Diego and Giorgina Vergani: The two hearts of translational autoimmunity.

Since the publication of the first textbook on autoimmune diseases in 1963, the knowledge in the field has exponentially grown into numerous tracks of research, particularly at benchside. Systemic and organ-specific autoimmune diseases, as in the case of the liver, have witnessed notable advances in terms of epidemiology, genetics, effector and regulatory mechanisms, and ultimately treatment. While the available tools for communication have provided accelerating progress rates, we recognize that key opinion leaders continue to provide significant contributions to the field. The present issue is dedicated to celebrate Giorgina Mieli-Vergani and Diego Vergani as two of the finest examples of excellence in autoimmune liver diseases and the broader field of autoimmunity. Diego and Giorgina are extremely well-liked Colleagues who fully represent the translational efforts between laboratory research and clinically relevant questions in the practice of pediatric liver diseases and autoimmune hepatitis.

Scoring systems for the diagnosis of autoimmune hepatitis: past, present, and future.

The diagnosis of autoimmune hepatitis (AIH) can be challenging due to the variable clinical and laboratory findings. The original diagnostic criteria published in 1993 by the International Autoimmune Hepatitis Group (IAIHG) were revised in 1999 in an attempt to standardize the diagnosis. However, these criteria are complex and can be cumbersome in clinical practice. In 2008, simplified diagnostic criteria were reported to facilitate the bedside diagnosis of AIH. The scoring systems have been evaluated in several retrospective case series and tested for their ability to reliably diagnose and exclude AIH. However, the scoring systems did not fare as well in patients with concomitant cholestatic disease, fatty liver disease, fulminant hepatitis, and pediatric patients. Both positive and negative predictive values are low in these patients. Prospective studies are needed to compare the two scoring systems to determine which (if not all) patients require liver biopsy and which patients would benefit from immunotherapy.

Historical reflections on autoimmune hepatitis.

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. Young women featured prominently in early 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 predisolone 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.

[Autoimmune hepatitis]. / Autoimmun hepatitis.

First the short history of the disease, then its etiopathogenesis, the role of genetic, environmental and immunologic factors are described. In the second part, the questions of diagnosis, differential diagnosis and the immunosuppressive treatment, with new therapeutic modalities and liver transplantation are discussed.

Historia de las manifestaciones gastrointestinales del lupus eritematoso sistemico / History of the gastrointestinal manifestations in systemic lupus erythematosus

En este articulo revisamos la historia de las manifestaciones gastrointestinales en el Lupus Eritematoso Sistemico desde el siglo XIX hasta nuestros dias, recorriendo cada uno de los organos involucrados en este sistema y haciendo especial mencion de la gastropatia, enteritis, ileitis, sindrome de malabsorcion, vasculitis y vasculopatia intestinal, trombosis mesenterica, pancreatitis, ascitis, peritonitis, hepatitis autoinmune, entre otros

Progress in diagnosis of hepatitis and the cirrhotic liver.

History of the concept and definition of hepatitis is briefly reviewed. The landmarks of progress are based on better understanding of liver structure and introduction of biopsy techniques to follow the pathologic alterations in acute and chronic hepatitis, cirrhosis, dysplasia and hepatoma. Modern achievements are recognition of the etiologic agents of viral hepatitis A through G, viral nucleic acid sequencing, viral genome and gene products leading to development of immunologic tests to etiologic diagnosis. Viral particles are visualized by electron microscopy. In tissue, localization of viral products is obtained by histochemical, immunologic and by in situ hybridization methods. Diagnostic criteria for each of the viral etiologic agents is reviewed, as is cirrhosis and its occurrence in viral hepatitis and alcohol abuse.

[Autoimmune hepatitis (history of the research, current aspects)]. / Autoimmunnyi gepatitis (istoriia izucheniia, sovremennye aspekty).

Important achievement in the study of autoimmune hepatitis are shown, particularly in establishing the role of hepatitis viruses, other hepatotropic viruses and some medicines. The last classification of chronic hepatitis based on the etiology, autoimmune hepatitis considers autoimmune hepatitis as a disease of unknown etiology. It is thought valid that investigation of autoimmune reactions produced by hepatitis viruses and other agents will enable a revision of classification of chronic hepatitis.