Features Of Autoimmune Hepatitis Research Articles

Navigating complexity: a case with overlapping features of autoimmune hepatitis and Wilson's Disease

Navigating complexity: a case with overlapping features of autoimmune hepatitis and Wilson's Disease

Diagnostic features of autoimmune hepatitis in SARS‑CoV‑2‑vaccinated vs. unvaccinated individuals.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of lives, leading to significant morbidity and mortality. With >772 million cases and nearly seven million deaths reported worldwide to date, the development of vaccines has been a critical step in mitigating the impact of COVID-19. However, concerns have arisen regarding the potential for SARS-CoV-2 mRNA vaccination to trigger autoimmune diseases, including autoimmune hepatitis (AIH). The present single-center, retrospective study aimed to compare the clinical and pathological features of AIH in patients with or without a history of SARS-CoV-2 mRNA vaccination. A total of 72 patients with AIH were examined. Among them, 10 had received the SARS-CoV-2 mRNA vaccination prior to AIH onset. These patients exhibited more pronounced CD4+ T cell infiltration into the liver tissue compared with those who were unvaccinated. No significant differences in the levels of other liver enzymes, autoimmune antibodies, or CD8+ T cell infiltration were observed between the groups. Moreover, the AIH patients with a history of SARS-CoV-2 mRNA vaccination had more extensive CD4+ T cell infiltration in their liver tissues than the unvaccinated patients. These findings suggested that the immune response to SARS-CoV-2 mRNA vaccination may influence the pathogenesis of AIH, highlighting the need for further research into the relationship between SARS-CoV-2 mRNA vaccination and autoimmune liver diseases. Such studies will also help clarify the distinction between vaccine-induced liver injury and traditional AIH.

Hepatic and Extrahepatic Characteristics of Autoimmune Hepatitis: A 23-year Hospital-Based Cohort Study.

The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive. A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan. From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010-1.138) and all-cause cancer (1.041;1.005-1.079); cirrhosis with mortality/liver transplantation (11.933;1.984-71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002). In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes.

Diagnosis and presenting features of autoimmune hepatitis at a central referral hospital in South Africa.

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 <0.001). Conclusion AIH is a disease most commonly affecting young females. Female sex and older age of onset is associated with AIH in HIV-infected individuals.

Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome

BackgroundPrimary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those with PBC or AIH alone. The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated.MethodsWhole-transcriptome sequencing was employed to discern differentially expressed (DE) RNAs within good responders (GR) and poor responders (PR) among patients with PBC/AIH VS. Subsequent gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for the identified DE RNAs. Plasma metabolomics was employed to delineate the metabolic profiles distinguishing PR and GR groups. The quantification of immune cell profiles and associated cytokines was achieved through flow cytometry and immunoassay technology. Uni- and multivariable logistic regression analyses were conducted to construct a predictive model for insufficient biochemical response. The performance of the model was assessed by computing the area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity.FindingsThe analysis identified 224 differentially expressed (DE) mRNAs, 189 DE long non-coding RNAs, 39 DE circular RNAs, and 63 DE microRNAs. Functional pathway analysis revealed enrichment in lipid metabolic pathways and immune response. Metabolomics disclosed dysregulated lipid metabolism and identified PC (18:2/18:2) and PC (16:0/20:3) as predictors. CD4+ T helper (Th) cells, including Th2 cells and regulatory T cells (Tregs), were upregulated in the GR group. Pro-inflammatory cytokines (IFN-γ, TNF-α, IL-9, and IL-17) were downregulated in the GR group, while anti-inflammatory cytokines (IL-10, IL-4, IL-5, and IL-22) were elevated. Regulatory networks were constructed, identifying CACNA1H and ACAA1 as target genes. A predictive model based on these indicators demonstrated an AUC of 0.986 in the primary cohort and an AUC of 0.940 in the validation cohort for predicting complete biochemical response.ConclusionA combined model integrating genomic, metabolic, and cytokinomic features demonstrated high accuracy in predicting insufficient biochemical response in patients with PBC/AIH VS. Early recognition of individuals at elevated risk for insufficient response allows for the prompt initiation of additional treatments.

