***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Among 120 consecutive patients with chronic active liver disease ( CALD ) r and omized to different treatments , those receiving maintenance doses of prednisone 20 mg daily ( Pred ) , prednisone in doses given on alternate days and titrated to secure resolution of clinical and biochemical abnormalities ( Pred-Titrad ) , or a combination of prednisone 10 mg and azathioprine 50 mg daily ( Comb ) survived and underwent resolution of clinical and biochemical features of disease more often than a control group receiving placebo or azathioprine 100 mg daily . Histological remission occurred significantly more often with Pred and Comb than with other regimens . Major side-effects of therapy were commoner with Pred than with Comb or Pred-Titrad , which did not differ . We conclude that Comb is the initial treatment of choice for CALD , since clinical , biochemical , and histological resolution of disease activity occurs as often as with Pred , whereas early side-effects are significantly less frequent To evaluate the efficacy of ursodeoxycholic acid as adjunctive therapy in type 1 autoimmune hepatitis , 37 patients who had experienced treatment failure , repeated relapse , or incomplete response were r and omized to ursodeoxycholic acid ( 13 - 15 mg/kg daily ) or placebo for 6 months in addition to their usual corticosteroid schedule . Serum aspartate transaminase ( 70 % vs. 31 % , P = .04 ) and alkaline phosphatase ( 47 % vs. 7 % , P = .02 ) levels improved more commonly in the 21 patients r and omized to ursodeoxycholic acid .  Mean serum levels , however , were similar before and after the treatment period . The frequency of dose reduction or corticosteroid withdrawal was comparable in both groups ( 29 % versus 31 % , P > .9 ) , and clinical improvement ( 48 % vs. 44 % , P > .9 ) or its absence ( 52 % vs. 56 % , P > .9 ) occurred as commonly in patients receiving ursodeoxycholic acid or placebo . The modified histological activity score ( 3.5 + /- 0.8 vs. 3 . 5 + /- 0.9 ) and the modified fibrosis score ( 2.4 + /- 0.4 vs. 2.4 + /- 0.4 ) were similar before and after treatment with ursodeoxycholic acid and no different than after placebo therapy . We conclude that ursodeoxycholic acid can improve certain laboratory tests in problematic patients with type 1 autoimmune hepatitis when administered adjunctively for 6 months . Short-term therapy , however , does not facilitate reduction in the dose of corticosteroids or its withdrawal , affect clinical outcome , or reduce histological activity Forty‐seven patients with autoimmune chronic active hepatitis in remission on azathioprine and /or prednisolone  were entered into a r and omized controlled trial to assess the value of azathioprine alone in maintenance of remission . The trial design involved administering azathioprine at a dose of 2 mg per kg to one‐half of the patients , in whom prednisolone  was then gradually withdrawn , whereas the remaining patients , the “ control ” group , were maintained on the conventional combination regimen of azathioprine ( 1 mg per kg ) with prednisolone . At 1 year there was no significant difference in respect of st and ard liver function tests or histological appearances between the two groups . Two patients in the azathioprine group required dosage reduction because of myelosuppression and both subsequently relapsed . Following withdrawal of corticosteroids Cushingoid features were lost with a return of weight and blood pressure to normality . In 75 % of the patients , corticosteroid withdrawal was marked by arthralgias and myalgias which lasted for up to 12 months : no other major side effects of corticosteroid withdrawal were noted . Thus in the majority of cases , remissions in autoimmune chronic active hepatitis which are induced by corticosteroids can be maintained with azathioprine alone In view of promising , but uncontrolled , reports of the use of D-penicillamine in active chronic hepatitis , a r and omised , prospect i ve , controlled trial of this drug against prednisone was carried out . Of the 35 patients entered , 18 received  D-penicillamine  ( increasing to 1 - 2 g daily ) and 17 prednisone ( 15 mg daily ) . In all patients the disease had already been brought under biochemical control with corticosteroids . During the first year of the trial , the treatment of nine patients in the D-penicillamine group was discontinued ( two because of lack of disease control and seven because of side-effects ) compared with six patients in the prednisone group ( four because of lack of disease control , one because of side-effects , and one because of