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Treat autoimmune hepatitis based on history.


CHICAGO - A diagnosis of autoimmune hepatitis does not necessarily mandate therapy.

Rather, a decision about therapy should be based on the natural history of the disease, according to Dr. Bruce Luxon.

Patients for whom treatment is mandatory are those with aspartate aminotransferase (AST) levels greater than 10 times the upper limit of normal, or 5 times the upper limit of normal plus gamma globulin levels greater than twice the upper limit of normal. Data from the 1970s showed that patients with these disease characteristics had a 6-month mortality of 60%, said Dr. Luxon, professor and chair of the department of internal medicine at Georgetown tiniversity, Washington.

Similarly, treatment Is needed when a biopsy shows "bridging"--or multilobular necrosis, as studies have shown that progression to cirrhosis occurs in more than 80% of such patients, and 5- year mortality is about 45%.

In contrast, there is a group of patients whose AST and [alanine transaminase (ALT)] were quite normal or very close to normal [less than twice the normal value]. Those people had a 10-year life expectancy greater than 80%." he said, noting that these patients generally don't require treatment.

Cirrhotic patients with significant inflammation, on the other hand, might benefit from a 3- to 6-month trial of therapy to slow down progression, he said adding: "That's really a decision for a hepacologist to make."

In those who will be treated, prednisone remains the mainstay of therapy, as it has for 50 years, he noted.

It is given initially at a high dose of 60 mg for the first week (or 30 mg plus 50 mg of azachioprine. which is usually given to allow lowering of the prednisone dose). Prednisone is lowered to 40 mg for week 2 (or 20 mg and so mg of prednisone and azathioprine, respectively), and to 30 mg for weeks 3 and 4 (or 15mg and 50 mg of prednisone and azathioprine, respectively).

After week 4, the dose remains 20 mg (or 10 mg and 50 mg of prednisone and azathioprine, respectively) until the clinical end point is reached.

Use of the combination therapy i associated with a much lower occurrence of corcicosteroid-related side effects (10% vs. 44%), but not all patients can tolerate the azathioprine. It is fine to give prednisone monotherapy in such patients, he said.

The typical side effects of steroid therapy can occur, including weight gain, unwanted hair growth, acne, and - importantly - bone disease.

"You really want to make sure they are on calcium and vitamin D," he said, noting bisphosphonates. rather than controversial estrogen replacement are usually prescribed as well.

The efficacy of treatment should be evaluated on a biochemical or histological basis. But keep in mind chat while a failure to normalize liver enzymes suggests residual disease, about half of those who do have normalization will still go on to have significant liver fibrosis and inflammation on biopsy.

Since biopsy improvement lags behind biochemical improvement by about 6 months, a repeat biopsy at that time is warranted.

These serial biopsies, which are important in this disease, can also predict whether a patient can be taken off therapy, he said.

Patients with a normal liver biopsy at follow-up will have only about a 15%-20% risk of relapse, so it is reasonable to take them off treatment, he noted.

Conversely, those with interface hepatitis and inflammation on follow-up biopsy will relapse about 90% of the time and require ongoing treatment.

In most cases, autoimmune hepatitis can be controlled, although ongoing treatment might be required. About 65% of patients will remit within 18 months, while only about 10% of patients will fall treatment altogether - and those patients typically have other contributing factors, such as excessive alcohol use, concurrent viral infection such as hepatitis B or C, or an overlap syndrome.

Another 10% of patients wont tolerate treatment.

Among those who require treatment indefinitely due to relapse, maintenance therapy with 75 mg/day of prednisone and 2 mg per kg/day of azachioprine can be effective for maintaining control. In one study. 85% of patients who relapsed were managed effectively with this strategy at a mean follow-up of 149 months, Dr. Luzon noted.

These patients generally have survival similar to age- and gender-matched controls, so although they have to stay on these low doses of treatment for life, the treatment is quite effective.

Dr. Luxon reported no disclosures.
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Author:Worcester, Sharon
Publication:Internal Medicine News
Article Type:Disease/Disorder overview
Date:Jun 1, 2011
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