Autoimmune Hepatitis - Treatment

Controlled clinical trials have shown that corticosteroid therapy prolongs survival in severe chronic hepatitis type I.

The benefits of treating autoimmune hepatitis are especially evident in the first two years. Weakness decreases, appetite improves, fever and arthralgias are treatable. The menstrual cycle is restored. Bilirubin, γ-globulin and transaminase levels usually decrease. The changes are so pronounced that they can be used to establish a diagnosis of autoimmune chronic hepatitis. Histological examination of the liver during treatment reveals a decrease in the activity of the inflammatory process. However, it is not possible to prevent the outcome of chronic hepatitis into cirrhosis.

Liver biopsy should precede treatment. If coagulation disorders contraindicate this procedure, biopsy should be performed as soon as possible after corticosteroid-induced remission.

The usual dose of prednisolone is 30 mg/day for 1 week, then tapered to a maintenance dose of 10-15 mg daily. The initial course lasts 6 months. Once remission is achieved, as judged by clinical and laboratory testing and, if possible, a repeat liver biopsy, the dose is gradually tapered over 2 months. In general, prednisolone therapy is usually continued for about 2-3 years or longer, often for life. Premature discontinuation of the drug leads to an exacerbation of the disease. Although treatment is usually resumed after 1-2 months, fatal outcomes are possible.

It is difficult to determine when to stop therapy. Long-term maintenance therapy with low doses (less than 10 mg/day) of prednisolone may be preferable. Prednisolone can also be used at a slightly higher dose. Prednisolone administration every other day is not recommended because of the higher incidence of serious complications and the lower rate of achieving remission according to histological examination.

Complications of corticosteroid therapy include moon face, acne, obesity, hirsutism, and striae. They are especially undesirable for women. More serious complications include growth retardation in patients younger than 10 years, diabetes, and severe infections.

Bone loss has been detected even with a dose of 10 mg prednisolone daily and correlates with the duration of therapy. Side effects are rare if the dose of prednisolone does not exceed 15 mg/day. If this dose must be exceeded or if serious complications occur, alternative treatment options should be considered.

If remission does not occur with a dose of prednisolone 20 mg/day, azathioprine at a dose of 50-100 mg/day can be added to the therapy. It is not suitable for widespread use. Long-term (for many months or even years) treatment with this drug has obvious disadvantages.

Prednisolone Dosage Scheme for Chronic Autoimmune Hepatitis

First week

10 mg prednisolone 3 times a day (30 mg/day)

Second and third weeks

Reduction of prednisolone dose to maintenance (10-15 mg/day)

Every month

Clinical examination with liver function tests

By 6 months

Complete clinical and laboratory examination

Liver biopsy

Complete remission

Gradual withdrawal of prednisolone

Resumption of treatment in case of exacerbation

Lack of remission

Continue treatment with prednisolone at a maintenance dose for another 6 months, consider adding azathioprine (50-100 mg/day)

Maximum dose 20 mg prednisolone with 100 mg azathioprine

At least 2 years: until the disappearance of antinuclear antibodies in the serum until the level of bilirubin, γ-globulin and transaminase activity is normalized; no activity in liver biopsy (usually more than 2 years)

Other indications for prescribing azathioprine include worsening Cushing's disease, concomitant diseases such as diabetes mellitus, and other side effects that occur when prednisolone is used in doses required to achieve remission.

Azathioprine alone at a high dose (2 mg/kg) may be considered in patients who have achieved complete remission for at least 1 year with combination therapy. Side effects include arthralgia, myelosuppression, and increased cancer risk.

Cyclosporine may be used in patients resistant to corticosteroid therapy. This toxic drug should be used only as a last resort, when standard therapy is ineffective.

Indications for liver transplantation are discussed in cases where corticosteroids have failed to achieve remission or in advanced cases where complications of cirrhosis develop. Survival after liver transplantation is comparable to that of patients in whom remission has been achieved with corticosteroids. Repeated liver biopsies after transplantation do not reveal relapse of autoimmune chronic hepatitis.

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