Hepatic fibrosis and cirrhosis are possible consequences of corticosteroid-treated autoimmune hepatitis. Our aims were to determine the frequency of progressive fibrosis and the factors associated with this progression. Two hundred seventy-seven liver tissue specimens that had been obtained from 73 patients were interpreted in batch under code by a single pathologist. Fibrosis scores and histological activity indices were determined using the Ishak scoring system, and worsening fibrosis scores were correlated with clinical features, laboratory findings, and treatment responses. Fibrosis scores increased (2.3 ุ 0.4 points to 4.2 ุ 0.4 points; P < .0001) in 18 patients (25%) during 79 ุ 13 months. Only five patients (7%) developed cirrhosis, and 55 patients (75%) had stable (16 patients) or decreased (39 patients) fibrosis scores. Human leukocyte antigen (HLA) DR3/DR4 occurred more frequently in patients with progressive fibrosis than others (23% vs. 2%; P โซุโฌ .03). Patients with progressive fibrosis had higher histological activity indices at last follow-up than patients with stable or reduced fibrosis (3.2 ุ 0.7 vs. 1.7 ุ 0.2; P โซุโฌ .01), and these indices worsened more commonly during therapy (17% vs. 2%, P โซุโฌ .04). Relapse, treatment failure, and incomplete response did not affect progression of fibrosis. In conclusion, fibrosis progresses in only a minority of patients during corticosteroid therapy. Progression is associated with HLA DR3/DR4 and worsening histological activity. Exacerbations or persistence of disease activity does not increase disease progression after treatment has been instituted. (HEPATOLOGY 2004;39:1631-1638.)
C orticosteroids induce clinical, laboratory, and histological improvement in most patients with autoimmune hepatitis, 1,2 and recent studies have suggested that treatment may decrease hepatic fibrosis by reducing inflammatory activity and/or suppressing the immune mechanisms of liver injury. 3 Cirrhosis, however, still develops in as many as 40% within 10 years, 4,5 and the bases for histological progression remain uncertain.
Nine percent of patients with autoimmune hepatitis deteriorate despite compliance with corticosteroid therapy (treatment failure); 13% improve, but not to a degree to satisfy remission criteria (incomplete response); and at least 50% exacerbate after resolution of inflammatory ac-Abbreviations: HLA, human leukocyte antigen; anti-LKM1, antibodies to liver/ kidney microsome type 1; HAI, histological activity index.