Putting flesh and polish on autoimmune hepatitis and moving the disease of exclusion to inclusion
✍ Scribed by Albert J. Czaja
- Book ID
- 102239856
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 261 KB
- Volume
- 52
- Category
- Article
- ISSN
- 0270-9139
No coin nor oath required. For personal study only.
✦ Synopsis
Autoimmune hepatitis emerged during an era when concepts of neonatal immune tolerance, clonal selection of lymphocytes, and ''forbidden clones'' of activated immune cells were forming. The diagnosis had to be deduced from circumstantial evidence and by exclusion of other conditions. The goals of this review are to demonstrate how a clinician nonscientist can contribute to the maturation of autoimmune hepatitis and to illustrate the principles of clinical investigation that can be applied broadly to other projects. Autoimmune hepatitis initially had to be distinguished from other diseases, and improvements in the tests for viral and immune markers were instrumental in this regard. Diversification of the clinical phenotype to accommodate acute severe, asymptomatic, elderly, and variant forms enhanced the pertinence of the disease, and the formation of the International Autoimmune Hepatitis Group standardized the diagnosis, interconnected investigators, and promoted global acceptance of the condition. Subsequent studies refined current corticosteroid-based therapies, identified prognostic markers, assessed genetic predispositions, explored new pharmacological agents, and forecast the emergence of cellular and molecular interventions. Good fortune, stimulating mentors, career dedication, practical goal selection, protocol compliance, compulsive record keeping, personal resilience, and strong collaborations were the bases for progress. Autoimmune hepatitis exemplifies an evolutionary process in the science of autoimmunity and the people committed to its study. Lessons derived from this experience can be far-reaching. (HEPATOLOGY 2010;52:1177-1184) W hen I graduated from Harvard Medical School in 1968, the designation ''autoimmune hepatitis'' did not exist, and the clinical phenotype of ''lupoid hepatitis'' connoted cirrhosis in young amenorrheic women with hirsutism, acne, and cushingoid features. [1][2][3][4] The remarkable early observations associating the lupus erythematosus cell phenomenon with chronic hepatitis 5,6 were followed by the recognition that antinuclear antibodies 7 and smooth muscle antibodies 8 frequently accompanied the Abbreviations: CALD, chronic active liver disease; HBsAg, hepatitis B surface antigen; HLA, human leukocyte antigen; IAIHG, International Autoimmune Hepatitis Group; MELD, Model for End-Stage Liver Disease.