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Abstract Autoimmune hepatitis(AIH) is a chronic progressive inflammatory liver disease induced by loss of immune tolerance. The role of circulating metabolites in disease pathogenesis is unclear. This study aimed to investigate potential causal links between plasma metabolites and AIH risk by employing a two-sample Mendelian randomization approach. A comprehensive bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide significant variant-metabolite and variant-AIH associations in European ancestry individuals. Various methods assessed causal relationships among 1400 metabolites and AIH, incorporating sensitivity analyses to evaluate pleiotropy and heterogeneity. Fifty-eight metabolites displayed possible associations, including increased AIH risk with genetically predicted higher kynurenine (p = 2.79 × 10− 5, OR: 1.64, 95% CI 1.30–2.07) and a protective effect for the dopamine sulfate ratio (p = 1.06 × 10− 5,OR: 0.62, 95% CI 0.49–0.79). Reciprocal analysis revealed a causal effect of AIH on kynurenine( p = 2.79 × 10− 5, OR: 1.64, 95% CI 1.30–2.07), but not on the dopamine sulfate ratio(p = 0.691, OR: 1.05, 95% CI 0.67–1.64). Our genetics-based approach provides evidence supporting a causal role for specific metabolite levels in AIH risk. The results deliver evidence supporting a causal effect of a specific metabolite ratio(dopamine 4-sulfate/dopamine 3-O-sulfate) on AIH risk. Experimental validation and mechanistic examinations are warranted to confirm findings.

Autoimmune Hepatitis (AIH) is a rare autoimmune disease that damages the liver over time and, if left untreated, can progress to liver cirrhosis. Clinical manifestations range from asymptomatic patients to those with acute hepatitis or chronic liver failure. Chronic autoimmune liver disease causes persistent liver injury, which results in unresolved inflammation, proliferation of cells, and the formation of extracellular matrix proteins by stellate cells of the liver and portal myofibroblasts. Cirrhosis of the liver and the resulting loss of normal liver function are unavoidable. Cirrhotic patients have a higher risk of morbidity and mortality, and problems of portal hypertension and/or liver dysfunction result in substantial deterioration in the decompensated phase. The theory suggests that among idiopathic or cryptogenic chronic hepatitis, most of them are autoimmune in origin. It is considered one of the rare liver diseases, especially in the Indian population. Portal hypertension is a dangerous complication caused by an obstruction in portal blood flow, such as cirrhosis or portal vein thrombosis. Hepatic Haemangiomas (HH) are benign liver tumours that are made up of groups of blood-filled cavities lined by endothelial cells and fed by the hepatic artery. The vast majority of HH are asymptomatic and are discovered by chance during imaging studies for unrelated pathologies. Hereby, the authors present a case of 53-year-old female with chronic liver disease with ascites, fatty change, and nodular hepatocellular hyperplasia, which was later found to be cirrhosis of autoimmune origin.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ system in the body. It may also be complicated by other autoimmune diseases. This case report describes a patient who presented with massive splenomegaly on a background of clinical features of SLE. Splenomegaly in SLE however, is not common. The patient was evaluated further for haematological complications and liver involvement. She was diagnosed to have SLE-Autoimmune hepatitis overlap. SLE-AIH overlap syndrome is rare, but specific diagnosis is important because it influences the choice of immune-suppressants as well as long-term outcome. Liver biopsy helps clinch the diagnosis and should be encourage early in the diagnostic plan. It is also important to differentiate between the various causes of liver involvement in SLE.

The IgG4-associated autoimmune hepatitis (IgG4-AIH) is a newly proposed disease entity characterised by the accumulation of the IgG4-expressing plasma cells in the liver. Its pathophysiology and clinical significance remain unclear and have poor evidence in the paediatric population. Thus, our study aims at comparing the group of paediatric patients with classical AIH and the IgG4-AIH. We carried out a retrospective analysis of 23 children (median age 8.5 years) diagnosed with AIH, who were compared according to the presence of IgG4-positive plasma cells in the liver biopsy. IgG4-AIH was defined if 10 or more IgG4 positive plasma cells/high-power field were found in the biopsy. The presence of the IgG4 component seems to be clinically insignificant. That is why, the conventional immunosuppressive protocol should be considered the standard treatment in the case of the IgG4-associated AIH.

Background and Objectives: Juvenile autoimmune hepatitis (AIH) is an inflammatory, immune-mediated liver disease that affects individuals from infancy to adolescence. The clinical presentation of AIH can mimic other hepatic disorders, such as viral hepatitis, toxic hepatitis, and Wilson's disease, often manifesting with symptoms like fatigue, nausea, vomiting, jaundice, fever, and pruritus.Case Presentation: A 16-year-old male with a history of congenital ichthyosis, xerosis cutis, mild intermittent asthma, and environmental allergic rhinitis presented to the clinic with upper respiratory symptoms. Upon examination, the patient was found to be jaundiced, prompting an urgent referral for further evaluation. This led to a diagnosis of autoimmune hepatitis and inflammatory bowel disease.Discussion: Juvenile autoimmune hepatitis is a rare but serious inflammatory liver disorder that primarily affects infants and adolescents. Due to its similarities with various other liver diseases, differential diagnosis can be quite challenging. Overall, the prognosis for our patient appears to be positive.

Abstract Background Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases. Methods In this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases. Results Glycan traits bisection (OR: 3.78 [1.88–9.35], p-value: 5.88 × 10− 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75–5.16], p-value: 1.63 × 10− 3), IgG1 galactosylation (OR: 0.35 [0.2–0.58], p-value: 3.47 × 10− 5) and hybrid type glycans (OR: 2.73 [1.67–4.89], p-value: 2.31 × 10− 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity. Conclusions Compared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future.

Abstract Background The intricate etiology of autoimmune liver disease (AILD) involves genetic, environmental, and other factors that yet to be completely elucidated. This study comprehensively assessed the causal association between genetically predicted modifiable risk factors and AILD by employing Mendelian randomization. Methods Genetic variants associated with 29 exposure factors were obtained from genome-wide association studies (GWAS). Genetic association data with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also obtained from publicly available GWAS. Univariate and multivariate Mendelian randomization analyses were performed to identify potential risk factors for AILD. Results Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, 95%CI 1.423–1.843, P = 2.506 × 10− 13) was significantly associated with an increased risk of AIH. Genetically predicted smoking initiation (OR = 1.637, 95%CI 1.055–2.540, P = 0.028), lower coffee intake (OR = 0.359, 95%CI 0.131–0.985, P = 0.047), cholelithiasis (OR = 1.134, 95%CI 1.023–1.257, P = 0.017) and higher C-reactive protein (CRP) (OR = 1.397, 95%CI 1.094–1.784, P = 0.007) were suggestively associated with an increased risk of AIH. Genetically predicted inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127–1.303, P = 2.015 × 10− 7) and RA (OR = 1.417, 95%CI 1.193–1.683, P = 7.193 × 10− 5) were significantly associated with increased risk of PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI 1.005–1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1.086, 95%CI 1.017–1.160, P = 0.014) and higher CRP (OR = 1.199, 95%CI 1.019–1.410, P = 0.028) were suggestively associated with an increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560–0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699–0.995, P = 0.044) levels were suggestive protective factors for PBC. Genetically predicted smoking initiation (OR = 0.630, 95%CI 0.462–0.860, P = 0.004) was suggestively associated with a decreased risk of PSC. Genetically predicted IBD (OR = 1.252, 95%CI 1.164–1.346, P = 1.394 × 10− 9), RA (OR = 1.543, 95%CI 1.279–1.861, P = 5.728 × 10− 6) and lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141–0.510, P = 6.172 × 10− 5) were positively associated with an increased risk of PSC. Conclusions Evidence on the causal relationship between 29 genetically predicted modifiable risk factors and the risk of AIH, PBC, and PSC is provided by this study. These findings provide fresh perspectives on the management and prevention strategies for AILD.

