Diagnosis Of Autoimmune Hepatitis Research Articles

The etiology and differential diagnosis of “autoimmune hepatitis-like liver disease” in children: a single-center retrospective study

BackgroundChildren with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance.MethodsAll children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups.ResultsA total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05).ConclusionPositive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

Histopathology and its clinical correlation of liver biopsy in patients with treated autoimmune hepatitis

The diagnosis of autoimmune hepatitis (AIH) relies on well-established criteria encompassing histological, serological, and clinical features. Diagnosing AIH may become challenging when encountering patients who have undergone steroid therapy for other co-existing diseases. Thirty-nine liver biopsies from 25 patients with treated and untreated AIH were classified into three groups: 1) Newly diagnosed untreated biopsies (n = 16); 2) Newly diagnosed partially treated biopsies from patients already on steroid treatment for other co-existing diseases (n = 9); 3) Previously diagnosed biopsies from patients who had undergone complete treatment (n = 14). In the untreated AIH group, at least 50 % of the cases exhibited the following features: at least moderate portal inflammation (81 %), at least moderate lobular inflammation (56 %), ductular reaction (94 %), inflammation gradient from bile duct to interface (88 %), unequivocal interface hepatitis (100 %), emperipolesis (56 %), plasma cell cluster (88 %), apoptosis or necrosis (63 %), pericentral inflammation (63 %), and periportal fibrosis (88 %). Although all these diagnostically sensitive histologic features were present in significantly fewer cases after treatment (p < 0.05), the features of ductular reaction, inflammation gradient from bile duct to interface, pericentral inflammation, and periportal fibrosis were likely to persist after treatment, especially in partially treated cases; these features did not show a significant association with higher transaminase levels (P > 0.05) and were considered as indirect features of hepatocytic injury. Our data suggest categorizing AIH histological features into direct and indirect hepatocytic injuries. Direct hepatocytic injury features significantly correlate with transaminase levels and respond well to treatment, while indirect ones show weaker transaminase correlation and relative treatment resistance.

Simultaneous occurrence of autoimmune hepatitis and autoimmune hemolytic anemia after COVID-19 infection: case report and literature review.

Various autoimmune diseases have been reported to develop as a result of a coronavirus disease 19 (COVID-19) infection. There have been some reports of COVID-19-triggered autoimmune hepatitis and autoimmune hemolytic anemia infection, but none have reported simultaneous onset of these diseases. A 15-year-old girl was admitted to our hospital with severe liver injury and anemia. Three weeks before admission, her father was diagnosed with COVID-19, after which she became aware of a sore throat. Two weeks later, she visited her doctor for malaise. She was referred to our hospital due to severe anemia, elevated hepatobiliary enzymes, and jaundice. A COVID-19 polymerase chain reaction test was positive at the time of referral. She was diagnosed with autoimmune hemolytic anemia based on decreased hemoglobin and haptoglobin, positive direct Coombs test, and increased urinary urobilinogen. Blood tests were positive for antinuclear antibodies, and a liver biopsy revealed interface hepatitis and plasma cell infiltration, consistent with autoimmune hepatitis. Based on these findings, a diagnosis of autoimmune hepatitis and autoimmune hemolytic anemia triggered by COVID-19 infection was made. Steroid therapy was initiated, which resulted in rapid improvement of blood markers and symptoms.

Autoimmune hepatitis as a rare cause of cirrhosis development

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.

Autoimmune Hepatitis: From Evolution to Current Status-A Pathologist's Perspective.

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune-mediated liver disease that progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance in young women but may be seen in children and the elderly. Diagnosis requires the integration of clinical, biochemical, and serologic parameters, along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a prerequisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities, and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the original scoring system was proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, the IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH, with their limitations and utility, and with an emphasis on the role of liver histology in the diagnosis and management of AIH.

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

One-third of patients with autoimmune hepatitis (AIH) have cirrhosis at the time of diagnosis. The relevance of these variables, although unknown, is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors. Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor (pIgR) levels have been observed in both patients and mouse models. Moreover, there is a direct relationship between pIgR expression and transaminase levels in patients with AIH. In this study, we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta (Reg3b) and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH. Reg3b expression was reduced in pIgR gene (Pigr)-knockout mice compared to that in wild-type mice, leading to increased microbiota disruption. Conversely, exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis. RNA sequencing revealed the participation of the interleukin (IL)-17 signaling pathway in the regulation of Reg3b through pIgR. Furthermore, the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH, and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3 (STAT3). In this study, pIgR facilitated the upregulation of Reg3b via the STAT3 pathway, which plays a crucial role in preserving the balance of the intestinal microbiota in AIH. Through this research, we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Have serum vitamin D and ferritin a role in predicting the prognosis of autoimmune hepatitis treatment in children?

