Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis☆
Introduction
Hepatic fibrosis can be reduced in various chronic liver diseases by eliminating the etiologic agent or pathogenic basis for the liver injury [1], [2], [3]. Regression of fibrosis has followed phlebotomy for hemochromatosis [4], relief of chronic biliary obstruction [5], bone marrow transplantation for thalessemia [6], treatment of primary biliary cirrhosis with ursodeoxycholic acid and methotrexate [7], reversal of jejuno-ileal bypass surgery [8], penicillamine therapy of Wilson disease [9], and antiviral treatment of chronic hepatitis B and C [10], [11], [12], [13]. These observations in humans have been supported by murine models of hepatic injury in which biliary fibrosis has decreased after biliary decompression [14], and rabbit models in which liver fibrosis has regressed after treatment of schistosomiasis [15].
Previous reports of the disappearance of cirrhosis in corticosteroid-treated autoimmune hepatitis (AIH) have been limited by the small study populations [16], [17], [18] and concerns about sampling and interpretative errors [19], [20], [21]. Under these circumstances, estimates of the frequency and degree that fibrosis improves during corticosteroid therapy have not been possible, and the anti-fibrogenic actions of corticosteroid therapy have not been promulgated. Fibrosis can now be assessed more accurately by applying a standardized scoring system, interpreting all specimens in batch under code by a single pathologist, and focusing on changes in fibrosis rather than the complex histological requirements for cirrhosis [3], [22], [23], [24].
In this retrospective review of tissue samples prospectively acquired to assess treatment response, we evaluate changes in fibrosis and inflammatory activity in corticosteroid-treated AIH. We determine the association between fibrosis and inflammatory activity, and assess the role of corticosteroids in preventing and/or reducing fibrosis. Our primary goal is to determine if corticosteroids have an anti-fibrogenic action that can be exploited in the treatment of AIH.
Section snippets
Study population
Eighty-seven patients who satisfied international criteria for AIH [25] were selected for study because each had been enrolled in our treatment program, treated with conventional corticosteroid regimens, and monitored by liver biopsy examination. These patients constituted 64% of the 136 patients in our program who had been treated and followed similarly. Their clinical features at presentation are shown in Table 1. Our investigation had been approved by the Institutional Review Board of the
Fibrosis scores and HAI in successive tissue specimens
The fibrosis scores improved significantly during 63±6 months of treatment and follow-up (range, 6–225 months) (Fig. 1A–C). The HAI also improved significantly during this interval (Table 2). Fourteen patients (16%) had histological cirrhosis at accession, but only 10 patients (11%) had histological cirrhosis at the end of treatment.
Sixteen of 79 patients (20%) with initial fibrosis scores of 1–6 (mean score, 3.3±0.3 points) had histological resolution of fibrosis during 54±10 months of
Discussion
Our study indicates that hepatic fibrosis scores improve or do not progress in most patients with AIH who are treated with corticosteroids. Improvement in the fibrosis score typically concurs with reduction in the HAI, and liver biopsy samples obtained during active inflammation have higher HAI and fibrosis scores than biopsies obtained during quiescent phases of the disease. These findings suggest that hepatic fibrosis in AIH can frequently improve with corticosteroid therapy and that
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Presented in part at the meeting of the American Association for the Study of Liver Diseases, October 26, 2003, Boston, Massachusetts.