This is a case of multiple autoimmune syndrome with the co-occurrence of vitiligo, pernicious anemia, celiac disease and autoimmune hepatitis is extremely rare. We are presenting a case is a 40-year-old woman with autoimmune hepatitis who is suffering from poor appetite, weight loss and skin lesions. Laboratory investigation shows hypochromic microcytic anemia, B12, and iron deficiency. The testing for parietal cell antibody was positive so pernicious anemia was diagnosed with positive Tissue transglutaminase antibody IgA so the diagnosis of celiac disease was confirmed.

Objective To investigate the impacts of wogonin (WG) on Th17/Treg cell balance in autoimmune hepatitis (AIH) rats. Methods A total of 10 rats were randomly selected as the control group. The remaining rats were injected with concanavalin A (ConA, 12.5 mg/kg) solution via tail vein to construct AIH model rat, which were randomly divided into AIH group, L-WG group (10 mg/kg), M-WG group (20 mg/kg), H-WG group (30 mg/kg), H-WG+VPA group (30 mg/kg WG+300 mg/kg Notch signal pathway activator VPA), 10 rats in each group and administered once a day for 10 days. Serum inflammatory factors and liver function indexes were detected by ELISA; HE staining was used to observe the pathological morphology of liver tissue; the level of spleen Th17/Treg cells was detected by flow cytometry; Western blot was used to detect the expression of spleen retinoid acid related orphan receptor γ t (RORγt), fork head box protein P3 (Foxp3) and liver Notch signal pathway proteins. Results The liver tissue structure of control group was normal and the staining was clear; In AIH group, the cells of liver tissue showed edema, the increase of cell volume led to the compression and narrowing of liver sinuses, and a large number of inflammatory cell infiltration and a small amount of necrosis occurred. The contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-17 and IL-23, level of Th17 cells, Th17/Treg, the expression of RORγt, Notch, hes family bHLH transcription factor 1 gene (HES1) and hes related family bHLH transcription factor with YRPW motif 1 (HEY1) protein in AIH group were greatly higher than those in control group (P＜0.05), the contents of IL-10 and TNF-β, level of Treg cells, and level of Foxp3 protein were greatly lower(P＜0.05); Compared with AIH group, the liver injury in L-WG group, M-WG group and H-WG group was improved, the contents of ALT, AST, IL-17 and IL-23, level of Th17 cells, Th17/Treg, the expression of RORγt, Notch, HES1 and HEY1 protein were greatly lower (P＜0.05), the contents of IL-10 and TNF-β, level of Treg cells, and level of Foxp3 protein were greatly higher (P＜0.05); VPA reversed the improvement effect of H-WG on AIH rats. Conclusions WG could promote Th17/Treg cell balance in AIH rats by down-regulating Notch signal pathway.

Khat is a plant that is commonly used for its stimulating effects and is chewed for its psychoactive properties. It creates feelings of euphoria that are similar to when taking amphetamines. There is an association between khat and liver injury, but the mechanism is not well known. We present three cases of khat-induced liver injury. All cases have elevated IgG and either positive antinuclear antibodies (ANA) or anti-smooth muscle antibody (ASMA); each case has a different course and requires different management. One case improved only by stopping khat, one required a short course of steroids and the last case required treatment such as that for autoimmune hepatitis (AIH).

Introduction Autoimmune hepatitis (AIH) has scarcely been reported on in patients of black African descent. Similarly, few studies have focused on the relationship between AIH and Human-Immunodeficiency Virus (HIV) infection. Aim We aim to describe the presenting features of AIH from a single referral centre in a Sub-Sahara African setting. We also compare the presenting features of HIV-infected and HIV-uninfected patients. Methods This study was a retrospective chart review. Patients were included if they fulfilled criteria for the International AIH Group simplified score for probable or definite AIH, were 18 years or older at inclusion, and attended the adult Gastroenterology clinic at Inkosi Albert Luthuli Central Hospital (IALCH) for the period 1/1/2015 to 31/12/2020 on at least 2 occasions. Results Forty cases were included, of which 33 (82.5%) were female and 33 (82.5%) were black African. Median age at diagnosis was 26 years. A diagnosis of a coexistent autoimmune disease was made in 22.5% of patients, with Systemic Lupus Erythematosus (SLE) being the most common (12.5%). Sixteen patients were HIV-infected, all of whom were female (p =0.03), with a significantly older age of disease onset as compared to their HIV-uninfected counterparts (median age 38 vs 17.5 years, p

Abstract This report described a patient not known to have a hepatic disease, found to have a drug‐induced autoimmune hepatitis from denosumab. This is an unreported side effect, and here, we presented the possible predisposing factors and suggested monitoring parameters.

Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease with various immune system manifestations, showing a global trend of increased prevalence. AIH is diagnosed through histological abnormalities, clinical manifestations, and biochemical indicators. The biochemical markers involve interfacial hepatitis, transaminase abnormalities, positive autoantibodies, etc. Although AIH pathogenesis is unclear, gene mutations and immunological factors could be the leading factors. AIH usually presents as a chronic liver disease and sometimes as acute hepatitis, making it challenging to distinguish it from drug-related hepatitis due to similar clinical symptoms. Normalizing transaminases and serum IgG levels is essential in assessing the remission status of AIH treatment. Glucocorticoids and azathioprine are the first-line AIH treatment, with lifelong maintenance therapy in some patients. The quality of life and survival can be improved after appropriate treatment. However, certain limitations jeopardize the quality of treatment, including long treatment cycles, side effects, poor patient compliance, and inability to inhibit liver fibrosis and cirrhosis. Accurate AIH animal models will help us understand the pathophysiology of the disease while providing fresh perspectives for avoiding and treating AIH. This review will help us understand AIH better, from the cellular and molecular causes to the clinical features, and will provide insight into new therapy techniques with fewer side effects.

