Prednisone for chronic active liver disease: dose titration, standard dose, and combination with azathioprine compared.

Abstract

SUMMARY Among 120 consecutive patients with chronic active liver disease (CALD) randomized 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.Advances in treatment of the related conditions comprising chronic active liver disease (CALD) include three recent controlled trials with steroids, azathioprine, or both. Cook and associates (1971) showed that variable doses of prednisolone (from 10 to 2.5 mg daily) improved certain liver function tests and survival. Therapy with prednisone 15 mg daily was found by Murray-Lyon and his colleagues (1973) to be more effective than azathioprine 75 mg daily for increasing the life expectancy of patients with chronic active hepatitis with or without cirrhosis. We showed that daily maintenance with prednisone 20 mg, or a combination of prednisone 10 mg with azathioprine 50 mg, were not only equally successful in improving survival but also secured clinical, biochemical, and histological remission of disease features significantly more often than azathioprine

Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly

“…Each schedule had been shown previously to be equally effective in treating autoimmune hepatitis. 28 Twenty-six patients (13%) either did not satisfy criteria for treatment (17 patients) or received investigational therapies (9 patients). These 26 patients were not included in the analyses of outcome.…”

Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease

“…It was previously shown that the 2 treatment regimens were of comparable efficacy. 43 All patients satisfied pretreatment scoring criteria for a definite diagnosis of autoimmune hepatitis (mean score, 18 Ϯ 0.1 points; median, 18 points, range, 16-24 points) and had smooth muscle antibodies (65 patients), antinuclear antibodies (56 patients), or both (93 patients) at accession. One hundred ninety-six patients tested for antibodies to liver kidney microsome type 1 (anti-LKM1) were negative for this marker.…”

Autoimmune hepatitis with incidental histologic features of bile duct injury

“…Intolerable cosmetic effects, osteopenia with vertebral compression, emotional instability, brittle diabetes, and/or labile hypertension constituted drug intolerance. 25,26 Clinical and laboratory improvement insufficient to justify drug withdrawal constituted an incomplete response. Under such circumstances, therapy was continued, and dosages of medication were adjusted to the lowest levels needed to maintain serum AST levels below 5-fold normal.…”

“…Fifty-eight patients (69%) were treated with prednisone in combination with azathioprine, and 26 patients (31%) received a higher dose of prednisone alone. These treatments had been shown previously to be of comparable efficacy, 25 and outcomes were analyzed in all patients regardless of individual regimen.…”

“…Recrudescence of inflammatory activity after drug withdrawal indicated relapse, whereas continued inactivity after discontinuation of therapy (serum AST levels less than 3-fold normal) connoted sustained remission. 25,26 All patients were followed in a uniform fashion during 154 Ϯ 11 months (range, 12-397 months).…”