twice normal and sometimes antinuclear antibodies and/or anti-smooth
muscle (anti-actin) antibodies. Patients with another subtype may have normal
or only slightly elevated serum gamma-globulin concentrations but will have
antibodies against a particular cytochrome p450 isoenzyme that are called anti-LKM
(liver kidney microsome).
Patients in whom a diagnosis of autoimmune hepatitis is suspected should have
a liver biopsy. If the biopsy is consistent, treatment with steroids (prednisone
or pednisolone) and azathioprine (Imuran) is begun immediately. These are tapered
over the next 6 to 24 months depending upon the patient's course. If immediate
liver biopsy is contraindicated because of a prolonged prothrombin time or thrombocytopenia,
steroids and azathioprine should be started prior to biopsy if the diagnosis
of autoimmune hepatitis is likely based on clinical criteria (e.g. a young woman
with severe hepatitis, elevated serum gamma-globulin concentration, negative
risk factors and serologies for viral hepatitis). The patient will often rapidly
improve and biopsy should be performed to confirm the diagnosis as soon as the
prothrombin time decreases and platelet count increases to within safe ranges.
About two thirds to three quarters of patients with autoimmune hepatitis respond
to treatment based on the return of serum ALT and AST activities to normal and
an improved biopsy after several months. Some patients relapse as steroids and
azathioprine doses are tapered or stopped and need chronic maintenance medications.
Over the long term, many patients develop cirrhosis despite having a response
to treatment, and patients who do not respond totreatment will almost always
progress to cirrhosis. If end-stage liver disease develops, orthotopic liver
transplantation is an effective procedure.
Krawitt, E. L. 1996. Autoimmune hepatitis. New England Journal of Medicine.
334:897-903.
|
