Historical reflections on autoimmune hepatitis

Abstract

Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisystem features and immunological aberrations. Yo u n g w o m e n f e a t u r e d p r o m i n e n t l y i n e a r l y descriptions of CAH. AIH was first applied in 1965 as a descriptive term. Disease-characteristic autoantibodies were defined from the early 1960s, notably antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody. These are still widely used diagnostically but their relationship to pathogenesis is still not evident. A liver and disease specific autoantigen has long been searched for but unsuccessfully. Prolonged immunosuppressive therapy with prednisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today. AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8, DR3 haplotype, and also with DR4. Looking forwards, AIH is one of the several enigmatic autoimmune diseases that, despite being (relatively) organ specific, are marked by autoimmune reactivities with non-organ-specific autoantigens. New paradigms are needed to explain the occurrence, expressions and pathogenesis of such diseases.

A Rare Cause of Elevated Tumor Markers: Autoimmune Hepatitis

“…Hastalığın patofizyolojisi tam olarak bilinmemekle birlikte, tetikleyici risk faktörleri sonucunda oluşan otoimmünitenin hepatoselüler inflamasyona neden olduğu düşünülmektedir. 4 Otoimmüniteyi tetikleyen bu risk faktörleri ise, kızamık, kızamık-çık, akut hepatit A, akut hepatit B, Ebstein-Barr virüs gibi viral enfeksiyonlar, insan lökosit antijen sınıf 1 B8 veya sınıf 2 DR3 ve DR52A gibi genetik predispozan faktörler, metildopa, diklofenak, minosiklin, nitrofurantoin, atorvastatin gibi farmakolojik etmenlerdir. 5 Otoimmün hepatit tanısı zor konulan bir hastalıktır.…”

Otoimmün hepatitli olgularımızın irdelenmesi: 11 yıllık deneyimimiz

“…80% of autoimmune hepatitis is type 1, 4% is type 2 and 3% is type 3 which is a rare type (2,3,5,8). The type in which autoantibodies can not be identified, but clinical and histological examination are compatible with AIH is called undefined AIH (11).…”

“…It is characterised by the presence of various autoantibodies in the serum, high level of gammaglobulin and mononuclear cell infiltration in the periportal or portal area histopathologically (motheaten necrosis) (1)(2)(3)(4)(5). According to immunoserologic findings four types of AIH were defined as type 1, type 2, type 3 and undefined autoimmune hepatitis (6)(7)(8)(9)(10)(11).…”

Relations between human leukocyte antigens and autoimmune hepatitis in Turkish children

“…AIH has a complex genetic transmission pattern that is not clearly established. One or more genes increase or decrease the possibility of genetic transmission alone or in combination (1,2,5). In several studies, some alleles were found to display differences in amino acid sequences (6)(7)(8), and an increased frequency of human leukocyte antigen (HLA) A1, B8 and DR3/DR4 has been reported in patients with type 1 AIH [9].…”

“…Presently, three types of AIH are distinguished: type 1 AIH is characterized by antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA) in the serum in association with hypergammaglobulinemia; type 2 AIH patients have anti-LKM 1 (type 1 liver/kidney microsome) antibodies in serum, and the majority of the cases are children; and type 3 AIH is characterized by the presence of antibodies against soluble liver antigen/liver-pancreas antigen (SLA/LP) (1,3). Some patients share the clinical and histological features of AIH without the presence of immunological markers (autoantibodies) required for sub-classification.…”