the development of carcinomatosis . Detailed statistical analysis of the liver function tests in the patients remaining in the trial at the end of the year showed no significant differences . D-penicillamine is associated with a higher frequency of side-effects than is prednisone . However , in some patients it is as satisfactory as prednisone in keeping the disease under control To assess the efficacy of oral pulse prednisone therapy  after relapse of severe autoimmune chronic active hepatitis and to determine the effects of such therapy on serum immunoglobulin G levels and peripheral blood lymphocyte subsets , 16 patients were r and omized after relapse to therapy with prednisone 90 mg daily for 5 days each month or  conventional daily dose therapy with prednisone in combination with azathioprine . Seven of the eight patients r and omized to pulse therapy failed treatment after 1.9 + /- 0.7 months ( range , 24 days to 6 months ) . Treatment failure occurred more commonly ( 87 vs. 0 % , p < 0.01 ) and remission occurred less frequently ( 0 vs. 87 % , p < 0.01 ) in patients receiving pulse therapy . The percentage and absolute numbers of circulating CD2 and CD4 cells decreased during relapse , while CD8 and CD20 cell counts were not significantly altered . Pulse therapy was associated with a significant increase in the percentage of CD4 cells and decrease in aminotransferase levels after 5 days . Serum immunoglobulin G levels , however , were not affected by treatment and after 1 month the biochemical findings and lymphocyte subsets were again similar to those at relapse . In contrast , serum immunoglobulin G levels decreased after 14 days of combination therapy and by 1 month the numbers in all lymphocyte subsets were higher than at relapse . We conclude that oral pulse prednisone therapy is ineffective for patients in relapse . The numbers of circulating CD2 and CD4 cells fall during relapse and increase as inflammatory activity subsides during corticosteroid therapy . Combination therapy reverses the biochemical changes and alterations in peripheral blood lymphocyte subsets that accompany relapse BACKGROUND In most patients with autoimmune hepatitis , remission can be maintained with prednisolone , usually in combination with azathioprine , but the majority of patients have a relapse when treatment is stopped and therefore require long-term therapy . Because prolonged corticosteroid therapy may have serious toxic effects , in 1984 we undertook a controlled trial of maintenance therapy with azathioprine alone . None of the 25 patients in that trial had relapses during the follow-up period of one year . We have now followed these 25 patients for 10 years and have treated an additional 47 patients in a similar manner . METHODS The 72 patients ( median age , 47 years ; range , 14 to 71 ) had been in complete remission for at least one year with 5 to 15 mg of prednisolone per day and 1 mg of azathioprine per kilogram per day . The dose of azathioprine was increased to 2 mg per kilogram per day , and the prednisolone was gradually withdrawn . Remission was defined as the absence of symptoms suggestive of a relapse and serum globulin and aspartate aminotransferase concentrations within the normal range , with or without a liver biopsy showing only minimal inflammation . RESULTS Sixty patients ( 83 percent ) remained in remission while receiving azathioprine alone for a median of 67 months ( range , 12 to 128 ) . Of 48 follow-up liver biopsies in 42 patients , 45 showed inactive or minimal disease , and 3 showed moderate disease ( 2 after one year of therapy and 1 after eight years ) . After the prednisolone had been withdrawn , 26 patients lost their cushingoid facies , and 32 patients lost weight ( median loss , 6.4 kg ; range , 1.5 to 22.3 ) . The most common adverse effect was arthralgia ( in 38 patients ) . With the higher dose of azathioprine , four patients had myelosuppression , defined as a decrease in the leukocyte and platelet counts to less than 4000 and 150,000 per cubic millimeter , respectively . Two of these patients ( both with pancytopenia ) relapsed when the azathioprine was withdrawn ; in the other two , remission was maintained with the resumption of prednisolone .  