Autoimmune Hepatitis (AIH) is an inflammatory lesion of the liver parenchyma mediated by an abnormal autoimmune response and characterized by hypergammaglobulinemia, positive serum autoantibodies and response to immunosuppressive therapy [1]. Under the combined effect of environmental factors, immune tolerance imbalance and genetic susceptibility status, the body develops T cell-mediated abnormal immune attack against liver antigens, which in turn leads to progressive inflammatory necrosis and fibrotic processes in the liver. niantai With the increased awareness of AIH among clinicians and the wide availability of autoantibody testing and liver biopsy, the detection rate of AIH patients in China has increased significantly, allowing These patients are diagnosed in a timely manner. Appropriate immunosuppressive therapy treatment can put most AIH patients into remission and even reverse liver fibrosis, thus significantly improving the prognosis and quality of life of patients. There is an urgent need to develop suitable diagnostic criteria and treatment protocols for patients in China in order to further standardize the clinical diagnosis and treatment of AIH. Ma Xiong, Department of Gastroenterology, Shanghai Renji Hospital I. Diagnosis AIH is more common in middle-aged and elderly women, while the younger female patients seen clinically are generally sicker and have a higher incidence of cirrhosis at the time of consultation. About 50% of AIH patients have an insidious onset, and about 30% of patients have already developed cirrhosis at the time of diagnosis, even with vomiting blood and black stool as the first symptoms caused by ruptured esophagogastric varices and bleeding. Some patients with AIH present with acute attacks, often with marked jaundice and histological manifestations of marked inflammatory activity, along with some degree of fibrosis, suggesting that such patients may have acute exacerbation of the chronic process and must be identified early and treated promptly to avoid progression to subacute liver failure. Some patients are asymptomatic and are often found to have elevated serum transaminase activity in the course of investigations for other diseases, most commonly concurrent endocrine or rheumatoid diseases. These asymptomatic patients tend to have milder disease and respond better to immunosuppressive therapy.AIH can first develop during pregnancy or postpartum, and prompt diagnosis and timely treatment are important to avoid fetal risk.AIH patients often present with other extrahepatic autoimmune diseases, such as thyroiditis, ulcerative colitis, type I diabetes, rheumatoid arthritis, and celiac disease [1]. Although AIH is more prevalent in women, men with AIH can still be seen clinically and they also have a good response to immunosuppressive therapy. The descriptive diagnostic criteria of AIH include the following five aspects: (i) liver histology: the main manifestations are moderate or severe interface hepatitis, lobular hepatitis, or bridging necrosis in the central zone – confluent area, without obvious bile duct lesions or definite granulomas or other lesions suggesting a different etiology. ②Serum biochemical examination: serum transaminase level is elevated to varying degrees, while biochemical indicators suggestive of cholestasis, such as serum alkaline phosphatase and total bilirubin level, are not significantly elevated. ③Serum immunoglobulin: total serum globulin or g-globulin or IgG concentration exceeds 1.5 times the upper limit of normal. ④Serum antibodies: serum antinuclear antibody (ANA), anti-smooth muscle antibody (SMA) or anti-liver and kidney microsomal antibody-1 (LKM-1) titers of 1:80 or more; ⑤Exclusion of other pathogenic factors, such as HBV, HCV presenting infection, drug or alcoholic liver disease, and normal serum a1-antitrypsin, serum copper and copper blue protein concentrations [3]. AIH can be divided into 2 serological subtypes based on serum autoantibody profile [1]. Type I AIH is the most common, accounting for approximately 60% to 80% of all AIH. positive for ANA, SMA, anti-soluble liver antigen/hepatopancreatic antigen antibodies (SLA/LP) or perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are characteristic. Type II AIH occurs mainly in children and is characterized by positivity for LKM-1 or anti-hepatocyte plasma type I antibodies (LC-1). An AIH diagnostic score system was developed by the International AIH Group in 1999 to improve the accuracy of AIH diagnosis [3]. This system avoids the errors associated with isolated inconsistent features by measuring