To investigate whether serum ferritin and vitamin D levels before starting autoimmune hepatitis (AIH) treatment have a role in disease prognosis regarding a therapeutic response. The prospective study included 100 children diagnosed with AIH according to simplified criteria for diagnosis of AIH. They attended the Pediatric Hepatology Department, National Liver Institute, Menoufia University. The patients underwent measurement of liver transaminases before starting AIH treatment after 6 months from starting therapy. They underwent liver biopsy before starting treatment for proper diagnosis, grading, and staging; only 25 cases were compliant and underwent liver biopsy before treatment withdrawal. Serum ferritin and 25 hydroxy vitamin D levels were significantly higher among those with a complete response (1000-3100 ng/ml, 29-48 ng/ml) than a partial response (550-600 ng/ml, 23-28 ng/ml) and non-response (29.28-92.14, 2.16-8.72) (p < 0.001). Our study showed a relation between serum vitamin D before starting AIH treatment, the severity of AIH and response to therapy. This opens a new area of research on the potential use of vitamin D in patients with AIH. Also, hyperferritinemia at the diagnosis can predict the treatment response.

The Diagnostic Value of ANA and Anti-SMA in Suspected Patients with Autoimmune Hepatitis

BACKGROUND: Autoimmune hepatitis (AIH) is an unknown chronic disease characterized by hepatocellular inflammation with a tendency to progress to cirrhosis. AIH can present with symptoms of acute hepatitis with symptoms of chronic liver disease. AIH occurs globally; it is more commonly found in females. Autoantibodies such as antinuclear, smooth muscle, liver kidney microsome, and soluble liver antigen are used to aid in the diagnosis of AIH, which presents with a variety of symptoms that also contribute to the classification of AIH. AIM: Evaluation of anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (SMA) positivity in hepatic diseases, gastrointestinal diseases, viral hepatitis, and extra-hepatic diseases, providing better markers for the early diagnosis of AIH-type 1. MATERIALS AND METHODS: The study included 207 individuals. 62.4% of them were female. Regarding the diagnoses, we grouped them into 4 groups: hepatic diseases (n = 73), viral hepatitis B and C (n = 54), gastrointestinal diseases (n = 34), and extra-hepatic diseases (n = 46). Serum levels of ANA and anti-SMA were measured using an indirect immunofluorescence method following the manufacturer’s instructions (Aesku Diagnostics, Germany). Fluorescence intensity was interpreted semi-quantitatively based on negative control (0) and positive control (+4). RESULTS: The positivity of ANA and anti-SMA resulted as follows: In hepatic diseases 34.2% and 48%, in viral hepatitis B and C, ANA positivity was 14.8% and SMA positivity was 22.2%; in gastrointestinal diseases, ANA and SMA positivity were, respectively, 11.8% and 20.6%; and in extrahepatic diseases, positivity of ANA resulted in 32.6% and SMA in 26%. When compared to the viral hepatitis patient group, the ANA specificity for hemagglutination inhibition (HAI) was 85.2% and that of anti-SMA was 77.8%. The analysis of 46 extrahepatic patient groups provided an ANA specificity of 67.4% and an anti-SMA specificity of 74% for HAI. The comparison to gastrointestinal disease showed that ANA specificity for HAI was 88.2% and anti-SMA specificity was 79.4%. CONCLUSION: Diagnosing AIH is difficult because the clinical spectrum ranges from an asymptomatic presentation to an acute and severe disease. So in all cases, AIH must be suspected. Both males and females can develop AIH, but the disease is more common in females. Based on our diagnostic parameters, we can say that ANA and anti-SMA provide moderate sensitivity for AIH, but they are more specific to AIH type 1.

Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.

Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.

Liver Disease and Sickle Cell Disease: Auto-Immune Hepatitis more than a Coincidence; A Systematic Review of the Literature.

In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment. However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises, providing a treatment dilemma. The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.

Commentary: Commentary: Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.

Commentary: Commentary: Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.

Investigating Acute Hepatitis after SARS-CoV-2 Vaccination or Infection: A Genetic Case Series.

