Hepatic fibrosis is the common end point for most types of chronic liver injury. It is usually considered to be an irreversible process, especially when there is evidence of cirrhosis . Recent data have challenged this belief by showing that hepatic fibrosis is a dynamic process involving an imbalance between the deposition and the degradation of fibrillar collagens and other extracellular matrix proteins . Hepatic fibrosis is amenable to intervention by removing the insult and stopping the persistent inflammatory stimuli .
We studied thirteen patients with documented cirrhosis or extensive fibrosis at the time of diagnosis of AIH in whom clinical and biochemical remission was achieved by prednisone and/or azathioprine therapy, with significant reduction in the necroinflammatory injury in post-treatment liver biopsies. We discovered a significant regression of fibrosis in these patients after 6 to 12 months of clinical and biochemical remission.
Previous studies have demonstrated that hepatic inflammation stimulates perivascular hepatic stellate cells by cytokines, such as transforming growth factor β1 (TGF-b), These activated stellate cells are transformed into myofibroblasts; they proliferate, migrate, and degrade the normal extracellular matrix and replace it with fibril-forming collagens types I and III . The matrix proteins accumulate because tissue inhibitors retard the counteractive degradative actions of matrix metalloproteinases . Suppression of inflammatory activity promotes disappearance of the metalloproteinase inhibitors, degradation of the fibrotic liver matrix by unrestricted metalloproteinases, and apoptosis of the hepatic stellate cells [29, 30]. Our findings suggest that treatment with prednisone and/or azathioprine may inhibit the inciting stimulus for fibrogenesis and facilitate these anti-fibrotic actions in AIH by suppressing liver inflammation.
On the other hand, a glucocorticoid response element has been described in the human TGF-b1 gene promoter which may inhibit its expression . Thus, corticosteroids may impair activation of TGF-b , alter its binding characteristics to matrix sites  and affect the ligation of TGF-b activator protein to the TGF-b element . These putative anti-fibrotic actions of corticosteroids may complement their known anti-inflammatory effects to retard fibrogenesis and favour the counter-regulatory mechanisms of fibrinolysis [35, 36].
Regression of hepatic fibrosis in AIH has been reported in adult patients [16, 17, 37–39], and there is one report on regression of hepatic fibrosis in paediatric cases of AIH . In all these studies the assessment of fibrosis was done only semi-quantitatively by applying Ishak score. In our study we assessed hepatic fibrosis by semi-quantitative methods applying both Ishak and METAVIR scores and by a quantitative assay, morphometry. Regression of fibrosis was evident by both methods; however, by morphometry reduction of fibrosis was more significant. Moreover, cases in which no significant reduction of fibrosis was assessed by the semi-quantitative methods, morphometry could show a significant change. Ferreira et al found no change in fibrosis score in 25% of their patients but in one patient incomplete cirrhosis developed into complete cirrhosis . In 70% of their patients there was reduction in fibrosis; however, the meantime elapsed from remission to liver biopsy was longer (4.1 ± 1.5 years) than in our study (17.8 ± 8.5 months) . To the best of our knowledge, this is the first time that fibrosis reversibility has been assessed by the morphometric method in paediatric patients. Our findings suggest that quantitative assessment of fibrosis may be more sensitive in assessing regression of fibrosis following treatment of AIH. It has the benefit of avoiding the inter-observer variation in the assessment of fibrosis by semi-quantitative methods. Also, morphometry can assess the actual amount of fibrosis and not only its pattern, as in semi-quantitative methods. Moreover, application of morphometry on a mosaic picture of the entire core enabled the assessment of the portal as well the parenchymal fibrosis at the same time.