each component of the syndrome, which can accommodate conflicting features. Summarizing the data from six studies containing 983 patients, the sensitivity of this integral system for the diagnosis of AIH was calculated to be between 97% and 100%, with a diagnostic accuracy of 89.8%. In particular, in addition to the typical presentation of AIH, the score system has a high sensitivity for those who lack characteristic features (e.g., no hypergammaglobulinemia or autoantibodies) or for those with atypical presentations (e.g., presence of antimitochondrial antibodies, cholestasis, or atypical hepatic histological features). Although the above point system has good sensitivity and specificity for the diagnosis of AIH, it includes 13 major clinical components with a total of 29 scoring levels, which is too complex to make it fully applicable in clinical practice. For this reason, the IAIHG recently proposed a simplified diagnostic criteria for AIH (Table 1), which aims to develop a point system more suitable for daily clinical work. We compared the 1999 point system with the simplified point system in 405 patients with histologically based chronic liver disease, including 127 patients with AIH, 5 with AIH-PBC overlap syndrome, 47 with drug-related liver disease, 36 with nonalcoholic steatohepatitis, 82 with chronic hepatitis B, and 30 with chronic hepatitis C. Both the 99 point system and the simplified point system had high diagnostic sensitivity (100% and 90%) and specificity (93% and 95%). To address the discrepancy between autoantibody titers in international standards (e.g., 1:40, 1:80) and those used in most hospitals in China (1:100, 1:320, etc.), we attempted to correct the autoantibody portion of the simplified criteria, i.e., 1 point for ANA or SMA ³ 1:100 and 2 points for ANA or SMA ³ 1:320. The sensitivity of the modified simplified point system was 83% and the specificity was 97%. Therefore, the modified simplified criteria can be used for our clinical diagnosis, but the simplified criteria are easy to miss the diagnosis for patients with atypical autoimmune features, so we suggest that we can first score with the simplified criteria in clinical practice, and then score with the 99-year point system for patients who do not meet the simplified criteria but are still highly suggestible, in order to further improve the diagnostic sensitivity of AIH. Table 1 Simplified autoimmune hepatitis diagnostic point system Variable Criteria Score Remarks ANA or SMA ³1:40 1 point ANA or SMA or LKM-1 or SLA ³1:80 ³1:40 positive 2 points* *Maximum 2 points if multiple present simultaneously; IgG > upper limit of normal >1.10 times upper limit of normal 1 point 2 points Liver histology Consistent with AIH Typical AIH presentation 1 point 2 points Interface Hepatic hepatitis, lymphoplasmacytic infiltration in the confluent area and lobules, and hepatocellular rosette nodules are considered characteristic AIH histologic changes, and typical AIH manifestations when all 3 are present together Exclusion of viral hepatitis Yes 2 points ³ 6 points: AIH possible ³ 7 points: confirmed AIH III. Treatment The goal of AIH treatment is to obtain remission of clinical symptoms, improvement of biochemical parameters and histologic inflammation, and ultimately to be able to sustain remission after drug discontinuation sustained maintenance of remission [5]. Three randomized controlled treatment trials have confirmed that prednisone alone or in combination with azathioprine significantly relieves symptoms, biochemical and histological findings, and survival in patients with AIH. 1. treatment indications and regimens: AIH responds well to immunosuppressive therapy, but immunosuppressive therapy is associated with a high number of adverse effects, and treatment indications should be strictly controlled (Table 2), and experimental therapy should be avoided as much as possible. Overall, the more severe the intrahepatic inflammation in AIH patients, the more they need to receive immunosuppressive therapy and the more they will benefit from immunosuppressive therapy. Prednisone (Long) alone or low-dose prednisone (Long) in combination with azathioprine resulted in symptomatic remission, improved laboratory abnormalities and histologic changes, and improved survival in patients with severe AIH. 65% of patients achieved clinical, biochemical, and histologic remission within 18 months, and 80% remission at 3 years of therapy. Survival at 20 years for those who responded well was 80%, with no significant difference compared to an age- and sex-matched normal population in the same region. In contrast, patients with AIH of the same severity have a mortality rate of 50% at 3 years and up to 90% at 10 years if left untreated [2]. relapse after remission of AIH is more common, with 50% to 86% of remission cases relapsing after drug withdrawal. 