Serum markers for detecting histological features of autoimmune hepatitis and predicting prognosis in patients with antinuclear antibody‐positive drug‐induced liver injury

AbstractAimsAlthough useful for distinguishing drug‐induced liver injury (DILI) from autoimmune hepatitis (AIH), liver biopsy is an invasive examination, and the presence of antinuclear antibody (ANA) positivity in patients with DILI could lead to excessive use of biopsy. Hence, we aimed to identify screening markers for histological features of AIH in patients with ANA‐positive DILI and verify their clinical outcomes after 1 year.MethodsThis retrospective study included patients with ANA‐positive DILI, who underwent liver biopsy between January 2017 and April 2022. Two pathologists identified histological features of AIH. We detected the independent indicators associated with histological features of AIH using logistic regression. We evaluated their diagnostic ability for histological features of AIH using the receiver operating characteristic curve. The follow‐up period to determine clinical outcomes was 1 year after DILI onset. The χ2 test or Fisher's exact test was used to compare categorical data and the Wilcoxon rank‐sum test was used to compare continuous variables. Two‐sided p &lt; 0.05 was considered to indicate significance.ResultsThe final analysis included 125 patients with ANA‐positive DILI, of whom 18 had AIH‐like histology. Factors independently associated with AIH‐like histology included globulin levels (odds ratio [OR] = 1.154, 95% confidence interval [CI] = 1.046–1.288; p = 0.006) and ANA titer ≥ 1:1000 (OR = 3.531, 95% CI = 1.136–11.303; p = 0.029). The optimal globulin cutoff indicating AIH‐like histology was 31.8 g/L. This globulin level in combination with ANA titer ≥ 1:1000 (area under the curve = 0.785, 95% CI = 0.738–0.832) provided a sensitivity of 100% and a specificity of 57% for indicating histological features of AIH in patients with ANA‐positive DILI. During follow‐up, more patients developed AIH in the group with AIH‐like histology than in the group without AIH‐like histology (35.3% vs. 0, p &lt; 0.001).ConclusionsFor patients with ANA‐positive DILI and ANA titer ≥ 1:1000 or globulin ≥ 31.8 g/L, liver biopsy is recommended to determine the presence of histological features of AIH and guide further monitoring.

Retrospective, single-center analysis of autoimmune hepatitis in Jordanian children: clinical features, treatments, and outcomes

ObjectivesThis study describes clinical, biochemical, and histological features and long-term outcomes in pediatric patients diagnosed with autoimmune hepatitis (AIH) at King Abdullah University Hospital, Jordan.DesignRetrospective, single-center study.SettingKing Abdullah University Hospital, Jordan.ParticipantsInclusion of all pediatric patients with AIH diagnosed at our hospital from 2015 to 2023. Exclusion criteria was patients aged over 18 at time of diagnosis and those diagnosed elsewhere.Outcome measuresUnderstanding clinical, biochemical, and histological AIH features in children, evaluating treatment responses, and reporting short- and long-term complications, including mortality.ResultsSixteen pediatric cases were diagnosed, with an average age of 9.84 ± 4.13 years. Females comprised 75% of patients, and 31.3% presented with acute liver failure. Jaundice was the most common symptom, and hepatosplenomegaly was observed in 18% of cases. Most patients had elevated transaminase levels, along with positive anti-smooth muscle antibody (ASMA) and antinuclear antibodies (ANA). Common hematological abnormalities included anemia (56.3%) and thrombocytopenia (37.5%). All patients underwent liver biopsy, with interface hepatitis present in 81.3% of cases. Treatment mainly involved prednisone and azathioprine. Three patients died, one discontinued therapy, two patients were lost to follow-up, and 10 remained on treatment.ConclusionAutoimmune hepatitis affects Jordanian children, primarily female children. Jaundice is the most common presenting symptoms. Only Type I AIH occurred in our cohort. Although of good response to conventional treatment with steroids and immunosuppression, mortality reached 18.8%.

DOP14 Proctocolectomy is associated with improved transplant-free survival in patients with primary sclerosing cholangitis: results from a pooled collaborative international study