(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a case series of patients who experienced the onset of acute hepatitis, with or without autoimmune features, following SARS-CoV-2 vaccination or infection and to hypothesize a genetic susceptibility in the pathogenesis. (2) Methods: A group of patients with acute onset hepatitis following SARS-CoV-2 vaccination or infection were evaluated in our hepatology outpatient clinic, where they underwent biochemical and autoimmune tests. Hepatitis A (HAV), B (HBV), and C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV) infections were excluded. Patients with a diagnosis of autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) underwent HLA typing and histological testing. (3) Results: Five patients experienced new-onset AIH after COVID-19 vaccination, one of which developed mild symptoms after vaccination that strongly worsened during subsequent SARS-CoV-2 infection. One patient had AIH relapse after COVID-19 vaccination while on maintenance immunosuppressive treatment. All of them had HLA DRB1 alleles known to confer susceptibility to AIH (HLA DRB1*03,*07,*13,*14), and in three of them, HLA DRB1*11 was also detected. Two patients developed acute hepatitis without autoimmune hallmarks which resolved spontaneously, both positive for HLA DRB1*11. (4) Conclusions: An association between AIH and COVID-19 vaccine or infection can be hypothesized in individuals with a genetic predisposition. In patients without autoimmune features and spontaneous improvement of hypertransaminasemia, the diagnosis of drug-induced liver injury (DILI) is probable. Further studies are needed to determine the presence of an actual association and identify a possible role of HLA DRB1*11 in the pathogenesis of acute liver injury after SARS-CoV2 vaccination or infection.

THU242 An Adolescent Female With Autoimmune Hepatitis And Graves’ Disease: An Unusual Presentation And Challenges In Management

Abstract Disclosure: H.J. Velasquez: None. M.A. Ruiz Santillan: None. D.L. Paul: None. M. Tosur: None. Background: Presence of multiple autoimmune disorders in an individual is not uncommon. Simultaneous diagnoses of autoimmune hepatitis (AIH) and Graves’ disease in a previously healthy adolescent individual has not been previously reported. Here we report an unusual clinical presentation of both autoimmune conditions in an adolescent female. Case Presentation: A 13-year-old Hispanic female presented with jaundice, fatigue, and weight loss, was found to have hepatic failure. She tested positive for autoantibodies (Ab) associated with AIH (Kidney-Liver Microsome Ab &amp;gt;1:2560, n &amp;lt;1:20; IgG 3480 mg/dl, n 641-1353 mg/dl; Anti Smooth muscle Ab &amp;lt;1:20, n &amp;lt;1:20; ANA 1:1280, n &amp;lt;1:160). Family history was negative for autoimmune diseases. During admission she remained with tachycardia (heart rate &amp;gt;100 beats per minute) and elevated systolic blood pressure (&amp;gt;120 mm Hg). Family confirmed tachycardia and mild exophthalmos started recently before admission. Due to concern for additional autoimmune diseases, thyroid function tests were performed and resulted abnormal (TSH &amp;lt;0.010 uIU/ml, n 0.7-4.1 uIU/ml; Free T4 4.7 ng/dl, n 0.8-2.0 ng/dl; Free T3 1023 pg/dl, n 286-556 pg/dl; total T3 199 ng/dl, n 80-210). Further autoantibody tests were consistent with Graves’ disease (TSI Ab 7.67IU/L, n&amp;lt;=0.54), other thyroid antibodies were negative (Thyroid Peroxidase Ab &amp;lt; 3 IU/ml, n&amp;lt;= 5.6 IU/L and Anti-Thyroglobulin Ab &amp;lt; 3 IU/ml, n&amp;lt;= 4 IU/L). Due to liver failure, antithyroid medications were contraindicated. Pending liver biopsy to confirm AIH made steroids not an option due to risk of alteration in biopsy results. The patient was treated with propranolol alone. Once her thyroid hormone levels stabilized, she had liver biopsy and then was placed on a steroid regimen. Her hospitalization was complicated by decompensated cirrhosis with hyperammonemia (ammonia 180 umol/l, n 22-48 umol/l), hepatic encephalopathy and hemodynamically unstable requiring intubation and ICU transfer. Hyperammonemia responded well to rifaximin and lactulose. After clinical improvement, she was discharged home with high dose prednisone, propranolol, ursodiol, phytonadione, lactulose, rifaximin, and spironolactone. Total thyroidectomy was performed two months later for permanent treatment of Grave’s disease. She was evaluated for liver transplantation and approved for listing but given her clinical improvement, she was listed as inactive status. Conclusions: AIH and Graves’ disease can present simultaneously. Screening for thyroid disorders should be considered when AIH is suspected. Co-presence of AIH makes acute management of Graves’ disease particularly challenging. An individualized treatment approach should be implemented after carefully reviewing risk/benefit ratios of each treatment option. Presentation: Thursday, June 15, 2023

Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis

Autoimmune hepatitis (AIH) is a rare chronic liver disease of unknown aetiology; the risk of hepatocellular carcinoma (HCC) remains unclear and risk factors are not well-defined. We aimed to investigate the risk of HCC across a multicentre AIH cohort and to identify predictive factors. We performed a retrospective, observational, multicentric study of patients included in the International Autoimmune Hepatitis Group Retrospective Registry. The assessed clinical outcomes were HCC development, liver transplantation, and death. Fine and Gray regression analysis stratified by centre was applied to determine the effects of individual covariates; the cumulative incidence of HCC was estimated using the competing risk method with death as a competing risk. A total of 1,428 patients diagnosed with AIH from 1980 to 2020 from 22 eligible centres across Europe and Canada were included, with a median follow-up of 11.1 years (interquartile range 5.2-15.9). Two hundred and ninety-three (20.5%) patients had cirrhosis at diagnosis. During follow-up, 24 patients developed HCC (1.7%), an incidence rate of 1.44 cases/1,000 patient-years; the cumulative incidence of HCC increased over time (0.6% at 5 years, 0.9% at 10 years, 2.7% at 20 years, and 6.6% at 30 years of follow-up). Patients who developed cirrhosis during follow-up had a significantly higher incidence of HCC. The cumulative incidence of HCC was 2.6%, 4.6%, 5.6% and 6.6% at 5, 10, 15, and 20 years after the development of cirrhosis, respectively. Obesity (hazard ratio [HR] 2.94, p=0.04), cirrhosis (HR 3.17, p=0.01), and AIH/PSC variant syndrome (HR 5.18, p=0.007) at baseline were independent risk factors for HCC development. HCC incidence in AIH is low even after cirrhosis development and is associated with risk factors including obesity, cirrhosis, and AIH/PSC variant syndrome. The risk of developing hepatocellular carcinoma (HCC) in individuals with autoimmune hepatitis (AIH) seems to be lower than for other aetiologies of chronic liver disease. Yet, solid data for this specific patient group remain elusive, given that most of the existing evidence comes from small, single-centre studies. In our study, we found that HCC incidence in patients with AIH is low even after the onset of cirrhosis. Additionally, factors such as advanced age, obesity, cirrhosis, alcohol consumption, and the presence of the AIH/PSC variant syndrome at the time of AIH diagnosis are linked to a higher risk of HCC. Based on these findings, there seems to be merit in adopting a specialized HCC monitoring programme for patients with AIH based on their individual risk factors.

Wilson’s Disease and Autoimmune Hepatitis Coexistence: A Cause of Diagnostic Delay

This case report describes a 27-year-old housewife who presented with a progressive and insidious onset of abdominal distension, loss of appetite, and fatigue which started 3 months before her presentation. The physical assessment showed moderate ascites and small liver size, and no other peripheral evidence of chronic liver disease was observed. A diagnosis of liver cirrhosis and was confirmed by investigations and imaging, where ascites responded well to therapy with diuretics. Investigations for the cause of cirrhosis was established through the diagnosis of autoimmune hepatitis, and she was started on steroids and azathioprine with partial improvement in liver biochemistry. She presented 8 months later with neuropsychiatric symptoms in the form of slurred speech and difficulty walking. Accordingly, Wilson’s disease was suspected to be the cause and further investigations confirmed this. A chelating agent, D penicillamine, was added to her immunosuppressive treatment. Nine months later she showed slow improvement in her neurological symptoms and was referred for assessment for liver transplantation. Wilson’s disease, although rare, should be suspected in patients with decompensated liver disease. The dominance of clinical and epidemiological features of autoimmune hepatitis as a common causative pathology for chronic liver disease in young and middle-aged ladies may hide the presence of other serious different pathologies such as Wilson’s disease.