3% of patients experience treatment-related adverse effects and have to be discontinued prematurely. 9% of patients deteriorate despite standard treatment. 13% of patients are in partial Relapse. Relapse, drug toxicity, treatment failure, and incomplete response are shortcomings of current AIH treatment, and the search for more specific and effective treatment strategies must continue. Successful treatment of AIH depends on proper case selection, selection of an appropriate treatment regimen, adequate duration of therapy, and appropriate management of an unsatisfactory prognosis [6]. Table 2 Indications for treatment of AIH Absolute indications Relative indications No indications Serum aspartate aminotransferase (AST) >10 times the upper limit of normal Symptoms (fatigue, joint pain, jaundice) Asymptomatic and mild interface hepatitis or confluent area hepatitis Serum AST >5 times the upper limit of normal and g-globulin or IgG >2 times the upper limit of normal Serum AST and/or g-IgG levels below the absolute indications Non Active cirrhosis Bridging necrosis or multilobular necrosis Interface hepatitis Decompensated inactive cirrhosis Severe symptoms Osteoporosis, emotional instability, hypertension, diabetes mellitus, hematocrit (white blood cell count ³2.5´109/L or platelet count ³50´109/L) Compression fractures, psychiatric abnormalities, fragile diabetes mellitus, intractable hypertension, intolerant of prednisone or azathioprine Treatment options include prednisone (Long) monotherapy and prednisone/azathioprine combination therapy, which have similar efficacy, but the incidence of glucocorticoid-related side effects is 44% and 10% for single-dose prednisone and combination therapy, respectively, and thus combination therapy is generally recommended as the preferred option. Although progressive cirrhosis can affect the conversion of prednisone to prednisolone, it is generally not sufficient to affect the clinical efficacy of prednisone. Single-agent therapy is indicated for patients with severe hematocrit, short-term experimental therapy, pregnancy or short-term preparations for pregnancy, patients with oncology, or patients with known complete mercaptopurine methyltransferase deficiency. In contrast, combination therapy is indicated for those with an expected course of more than 6 months, those at increased risk of hormonal side effects such as postmenopausal women, those who are emotionally unstable, those with osteoporosis, brittle diabetes, intractable hypertension, or obesity. Initial treatment should be continued until remission (disappearance of symptoms, serum transaminases ≤ 2 times the upper limit of normal and no or only mild inflammatory activity on liver histology). Treatment must be interrupted in the event of treatment failure or intolerable adverse drug reactions. Dose reduction of prednisone (Long) is a long-term taper. Single doses of prednisone (Long) (starting dose 40-60 mg/d) may be reduced by 10 mg/week for 4 weeks to 20 mg/d, and then by 2.5-5 mg/week until the maintenance dose is reached. Typically, the maintenance dose of prednisone (Long) is 10 mg/d, but may be tapered to 5-7.5 mg/d or 10 mg every other day. In combination therapy, prednisone (Long) (starting dose 30 mg/d) can be reduced by 5-10 mg per week up to 15 mg/d and then by 2.5 mg per week up to the maintenance dose, and these patients can also be treated with azathioprine alone as maintenance therapy [6]. Individualized treatment needs to be implemented in the clinical workup, with sequential dose reduction for good responders and appropriate extension of treatment at a given dose for incomplete responders, with a significant decrease in serum transaminase levels (less than half of the previous level) before dose reduction. Maintenance therapy should be continued for at least 6 months after improvement in liver histology and for a total duration of at least 2 years, but there is no consensus on how long it should last. 2. Efficacy determination and management: Remission is defined as complete resolution of symptoms, return to normal serum transaminases, bilirubin and serum gammaglobulin/IgG levels, and improvement in liver histology (return to normal or only mild inflammation of the confluent area). It should be noted that normal serum aminotransferase levels do not