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Liver biopsy is a crucial diagnostic tool for chronic liver diseases， allowing for direct observation of lesion morphology and aiding in precise evaluation. It is especially valuable in cases of autoimmune hepatitis， which exhibits complex morphological characteristics. This includes assessing grading and staging criteria， recognizing overlap syndrome， and considering the morphological features of immune-mediated hepatitis and post-COVID-19 vaccination autoimmune hepatitis. Furthermore， significant morphological differences exist between type 1 and type 2 autoimmune pancreatitis， necessitating further research into type 3 autoimmune pancreatitis.
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Autoimmune hepatitis （AIH） is an immune-mediated inflammatory disease of the liver parenchyma， which is characterized by hypergammaglobulinemia， the presence of autoantibodies， and typical abnormalities in liver histology； however， the diverse clinical manifestations of AIH and the lack of specific serological markers have brought difficulties and challenges in the diagnosis of AIH. Although portal lymphoplasmacytic infiltration， interface hepatitis， lymphocyte emperipolesis， and hepatocyte rosettes are the typical histological features of AIH， many other histological features can also be observed in AIH， including centrilobular necrosis and Kupffer cell hyaline globules. Therefore， no single histological feature can be used for the diagnosis of AIH， and a confirmed diagnosis should be made with reference to clinical and laboratory examinations， with the exclusion of liver diseases due to other causes. This article summarizes the histological features of AIH， different histopathological spectrum， common clinical issues， differential diagnosis， and recent advances.
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Drug-induced autoimmune-like hepatitis （DI-ALH） is a special clinical phenotype of drug-induced liver injury and has similar clinical features and laboratory test results to autoimmune hepatitis， and it is often difficult to distinguish them through liver biopsy. Therefore， correct differential diagnosis DI-ALH and autoimmune hepatitis is a crucial and difficult point in clinical practice. This article analyzes the research advances in the pathogenesis， clinical features， diagnosis and treatment， and prognosis of DI-ALH， in order to provide ideas for the diagnosis and treatment of such diseases among clinicians.
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Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system， and with the prolongation of disease course， it may gradually progress to liver cirrhosis and even hepatocellular carcinoma. Although great achievements have been made in the understanding and treatment of AIH， its etiology and pathogenesis still remain unclear. T cells play a crucial role in the development and progression of AIH， and by focusing on follicular helper T cells， this article elaborates on the research advances in follicular helper T cells in AIH， in order to provide new ideas and strategies for the clinical treatment of AIH.
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ObjectiveTo investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis. MethodsA total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group， model group， and treatment group using a random number table， with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A （Con A） via the caudal vein to establish a mouse model of autoimmune hepatitis， and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction （4.68 g crude drug/kg） by gavage at 14 days before modeling， and Con A was injected after the last gavage. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interferon gamma （IFN-γ）， tumor necrosis factor-α （TNF-α）， iron ion， glutathione （GSH）， reactive oxygen species （ROS）， adenosine triphosphate （ATP）， and malondialdehyde （MDA） were measured； liver index and spleen index were calculated； the expression levels of GPX4 and SLC7A11 were measured； liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. Compared with the model group， the treatment group had significant reductions in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. HE staining showed that compared with the normal group， the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area， and compared with the model group， the treatment group had alleviation of liver necrosis and inflammatory infiltration. ConclusionLiver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.
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Autoimmune hepatitis （AIH） is an autoimmune disease characterized by chronic liver inflammation， with a gradually increasing incidence rate， and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years， it has been believed that changes in intestinal microecology can cause changes in autoimmune state， microbial metabolites， and intestinal barrier， which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients， elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH， and briefly describes related treatment regimens from the perspective of intestinal microecology， so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis， diagnosis， and treatment of AIH.