Annually increasing quantity of liver transplants and the growing population of long-survived recipients determine the relevance of late allograft dysfunction study. Variety of morphological and functional disorders of the transplanted liver complicates their timely diagnostics. Moreover, in some patients, serious graft damage may proceed for a long time without clinical manifestations and laboratory abnormalities.The review summarizes the structure, prevalence, risk factors and prognostic value of different liver allograft pathology determined by histological examination in the long term after transplantation.

The overlap syndrome indicates an association between autoimmune hepatitis (AIH) and sclerosis cholangitis or primary biliary cholangitis (PBC). We report a case of a 32-year-old patient who experienced overlap syndrome ten days after receiving the first dose of the mRNA Coronavirus disease-2019 (COVID-19) vaccine. Liver biopsy showed primarily AIH and “overlap syndrome” for PBC. Serum IgG was elevated, and ANA (1/100) and anti-mitochondrial antibody was positive. The patient’s treatment plan included prednisolone, ursodeoxycholic acid and azathioprine. Overlap syndrome related to the mRNA COVID-19 vaccines is a very rare entity. After the histopathological diagnosis of the patient, remission was achieved following treatment.

Abstract Background Hepatocellular carcinoma (HCC) is a primary tumor of the liver. The majority of HCCs are associated most frequently with chronic B or C viral hepatitis, alcohol intake or aflatoxin exposure. Cirrhosis is a strong risk factor associated with HCC. The causes of liver cirrhosis are chronic viral hepatitis, alcohol intake, metabolic diseases (NAFLD), hemocromathosis, alfa 1 antitrypsisn deficiency. All aetiologic forms of cirrhosis are at risk to be complicated by HCC development, but the risk is higher for patients diagnosed with chronic viral hepatitis. Comparing to the above-mentioned causes, PBC and AIH are less associated with the risk of HCC development. Case summary A 71-year old Caucasian female previously diagnosed with overlap syndrome (AIH type 1 and PBC—ANA, SMA and AMA antibodies positive), liver cirrhosis, a nodule in the VI/VIIth hepatic segment, systemic sclerosis sine scleroderma, Hashimoto's thyroiditis, antiphospholipid syndrome, gastric antral vascular ectasia (GAVE) (with 2 previous sessions of argon plasma coagulation), cholecystectomy, arterial hypertension and nephro-angiosclerosis presented to the 2nd Department of Internal Medicine in Cluj-Napoca for a follow-up. The patient was following treatment with UDCA (Ursodeoxycholic acid), azathioprine, Plaquenil, calcium channel blockers, angiotensin-converting-enzyme inhibitor, calcium and vitamin D supplementation. The abdominal ultrasound showed a subcapsular hypoechoic nodule with a diameter of 29 mm (at the moment of the diagnosis the diameter was 9/10 mm) in the VI/VIIth hepatic segment. The contrast-enhanced ultrasound (CEUS) characterised the nodule as specific for hepatocellular carcinoma (LI-RADS 5). On MRI with gadoxetate disodium the nodule was hypovascular, non-specific, being classified as LI-RADS 3. An atypical resection of the VIIth hepatic segment was performed and the histohistological examination and imunohistochemistry (Hep Par-a positive, Glypican3 positive, CD34 positive) revealed a moderately differentiated hepatocellular carcinoma (G2), pT2 N0 M0 L0 V1 R0. Conclusion Autoimmune hepatitis, PBC and the overlap syndrome are less associated with the development of liver cirrhosis and HCC than other chronic liver diseases, especially if other risk factors are not associated. This case highlights the importance of a proper surveillance of cirrhotic patients every 6 months including abdominal ultrasound and AFP levels is crucial for an early diagnosis of a HCC.

Cirrhosis is a serious condition associated with progressive damage to this organ. Autoimmune hepatitis (AIH) is one of the causes leading to the development of cirrhosis. This disease is characterized by chronic inflammation with damage to hepatocytes and presence of specific immune markers. The diagnosis of AIH is based on biochemical, immunoserological and histopathological tests. There are defined diagnostic criteria, liver biopsy is important in determining the extent of the disease. Symptoms of AIH are nonspecific and include weight loss, fatigue, jaundice, abdominal pain and symptoms associated with the overactivity of an immune system. Advanced cases of AIH can lead to cirrhosis. AIH most often affects middle-aged women, although it can occur in people of any age. Epidemiological data indicate an increase in the incidence of AIH, which may be related to various environmental factors. The rate of progression of AIH to cirrhosis and depends on a number of factors. Effective treatment includes immunosuppression, mainly the use of glucocorticosteroids and azathioprine. Monitoring, healthy lifestyle and patient education are key. In severe cases, liver transplantation may be necessary.

Background and purpose: Biopsy is the standard criterion for the diagnosis of liver fibrosis, but it is not widely used for liver fibrosis monitoring due to its invasive nature, risk of complications, and sampling errors. This study aimed to evaluate the clinical significance of several noninvasive indices in diagnosis of the disease and in prediction of advanced liver fibrosis in children with autoimmune hepatitis (AIH). Materials and methods: In a prospective cross-sectional study, in 40 children with AIH, complete blood count and liver function tests were performed and their derived indices were calculated. Based on liver biopsy, all patients with AIH were divided into two groups: absent/mild fibrosis and moderate/severe fibrosis (advanced fibrosis). Results: In patients with AIH, aspartate aminotransferase to platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) increased significantly (P

Background. Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown. Aim. To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD. Materials and methods. A single-center case-control study included 139 patients with AILD: autoimmune hepatitis AIH (n=46), primary biliary cholangitis PBS (n=74), primary sclerosing cholangitis PSC (n=19). Median age 56 years, IQR 4865 years. 125 patients without liver disease control group (median age 55 years, IQR 4665 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5). Results. Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.4814.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.6335.542] and OR 2.515, 95% CI [1.2425.093]). In patients with severe liver fibrosis (F3F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0F2 [85% vs 65%; p=0.008]. Conclusion. In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.

Inflammatory tissue damage plays a role in the onset, progression, and exacerbation of various chronic autoimmune and metabolic diseases such as autoimmune hepatitis. Here we present a case of autoimmune hepatitis with liver eosinophilic infiltrate in a severe eosinophilic asthma patient who failed conventional immunosuppressive treatment and showed improvement in gastrointestinal symptoms after anti-interleukin-5 receptor treatment. Our case highlights the potential role of eosinophils in initiating or worsening liver inflammation in autoimmune liver disease. The link between eosinophilic inflammation, barrier damage, and chronic autoimmune diseases should be considered in clinical practice.

Autoimmune hepatitis (AIH) is a chronic liver disease, characterized by elevated levels of transaminases, immunoglobulin G, and positive autoantibodies. The disease course is dynamic and presents heterogeneous disease manifestations at diagnosis. This review summarizes the issues regarding the treatment and monitoring of AIH in adult patients. Glucocorticoids and azathioprine are the first line of treatment. Alternative first-line treatments include budesonide or mycophenolate mofetil (MMF). Although no randomized controlled trials have been performed, MMF, cyclosporine, tacrolimus, 6-mercaptopurine, 6-thioguanine, allopurinol, sirolimus, everolimus, infliximab, or rituximab have been attempted in patients not responding to or intolerant to first-line treatments. Most patients require life-long special monitoring, with or without maintenance treatment.