necessarily mean that liver histology returns to normal, usually at intervals of more than 6 months. The evaluation of the treatment effect can be based on the following points: (i) a decrease in serum transaminase and bilirubin levels, suggesting a reduction in disease activity; (ii) protein synthesis as judged by prothrombin time and serum albumin, thus suggesting improvement in liver function; (iii) a significant decrease in serum gammaglobulin/IgG, suggesting suppression of an overwhelming immune response. Serum autoantibody levels are not closely related to disease activity and should not be used as a marker to monitor activity. ④ Liver biopsy remains the standard method for determining efficacy; however, there is no consensus on how often a liver biopsy should be performed. Interfacial hepatitis strongly predicts relapse after drug discontinuation. Up to 80% of patients with normal liver histology are able to eventually withdraw the drug, compared with less than 50% of patients with persistent confluent zone inflammation or interfacial hepatitis [7]. Relapse should be considered if serum transaminase levels rise to more than three times the upper limit of normal after drug discontinuation. Most relapses occur within 15-20 months after discontinuation of immunosuppressive drugs, especially in those whose initial biopsy shows cirrhosis, and patients with AIH should be monitored for relapses with regular checks of serum transaminases, bilirubin and gammaglobulin levels. Patients who relapse should be given an initial induction dose of medication until clinical remission is achieved and then considered for dose reduction. Adult patients with more than one relapse should be treated with a combination of prednisone (Long) and azathioprine, low-dose prednisone (Long), or long-term maintenance therapy with azathioprine alone. Despite good compliance with immunosuppressive therapy, clinical and laboratory markers may deteriorate in approximately 10% of patients. failure of AIH therapy is defined as active, progressive or worsening liver histological lesions leading to cirrhosis and death or the need for liver transplantation. The optimal treatment regimen for those who fail initial therapy or have incomplete effects has not been determined. Treatment of such patients with higher than standard therapeutic doses may result in clinical remission in up to 70% of patients within 2 years. The American Association for the Study of Liver Diseases (AASLD) guidelines recommend prednisone (Long) (60 mg/d) monotherapy or a combination of prednisone (Long) (30 mg/d) and azathioprine (50 mg/d) for at least 1 month, with a 10 mg monthly reduction in prednisone (Long) after clinical improvement, and a gradual reduction in the prednisone dose until a regular maintenance dose is reached [7]. Among the above treatment regimens, the higher dose and longer duration of prednisolone treatment should pay extra attention to the occurrence of adverse effects, and should focus on gastric mucosal protection and calcium supplementation therapy. Prednisone (Long) should be used with caution in moderate-to-severe esophagogastric fundic varices, especially in those with red signs, to avoid the occurrence of gastrointestinal bleeding. Recently, budesonide and mortification (MMF) have received increasing clinical attention as alternative treatments to prednisolone and azathioprine, respectively. Available data suggest that budesonide has similar efficacy to prednisolone and MMF to azathioprine in AIH, but budesonide and MMF avoid the adverse effects of the corresponding drugs and can be used as alternative therapy for those who cannot tolerate them [8]. Recently, the American Association for the Study of Liver Diseases updated its guidelines for the clinical management of autoimmune hepatitis [9], which has a greater value in guiding the clinical management of AIH. There is an urgent need to establish nationally appropriate diagnostic and treatment criteria in China to better guide daily practice and facilitate clinical research. In addition, since the current treatment regimens are all non-specific immunosuppressive treatments, there is an urgent need to develop more specific and efficient therapeutic drugs or regimens with fewer side effects to further enhance the efficacy and improve the quality of life of AIH patients. References 1 Krawitt EL. Autoimmune hepatitis. N Engl J Med, 2006, 354 (1): 54-66. 2 Czaja AJ, Manns MP, McFarlane IG, et al. Autoimmune hepatitis: the investigational and clinical challenges. 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