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Abstract Objective: To determine the frequency and interobserver reproducibility of the magnetic resonance imaging (MRI) features considered diagnostic for autoimmune hepatitis. Materials and Methods: Two abdominal radiologists, blinded to pathology data, reviewed the MRI examinations of 20 patients with autoimmune hepatitis, looking for liver enhancement, lymphadenopathy, portal hypertension, and chronic liver disease. The pattern of liver fibrosis was categorized as reticular, confluent, or mixed. Interobserver agreement was assessed by calculating intraclass correlation coefficients and kappa statistics. Results: The most common abnormal finding on MRI was surface nodularity (in 85%), followed by liver fibrosis with a reticular pattern (in 80%)—categorized as mild (in 25.0%), moderate (in 43.8%), or severe (in 31.2%)—; heterogeneous liver enhancement (in 65%); splenomegaly (in 60%); caudate lobe enlargement (in 50%); and lymphadenopathy (in 40%). The interobserver agreement was almost perfect for surface nodularity (0.83), ascites (0.89), and liver volume (0.95), whereas it was just slight and fair for the degree of fibrosis and for heterogeneous liver enhancement (0.12 and 0.25, respectively). It was also slight and fair for expanded gallbladder fossa and enlarged preportal space (0.14 and 0.36, respectively), both of which are indicative of chronic liver disease. Conclusion: The interobserver agreement was satisfactory for surface nodularity (the most prevalent abnormal MRI finding), ascites, liver volume, and splenomegaly. Conversely, it was only slight or fair for common but less objective criteria.
Resumo Objetivo: Determinar a frequência e reprodutibilidade interobservador das características de imagem por ressonância magnética na hepatite autoimune. Materiais e Métodos: Dois radiologistas abdominais, cegos para dados patológicos, revisaram ressonâncias magnéticas de 20 pacientes com hepatite autoimune quanto ao realce hepático, linfadenopatia, hipertensão portal e doença hepática crônica. A fibrose foi classificada como reticular, confluente ou ambas. A concordância interobservador foi avaliada por coeficientes de correlação intraclasse e estatística kappa. Resultados: O achado anormal mais comum foi nodularidade superficial (85%), seguido de fibrose reticular hepática (80%) — leve (25%), moderada (43,8%), grave (31,2%) —, realce heterogêneo (65%), esplenomegalia (60%), aumento do lobo caudado (50%) e linfadenopatia (40%). A concordância interobservador foi quase perfeita para nodularidade superficial (0,83), ascite (0,89) e volume hepático (0,95); entretanto, foi apenas leve (0,12) e razoável (0,25) para grau de fibrose e realce heterogêneo, respectivamente. Também foi leve (0,14) ou regular (0,36) para achados de doença hepática crônica, como fossa da vesícula biliar expandida e espaço pré-portal alargado, respectivamente. Conclusão: A concordância geral foi satisfatória para nodularidade superficial (achado anormal mais prevalente), ascite, volume hepático e esplenomegalia. Critérios frequentes, porém menos objetivos, tiveram apenas concordância leve a razoável.
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Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease. At present, standard treatment is effective in most AIH patients, and second- or third-line pharmacotherapy can be selected for patients who have suboptimal response to standard treatment or cannot tolerate the side-effects of the drugs. Novel therapies are undergoing clinical trials with the further exploration of the pathogenesis of AIH. This article reviews the current research advances in pharmacotherapy for AIH.
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Autoimmune hepatitis has become the main type of non-infectious hepatitis in China. This article summarizes its characteristic manifestations and the current status of diagnosis and treatment and points out that pathological histology plays an indispensable role in the diagnosis and treatment of autoimmune hepatitis.
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As a chronic liver inflammation disease caused by the lack of immune tolerance, autoimmune hepatitis is regulated by various signaling pathways, such as the NF-κB/NLRP3 pathway, the SIRT1/Nrf2/HO-1 pathway, the Hippo-YAP/TAZ pathway, the JAK/STAT pathway, the PI3K/Akt pathway, and the TRAF6/JNK pathway. These pathways can play a role against autoimmune hepatitis by participating in the processes including the proliferation and apoptosis of cytokines, immune response, and oxidative stress. In view of the problems of suboptimal response, obvious adverse reactions, and high recurrence rate in the clinical application of hormones and immune preparations for the treatment of autoimmune hepatitis, this article summarizes the research articles on autoimmune hepatitis-related signaling pathways and the mechanism of effective constituents (glycosides, terpenoids, flavonoids, quinones, and phenols) in traditional Chinese medicine intervening against the disease process of autoimmune hepatitis through the above signaling pathways, in order to provide a theoretical basis for scientific and effective utilization of effective constituents in traditional Chinese medicine to develop anti-autoimmune hepatitis drugs.
