Autoimmune hepatitis is a rare condition that leads to inflammation of liver. It can be further classified into type 1 and type 2 autoimmune diseases, of which type 1 is more common. Autoimmune hepatitis can have serious implications if not treated, so it should be diagnosed early. It can lead to acute hepatic failure and end stage liver disease if it is left untreated and even may lead to death. It should be differentiated from other forms of chronic hepatitis such as primary biliary cirrhosis, primary sclerosing cholangitis, alcohol induced hepatitis, drug induced hepatitis and viral hepatitis. These exclusions will best help diagnose autoimmune hepatitis and assist in the early management of the disease.
What Is The Best Treatment For Autoimmune Hepatitis?
The best treatment for autoimmune hepatitis is immunosuppressive therapy with corticosteroids, which have resulted in very good outcomes with remission in 80% cases. The treatment is directed at liver inflammation and sequelae following it.
The criteria for starting the treatment include ALT/AST elevation about 5-10 times the upper limit of normal, IgG and gamma globulins > 1.5 times the upper limit normal, presence of interface hepatitis in biopsy, presence of ANAs (antinuclear antibodies) and SMAs (smooth muscle antibodies) in type 1 autoimmune hepatitis and presence of liver/kidney microsomal antibody (LKM) in type 2 autoimmune hepatitis along with symptoms of arthralgia and fatigue.
The immunosuppressive therapy that is most commonly used is either a combination of prednisone and azathioprine, a combination of budesonide and azathioprine or high dose prednisone monotherapy. High dose prednisone monotherapy is associated with greater side effects including osteoporosis, diabetes, hypertension, emotional instability, cataracts, acne, hirsutism and weight gain. Prednisone is contraindicated in cases of psychosis, vertebral compression, diabetes and uncontrolled hypertension. Therefore, a combination therapy of prednisone and azathioprine is preferred (due to lesser side effects of azathioprine), until azathioprine is contraindicated otherwise. The side effects of azathioprine include nausea, vomiting, pancreatitis, liver toxicity, myelosuppression, rash and lymphoma. It is contraindicated in pregnancy, severe leucopenia, severe thrombocytopenia and malignancies. A combination of budesonide and azathioprine showed better results with minimal steroid side effects; however, its main drawback is its expensiveness and fewer clinical data on long-term effects. It can be used safely in patients with osteoporosis, obesity, diabetes, acne and hypertension; its only contraindication is cirrhosis.
The treatment of autoimmune disease can be divided into two phases, namely induction of remission and maintenance of remission.
The induction phase consists of four-week therapy with tapering dose of steroids. In prednisone monotherapy, it is taken as 60 mg in the first week followed by 40 mg in the second week, then 30 mg in the third week and 20 mg in the fourth week. In combination of prednisone and azathioprine, azathioprine is taken as 50 mg dose in all four weeks, whereas, prednisone is tapered from 30 mg in the first week, 25 mg in the second week, 20 mg in the third week to 15 mg in the fourth week. In combination therapy of budesonide and azathioprine, again, azathioprine is maintained at 50 mg dose throughout four-week course, whereas, budesonide is taken as 9 mg dose in the first two weeks then tapered to 6 mg dose in the last two weeks.
In maintenance phase of prednisone monotherapy, it is taken at 20 mg or less daily for a period of 24 months. In maintenance phase of combination of prednisone and azathioprine, for the first 12 months, prednisone is taken at 10 mg daily dose and azathioprine 50 mg daily; in the 2nd year of maintenance phase prednisone is tapered to 2.5 mg/week and azathioprine is continued at 50-100 mg daily. In the maintenance phase of combination of budesonide and azathioprine, for the first 12 months budesonide is taken 6 mg daily and azathioprine 50 mg daily; in the 2nd year budesonide is tapered and azathioprine is taken 50-100 mg daily dose. Treatment is withdrawn if there is complete remission after 24 months. Generally, the treatment outcome is very good with the above treatment with 80% remission rate after 1 to 2 years of treatment.
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