Autoimmune Liver Disease

Autoimmune hepatitis is a clinical and laboratory diagnosis that indicates one's immune system is inappropriately attacking liver cells, including bile duct cells. The immune system's lack of control can result in liver destruction, cirrhosis, liver cancer and liver transplantation.

A patient who is diagnosed with autoimmune hepatitis has one of more of the following conditions:

  • Increased globulins or antibody levels (>5 gm/dl) (Quantitative immune globulins can be helpful in making the diagnosis of autoimmune hepatitis)
  • Positive auto-antibody
  • Multi-system disease (thyroid, arthritis, other organs)
  • HLA A1,B8,DR3,DW3
  • Responsive to steroids

Autoimmune Hepatitis Subtypes  |  Treatment  |  Side Effects  |  Prognosis  |  Glossary

Autoimmune Hepatitis Subtypes

There are subtypes of autoimmune hepatitis that physicians at California Pacific use to assess the status of the disease. A description of these subtypes follows:

Type 0 autoimmune hepatitis

  • Defined by a patient's negative antibody tests
  • Twelve to 26% of autoimmune hepatitis patients fall into this category
  • HLA markers are like I, B8, DR3, A1-B8-DR3 (HLA B8 may be best market)
  • Prognosis same as that for Type 1

Type 1 autoimmune hepatitis
  • Defined by positive classical, nuclear antibody and/or smooth muscle antibody
  • ANA + 28% to 80% antinuclear antibody (ANA)
  • ASMA + 40% antismooth muscle antibody (ASMA)
  • 50% of patients are over 40 years at diagnosis; 60% of patients are associated with a false-positive Hepatitis C virus (HCV) antibody and 10% - 15% are LE cell positive;
  • Affects females four times as often as men (4:1 ratio)
  • Patients have 45% chance of progression to cirrhosis
  • Patients have 80% rate of steroid response
  • Following steroid withdrawal, 75% of patients relapse
  • 83% of patients have ANCA, another antibody

Other autoantibodies that are seen include:
  • Liver specific membrane lipoprotein antibodies (LSMP)
  • Liver cytosol antibodies (LCA)
  • F-actin antibodies
  • Soluble liver antigen (SLA)

Type 2 autoimmune hepatitis
  • Defined by reactive liver kidney antibody (LKM)
  • In 10% of cases, LKM-1 antibody is positive
  • LKM antibody is not seen in patients with Type 1 autoimmune hepatitis
  • LKM antibody can be mistaken for positive AMA if lab results are inaccurate
  • Type 2 is an aggressive form of autoimmune hepatitis and responds poorly to treatment with steroids
    Type 2a autoimmune hepatitis
  • This variation is seen in young women and is defined by a high-titer LKM-1

Type 2b autoimmune hepatitis
This variation is associated with hepatitis C and is defined by a low-titer LKM-1

Autoimmune cholangitis
Defined by positive anti-soluble liver antigen and/or liver pancreas antibody

Overlap autoimmune hepatitis
Defined by overlap of primary biliary cirrhosis (PBC) and Type 1 autoimmune hepatitis

Primary biliary cirrhosis (PBC)
Defined by destruction of small
bile ducts by the immune system

Primary sclerosing cholangitis (PSC)
Defined by destruction of large and intermediate bile ducts by the immune system; this disease can lead to cholangiocarcinoma.

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Treatment

Patients with autoimmune hepatitis are typically treated with drug therapy, including immunosuppression or steroids. Immunosuppressives are drugs that decrease the activity of the immune system. If laboratory tests and liver biopsy results indicate, immunosuppresion is typically the best therapy for autoimmune hepatitis.

Usually, the following immunosupprives are prescribed together:

  • 50 mg imuran each day (watch for bone marrow suppression, decreased white blood cells, anemia and platelets)

  • 30 mg prednisone for first week; 20 mg prednisone for second week; 15 mg prednisone for third and fourth weeks; 10 mg prednisone every day thereafter

  • Steroids may be prescribed if a patient's AST>10x or AST>5x and gamma globulin is 2x. Other indicators that may lead to treatment with steroids include bridging necrosis, multilobular necrosis, incapacitating symptoms or progressive decompensation.

    Other medications that can be used for autoimmune hepatitis include cyclosporine, tacrolimus and methotrexate. These medications are currently being used in special cases for patients who do not respond to standard therapy.
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    Side Effects

    The use of both prednisone and tacrolimus (Prograf, FK506) can cause side effects. Patients taking prednisone may experience osteoporosis (especially if post-menopausal), diabetes, hypertension, obesity, psychiatric problems (including depression), Cushingoid symptoms (moon face, shoulder hump, edema), cataracts, aseptic necrosis of the hip (type of hip fracture), acne, thinning of the skin, easy bruising and hirsutism (hairy face and body).

    Side effects associated with tacrolimus include hypertension, diabetes, seizures, kidney injury, mental confusion, unusual infections, nausea, diarrhea and weight loss. Cellcept can result in ulcer disease and a proton pump inhibitor needs to be taken daily, such as Prilosec (omeprazole). Also, this medication can result in bone marrow suppression and monthly cell counts are required for monitoring. Observation for opportunistic infections is required with all medications.
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    Prognosis

    If patients with autoimmune hepatitis are not treated, the six-month mortality rate is less than 40%, three-year mortality 50% and 10-year mortality 90%.

    For patients with AST<5 times normal and gamma globulin <2 times normal, 55% will develop cirrhosis of the liver. The 15-year mortality rate for these patients is 10%.

    Finally, for patients whose liver biopsy indicates bridging necrosis, 82% will develop cirrhosis and the five-year mortality rate is 58%.
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    Glossary

    Autoimmune cholangiopathy: a disease suspected to represent an overlap between autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis. This disease may respond to prednisone therapy.

    Primary biliary cirrhosis: an autoimmune condition in which the immune system attacks the small bile ducts (tubes) that drain the liver.

    Primary sclerosing cholangitis: a suspected autoimmune condition that attacks the medium and big bile ducts (tubes) in the liver.

    For further information on autoimmune hepatitis, visit www.autoimmunehepatitis.co.uk.
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