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Due to limited options and modalities for the etiological treatment of autoimmune liver diseases, it is urgent to seek new therapeutic methods for liver autoimmune diseases. As the most common source of cells for stem cell therapy, mesenchymal stem cells (MSCs) play an important role in regulating innate and adaptive immune responses and have been widely used in clinical trials for the treatment of autoimmune diseases and inflammatory diseases. Recent experimental and clinical studies have shown that MSCs and MSC-EVs can inhibit the activation and proliferation of a variety of liver proinflammatory cells (such as Th1, Th17, and M1 macrophages), regulate the differentiation of different subsets of T and B cells, reduce the secretion of proinflammatory cytokines, and promote the proliferation of anti-inflammatory cells, thereby playing an immunoregulatory role. This article reviews the clinical trials of MSCs and MSC-EVs in the treatment of autoimmune liver diseases and their mechanism in regulating immune function and promoting hepatocyte regeneration and briefly describes the potential application and limitations of MSCs and MSC-EVs in clinical practice.
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Objective To explore the diagnostic value of Young's modulus obtained by real-time shear wave elastography (SWE) for liver fibrosis in autoimmune hepatitis (AIH) patients. Methods A total of 75 AIH patients in the First Affiliated Hospital of Zhengzhou University from January 2013 to April 2022 were retrospectively enrolled. Scheuer scoring system was used to evaluate degrees of liver fibrosis (S0-S4). By using pathological examination of liver tissues as the golden standard, the receiver operating characteristic curve (ROC) was plotted and the area under the curve (AUC) was used to evaluate the diagnostic value of SWE for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3), and liver cirrhosis (S4), respectively. Independent sample t test was used for comparison of continuous data with normal distribution between the two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and Bonferroni method was used for further comparison between two groups. The Spearman correlation coefficient was used for correlation analysis. The logistic regression analysis was used to predict the impact factors in diagnosis accuracy. Results The Young's modulus measured by SWE was statistically significant different among various fibrosis groups ( H =35.186, P 0.05). The Young's modulus measurement was positively correlated with liver fibrosis ( r =0.675, P < 0.05). The AUCs of SWE in the diagnosis of≥S2, ≥S3, and S4 were 0.839, 0.820 and 0.898, respectively and the corresponding optimum cut-off values were 9.2, 10.9, and 14.4 kPa, respectively. The overall concordance rate of the liver Young' s modulus measurements vs . fibrosis stages was 57.33%. Moreover, the alkaline phosphatase level was an independent predictor for diagnostic accuracy of SWE for stage 0-1 fibrosis ( OR =1.009, 95% CI : 1.001-1.018, P =0.029). Conclusion The SWE possessed a diagnosis value for the significant fibrosis (≥S2), advanced liver fibrosis (≥S3) and liver cirrhosis (S4), although there was a low overall concordance rate in the liver Young's modulus measurements obtained using SWE vs. fibrosis stages.
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Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the autoimmune system attacking hepatocytes， and its chronic progression may lead to liver cirrhosis and even hepatocellular carcinoma. Currently， pharmacotherapy and liver transplantation are the main treatment methods for AIH， but both methods have their own limitations， which limits the clinical benefits of patients. Therefore， it is a critical issue to search for new therapeutic agents and methods. Recent studies have shown that mesenchymal stem cells （MSC） and their exosomes can improve the symptoms of patients with AIH by suppressing inflammatory response， enhancing the regeneration of hepatocytes， and regulating the immune system and thus have wide application prospects in the treatment of AIH. By summarizing related articles， this article reviews the possible mechanisms and application of MSC and their exosomes in the treatment of AIH， in order to provide new ideas for the clinical treatment of AIH.