Autoimmune hepatitis (AIH) is a disorder causing chronic hepatic inflammation. Its clinical presentation is highly variable from the affected child might have only biochemical evidence of liver dysfunction or present in hepatic failure. It is important to distinguish AIH from other forms of chronic hepatitis because a high percentage of cases respond to immunosuppressive therapy. In this article, we describe the clinical presentation, biochemical and histological findings, treatment, and clinical outcome of the four children with AIH in a tertiary care center in Mumbai. Most patients with AIH have high levels of immunoglobulin. All four cases showed high serum Ig G levels and responded to oral prednisolone only. AIH should be excluded for all patients with symptoms or signs of prolonged, relapsing, or severe liver disease so that treatment can be promptly initiated and morbidity can be reduced.

Background. The recurrence of autoimmune liver diseases can lead to reduced survival of recipients and grafts.Aim. To study the incidence and impact of the recurrence of autoimmune liver diseases on graft survival; the effect of maintenance immunosuppression on the recurrence of autoimmune diseases in liver transplant recipientsMaterial and methods. Transplantation outcomes in 111 recipients (21 recipients operated on for autoimmune hepatitis, 50 recipients operated on for primary biliary cirrhosis, and 40 recipients operated on for primary sclerosing cholangitis) were analyzed retrospectively.Results. The recurrence of autoimmune hepatitis is observed in 5%, the recurrence of primary biliary cirrhosis is in 10%, and the recurrence of primary sclerosing cholangitis is in 17% of cases. Among patients with recurrence of autoimmune diseases, men accounted for 54%, while for only 31% in the subgroup of patients without relapse (p=0.004). The followup for recipients with relapse (64.5 (42.8;82.0) months) was comparable to the follow-up for recipients without relapse (46.5 (17.9;103.5) months, p=0.54). A ten-year graft survival was significantly higher in the group of recipients with recurrent autoimmune diseases compared with recipients without autoimmune diseases recurrence (p

Abstract Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. It is known that AIH originates not from the spleen but from the liver itself. Nonetheless, most details of the etiology and pathophysiology are unknown. We induced experimental murine AIH (emAIH) in NOD/Ltj mice by single administration of a replication-deficient adenovirus and performed splenectomy during late-stage disease. Biochemical disease remission occurred, which was characterized by improvement in transaminase levels. The causes of this remission included a shift in the transcriptomic signature of serum proteins toward regeneration. At the cellular level, there was a marked decrease in activated CD8+ T cells and an increase in intrahepatic regulatory T cells (Tregs). Here, intrahepatic Treg numbers correlated with biochemical remission. Notably, an imbalance in the T-cell/B-cell ratio was observed, with a disproportionate increase in total B cells. In summary, intrahepatic increases in Tregs, biochemical remission, and regeneration could be induced by splenectomy in the late stage of emAIH.

Abstract Background There is ample evidence indicating that immunosuppressive therapy or immune dysregulation in systemic lupus erythematosus increases the risk for tuberculosis. Interestingly, a few case reports suggest that tuberculosis could also be a risk factor for systemic lupus erythematosus and other autoimmune diseases. Case presentation We report the case of a 32-year-old Indian patient who was co-diagnosed with tuberculosis, systemic lupus erythematosus, and autoimmune hepatitis without any history of prior immunosuppression. This stresses the complex relationship between tuberculosis and autoimmune diseases. Conclusion Further research is warranted in this field to unfold the complex relationship between tuberculosis and systemic lupus erythematosus. It is essential to establish clear guidelines for the management of coexisting tuberculosis and systemic lupus erythematosus to promote individualized treatment.

Key Clinical Message The characteristics of liver dysfunction due to adult‐onset Still's disease are not specific. Differentiating from autoimmune hepatitis is important in deciding whether to continue corticosteroid therapy, and also in terms of management of cirrhosis and surveillance of hepatocellular carcinoma. Liver biopsy is thought to be the most important determinant for differential diagnosis.

Introduction Guillain-Barré syndrome is a polyradiculoneuropathy of autoimmune origin, considered the most frequent cause of acute flaccid paralysis. Various associations of Guillain-Barré syndrome with other non-neurological autoimmune diseases have been reported, some of them extremely rare, such as that which occurs with primary biliary cholangitis, a chronic disease of autoimmune etiology whose diagnosis is also supported by the clinical picture. , in the alteration of liver enzymes and the presence of anti-mitochondrial antibodies. Clinical case A 38-year-old male patient, with no history of previous comorbidities, who, after presenting with diarrheal disease two weeks prior, developed subacute onset ascending weakness associated with paresthesias in four extremities that progressed to quadriplegia and respiratory distress. Cerebrospinal fluid cytochemistry was performed, which showed albuminocytological dissociation and electromyography, which showed findings compatible with acute motor axonal neuropathy, for which he received treatment with intravenous immunoglobulin at 0.4g/kg/day, achieving improvement in the neurological condition. Since admission and during hospitalization, he presented persistent changes in liver enzymes which followed a cholestatic pattern, in addition to mild abdominal pain and generalized itching, for which he was evaluated by gastroenterology, who requested anti-mitochondrial antibodies that were positive. Concluding in the diagnosis of primary biliary cholangitis. Conclusion The present case shows an extremely rare association of two autoimmune diseases Guillain-Barré syndrome and primary biliary cholangitis, so much so that it represents the first case reported, not linked to SARS-CoV-2.

Abstract Yellow urticaria is a variant of urticaria that is rarely reported in the literature. It usually occurs in the setting of a chronic liver disease and reflects the accumulation of bilirubin in the skin tissues. We report a case of yellow urticaria that occurred in a 33‐year‐old female patient suffering from systemic lupus erythematosus and overlap syndrome of autoimmune hepatitis and primary biliary cholangitis revealed by a migratory pruritic yellowish urticarial eruption on the trunk and limbs. Yellow urticaria may be an important clue to previously unknown liver or biliary disease as it generally occurs in the setting of hyperbilirubinemia.

Over the past two years, the entire medical community has taken up the fight against the new coronavirus infection. At the initial encounter with COVID-19, it seemed that this virus mainly affects the respiratory system. Still, with long-term observation, it turned out that the consequences of this disease can be much more severe and associated with lung damage and thromboembolic complications, and be a trigger for autoimmune diseases. According to the literature, after suffering COVID-19, some patients debuted systemic lupus erythematosus, hemolytic anemia, thrombocytopenia, developed GuillainBarr syndrome, vasculitis, and multiple sclerosis, and a case of autoimmune hepatitis (AIH) was described in foreign literature. AIH is a fairly rare disease, the prevalence of which in Europe is 1618 cases per 100 thousand inhabitants, affecting mainly women. It is known that chemicals and drugs (minocycline, diclofenac, methyldopa, infliximab, etanercept), viruses (HAV, HEV, EBV, HCV, CMV), environmental factors can serve as triggers of the autoimmune process in the liver. This article presents two clinical cases of AIH that developed after suffering a new coronavirus infection, which we consider as the initial provoking factor of autoimmune inflammation. Given the rarity of AIH, the description of new triggers is of clinical interest. It may be useful for doctors of different specialties since they faced drug-induced liver damage against the background of antiviral and immunobiological therapy. In the domestic literature, there have not yet been any publications devoted to the debut of AIH in adults after coronavirus infection.

