Complete Resolution of Inflammatory Activity Following Corticosteroid Treatment of HBsAg-Negative Chronic Active Hepatitis†

Abstract

To assess the frequency and significance of complete resolution of inflammatory activity following corticosteroid therapy, 115 patients with severe HBsAg-negative chronic active hepatitis were followed regularly for 84 +/- 5 months. Of 83 patients eligible to revert to normal liver tissue, 18 did so after 56 +/- 8 months. Five of the 18 relapsed after treatment withdrawal. Only patients who improved spontaneously after cessation of treatment from histologic features of chronic persistent hepatitis to normal invariably sustained the improvement. Of 32 patients with cirrhosis at presentation, 17 reverted to inactive cirrhosis after 48 +/- 10 months, but only 3 remained inactive after discontinuation of treatment. Mortality was similar in patients with and without reversion to normal tissue (0 vs. 14%, p greater than 0.2), but the frequency of relapse was less after complete resolution (28 vs. 76%, p less than 0.001). Reversion to inactive cirrhosis did not improve survival or reduce relapse frequency after remission and treatment withdrawal. Findings prior to therapy did not predict outcome. We conclude that complete resolution of inflammatory activity is possible, but that it occurs slowly, infrequently and unpredictably after therapy. In patients without cirrhosis, reversion to normal liver tissue decreases the likelihood of relapse and the requirement for retreatment. In patients with cirrhosis at presentation, elimination of inflammatory activity is rarely sustained and does not improve prognosis after remission and treatment withdrawal.

Ursodeoxycholic acid as adjunctive therapy for problematic type 1 autoimmune hepatitis: A randomized placebo-controlled treatment trial

“…1,2 Patients with less inflammatory activity 1,2 and those with HLA DR4 28 have better outcomes. Conversely, patients who have failed conventional therapy, 1,2 those who have relapsed multiply, [3][4][5] and individuals with HLA DR17 28 have poorer outcomes than patients with other treatment responses or HLA phenotypes. Our patients had been selected because of their suboptimal response to standard corticosteroid regimens.…”

“…1,2 These latter patients require repeated or indefinite treatment, and side effects associated with long-term management may be limiting. [3][4][5][6] Ursodeoxycholic acid is the 7␤-hydroxy epimer of chenodeoxycholic acid, 7 and its administration has been associated with improvements in hepatic dysfunction. [8][9][10] It is now a standard therapy for primary biliary cirrhosis (PBC), 11 and preliminary reports have suggested efficacy in chronic hepatitis, 12 including AIH.…”

Autoimmune hepatitis with incidental histologic features of bile duct injury

“…4,13,27 The reproducibility of grading inflammatory changes in a needle biopsy specimen by a single observer using these criteria had been documented previously. 28,29 The consistency of grading histologic characteristics was 90%, the reproducibility of the diagnostic interpretation was 94%, and sampling error in the assessment of inflammatory changes was trivial. The same morphologic criteria for diagnosis used in these earlier studies were applied in this investigation.…”

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

“…The reproducibility of our histological interpretation has been 94%, and intraobserver consistency in diagnosing cirrhosis has been 88%. [51][52][53] Definitions of Treatment Response and Courses of Action. "Treatment failure" was defined as deterioration during therapy, characterized by a progressive increase in serum AST or bilirubin at presentation.…”