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Objective:To study the characteristics and clinical significance of mitochondrial injury of T lymphocyte subsets in patients with autoimmune hepatitis (AIH).Methods:The clinical data of 57 patients with AIH (AIH group) from June to December 2021 in Hangzhou Xixi Hospital were retrospectively analyzed, while 60 healthy physical examiners were included as healthy group. The peripheral blood T lymphocyte subsets (CD 8+ T lymphocyte count and CD 4+ T lymphocyte count) were detected by flow cytometry, and matched mitochondrial staining value according to certain algorithm was used to determine the mitochondrial damage of helper T lymphocyte (Th cell) and suppressor T lymphocyte (Ts cell). The levels of IgG, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Roche E170 automatic electrochemiluminescence immunoassay. Anti-nuclear antibody (ANA) titer was measured by immunofluorescence. Multivariate Logistic regression was used to analyze the independent risk factors of mitochondrial damage of Th cell and Ts cell in patients with AIH. Results:The ALT, AST, IgG, positive rate of ANA titer, CD 4+ T lymphocyte count, CD 8+ T lymphocyte count, rate of Th cell mitochondrial injury and rate of Ts cell mitochondrial injury in AIH group were significantly higher than those in healthy group: (118.90 ± 37.61) U/L vs. (30.96 ± 14.37) U/L, (102.40 ± 36.51) U/L vs. (31.12 ± 14.06) U/L, (18.40 ± 3.71) g/L vs. (13.89 ± 1.98) g/L, 96.49% (55/57) vs. 16.67% (10/60), 438 (323, 637) × 10 6/L vs. 398 (272, 469) × 10 6/L, 296 (211, 296) × 10 6/L vs. 270 (193, 322) × 10 6/L, 61.40% (35/57) vs. 8.33% (5/60) and 82.46% (47/57) vs. 11.67% (7/60), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that the AST elevated and CD 8+ T lymphocyte count reduced were the independent risk factors of Ts cell mitochondrial injury in patients with AIH ( OR = 1.06 and 0.99, 95% CI 1.01 to 1.10 and 0.99 to 1.00, P<0.05); the ALT elevated and IgG elevated were the independent risk factors of Th cell mitochondrial injury in patients with AIH ( OR = 1.08 and 1.66, 95% CI 1.02 to 1.14 and 1.11 to 2.48, P<0.05). Conclusions:It is of positive clinical significance to measure the T lymphocyte subtype mitochondrial injury in patients with AIH. The probability of mitochondrial injury of T lymphocyte subtype can be predicted by biochemical indexes such as ALT, AST and IgG, so as to indirectly evaluate the liver cell necrosis.
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Objective:To investigate the value of liver ultrasonic elasticity index combined with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4) and globulin platelet model (GP) in the diagnosis of autoimmune hepatitis complicated with liver cirrhosis.Methods:From January 2020 to January 2022, 82 patients with autoimmune hepatitis and cirrhosis treated in West China Hospital of Sichuan University were selected as observation group, and 90 patients with autoimmune hepatitis were selected as controls (control group). All of them underwent liver ultrasound elastic examination, and the APRI, FIB-4, GP of patients were calculated. The differences of shear wave velocity (SWV), liver hardness value (LSM), strain rate ratio (SR), APRI, FIB-4, GP between the two groups were compared. At the same time, the differences of SWV, LSM, SR, APRI, FIB-4 and GP among patients with autoimmune hepatitis with different degrees of liver fibrosis and inflammation were analyzed. The value of liver ultrasound elasticity index, APRI, FIB-4 and GP in predicting autoimmune hepatitis complicated with cirrhosis was evaluated by the receiver operating characteristic (ROC) curve.Results:The SWV, LSM, FIB-4 and GP in the observation group were (1.60±0.21)m/s, (13.98±1.82)kPa, (8.10±1.43) and (4.15±1.05) respectively, which were significantly higher than those in the control group (all P<0.05), while SR and APRI were (5.04±0.98) and (2.41±0.92) respectively, which were significantly lower than those in the control group (all P<0.05). With the aggravation of liver fibrosis, the levels of SWV, LSM, FIB-4 and GP in patients with autoimmune hepatitis were higher (all P<0.05), while the SR and APRI were lower (all P<0.05). There was no statistically significant difference in SWV, LSM, SR, APRI, FIB-4 and GP between patients with G1-G2 and G3-G4 inflammatory degree of autoimmune hepatitis (all P>0.05). SWV, LSM, SR, APRI, FIB-4 and GP were included in the binary logistic regression analysis, and SWV, FIB-4 and GP were finally selected as independent predictors for diagnosis of autoimmune hepatitis with cirrhosis (all P<0.05). The area under the ROC curve of combined prediction of SWV, FIB-4 and GP for autoimmune hepatitis with cirrhosis was 0.931, which was significantly higher than other indicators (all P<0.05), and the sensitivity and specificity were 95.00% and 84.00% respectively. Conclusions:Liver ultrasonic elasticity index, APRI, FIB-4 and GP are related to the degree of liver fibrosis in patients with autoimmune hepatitis. SWV, FIB-4 combined with GP have high application value in predicting autoimmune hepatitis complicated with liver cirrhosis.