Abstract Background and Aims Patients with pediatric‐onset primary sclerosing cholangitis (PSC) are at risk of developing hepatic complications with liver transplantation as only curative treatment. Complications usually occur over many years, underlining the need for reliable surrogate markers to predict the clinical course. Recently, gamma‐glutamyl transferase (GGT) has been suggested to allow prediction of the clinical course. In a single‐center cohort study, we tested the potency of GGT in this respect. Methods We used longitudinal data of patients from our academic center, diagnosed with pediatric‐onset PSC between 2000 and 2020. Patients with a GGT decrease from baseline >25% (n = 36) were compared with those who did not have this decrease (n = 7). We performed Kaplan–Meier analysis and log‐rank testing to assess the occurrence of portal hypertensive or biliary complications, hepatobiliary malignancies, liver transplantation, or death. Results The median age diagnosis was 15.2 years and 12.1 years in the group with ≤25% decrease of GGT and the group with >25% decrease, respectively (p = 0.078). The probability of developing ≥1 complications in the first 5 years after diagnosis was 50% in the group with ≤25% decrease of GGT and 20% in the group with >25% decrease of GGT (p = 0.031). The use of medication was not associated with the development of complications. Conclusion In a retrospective cohort study, we report that a GGT decrease of >25% within 1 year of diagnosis of pediatric‐onset PSC is associated with a lower occurrence of complications within 5 years. Our results provide further support for the recently hypothesized predictive value of first‐year GGT change in predicting the disease course in pediatric‐onset PSC.

Background Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. At present, it is largely unknown how the innate immune cells influence AIH development. Objective To inquiry about mechanism of liver resident macrophages in AIH development, thus offering a new direction for AIH targeted treatment. Methods The liver resident macrophages were eliminated by clodronate liposomes in AIH liver tissues, followed by HE and Picrosirius assay to detect liver fibrosis and lymphocyte infiltration. The liver resident macrophages polarization was detected by Immunohistochemistry and qPCR. The collagenase digestion was used to isolate Kupffer cells from AIH mice liver tissues and pro-/anti-inflammatory cytokines were determined by qPCR. Results M2 macrophages were the dominant phenotype at early immune response stage and hepatic inflammation was progressively aggravated after depletion of liver resident macrophages. M2 macrophages could effectively delay the development of AIH and could be polarized to M1 macrophages at the disease progresses. TLR2 ligands could promote M2 macrophages producing anti-inflammatory cytokines, whereas TLR4 ligands could promote M1 macrophages producing proinflammatory cytokines. The change of TLR2 and TLR4 ligands could lead to continuous high expression of TLR4 and decreased expression of TLR2 in macrophages to further affect liver resident macrophages polarization state. Conclusion TLR2 and TLR4 ligands mediated liver resident macrophages polarization to favor chronic autoimmune hepatitis development.

Abstract Background Autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome is a form of autoimmune hepatitis with cholestatic features and is characterized by negative anti-mitochondrial antibody and cholangiographic changes on magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. Peripheral blood hypereosinophilia in conjunction with autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome has not been reported yet. Here we present a case of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome with hypereosinophilia. Case presentation A 33-year-old Iranian man with the fatigue, jaundice, elevated liver enzymes and alkaline phosphatase, and hypereosinophilia was referred to our hospital. Viral and autoimmune hepatitis were excluded, and secondary workups for hypereosinophilia were all negative. Magnetic resonance cholangiopancreatography showed beaded appearance of intra- and extrahepatic biliary tree, and liver biopsy revealed interface hepatitis. Therefore, the diagnosis of autoimmune hepatitis–primary sclerosing cholangitis overlap syndrome was made, and prednisolone, azathioprine, and ursodeoxycholic acid was initiated. His jaundice and peripheral blood eosinophilia resolved after 2 weeks, and he became completely asymptomatic. Conclusion Eosinophils might contribute to the clinical presentation and disease complications.

Abstract We present a case of a 47‐year‐old female patient with a history of diagnosed Kikuchi disease and autoimmune hepatitis 13 years ago who presented with recurrent fevers and a desquamative rash on the lower extremities. Computed tomography neck showed enlarged lymph nodes, and with her daily fevers and skin rashes the presentation was concerning for recurrence of her Kikuchi disease. The patient was also found to have an elevated anti‐smooth muscle antibody titer, and subsequent liver biopsy confirmed the diagnosis of autoimmune hepatitis. She was started on methylprednisolone with improvement. Our case emphasizes the association of Kikuchi disease with autoimmune conditions other than systemic lupus erythematosus. Given the recurrence of the disease after a decade of quiescence, long‐term follow‐up of patients with Kikuchi disease should be implemented.

Abstract Paris criteria remain practical for retaining the diagnosis of overlap syndrome. While liver histology is mandatory, its absence should not be an obstacle to the diagnosis and delay the initiation of treatment in countries where biopsy not available.

Autoimmune hepatitis (AIH) is an inflammatory liver disease wherein the body’s immune system instigates an attack on the liver, causing inflammation and hepatic impairment. This disease usually manifests in genetically predisposed individuals and is triggered by stimuli or environments such as viral infections, environmental toxins, and drugs. The causal role of COVID-19 vaccination in AIH remains uncertain. This review of 39 cases of vaccine-related AIH indicates that female patients above the age of 50 years or those with potential AIH risk factors may be susceptible to vaccine-related AIH, and the clinical features of vaccine-associated AIH are similar to those of idiopathic AIH. These features commonly manifest in patients after the first dose of vaccination, with symptom onset typically delayed by 10–14 days. The incidence of underlying liver disease in patients with potential health conditions associated to liver disease is similar to that of patients without preexisting illnesses. Steroid administration is effective in treating vaccine-related AIH-susceptible patients, with most patients experiencing improvement in their clinical symptoms. However, care should be taken to prevent bacterial infections during drug administration. Furthermore, the possible pathogenic mechanisms of vaccine-associated AIH are discussed to offer potential ideas for vaccine development and enhancement. Although the incidence of vaccine-related AIH is rare, individuals should not be deterred from receiving the COVID-19 vaccine, as the benefits of vaccination significantly outweigh the risks.

