Autoimmune Hepatitis

Fifty-eight years after the discovery of autoimmune hepatitis (AIH) as a steroid-responsive liver disease in young women, and 10 years after this topic was last covered by Seminars in Liver Disease, it is our pleasure to introduce this issue on AIH. Autoimmune hepatitis is the first liver disease in which medical therapy was shown to improve survival. It is still a liver disease with many unanswered questions; in particular, its etiology is unknown because currently we do not recognize an autoimmune pathogenesis as an etiology on its own. However, we have seen significant progress within the last 10 years, especially in the areas of diagnosis, understanding of pathogenesis, and treatment.

The international AIH community—organized within the International Autoimmune Hepatitis Group (IAIHG), under the chairmanship of one of the Guest Editors of this issue of Seminars in Liver Disease—has continuously worked on the development of a scoring system for the diagnosis of AIH. This has proved to be very useful, and is especially important because single laboratory tests that can reliably diagnose the disease are not available. Furthermore, our understanding of the pathogenesis of autoimmune disease in general and AIH in particular has significantly improved, due in no small measure to various animal models, particularly genetically engineered animal models. The treatment of AIH still aims first at the remission of the disease and second at keeping the patient in remission with the lowest possible dose of immunosuppressive drugs. Because more than 80% of the patients have to receive long-term immune suppression, they are in danger of developing bone disease, diabetes, weight gain, and other steroid-specific side effects. In addition, many of them are treated in combination with immunosuppressive drugs, such as azathioprine, which has its own side effects such as hepatotoxicity, myelotoxicity, and oncogenic potential. Recent studies have shown that long-term remission may be achieved and maintained with reduced steroid-specific side effects with topical steroids such as budesonide. In ~4% of cases undergoing liver transplantation in the Western world, the underlying cause is AIH. Hopefully, in the future, with more individualized treatment, this can be further reduced, even though results for liver transplantation with AIH are among the best that can be achieved. A particular issue, however, is the recurrence of AIH after liver transplantation, which demands a specific approach with optimized immunosuppression both for preventing rejection and for controlling recurrent AIH.

Particular issues regarding AIH have to be considered in children. Children with AIH frequently have an overlap with primary sclerosing cholangitis and, compared with adults, suffer more frequently from AIH type 2; differ in their genetic background; and, possibly, differ in their response to treatment.

Finally, AIH is part of the autoimmune polyendocrine syndrome type 1 (APS-1); another term for this disease is autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome. Autoimmune polyendocrine syndrome type 1 is a monogenetic multiorgan autoimmune disease. It should not be missed on making a diagnosis of AIH. It is therefore important in the differential diagnosis of AIH, and it is also helpful for understanding the pathogenesis of multiorgan autoimmune disease, including the liver, because it is based on a single-point mutation in a transcription factor relevant in immunotolerance called AIRE (autoimmune regulator).

Autoimmune hepatitis and its management face several other specific issues, such as management in the elderly; management of males; and management of AIH before, during, and after pregnancy. Furthermore, AIH may start with a fulminant course, and the diagnosis should not be overlooked when dealing with patients with acute liver failure. Alternatively, AIH may behave as a slowly progressing disease. It is still controversial whether those patients need immunosuppressive treatment at all.

Finally, most or our knowledge concerning the management of autoimmune patients comes from the Western world, and in particular from series of European, North American, and Australian patients. However, AIH also occurs in other areas, such as Latin America; Asia; and, in particular, Japan, where different environmental influences and different responses to immunosuppressive therapy may be relevant.

Concerning treatment, we should acknowledge that the treatment regimens and standards we use today derive mainly from trials that were published decades before the discovery of the hepatitis C virus, and that the treatment of AIH may, therefore, need revisiting in light of newer studies that will become available.

The editors are proud to present this volume, which faces and tackles all of these issues that are still burning in the field of AIH. The authors are also proud to dedicate this issue to Karl Hermann Meyer zum Büschenfelde, a pioneer in AIH, on the occasion of his 80th birthday.