Abstract Background It is hypothesized that the gut-liver axis plays a pivotal role in the aetiology of primary sclerosing cholangitis (PSC). Colectomy before liver transplantation is associated with decreased rates of recurrent PSC.1 We previously observed that proctocolectomy with permanent ileostomy is associated with better transplant-free survival in a population-based Dutch cohort.2 The aim of the present study is to confirm the effect of colectomy on PSC disease course in an international context. Methods We conducted a retrospective analysis on the International PSC Registry (IPSCR), comprising patients from Finland, Norway, Sweden, and the Netherlands. Endpoints were defined as liver transplantation (LT) and PSC-related death (excluding colorectal carcinoma) and were censored in the first year after colectomy to allow for a delayed protective effect. Cox proportional hazards regression was performed, with correction for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, and inflammatory bowel disease (IBD) status (i.e. ulcerative colitis, Crohn’s disease or IBD unspecified). IBD status and colectomy status were included as time-dependent exposure variables, the latter stratified for extent and indication for colectomy. Results A total of 2595 patients were included, of which 1341 from the Netherlands, 560 from Finland, 528 from Norway, and 166 from Sweden. Of all patients 1900(73%) were diagnosed with IBD and 346(15%) had undergone a colectomy; 34(9%) hemi-, 91(26%) subtotal, and 172(50%) proctocolectomy with pouch and 65(19%) with ileostomy. During a total follow-up of 28,282 patient years, 848(33%) patients reached the endpoint LT or PSC-related death. Hazard ratio (HR) of reaching LT or PSC-related death was significantly decreased in patients with proctocolectomy (0.70(0.52-0.93)) compared to patients without colectomy with variation per country (Netherlands 0.82(0.56-1.19), Finland 0.52(0.24-1.13), Norway 0.59(0.31-1.03), Sweden 0.28(0.06-1.24)). This effect was less pronounced in case of a hemi- or subtotal colectomy (HR 0.84(059-1.20)). The effect was most pronounced in the proctocolectomy with permanent ileostomy group (HR 0.55(0.30-0.99)). Of the known risk factors only a concurrent IBD diagnosis had no significant effect on transplant-free survival. Conclusion Our extended data confirm that colectomy is associated with a decreased risk of liver transplantation and PSC-related death. An incremental effect was seen with the extent of the colectomy, with the most pronounced effect in the proctocolectomy group with permanent ileostomy. Our data support the putative role of the gut-liver axis in the disease course of PSC.

Add-on immunosuppressive therapy may benefit selected patients with primary biliary cholangitis and autoimmune phenomena.

Mildly elevated levels of transaminase and/or immunoglobulin G (IgG) are common in patients with primary biliary cholangitis (PBC). It is still unclear whether adding immunosuppressive therapy to ursodeoxycholic acid (UDCA) benefits those patients who are not fulfilling the diagnostic criteria of PBC with autoimmune hepatitis (AIH) features. To assess the efficacy of adding immunosuppressive therapy to UDCA for patients with PBC and autoimmune phenomena but not fulfilling the diagnostic criteria of PBC with AIH features. This is a retrospective-prospective cohort study in a tertiary medical center. Patients with PBC and autoimmune phenomena were defined by the elevation of IgG and/or transaminase but did not fulfill the diagnostic criteria of PBC with AIH features. We grouped these patients based on with and without add-on immunosuppressive therapy and balanced their baseline characteristics using inverse probability treatment weighting (IPTW). A total of 652 patients with PBC and autoimmune phenomena were included, with a median follow-up of 4.08 years. After IPTW, the pseudo sample size in the add-on therapy and monotherapy groups was 558 and 655, respectively. After 1 year of observation, patients in the add-on therapy group had a higher biochemical response rate (normalization of transaminase and IgG levels) (49% versus 17%, p < 0.001). Furthermore, add-on therapy improved the transplant-free survival in the subgroup of patients with PBC and transaminase ⩾3 × upper limit of normal (ULN) or IgG ⩾1.3 × ULN (p = 0.033). Add-on immunosuppressive therapy may improve the normalization rates of transaminase and IgG levels in all patients with PBC and mildly elevated transaminase and IgG levels and the long-term outcomes in the subgroup of the patients with transaminase ⩾3 × ULN or IgG ⩾1.3 × ULN.

Primary Biliary Cholangitis (PBC)-Autoimmune Hepatitis (AIH) Variant Syndrome: Clinical Features, Response to Therapy and Long-Term Outcome.