Abstract Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease with autoimmune features. It mainly affects middle-aged women. AIH is occasionally complicated with liver cirrhosis that worsens the prognosis. Genetic and environmental factors are involved in the pathogenesis of AIH. Genetic studies of other diseases have been revealing of pathogenesis and drug efficacy. In this review, we summarize the genetic risk factors for AIH, including human leukocyte antigen (HLA) and non-HLA genes. A genome-wide association study (GWAS) on European AIH revealed the strongest associations to be with single nucleotide variants (SNVs) in HLA. Predisposing alleles for AIH were DRB1*03:01 and DRB1*04:01 in Europeans; DRB1*04:04, DRB1*04:05, and DRB1*13:01 in Latin Americans; and DRB1*04:01 and DRB1*04:05 in Japanese. Other risk SNVs in non-HLA genes for AIH were found by a candidate gene approach, but several SNVs were confirmed in replication studies. Some genetic factors of AIH overlapped with those of other autoimmune diseases. Larger-scale GWASs of other ethnic groups are required. The results of genetic studies might provide an explanation for the phenotypic heterogeneity of AIH and biomarkers for drug responses.

Giriş: Bu çalışma trombosit parametreleri ve diğer biyokimyasal değerlerin otoimmün hepatit (OH) hastalarında karaciğer hasarının değerlendirilmesinde prediktif bir parametre olarak kullanılabilirliğini değerlendirmek amacıyla yapıldı. Gereç ve Yöntemler: Gastroenteroloji kliniğimizde OH hastalarının histolojik bulguları laboratuvar ve klinik parametreleri üzerinden retrospektif kesitsel tipte tanımlayıcı ve metodolojik bir çalışma planladık. Skorlama sınıflamasıyla yapılan değerlendirmeye göre, 0 ile 12 arasında histolojik aktivite indeksi (HAI) olan hastalar düşük aktivite, 13 ile 18 arasında HAI olan hastalar yüksek aktivite olarak tanımlandı. Fibrozis skoru 0-2 olan hastalar erken fibrozis, fibrozis skoru 3 ile 6 arasında olanlar ileri fibrozis olarak tanımlanmış ve buna göre karşılaştırmalar yapılmıştır. Bulgular: Otoimmün hepatitli hastalarda HAI skoru yüksek aktivite gösteren grupta ortalama trombosit hacmi (MPV) düzeyleri düşük aktivite gösteren gruba göre daha yüksek saptanmıştır (p=0,013). Otoimmün hepatitli hastalarda fibrozis sınıfları arasında MPV düzeyleri açısından istatistiksel olarak anlamlı bir fark saptanmıştır (p=0,034). Otoimmün hepatitli hastalarda HAI sınıflamasında yüksek aktivite ve fibrozis sınıflamasına göre ileri fibrozis düzeyinde olan hastaları ayırt etmede MPV ölçümlerinin ROC eğrisi altında kalan alan değerleri, sensitivite ve spesifitesi incelendiğinde istatistiksel olarak anlamlı olduğu saptanmıştır. Tartışma: Otoimmün hepatitli hastalarda MPV değerlerinin HAI sınıflamasına göre yüksek aktivite gösteren grup ile karşılaştırıldığında pozitif korelasyon saptanmıştır. Otoimmün hepatitli hastalarda MPV değerlerinin fibrozis sınıflamasına göre ileri fibrozis gösteren grup ile karşılaştırıldığında pozitif korelasyon saptanmıştır.

Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.

Abstract Omeprazole is a rare cause of DILI with autoimmune hepatitis features and should be considered when seeing patients with acute liver injury. The causative drug should be promptly identified and discontinued to avoid any permanent liver damage.

Girls and women make up 75% of patients with autoimmune hepatitis (AIH). The peak incidence of AIH occurs in childhood, when the disease is called juvenile AIH. The objective: to determine the features of the functional state of the pituitary-gonadal system of neuroendocrine regulation in adolescent girls with AIH. Material and methods. During 2010-2020, 66 girls of the main group AIH, patients with AIH, and 180 conditionally somatically and gynecologically healthy girls of the control group K at the age of 12-17 years were under observation. Comprehensive examination included history taking, assessment of sexual development, clinical and biochemical blood tests, determination of autoantibodies, markers of viral hepatitis, ultrasound examination of the abdominal cavity, liver biopsy (in main group). Peripheral serum hormone levels were determined in certain age groups (12, 13, 14, 15, 16 and 17 years): luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), estradiol (E2), progesterone (P4), free testosterone (fT). Results. Against the background of disorders of morphofunctional properties of the liver in 12-, 13-, 14- 15-, 16- and 17-year-old girls with AIH noted a significant decrease in the score of sexual development in all age groups compared to the same indicator in the relevant age control groups: 3.21 ± 0.40 vs. 4.94 ± 0.37, 3.46 ± 1.00 vs. 7.91 ± 0.58, 7.03 ± 1.44 vs. 11.08 ± 0.25, 7.80 ± 0.65 vs. 11.86, 10.65 ± 0.79 vs. 11.98 points. The average total level of LH in the Group AIHwas 3.77 ± 0.25 against 4.46 ± 0.10 mIU / ml in group K (p2– 124,15 ± 2.39 vs. 437.45 ± 9.59 pmol / ml (p4– 1.49 ± 0.09 vs. 2.78 ± 0.08 nmol / ml (p3– 3.50 ± 0.06 vs. 5.46 ± 0.07 pmol / l (p4– 12.54 ± 0.44 vs. 18.55 ± 0.20 pmol / l (pConclusions. In adolescent girls with AIH on the background of disorders of morphofunctional properties of the liver there is a delayed start of the hypothalamic-pituitary-gonadal system and suppression of hormone-producing function of the pituitary-gonadal link of the neuroendocrine system.

Autoimmune hepatitis (AIH) is a rare immune-mediated chronic disease that, when inadequately treated, leads to progressive liver damage, which in turn leads to cirrhosis, liver failure, or death. Features of physical and sexual development of girls with AIH at puberty are little studied. The objective: to determine the characteristics of physical and sexual development of girls with autoimmune hepatitis in puberty period. Materials and methods. A comprehensive clinical and paraclinical examination of 66 adolescent girls of the group AIH with autoimmune hepatitis and 180 conditionally somatically healthy girls of the control group aged 12-17 years was performed. The examination included clinical and anamnestic data, anthropometry, biochemical examination of liver function, determination of serum autoantibodies, markers of viral hepatitis, ultrasound and elastography of the hepatobiliary system, liver biopsy followed by histological examination of biopsy, assessment. Results. Age-related changes in body length and body weight, chest circumference, waist and hips among girls with AIH were characterized by a significant lag at all stages of pubertal development. In patients with AIH, the onset of pubertal development was manifested by the development of mammary glands to the stage of Mal in 43.94% of girls, the previous appearance of puberty to thelarchein 34.85% of patients, and in 21.21% of patients noted simultaneous puberty and thelarche. Delayed development of sexual characteristics was manifested in 12-, 13- 14-, 15-, 16- and 17-year-old girls with AIH by a decrease in the score of sexual development in all age categories compared to the same indicator in the respective age control groups: respectively 3.21 ± 0.40 vs 4.94 ± 0.37 points, 3.46 ± 1.00 vs 7.91 ± 0.58, 7.03 ± 1.44 vs 11.08 ± 0.25, 7.80 ± 0, 65 vs 11.86, 10.65 ± 0.79 vs 11.98. In the examined girls with AIH during puberty, such disorders of menstrual function were noted as: primary amenorrhea in 7.58% of cases, secondary amenorrhea – in 6.06%, oligomenorrhea – in 27.27%, opsomenorrhea– in 27.27%, juvenile uterine bleeding – in 9.09%, dysmenorrhea – in 31.82%, a combination of various disorders – in 18.18%. Conclusions. The presence of antinuclear antibodies, antibodies to microsomes of the liver and kidneys type 1, antibodies to smooth muscle, disorders of enzymatic, protein-forming, antitoxic, cytolytic activity of the liver in girls with autoimmune hepatitis is accompanied during puberty by a high frequency of abnormalities. formation of inverted puberty, delayed sexual development and delayed onset of menarche for 10-11 months, frequent menstrual disorders.

