Humans ; Child ; Immunoglobulin G ; Autoimmune Diseases ; Hepatitis, Autoimmune ; Pancreatic Diseases ; Pancreatic Neoplasms

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells

Background: There is a dearth of data on Filipino patients with autoimmune hepatitis (AIH). We aimed to describe the demographic and clinical profiles of patients with AIH and to characterize clinical outcomes and treatment responses. Methods: A retrospective cohort study involving patients from two tertiary centers diagnosed with AIH from January 1, 2007, to December 31, 2019, was included. Disease remission was defined as the normalization of ALT levels, while failure was defined as an increase in ALT levels over baseline or clinical deterioration. Results: A total of 48 patients were identified between 2007 to 2019. The median age at presentation was 51 (27-79 yrs.). Liver cirrhosis was already present in 37.5% (27.1% decompensated) on diagnosis. Aside from a higher histologic activity index in females (p=0.047), there were no gender-specific differences. Disease remission was achieved in 41.9% of patients at 6 months, while only 9.3% failed. At the final disposition, remission rates had slightly increased to 58%, but failure rates had risen to 12%. Treatment responses at both 6 and 12 months and MELD and Child-Pugh class influenced treatment responses at final disposition. Median overall survival was 102 weeks and was influenced by the presence of liver dysfunction and 12 months and final treatment responses. Conclusion Autoimmune hepatitis remains an important cause of morbidity and mortality. The results of the study highlight the need for immunosuppressive therapy to induce early remission for a higher likelihood of subsequent biochemical remission to reduce the risk of liver-related mortality.
Autoimmune Hepatitis ; Liver Cirrhosis ; Steroids ; Azathioprine

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.
Female ; Humans ; Child ; Glucocorticoids ; Retrospective Studies ; Hepatitis, Autoimmune/drug therapy* ; Alanine Transaminase ; Osteomyelitis/drug therapy*

Objective: To analyze the clinical features and prognosis of acute severe autoimmune hepatitis (AIH). Methods: A retrospective analysis of the clinical data of patients with acute severe AIH admitted to our hospital from 2008 to 2019 was divided into acute AIH (A-AIH) and chronic acute AIH (AC-AIH) according to the presence or absence of liver diseases. Patients' general condition, liver biochemistry, immunology, histological features of liver, hormonal therapies prognosis and related factors were analyzed. Results: A total of 41 cases [39 females, age (54.24 ± 10.55) years] were collected. Alanine aminotransferase (ALT) and total bilirubin (TBil) were significantly increased, and the international normalized ratio (INR) was > 1.5. Acute lobular inflammation was the feature of acute and severe AIH in the histology of liver. The serum IgG level was (28.36 ± 8.35) g / L. The positive rate of antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA) was 82.9%, and 17.1%, respectively. Over 70% of acute severe AIHs were AC-AIH. The duration of onset of AC-AIH was > 8 weeks, while most A-AIHs < 8 weeks, and the differences between the two groups were statistically significant (P = 0.001). The mortality rate within 30 days after hormonal treatment was 19.5%. There were statistically significant differences in TBil, Model for End-Stage Liver Disease (MELD) score and leukocyte count between the death and survival group. Conclusion: The mortality rate in acute severe AIH is high, and most of them have the basis of chronic liver disease. Serum IgG level, autoantibodies and acute lobular inflammation are important factors for diagnosis. The prognosis of hormonal therapy is related to the patients' condition and course of disease.
Adult ; Autoantibodies ; End Stage Liver Disease ; Female ; Hepatitis, Autoimmune/diagnosis* ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index

In recent years, the number of autoimmune hepatitis cases in the world has shown a significant upward trend, but its etiology and pathogenesis is still unclear. At present, it is generally considered to be caused by abnormal immune regulation mechanism of the body, especially the lymphocytes and their cytokines, which has attracted widespread concern and thus is reviewed here.
Cytokines ; Hepatitis, Autoimmune ; Humans ; Lymphocytes

As a secondary endocrine organ, the liver is closely related to the endocrine system. Liver involvement is not uncommon in endocrine diseases, such as hyper/hypothyroidism, diabetes, dysfunction of adrenal and gonadal. It can be manifested in a variety of forms, including hepatocyte injury (elevated transaminase), bile duct injury (cholestasis), hepatocyte steatosis, vascular injury and liver tumor. Direct and indirect liver injury caused by abnormal hormone levels and side effects of drugs for the treatment of endocrine diseases are common pathogenesis. In addition, endocrine diseases can be concomitant with liver diseases, such as autoimmune thyroiditis and autoimmune hepatitis. Systemic diseases can also involve the endocrine system and liver at the same time, such as systemic lupus erythematosus and IgG4 related diseases. For patients with unexplained liver injury, endocrine system diseases should be considered as the differential diagnosis.
Cholestasis/pathology* ; Endocrine System Diseases/pathology* ; Hepatitis, Autoimmune/pathology* ; Humans ; Liver/pathology* ; Liver Diseases/pathology*

Hepatitis, Autoimmune ; Humans ; Liver Failure ; Prognosis

Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine. Physical examination showed generalized icterus and splenomegaly. The laboratory findings suggested warm-type AHA with cholestatic hepatitis. Liver biopsy revealed giant cell transformation of hepatocytes and moderate lobular inflammation. The patient was successfully treated with four doses of rituximab. Early relapse of hemolytic anemia and hepatitis was observed, which prompted the use of an additional salvage dose of rituximab. He is currently in clinical remission.
Anemia, Hemolytic ; Anemia, Hemolytic, Autoimmune ; Biopsy ; Giant Cells ; Hepatitis ; Hepatocytes ; Humans ; Infant ; Inflammation ; Jaundice ; Liver ; Liver Diseases ; Male ; Pallor ; Physical Examination ; Rare Diseases ; Recurrence ; Rituximab ; Splenomegaly

autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.]]>
Diagnosis ; Flow Cytometry ; Hepatitis A ; Hepatitis ; Hepatitis, Autoimmune ; Humans ; Inflammation Mediators ; Liver Failure ; Liver Transplantation ; Necrosis ; T-Lymphocytes, Regulatory