Standardization of diagnostic criteria of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) variant syndrome (AIH-PBC VS) has not been achieved so far and evidence-based recommendations for monitoring and treatment of the disease are still lacking. Our study aimed to assess the prevalence, biochemical, and serological features, as well as the clinical course, of VS. We performed a retrospective study including all patients with VS between 1999 and 2020 in four German centers. Data on demographic parameters, biochemical and serological tests, treatment, and outcome were collected. Of 90 patients (3.1%) meeting Paris criteria for VS diagnosis, 65.6% showed AIH and PBC histological features, while biochemical Paris criteria were observed comparatively rarely. Further antibodies, which were not part of the diagnostic criteria of VS, were found in a subgroup of patients with available data (ACA: 30.0%; anti-CENP-A: 25.0%; anti-CENP-B: 33.3%; anti-SP100: 21.4%). Biochemical response was more frequently observed in patients treated with a combined therapy of ursodeoxycholic acid (UDCA) and immunosuppression (IS). Liver cirrhosis was detected in 31 patients (34.4%) and 25 patients (27.8%) developed clinical manifestations of portal hypertension. Biochemical Paris criteria of VS were rarely detected, thus implying that these cut-off values should be redefined. Regarding pharmacological treatment, combined therapy of UDCA and IS appeared to be more effective than monotherapy with UDCA.

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.

Regulatory T-cell deficiency leads to features of autoimmune liver disease overlap syndrome in scurfy mice.

Scurfy mice have a complete deficiency of functional regulatory T cells (Treg) due to a frameshift mutation in the Foxp3 gene. The impaired immune homeostasis results in a lethal lymphoproliferative disorder affecting multiple organs, including the liver. The autoimmune pathology in scurfy mice is in part accompanied by autoantibodies such as antinuclear antibodies (ANA). ANA are serological hallmarks of several autoimmune disorders including autoimmune liver diseases (AILD). However, the underlying pathogenesis and the role of Treg in AILD remain to be elucidated. The present study therefore aimed to characterize the liver disease in scurfy mice. Sera from scurfy mice were screened for ANA by indirect immunofluorescence assay (IFA) and tested for a wide range of AILD-associated autoantibodies by enzyme-linked immunosorbent assay, line immunoassay, and addressable laser bead immunoassay. CD4+ T cells of scurfy mice were transferred into T cell-deficient B6/nude mice. Monoclonal autoantibodies from scurfy mice and recipient B6/nude mice were tested for ANA by IFA. Liver tissue of scurfy mice was analyzed by conventional histology. Collagen deposition in scurfy liver was quantified via hepatic hydroxyproline content. Real-time quantitative PCR was used to determine fibrosis-related hepatic gene expression. Hepatic immune cells were differentiated by flow cytometry. All scurfy mice produced ANA. AILD-associated autoantibodies, predominantly antimitochondrial antibodies, were detected at significantly higher levels in scurfy sera. CD4+ T cells from scurfy mice were sufficient to induce anti-dsDNA autoantibodies and ANA with an AILD-related nuclear envelope staining pattern. Liver histology revealed portal inflammation with bile duct damage and proliferation, as in primary biliary cholangitis (PBC), and interface hepatitis with portal-parenchymal necroinflammation, as found in autoimmune hepatitis (AIH). In scurfy liver, TNFα and fibrosis-related transcripts including Col1a1, Timp1, Acta2, Mmp2, and Mmp9 were upregulated. The level of proinflammatory monocytic macrophages (Ly-6Chi) was increased, while M2-type macrophages (CD206+) were downregulated compared to wildtype controls. Despite severe hepatic inflammation, fibrosis did not develop within 25 days, which is close to the lifespan of scurfy mice. Our findings suggest that Treg-deficient scurfy mice spontaneously develop clinical, serological, and immunopathological characteristics of AILD with overlapping features of PBC and AIH.

A case of primary biliary cholangitis – diagnostic and treatment approaches

Primary biliary cholangitis (PBC) is a chronic, autoimmune, slowly progressive liver disease, characterized by the presence of antimitochondrial antibodies (AMA), cholestatic syndrome, and histological lesions of the interlobular bile ducts, with the potential progression to liver fibrosis and cirrhosis. AMA or AMA-M2 are specific markers for diagnosis of PBC, detected in about 90 % of patients. Antinuclear antibodies (ANA) specific for primary biliary cholangitis, anti-sp100 or anti-gp210 subtypes, can be used as markers of PBC diagnosis in case of patients with negative AMA. In addition to being specific for diagnosis of PBC, the presence of anti-gp210 was associated with more severe forms, rapid progression and poor prognosis of the disease. The first therapeutic option for PBC is considered ursodeoxycholic acid (UDCA), and for patients with a suboptimal response, it is recommended second-line treatment with obeticholic acid. 8-10 % of patients with PBC may have overlap syndrome with autoimmune hepatitis (AIH), which occurs with biochemical, serological and/or histological features of AIH in patients with cholestatic manifestations of PBC. „Paris Criteria” help to identify patients with PBC/AIH overlap syndrome. The article also examines a clinical case of PBC, AMA negative, which required additional investigations for evaluation, diagnostic discussion and current management of overlap syndrome associating PBC and autoimmune hepatitis.