B-113 Diagnostic Value of Autoantibodies against D-3-phosphoglycerate Dehydrogenase (PGDH) among Patients with Liver Diseases

Abstract Background We determined serum autoantibodies against D-3-phosphoglycerate dehydrogenase (anti-PGDH) in patients with liver diseases using a well-validated line immunoblot assay, and analysed their diagnostic significance. Methods The studied panel comprised serum samples from 383 patients with the following liver diseases: 87 autoimmune hepatitis (AIH), 88 primary biliary cholangitis (PBC), 76 chronic hepatitis B, 79 hepatitis C, 53 drug-induced liver injury as well as sera from 69 patients with autoimmune diseases (systemic lupus erythematosus or rheumatoid arthritis) and 30 healthy blood donors. The line immunoblot EUROLINE Autoimmune Liver Diseases 14 Ag (EUROIMMUN) was used to test for anti-PGDH. The intensities of the bands were automatically evaluated using the EUROLineScan software (EUROIMMUN). Indirect immunofluorescence was used to detect other autoantibodies, including anti-nuclear autoantibodies (ANA) and anti-smooth muscle antibodies (ASMA). Results The prevalence of anti-PGDH was 18.3% across all patients with liver diseases (36.8% in AIH; 10.2% in PBC), 1.5% in patients with autoimmune diseases, and 3.3% in blood donors. ANA but not ASMA were detectable in all anti-PGDH positive patients with liver diseases. Patients with anti-PGDH displayed no significant differences in age, liver function, IgG serum level and ANA patterns compared to those without anti-PGDH. Anti-PGDH positivity was observed at various stages of liver disease, including acute and chronic liver injury, liver cirrhosis, and liver cancer. Conclusion The anti-PGDH prevalence in AIH patients was highest among patients with liver or autoimmune diseases. Presence of anti-PGDH seems to be a specific marker for AIH and may support the diagnosis of AIH.

Commentary: Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.

Commentary: Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases

Background and Aims There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. Methods From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. Results A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776–0.891) in internal validation and 0.835 (95% CI: 0.752–0.919) in external validation. Conclusions ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Advances in Understanding and Managing Autoimmune Hepatitis: A Narrative Review.

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis. In recent years, significant advances have been made in understanding the pathogenesis, epidemiology, diagnosis, and treatment of AIH. This comprehensive narrative review aims to provide an up-to-date overview of these advances. The review begins by outlining the historical background of AIH, dating back to its initial recognition in the 1940s, and highlights the evolution of diagnostic criteria and classification based on autoantibody profiles. The epidemiology of AIH is explored, discussing its varying prevalence across different regions and the role of genetic predisposition, viral infections, and drug exposure as risk factors. Furthermore, the review delves into the pathogenesis of AIH, focusing on the dysregulated immune response, involvement of T cells, and potential contribution of the gut microbiome. Clinical presentation, diagnostic criteria, and liver biopsy as crucial tools for diagnosis are also discussed. Regarding management, the review provides an in-depth analysis of the standard first-line treatments involving glucocorticoids and azathioprine, as well as alternative therapies for non-responsive cases. Additionally, emerging second and third-line treatment options are examined. In conclusion, this narrative review highlights the complexity of AIH and underscores the importance of early diagnosis and individualized treatment approaches to improve patient outcomes. Further research and clinical trials are needed to optimize AIH management and ensure a better long-term prognosis for affected individuals.

Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment.

(Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against post-translational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively. We studied the presence of six anti-PTM antibodies in patients with the three AILDs and non-AILD. Antibodies against six PTMs (malondialdehyde-acetaldehyde adducts (MAA), advanced glycation end-products (AGE), CarP, acetylation (AL), Cit, and nitration (NT)) were tested in sera of patients with AILD (n = 106), non-AILD (n = 101) and compared with healthy controls (HC) (n = 100). Levels and positivity were correlated with clinical and biochemical features in a well-defined cohort of untreated AIH patients. Anti-PTM antibodies were more often detectable in sera from AILD patients compared with HCs (anti-MAA: 67.9% vs. 2.0%, anti-AGE: 36.8% vs. 4.0%, anti-CarP: 47.2% vs. 5.0% and anti-AL: 18.9% vs. 5.0%). In untreated AIH, time to complete biochemical response (CBR) was associated with anti-MAA, anti-AGE, anti-CarP and anti-AL antibodies. Significantly more patients with at least three anti-PTM antibodies attained CBR at 12 months of treatment (13 vs. 3 p = 0.01). Anti-PTM antibodies are frequently present in AILD. The presence of anti-MAA, anti-AGE and anti-CarP antibodies correlates with the presence of AIH within this cohort. In AIH, harboring at least three anti-PTM antibody responses is positively associated with CBR. Determination of anti-PTM antibodies in liver disease may have diagnostic and prognostic value.