Drug therapy of autoimmune hepatitis, drugs, treatment regimens
Autoimmune hepatitis is treated with immunosuppressants. These include the classic systemic glucocorticoid drugs Prednisone and prednisolone, modern locally acting drug budesonide (its effectiveness is still being studied in clinical trials). Already for several years proved itself combination azathioprine and prednisolone, while the use of azathioprine as monotherapy was ineffective. Line medicines, used in cases of inefficiency commonly used drugs are cyclosporin A (CsA), tacrolimus (of FK506), mycophenolate mofetil (MMF) and cytostatics. In the treatment of patients resistant to therapy, or in patients with end-stage disease should be considered the treatment of choice a liver transplant. Usually, however, autoimmune hepatitis is well amenable to conservative therapy.
Since all immunosuppressive drugs have side effects, treatment is carried out only in those patients in whom its expediency clearly outweigh the risk of adverse reactions. The treatment is considered absolutely shown only in patients with severe progressive course of the disease, in which the observed 10-fold, compared with the normal, elevated transaminases or 5-fold increase, while double, compared with the norm, increasing the level of gammaglobulin. Histological examination of these cases found in dense cell round infiltrates in periportal fields, stepped and / or bridging necrosis. Since patients with cirrhosis fledged respond well to treatment, it is indicated for active inflammation. The same applies to patients with moderate to severe symptoms of decompensation or held after bleeding from esophageal varices. Although the usefulness of treatment in patients with low active and maloprogressiruyuschim course of autoimmune hepatitis remains unproven (in relation kdalneyshemu progression and life expectancy), immunosuppressive therapy with low-dose formulations can significantly improve their overall health and quality of life.
Primary therapy of autoimmune hepatitis - the appointment of prednisone or prednisolone. Efficacy of these drugs is the same, however, prednisone prior to its action in the liver is converted into a pre-prednisolone. If the diagnosis of autoimmune hepatitis induced prior to initiating therapy in doubt, test the effectiveness of glucocorticoids confirms the correctness of his statement.
The treatment starts with a dose of 60 mg daily for 1 week. Subsequently, the dose is gradually reduced (to 10 mg per week) to 30 mg per day. Subsequent dose reduction occurs more gradually (in 5 mg weekly). Thus, after 6 weeks of treatment, a maintenance dose is 8-10 mg. In some cases it is possible to reduce the dose to 5 mg per day (or even less) without relapse. Dose reduction should be carried out under the control of the main laboratory liver function tests and adjusted according to their parameters.
In children, the initial daily dose is 2 mg / kg body weight, maintenance - 5 mg per day. Children respond to therapy with glucocorticoids as well as adults. However, during the development of acute liver failure, glucocorticoids are effective only in the treatment of adults but not children. Then the children show an urgent liver transplant. The reasons for unequal response to glucocorticoid therapy remain unclear. If during therapy with prednisone (prednisone) is re-transaminase elevation (and when applied dose has not yet reached the support), then either re-return to the previous higher dose of glucocorticoids or combine steroid treatment with azathioprine in a dose of 1 mg / kg body weight. By resorting combination therapy in those cases where the initial background on glucocorticoid monotherapy early experience side effects of medications.
Combination therapy with prednisone (prednisolone) and azathioprine may be carried out immediately as prednisone (prednisone) is assigned to a lower starting dose and risk of side effects is reduced. These drugs enhance the effect of each other. Azathioprine initial dose in adults is 50 mg per day and can be increased to 100 mg per day (1-1.5 mg / kg body weight). Babies azathioprine assigned by 0.5-1.0 mg / kg body weight per day.
Currently received preliminary results of the application of locally acting corticosteroid budesonide formulation. Budesonide, administered during 6 weeks in 13 patients, contributed to a significant reduction in levels of transaminases and IgG. cortisol concentration in plasma during treatment did not change, the side effects were rare and were mild. The maximum dose of budesonide is 6-8 mg per day and then decreased to the maintenance doses (2-6 mg per day). These results have been confirmed by studies carried out in 12 patients with autoimmune hepatitis, which showed that the use of budesonide in a dose of 9 mg per day promotes occurrence and remission associated with a low incidence of side effects.
Supportive care in remission
If initial therapy led to remission, the treatment of patients should be continued, or 80-90% of patients during the first year marked relapse. When maintenance therapy must be assigned at the lowest possible dose that manages to achieve through the combined use of prednisone (prednisolone) and azathioprine. In favor of the combined treatment is evidenced by the higher efficiency of the Tarapov. Thus, during the 18 months of combination therapy in remission retained more than 90% of patients with monotherapy - just 60%.
Supportive therapy in remission should last 2-4 years, even though in our observations have met patients who achieved complete remission after 5 years or more. A regular check-up and treatment-existing source or glucocorticoid-induced osteoporosis allow for long-term maintenance therapy without the risk of complications.
In case of continued remission maintenance therapy on the background of the dose of prednisone (prednisone) can be reduced (in milligrams) not earlier than 2 years since the start of its implementation. If dose reduction is accompanied by a deterioration in the laboratory liver function tests returned to the initial dose. Repeated achievement of remission followed by a second relapse, conduct long-term treatment with lower doses.
In some patients, long-term maintenance therapy with prednisone (prednisone) or azathioprine in remission is fraught with the risk of developing complications. In such cases justified attempt monotherapy in some drug. This is useful in young women of childbearing age, in patients with insulin-dependent diabetes mellitus or severe osteoporosis. If they retain remission of disease, it is sufficient monotherapy azathioprine 2 mg / kg of body weight within a year. Given that the dose is high enough to consider the possibility of side effects.