Abstract Background Autoimmune hepatitis (AIH) is a liver disease characterized by the autoimmune-induced injury of hepatocytes which can lead to cirrhosis and hepatic failure. The diagnosis and disease management of AIH patients remain challenging due to the diversity of clinical phenotypes and the presence of confounders such as alcohol and viruses. Recently, EN-RAGE and sRAGEs have been implicated in inflammatory-immune response. Nonetheless, their natural behaviour and relationship to disease activity as well as clinical predictive values in AIH development or therapy-induced remission have not been reported. Methods Sixty-seven AIH patients and thirty gender- and age-matched healthy controls (HC) were enrolled. The serum concentrations of EN-RAGE, sRAGE and their ratio (EN-RAGE/sRAGE) in these subjects were measured by ELISA. Besides, the correlations of three parameters with clinical features and therapeutic response were analyzed, respectively. Furthermore, their potential predictive values for monitoring the AIH progression and therapeutic response were also evaluated. Results Higher serum EN-RAGE, lower sRAGE and higher EN-RAGE/sRAGE value were observed in AIH patients. EN-RAGE and sRAGE as well as EN-RAGE/sRAGE were correlated with liver necroinflammation parameters, cirrhosis occurrence and therapeutic response. In addition, we identified that EN-RAGE/sRAGE, EN-RAGE and sRAGE had valuable predicting power for AIH patients, AIH patients with normal ALT and cirrhosis incidence, respectively. More importantly, EN-RAGE/sRAGE also exerted predicting power for the remission in AIH patients. Conclusions AIH patients rendered distinct patterns of serum EN-RAGE, sRAGE or EN-RAGE/sRAGE compared to healthy controls. Moreover, these three parameters exhibited potentials as novel biomarkers for AIH diagnosis and prognosis evaluation.

Autoimmune hepatitis may be frequently associated with chronic hepatitis C (HCV) infection, but there are few case reports regarding hepatitis B and Delta infection (HBV+HDV) as possible triggers. In this report, we present a 44 years old man who was diagnosed as autoimmune hepatitis (AIH) following the treatment of HBV+HDV hepatitis with pegylated interferon (PegIFN). He presented with complaint of fatigue. Laboratory indicated elevated liver enzymes, AST 64 IU/L and ALT 112 IU/L. The results revealed HBsAg and anti-delta antibody positivity. HBV-DNA was

Vitamin D undergoes important biotransformation and inactivation in the liver. Because vitamin D is metabolized in the liver, abnormal vitamin D metabolism can be expected to be associated with chronic liver disease, including autoimmune hepatitis (AIH). The prevalence of vitamin D deficiency in puberty was the justification for the objective of the study– to determine the characteristics of vitamin D supply in girls of puberty age with AIH with autoimmune hepatitis during this period. Materials and methods. To solve this goal, a comprehensive clinical and paraclinical examination of 66 girls withAIH and 180 relatively healthy girls of the control group aged 12-17 years. The complex included clinical and anamnestic data, biochemical study of liver function, determination of serum autoantibodies and markers of viral hepatitis, the level of 25- (OH) D in blood serum, ultrasound and elastography of the hepatobiliary system organs, liver biopsy. Results. The mean level of vitamin 25 (OH) D in the serum of girls with AIH of pubertal age was 17.14 ± 1.06 vs. 23.27 ± 0.53 ng / ml in the control (p 9 points, the share of patients with vitamin D deficiency was 79.41% compared with 53.13% of cases among girls with AIH, where the histological activity index was 2=5.13; pConclusions. Cytolysis, cholestasis, mesenchymal-inflammatory syndrome, hepatocellular insufficiency in AIH in girls of puberty agedevelops against the background of reduced vitamin D supply, which depends on the histological activity of the disease.

Introduction:Autoimmune hepatitis (AIH) is a form of chronic hepatitis of unknown etiology characterized by autoimmunological properties and circulating autoantibodies. It can be treated after early diagnosis and often requires a great effort during diagnosis and regular follow-up. In Turkey, the number of studies examining AIH patients from the point of diagnosis to treatment is very low. We retrospectively evaluated patients diagnosed with AIH in the last 10 years.Methods:Between 2009 and 2019, AIH patients who were diagnosed in our hospital or applied for ongoing treatment were evaluated retrospectively from the hospital information system. Patients who responded were invited to the clinic and missing data were added.Results:A total of 48 patients (10 males and 38 females) aged 18-73 years (44.8±14.8 years) were evaluated. Four patients (8.3%) were asymptomatic. In the pre-treatment evaluation, cirrhosis occurred in 31% of patients, acute hepatitis in 21% of patients, and chronic hepatitis in 39% of patients. Type 1 AIH was observed in 81.2% of patients, 4.2% had type 2 AIH, and 14.6% demonstrated autoantibody negative AIH. A total of 35.4% of patients (n=17) had overlap syndrome accompanied by biliary tract damage. A total of 68.8% of patients with type 1 AIH had antinuclear antibody, 41.7% were positive for anti-smooth muscle antibody, and 31.3% were positive for both autoantibodies. A total of 33.3% of patients had non-hepatic disease. The treatment response rates were: 68.8% (complete); 18.7% (partial); and 12.5% (non-responders). Of the patients with a mean follow up of 3.54±2.63 years, 37 patients continued the treatment.Conclusion:Our data demonstrated similar findings to previously published literature in terms of the ratio of female-to-male presentation, type 1, type 2 rates, rate of concomitant non-hepatic autoimmune disease, and response to treatment. They were different in terms of the low number of asymptomatic patients, lower percentage autoantibodies, and high proportion of overlap syndrome.

