autoimmune hepatitis (AIH) is a liver parenchymal inflammation mediated by the autoimmune response to hepatocytes. Its pathogenesis can be mainly attributed to the body's loss of tolerance to its own tissue proteins and produces autoantibodies and/or autosensitized lymphocytes, attacking its target antigen cells and tissues, and causing pathological changes and dysfunction.
Recently, Ma Xiong's team found that in the field of AIH:
1) Intestinal microbial disorder represented by Veillonella. dispar affects the activity of AIH disease and participates in the development of intrahepatic inflammation;
2) Tissue-settled CD8+ memory T cells are highly expressed in AIH and may participate in the disease process.
At present, a multi-center study on AIH whole genome association analysis led by Renji Hospital is in progress. As of today, the total number of cases enrolled in the study was 1,717, of which 1,622 AIH cases and 6,838 normal controls have completed Illumina GSA chip scans. 989 cases in the disease group and 5,064 cases in the control group were screened as the first stage, and the remaining 633 cases and 1,774 cases in the two groups are used as the second stage verification. I believe that it will soon bring new breakthroughs to the genetic study of AIH in my country.
In terms of epidemiological , foreign studies have shown that from 1997 to 2015, the incidence of AIH doubled from 127/100,000 people per year to 256/100,000 people, the cumulative all-cause mortality rate in 10 years was 31.9% (27.6-36.5), and the cumulative liver disease-related mortality rate in 10 years (including hepatocellular carcinoma) was 10.5%. Clinical studies of the AIH cohort of Renji Hospital show that the high incidence of AIH is about 55 years old, about 10 years lower than that of foreign countries. At the same time, the age group at the age of 20 is a small peak in the incidence of AIH, and the ratio of men to women is 1:5.
The AIH guideline issued by AASLD in 2019 proposed that the diagnosis of AIH must be supported by liver histological examination results that meet the characteristics of this disease, and meet the following characteristics: 1) Elevated serum transaminase levels; 2) Elevated serum IgG levels and/or one or more autoantibodies are positive; 3) Exclude other causes that can cause chronic hepatitis, such as viral, hereditary, metabolic, cholestatic and drugs that may induce AIH-like diseases. Initial serological tests for
AIH should include: 1) Adults: ANA and SMA; 2) Children: ANA, SMA and anti-LKM1; 3) If necessary, consider additional autoantibodies to test to ensure diagnosis. Before starting treatment, atypical or difficult cases should be reviewed or referred directly by an experienced liver disease center. The clinical diagnosis flow chart of
AIH is as follows:
In terms of AIH treatment, for untreated AIH children and adults, if not cirrhosis or acute severe patients, AASLD recommends using budesonide combined with azathioprine , or prednisone (long) combined with azathioprine as the initial first-line treatment plan, while for children and adults with cirrhosis and adults with AIH or acute severe AIH, AASLD does not recommend using budesonide. For children and adult patients with AIH who have failed first-line drug treatment, incomplete response or intolerance, AASLD is recommended to use mycophenolate (MMF) or tacrolimus to achieve and maintain biochemical remission. Based on ease of use and side effects, the guidelines recommend that MMF use in AIH patients take priority over tacrolimus as a second-line clinical medication.
AIH specific treatment plan is summarized as follows:
If both first-line drugs and second-line drugs are not effective or tolerated, the reference for selection of AIH third-line drugs is as follows:
AIH has diverse clinical manifestations, and most AIH patients have hidden diseases, generally manifestations as chronic liver disease, and about 25% of AIH patients have acute attacks, and may even progress to acute liver failure. Characteristic liver histological manifestations of AIH include interfacial hepatitis, lymphomaplasmic cell infiltration, rose garland-like changes in hepatocytes, lymphocyte penetration phenomenon and central lobular necrosis.
For AIH with different clinical manifestations, the hormone therapy indications and timing of liver transplantation are referenced as follows:
In terms of the discontinuation and recurrence of AIH, a few patients can stop the drug and achieve long-term remission of AIH. Those who have persisted in normal serum aminotransferase and IgG levels for more than 2 years can consider discontinuation of drugs. It should be noted that liver tissue biopsy before discontinuation is valuable for eliminating suspected inflammation and reducing recurrence rates, but is not mandatory in adult patients. Patients should be closely monitored for the first 12 months after discontinuation of treatment and then undergo a laboratory test every year. If the patient relapses, treatment needs to be restarted immediately until biochemical remission, and then transition to long-term maintenance treatment.
Professor Ma Xiong pointed out that the treatment endpoint of AIH can also be emulated in the three stages of hepatitis B cure. The "bronze medal" is biochemical relief, and the "silver medal" is histological relief, until it successfully "gained gold" to achieve clinical cure .
Finally, Professor Ma Xiong briefly explained the currently unmet clinical needs and future research directions of AIH. First, we must continue to improve simple and specific AIH diagnostic standards, identify new biomarkers in high-risk patients during diagnosis, and better reflect the alternative endpoint of clinical trials for liver histological response; second, the second-line treatment plan for non-responsive/partial response patients needs to be optimized to develop the application of biological agents; finally, the treatment of recurrence after liver transplantation cannot be ignored.
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