62 CALD was splitting apart and

assuming a more complex phenotype65 (Fig. 1). Terms such as idiopathic chronic active hepatitis, HBsAg-negative chronic active hepatitis, chronic persistent hepatitis, and plasma cell hepatitis were no longer appropriate, and a codification of diagnostic criteria and nomenclature was sorely needed.86 The discovery of the www.selleckchem.com/products/PLX-4032.html hepatitis C virus in 198987 initially challenged the concept of autoimmune hepatitis, but later validated its existence by demarking a subset of liver disease that was not virus-related.60,81,88,89 The clinical, laboratory and histological trappings of autoimmunity, the confident exclusion of viral infection in most cases, and the responsiveness of the disease to corticosteroid therapy ultimately

justified its formal designation as autoimmune hepatitis.90 In 1992, Philip Johnson and Ian McFarlane organized an international panel in Brighton, United Kingdom to address the issues of nomenclature, diagnosis and treatment, and the International Autoimmune Hepatitis Group (IAIHG) was formed.91 Diagnostic criteria were codified, reviewed, and updated. The diagnostic scoring system, initially sketched on a tabletop napkin by Drs Johnson and McFarlane, was tested,92,93 refined,94 and simplified.95,96 The IAIHG continues to identify key clinical and investigational issues,97,98 develop strategies for the standardization of serological testing,99 modify diagnostic criteria,94,95 and explore Smoothened Agonist manufacturer new therapies. It has repeatedly demonstrated the importance of dialogue within a cadre of like-minded clinical investigators to maintain research direction and motivation (Table 1). The next objective was to refine the treatment of autoimmune hepatitis and identify prognostic factors. The indications for therapy had been established for only the most severe life-threatening forms of the disease.100 An appropriate endpoint of treatment was uncertain21; relapse after drug withdrawal was common56,101; side effects frequently prompted premature discontinuation

of medication57,102; disease progression was possible58,103; and improvements were often incomplete despite protracted check details therapy104 (Fig. 2). A controlled clinical trial was developed in the 1980s to randomize patients with mild autoimmune hepatitis to prednisone or placebo, but this project was abandoned when asymptomatic patients with mild disease frequently refused liver biopsy assessment or the possibility of taking prednisone. Furthermore, the recently available test for hepatitis C virus disclosed that 37% of asymptomatic patients were virus-infected.89 We learned that mild autoimmune hepatitis was not “a submerged iceberg” and that controlled clinical trials were not always doable or appropriate (Table 1).