Lymphopenia developed in 32 of 56 patients treated with 2 mg of azathioprine per kilogram per day for more than two years . During follow-up , nine patients died : one of liver failure and eight of causes not directly related to their liver disease . CONCLUSIONS Many patients with autoimmune hepatitis who have been in complete remission for at least one year with prednisolone and azathioprine can remain in remission with a higher dose of azathioprine alone A prospect i ve , controlled , double blind , r and omized trial of treatments for severe chronic active liver disease  , involving 63 consecutive patients chosen by predefined criteria , showed that 20 mg of prednisone daily or a combination of 10 mg of prednisone and 50 mg of azathioprine daily was superior to 100 mg of azathioprine daily or placebo . Prednisone or a combination of 10 mg of prednisone and 50 mg of azathioprine daily significantly improved ( 1 ) life expectancy ; ( 2 ) resolution to normal of clinical , biochemical , and immunochemical abnormalities ; and ( 3 ) histological resolution from chronic active hepatitis , often with subacute changes , to nonspecific hepatitis . By contrast , clinical and biochemical deterioration usually occurred with azathioprine or placebo , although spontaneous remission occurred in 20 % of patients receiving these treatments . Side effects with prednisone were common , and 20 % of patients experienced complications . Azathioprine toxicity closely resembled the natural course of the disease . Prognosis could not be determined initially , since it depended on the treatment allocated These guidelines provide a data -supported approach to the diagnosis and management of patients with autoimmune hepatitis . They are based on the following : ( 1 ) a formal review and analysis of the published world literature on autoimmune hepatitis ( 914 articles ) ( Medline Search from 1966 - 2002 ; the search term was autoimmune hepatitis ) ; ( 2 ) recommendations developed and published by the International Autoimmune Hepatitis Group ; ( 3 ) concepts developed at the AASLD Single Topic Conference on autoimmune hepatitis in September 1999 ; and ( 4 ) 40 years of combined experience by both authors in the clinical and laboratory investigation and care for patients with this disease . The guidelines , intended for use by physicians , are meant to be flexible , in contrast to “ st and ards of care , ” which are inflexible policies to be followed in almost every case . They have been developed in a manner consistent with the American Association for the Study of Liver Diseases ’ Policy Statement on Development and Use of Practice Guidelines . Specific recommendations are based on relevant published information . In an attempt to st and ardize recommendations , the Practice Guidelines Committee of the American Association for the Study of Liver Diseases modified the categories of the Infectious Diseases Society of America ’s Quality St and ards . These categories are reported with each recommendation , using the Roman numerals I through IV to determine the quality of evidence upon which the recommendations are based . The categories are as follows : I , evidence from multiple well- design ed r and omized controlled trials , each involving a number of participants to be of sufficient statistical power ; II , evidence from at least one large , well- design ed clinical trial with or without r and omization , from cohort or case-control analytic studies , or from well- design ed meta- analysis ; III , evidence based on clinical experience , descriptive studies , or reports of expert committees ; and IV , not rated By a method using sealed envelopes a series of patients with active chronic hepatitis who had not received corticosteroids or adrenocorticotrophic hormone  was divided into two groups ; one was given prednisolone and the other was used as a control . Fifty-four patients were initially included in the study over a period of 48 months , but five were subsequently withdrawn when it became clear that the diagnosis was incorrect . The  corticosteroid group then contained 22 and the control group 27 patients . The two groups were reasonably well matched ; the corticosteroid group , however , contained rather more females of a lower age . Although the mean serum bilirubin was higher in the control group , the mean serum aspartate aminotransferase and total globulin were higher in the corticosteroid group , indicating that that group contained more patients with a high degree of ‘ activity ’ of the hepatic lesion . The mean erythrocyte sedimentation rate was also higher in the corticosteroid group . An initial dose of 15 mg prednisolone daily was used in the corticosteroid group , and this was reduced whenever biochemical tests of liver function became normal or when 
    Output:
    
Based on available RCTs , PRED monotherapy and PRED+AZA combination therapy are both viable induction therapies for AIH treatment naives and relapsers , while for maintenance therapy PRED+AZA and AZA therapy are superior to PRED monotherapy