THU-393 - Non-invasive screening for histological features of autoimmune hepatitis and prognosis of patients with antinuclear antibody-positive drug-induced liver injury

THU-393 - Non-invasive screening for histological features of autoimmune hepatitis and prognosis of patients with antinuclear antibody-positive drug-induced liver injury

Clinical Features of COVID-19 Vaccine-Associated Autoimmune Hepatitis: A Systematic Review

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.

Clinical significance of serum antinuclear antibodies in patients with autoimmune hepatitis and comorbidity.

Autoimmune hepatitis (AIH) is often complicated with immune diseases, which greatly affected the course and clinical outcome of AIH. We aimed to systematically assess clinical characteristics, prognosis in autoimmune hepatitis accompanied by immune diseases. Clinical records of 358 patients with AIH from Beijing Ditan Hospital in China were retrospectively reviewed. The clinical features of AIH with immune diseases were compared retrospectively, including clinical characteristics, prognosis and outcome. Prevalence of immune diseases in patients with AIH was 26.5%. Connective tissue disease (CTD) was the commonest immune diseases associated with AIH (33/358, 9.2%), and the incidence of primary biliary cholangitis (PBC) and thyroid dysfunction (TD) was low (4.7% and 8.5%, respectively). At diagnosis, AIH-PBC patients had higher IgM and ALP, lower weight, Hgb, ALT and AFP (P < 0.05). Meanwhile, AIH-CTD patients had lower mean platelet volume, serum K and triglyceride (P < 0.05). AIH-TD patients had a lower proportion of ANA positive (P < 0.05). The overall survival time of AIH-TD was significantly shorter than AIH patients (P = 0.0011), but there were no differences in AIH-PBC and AIH-CTD. Furthermore, ANA negative (HR: 0.21, 95%CI 0.13-0.35, P < 0.001) can be a factor to predict the poor prognosis of AIH, and also in AIH-TD patients. About 26.5% of AIH patients had at least one immune disease, and TD coexisted with AIH impaired patients' survival. ANA negative can be used as an independent indicator to predict the poor prognosis of AIH and AIH-TD.

Spontaneous development of an autoimmune hepatitis - primary biliary cholangitis overlap syndrome in dnTGFβRII Aire-/- mice.

Autoimmune regulator (Aire) and TGF-β signaling play important roles in central tolerance and peripheral tolerance, respectively, by eliminating or suppressing the activity of autoreactive T cells. We previously demonstrated that dnTGFβRII mice develop a defect in peripheral tolerance and a primary biliary cholangitis (PBC)-like disease. We hypothesized that by introducing the Aire gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrated that, while dnTGFβRII Aire-/- mice do manifest key histological and serological features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA sequencing (RNA-seq) and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFβRII Aire-/- mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti-CD8α antibody significantly alleviated hepatic inflammation and prolonged the life span of these mice. Finally, RNA-seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice developed an autoreactive CD8+ T-cell-mediated autoimmune cholangitis with concurrent hepatitis that exhibited key histological and serological features of the AIH-PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease. © 2023 The Pathological Society of Great Britain and Ireland.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

Factors and cytokine signatures associated with the response to therapy in patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome: a real-world study.

OP10 Proctocolectomy with permanent ileostomy is associated with better transplant-free survival in patients with primary sclerosing cholangitis: a retrospective cohort study

