Editor’s Note: Autoimmune Hepatitis (AIH) is an acute or chronic liver inflammatory disease caused by unknown immune abnormalities. Without timely treatment, it can progress to liver cirrhosis, liver failure, and even lead to death. The diagnostic scoring systems and criteria proposed in current domestic and international guidelines have significantly advanced the diagnosis and treatment of AIH. Moreover, continuous progress in research on new strategies and medications for AIH treatment internationally and domestically offers valuable references for clinical diagnosis and treatment. At the 21st National Viral Hepatitis and Hepatology Academic Conference and the 2023 Annual Meeting of the Chinese Medical Association’s Hepatology and Infectious Disease Branches, Dr. Xiong Ma from Renji Hospital affiliated with the Shanghai Jiao Tong University School of Medicine delivered a keynote report on the latest advancements in AIH diagnosis and treatment. He also provided an insightful analysis of the similarities and differences between international and Chinese treatment guidelines. In this exclusive interview, Dr. Ma discusses these topics, and we have compiled the content for our readers’ benefit.
Hepatology digest: states that Autoimmune Hepatitis (AIH) is an abnormal immune-mediated liver inflammatory disease. What are the similarities and differences in the diagnosis of AIH in the latest domestic and international guidelines?
Dr. Xiong Ma: In 2015, the Chinese Medical Association’s branches of Hepatology, Gastroenterology, and Infectious Diseases collaborated with domestic experts to formulate China’s first “Consensus on Diagnosis and Treatment of Autoimmune Hepatitis (2015)”. This played a significant role in standardizing the diagnosis and treatment of AIH in China. Based on this, a new version of the “Consensus on Diagnosis and Treatment of Autoimmune Hepatitis” was released in 2021 by the Hepatology branch of the Chinese Medical Association, incorporating the latest domestic and international advancements. Compared to the American Association for the Study of Liver Diseases (AASLD) AIH guidelines (2019 edition), both agree that liver histology biopsy is indispensable. In addition to this, they both integrate autoantibodies, serum IgG levels, and non-viral liver inflammation (like elevated ALT) for a comprehensive diagnosis. However, there are some differences in testing methods, such as the lowest dilution of ANA 1:40 used internationally being roughly equivalent to the 1:100 dilution commonly used in China.
Hepatology digest: The clinical treatment of AIH is still dominated by non-specific immunosuppression, but non-response and intolerance are the main problems affecting the curative effect. What are the differences and similarities in the current guidelines on the first, second and third line treatment recommendations for AIH?
Dr. Xiong Ma: Without clinical intervention, patients with AIH can rapidly progress to cirrhosis or end-stage liver disease. In the AASLD guidelines, budesonide in combination with azathioprine or prednisone/prednisolone in combination with azathioprine is recommended as the initial first-line treatment for children and adults with untreated AIH who do not have cirrhosis or non-acute severe AIH. In China, since budesonide is not yet available, our guidelines recommend prednisone (prednisolone) combined with azathioprine (AZA) or prednisone (one) monotherapy as first-line treatment for AIH. In addition, budesonide should not be used in children and adults with AIH with cirrhosis, or in patients with acute severe AIH. For children or adults with AIH who have failed, incomplete response or intolerance to first-line drug therapy, domestic and foreign guidelines recommend the use of MMF or tacrolimus as second – and third-line therapeutic agents to achieve and maintain biochemical remission. Of course, the use of cyclosporin A is also becoming more and more widespread, which is the common point of domestic and foreign guidelines.
Hepatology Digest: The prognosis of Autoimmune Hepatitis (AIH) varies significantly, mainly depending on whether it is treated and the timing of treatment. In this regard, what are the similarities and differences between domestic and international guidelines?
Dr. Xiong Ma: Regarding the timing of AIH treatment, we advocate for early diagnosis and treatment, meaning diagnosing and treating the disease before the onset of cirrhosis. If the patient is already diagnosed with cirrhosis, traditional treatment plans can still be adopted. However, due to potential splenomegaly, patients may have relatively low white blood cell and platelet levels, reducing their tolerance to azathioprine. In such cases, mycophenolate mofetil or cyclosporin A, particularly the latter due to its minimal bone marrow suppression effects, becomes a safer choice, even in patients with significantly low white blood cell counts. Additionally, in patients with decompensated cirrhosis, the Chinese guidelines recommend inducing with low doses of corticosteroids. If the condition improves or shifts from decompensated to compensated, i.e., ‘recompensated’, it is advised to combine immunosuppressants to further improve the condition. In summary, the Chinese guidelines suggest appropriate treatment based on the patient’s condition.
There are some differences in treatment between domestic and international guidelines. International guidelines pay more attention to the quality of life, prognosis evaluation, and special populations like pregnant women, which is an area we can learn from and need to improve further.
Hepatology Digest: Finally, could you share the latest advancements in clinical research on new medications for AIH?
Dr. Xiong Ma: As an immune-mediated disease, research on immunosuppressants is quite crucial for AIH. Currently, domestic efforts are leading the Phase II clinical study of Budesonide, hoping it will soon be available in China. In addition to mycophenolate mofetil, clinical studies on some new targeted medications as first-line treatment options are also actively underway. Clinical trials for new biologics, such as CD20 monoclonal antibodies and TNF-α inhibitors, are being conducted with the hope of achieving further breakthroughs soon.