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Current Status of Therapy in Autoimmune Liver Disease

Abstract

Therapeutic strategies for autoimmune liver diseases are increasingly established. Although proportionately uncommon, specialist centers have with time refined the best approaches for each disease, based on an improved understanding of the spectrum of presentation. The major treatment aims are to prevent end-stage liver disease and its associated complications. As a result of drugs such as ursodeoxycholic acid, predniso(lo)ne and azathioprine, both primary biliary cirrhosis and autoimmune hepatitis are now less commonly indications for liver transplantation. Unfortunately, the same inroads in treatment efficacy have as yet not been made for primary sclerosing cholangitis, although the recognition that a subset of patients may have a treatable secondary sclerosing cholangitis (IgG4 related) is helping a proportion. With better biological understanding, more specific interventions are expected that will benefit all those with autoimmune liver diseases.
Introduction

Autoimmune liver diseases are chronic inflammatory processes in which an immunological attack is directed against hepatocytes and/or the biliary epithelium [Kumagi et al. 2008]. Table 1 illustrates the presently recognized common disease divisions. Such divisions may be artificial since broadly it is suggested that 10% of those with primary biliary cirrhosis (PBC) will have features of autoimmune hepatitis (AIH) [Chazouilleres et al. 1998; Czaja, 1998], 10% of adults with AIH have radiological evidence for sclerosing cholangitis (SC) [Abdalian et al. 2008] and a similar number of those with primary sclerosing cholangitis (PSC) will have histological evidence of AIH [van Buuren et al. 2000]. The rate of overlap seems higher in children with AIH, in whom 50% will have sclerosing cholangitis on endoscopic retrograde cholangiopancreatography (ERCP) [Gregorio et al. 2001].

The diseases reflect a balance of environmental and genetic factors [Weismuller et al. 2008; Mackay, 2007] and whilst broadly autoimmune in etiology, both immune and nonimmune pathways are likely involved in tissue damage. Once the balance is tipped towards tissue destruction a chronic process ensues and clinicians are now well placed to modify disease by direct immunosuppression (e.g. predniso(lo)ne/azathioprine) or indirect modification to the bile acid milieu (e.g. ursodeoxycholic acid [UDCA]). These diseases are uncommon, may progress slowly, and are recognized now to have a broad spectrum of presentation. Together these make clinical trial design and interpretation harder but herein we review the basis for the use of disease-modifying agents. Symptom control is covered more fully elsewhere [Hirschfield et al. 2008] and similarly the management of the poorly defined autoimmune overlap syndromes is also not detailed [Rust and Beuers, 2008].