Abstract Background Inflammatory bowel disease (IBD) is the strongest known risk factor for primary sclerosing cholangitis (PSC) and seems associated with a worse prognosis. After liver transplantation, colectomy is associated with decreased rates of recurrent PSC and better graft survival.1 At the same time, the effect of colectomy on the disease course of PSC remains unclear.2 Available evidence depends either on small patient numbers, may be confounded by unobserved risk factors or colectomy was not considered as time-depending covariate. The aim of our study is to estimate the effect of colectomy on the disease course of PSC by taking time dependency and known risk factors into account. Methods We conducted a retrospective cohort study between January 1st 2008 and December 31st 2021 based on the Dutch population-based EpiPSC2 cohort. Transplant-free survival was defined as liver transplantation or PSC-related death (excluding colorectal carcinoma). The effect of colectomy was determined as time depending variable via Cox proportional hazards regression and was corrected for the following known risk factors; sex, age at diagnosis, large or small duct PSC, features of auto-immune hepatitis, time depending IBD status (i.e. no IBD, ulcerative colitis (UC), Crohn’s disease (CD) or IBD Unspecified (IBD-U)), and tertiary centre inclusion. Effect of colectomy was stratified for extent (i.e. hemi-, subtotal, or proctocolectomy with pouch or ileostomy). Indication of colectomy (i.e. active disease, dysplasia and colorectal carcinoma or other) was also considered as predictor variable. Events in the first year after colectomy were censored due to a presumed delayed effect of colectomy on disease course. Results Of the 1341 patients included, 912(68%) were diagnosed with IBD and 187(14%) had undergone a colectomy. During a total follow-up of 14,393 patient years, 370(28%) patients underwent liver transplantation and 318(24%) patients died due to a PSC-related cause. Median transplant-free survival time was 20 years. Hazard ratio (HR) was significantly decreased in patients who had undergone proctocolectomy with ileostomy (HR 0.47(0.24-0.93)) compared to patients without colectomy. This effect was absent in the group with any other type of colectomy (HR 0.90(0.67-1.19)). Indication of colectomy had no apparent effect. Presence of UC, CD or IBD-U was not associated with a worse prognosis compared to absence of IBD (HR 0.99(0.81-1.21), HR 0.85(0.64-1.13), HR 0.75(0.43-1.29)). Conclusion Our data suggest that proctocolectomy with ileostomy confers protection for liver transplantation and PSC-related death. This points towards the putative pathophysiologic role of the colonic microbiota in PSC and may open avenues to a better understanding of the aetiology of PSC.

LBODP039 Glycogenic Hepatopathy- An Underrecognized Complication Of Diabetes

Abstract Introduction Glycogenic hepatopathy (GH) is an infrequently described complication of predominantly type 1 diabetes characterized by liver dysfunction and hepatomegaly. This condition is different from the more common nonalcoholic fatty liver disease (NAFLD) which is clinically indistinguishable. Liver biopsy is currently the only way to differentiate the two conditions. We present a 19 year old female with persistent transaminasemia secondary to glycogenic hepatopathy associated with poorly controlled type 1 diabetes. Case Description A 19 year old female was admitted with DKA secondary to facial cellulitis. She had a past history of poorly controlled type 1 DM since age 9, proteinuria, and transaminasemia since age 14. Initial labs showed elevated plasma glucose 365 mg/dL, bicarbonate 15 mEq/L, anion gap 22, positive betahydroxybutyrate, AST 208 mmol/L, ALT 136 mmol/L, and HbA1c 12. 0%. She was successfully resuscitated from DKA. Repeat liver function tests showed further elevation of AST 819 mmol/L and ALT 346 mmol/L. Ultrasound of liver showed increased echotexture reported as steatosis. Further history revealed significant financial difficulty due to which patient was using different kinds of basal and bolus insulins interchangeably. She would sometimes use bolus insulin to cover for lack of basal insulin. Prior gastroenterology workup showed ANA positivity in a speckled pattern but was otherwise unrevealing for infective, autoimmune, or alcoholic hepatitis. Liver biopsy was therefore recommended by inpatient gastroenterology. Liver biopsy revealed spotty mild lobular hepatitis and focal portal fibrosis consistent with glycogenic hepatopathy. Features of autoimmune hepatitis were not seen in liver biopsy. Discussion Glycogen hepatopathy seems to represent an acquired form of glycogen storage disorder. Pathophysiology is suspected to be a combination of hyperglycemia and hyperinsulinemia leading to increased glycogen accumulation in hepatocytes while glycogenolysis is suppressed. This mechanism seems to correlate with our patient who reported use of large doses of short acting insulin followed by glucose administration to counteract hypoglycemia. Abnormal glucagon activity or enzymes deficiencies in glycogenolysis pathway (as reported with congenital glycogenstorage disorders) have not been elucidated. Recent data has also questioned reversibility and long term safety as liver biopsies of patients with glycogenic hepatopathy have demonstrated varying degrees of fibrosis. Newer MRI protocols seem to be able to distinguish GH from NAFLD, and this is important as these are pathophysiologically distinct and will have different management strategies. This case highlights glycogenic hepatopathy as an underrecognized complication of diabetes that will require improved recognition and further investigation to evaluate long term consequences. Presentation: No date and time listed