Abstract Background The prevalence of autoimmune hepatitis (AIH) is increasing, and its early clinical diagnosis is difficult. The pathogenesis of AIH remains unclear, and AIH-related studies are largely limited because of lack of suitable mouse models. Methods To obtain a good tool for research on AIH, we first established an improved immune-mediated mouse model that can mimic the pathological process of AIH as in the human body, through repeated injections of human cytochrome P450 2D6 (CYP2D6) plasmid. Next, a proteomic analysis based on isobaric tag (IBT) technology was performed to detect the differentially expressed proteins (DEPs), and related biological functions and pathways in the plasma of AIH and normal mice. Finally, we performed enzyme-linked immunosorbent assay (ELISA) to further confirm the most abundant DEP in the plasma of patients with AIH. Results Autoantibodies and the characteristic pathology of AIH were observed in our mouse model. Inflammatory infiltration also increased in the livers of AIH mice over time and plateaued by day 42 post the first injection. Chronic hepatitis was most severe on day 35 with the development of fibrosis as well, and the plasma of AIH mice were collected for proteomic analysis. A total of 176 DEPs were found in this experiment, of which 148 DEPs were up-regulated and 28 DEPs were down-regulated. Thirty significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (P

Diffuse liver disease can have a pronounced detrimental effect on the developing reproductive system. Hepatoprotection in gynecological practice is not so much in the choice of drugs that protect or restore the liver, as in the appointment of optimal safe therapy for this category of patients, especially in adolescence. The aim: to study the effectiveness of therapeutic and prophylactic drugs for disorders of the reproductive system in adolescent girls with diffuse liver disease. Material and methods. Under observation for the period 2010-2020 were 486 girls aged 12-17 years, of which 120 - with chronic viral hepatitis (CVH), 120 - with non-alcoholic fatty liver disease (NAFLD), 66 - with autoimmune hepatitis (AIH), 180 - conditionally somatically and gynecologically healthy girls with normal sexual development of the control group. All patients underwent general clinical, hepatological examination, determination of features of neuroendocrine status, sexual development. The author proposed a differentiated method of treatment and prevention measures to restore reproductive health in adolescents with chronic diffuse liver disease, which included the appointment of vitamin D, phytocompositions, vitamin-mineral complexes with myo-inositol, if necessary - hormonal hemostasis. Results. Against the background of improved neuroendocrine status in the examined girls there was a decrease in the number of cases of amenorrhea in the group with CVH from 5.00% to 0.00% (p Conclusions. The applied personalized treatment-and-prophylactic measures taking into account individual disorders of neuroendocrine status and menstrual health in adolescent girls with diffuse liver diseases are effective and allow to recommend this complex as a means of treatment and prevention of reproductive disorders.

Novel treatments for autoimmune hepatitis (AIH) are highly demanded due to the limitations of existing therapeutic agents. Costunolide is a promising candidate due to its anti-inflammatory and hepatoprotective function, but its effect in AIH remains obscure. In this study, we integrated network pharmacology and experimental validation to reveal the effect and mechanism of costunolide in AIH. A total of 73 common targets of costunolide and AIH were obtained from databases. Pathway enrichment analysis indicated that PI3K-AKT pathway was the core pathway of costunolide in AIH. Protein–protein interaction network analysis and molecular docking revealed that SRC and IGF1R might play critical roles. In two murine AIH models, costunolide significantly attenuated liver injury, inflammation, and fibrosis reflected by the liver gross appearance, serum transaminases, necrosis area, spleen index, immune cell infiltration, and collagen deposition. Western blot and immunohistochemistry confirmed that phosphorylated AKT, SRC, and IGF1R were upregulated in AIH models, and costunolide administration could inhibit the phosphorylation of these proteins. In summary, costunolide significantly ameliorates murine AIH. The therapeutic effect might work by suppressing the activation of PI3K-AKT pathway and inhibiting the phosphorylation of SRC and IGF1R. Our research reveals the potent therapeutic effect of costunolide in AIH and the potential role of SRC and IGF1R in AIH for the first time, which may further contribute to the novel drug development for AIH and other autoimmune diseases.

Summary: The study of the role of the spleen in the pathogenesis of liver cirrhosis is important for treatment. Currently available literature data indicate the role of altered spleen functions in the pathogenesis of liver cirrhosis. The aim of this study was to clarify the features of the etiology and pathogenetic disorders in patients with hepatosplenomegaly. Materials and methods. We investigated the uniform elements of blood and blood serum from 58 patients with hepatosplenomegaly amid cirrhosis, portal hypertension complicated. Patients were divided into two groups depending on the antigenic load: I - patients with liver cirrhosis against the background of hepatitis viruses HBV/HCV and II - patients with autoimmune hepatitis against the background of herpes viruses CMV/VEB. Treatment of patients included the use of antiherpetic immunoglobulins and hematopoietic cord blood progenitor cells. Results. In patients of group I was detected an increase in the spontaneous oxidative activity of neutrophils and depletion of the oxidative reserve in oxygen-dependent phagocytosis. It activated the signaling pathways of pro-inflammatory cytokines IL-6 (an increase of 60 times). We found an increased content of CD22+ -plasma B-lymphocyte that elevated synthesized concentrations of IgA. In patients of group II were found an increase in the activity of C3 and a decrease in the C4-components of complement; thrombocytopenia due to the presence of platelet autoantibodies; increased synthesis of immunoglobulins IgM, IgG, increased synthesis of IFN-. All patients showed disturbances in the metabolism of amino acids in various metabolic cycles - ornithine, which disrupted the formation of urea and indicates the accumulation of ammonia, which can enhance the cytotoxic effect in group I; methionine with a violation of the formation of cystine from cysteine and the accumulation of homocysteine, which enhances the synthesis of IFN-γ, which was increased in group II by 4 times. Conclusions. Some etiological and pathogenetic features of the formation of liver cirrhosis complicated by portal hypertension and recurrent bleeding from varicose veins of the esophagus were revealed. The immunological and metabolic changes verified by us correlated with the disappearance of the clinical manifestations of the disease, improved well-being, and the absence of recurrence of bleeding.

Background: There is an increasing number of liver injury cases resembling autoimmune hepatitis (AIH) following SARS-CoV-2 vaccination; however, an association has not yet been established. Methods/Materials: A literature review was performed to identify articles regarding the association of AIH with vaccination, emphasizing on SARS-CoV-2 vaccines, and the proposed mechanisms. We then performed a literature search for AIH-like cases following SARS-CoV-2 vaccination, and we evaluated the included cases for AIH diagnosis using simplified diagnostic criteria (SDC), and for vaccination causality using the Naranjo score for adverse drug reactions. Results: We identified 51 AIH-like cases following SARS-CoV-2 vaccination. Forty cases (80%) were characterized as “probable”, “at least probable”, or “definite” for AIH diagnosis according to SDC. Forty cases (78.4%) were characterized as “probable”, four (7.8%) as “possible”, and three (5.8%) as “definite” for vaccine-related AIH according to the Naranjo score. Conclusion: SARS-CoV-2 vaccine-related AIH carries several phenotypes and, although most cases resolve, immunosuppressive therapy seems to be necessary. Early diagnosis is mandatory and should be considered in any patient with acute or chronic hepatitis after SARS-CoV-2 vaccination, especially in those with pre-existing liver disease.