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Autoimmune liver diseases （ALD） are a group of chronic inflammatory liver diseases mediated by autoimmune response and can progress to liver fibrosis， liver cirrhosis， and even liver failure. Early diagnosis， early treatment， and dynamic follow-up of liver fibrosis in ALD may help to improve the prognosis of the disease and even reverse early-stage liver cirrhosis. Due to the limitations and potential risks of liver biopsy， the search for noninvasive techniques has become a research hotspot in the field of liver fibrosis. This article reviews the recent research advances in serum markers and imaging techniques for liver fibrosis in ALD and analyzes the advantages and disadvantages of each detection method and their development trends.
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ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.
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ABSTRACT Objective Published studies have shown associations between anti-ribosomal P (anti-P) antibody and systemic lupus erythematosus with hepatic manifestations. This has been reported also in autoimmune hepatitis. However, the consistency of the latter association remains controversial. This study aimed to evaluate the frequency of anti-P antibodies in autoimmune hepatitis using two different immunoassays. Methods One-hundred and seventy-seven patients with autoimmune hepatitis were screened, and 142 were analyzed for anti-P antibody positivity. The samples were first analyzed using two different immunoassays: enzyme-linked immunosorbent assay (ELISA) and chemiluminescence and then compared with a group of 60 patients with systemic lupus erythematous. The positive samples were subjected to western blot analysis. Results Anti-P was found in 5/142 autoimmune hepatitis cases (3.5%) by chemiluminescence and in none by ELISA. Among the five chemiluminescence-positive autoimmune hepatitis samples, on anti-P western blot analysis one was negative, two were weakly positive, and two were positive. In contrast, anti-P was detected in 10/60 patients with systemic lupus erythematosus (16.7%) and presented higher chemiluminescence units than the autoimmune hepatitis samples. Conclusion A low frequency of anti-P antibodies was observed in autoimmune hepatitis, suggesting that this test is not useful for the diagnosis or management of this disease.
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Autoimmune hepatitis (AIH) is a chronic progressive inflammatory disease of the liver caused by the attack of liver cells by the autoimmune system, with the features of positive serum autoantibodies, high IgG, and/or γ-globulinemia. Current studies on pregnancy in patients with AIH mainly focus on labor complications, and there is still a lack of systematic recommendations for the evaluation, treatment, and management of diseases in the progestational stage, during pregnancy, and after delivery. Although immunity is suppressed during pregnancy, poor disease control within one year before pregnancy and spontaneous drug withdrawal during pregnancy can significantly increase adverse pregnancy outcomes. Therefore, this article describes how to implement multidisciplinary collaboration and management of the whole cycle of pregnancy, so as to improve maternal and fetal safety.
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The imbalance of immune tolerance plays a key role in the pathogenesis of autoimmune hepatitis (AIH), and the abnormal expression of coinhibitory signal molecules for regulatory T cells (Treg) may be one of the important reasons for the destruction of autoantigen tolerance. As a coinhibitory signal molecule, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory receptor mainly expressed on Treg. This article elaborates on the immune mechanism of Treg associated with AIH and the role of TIGIT in the development, progression, and treatment of autoimmune diseases, so as to find the treatment strategy with TIGIT as the candidate target for AIH.