Anti-smooth Muscle Antibodies Research Articles

Lower modified rodnan skin score values and complement 4 levels are associated with arterial endothelial dysfunction in patients with systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is a multisystem autoimmune disease affecting skin and multiple organs. Although immunopathological evidence supports direct arterial involvement leading to tissue ischemia in SSc, factors associated with arterial involvement are not precisely determined due to the rarity of SSc. In this study, we aimed to investigate aortic stiffness and endothelial functions in patients with SSc. Methods Patients under treatment of our Rheumatology department and healthy controls have been included in our study. Aortic stiffness was examined by pulse wave velocity (PWV) exam and endothelial functions were assessed by flow mediated dilation (FMD). Individuals with known atherosclerotic risk factors were excluded from our study. A thorough biochemical examination of all individuals and immunologic markers of patients with SSc was completed. All of the organ involvements in patients with SSc were noted and modified Rodnan skin score (MRSS) was calculated. Results A total of 61 patients and 75 healthy controls were included in our study. Brachial-ankle PWV values were significantly higher (6.89±0.93 vs 6.49±0.22 m/sec; p:0.001) and brachial FMD values were significantly lower (16.7±6.7 % vs 18.7±3.8 %; p: 0.03) in patients with SSc. We have also grouped individuals according to severe FMD impairment (FMD < 10%). None of the healthy controls had severe impairment whereas 15 patients with SSc had FMD values lower than 10%. Higher anti-smooth muscle (Sm) antibody positiveness (40 % vs 15.4 %), lower complement 4 levels (23.6±16.7 vs 31.1±11.1 mg/dL), higher plasma iron values (70.3±43.6 vs 31.4±45.2 mcg/dL) and lower MRSS values (11.4±4.8 vs 20.7±10.9) were observed in SSc patients with severe FMD impairment. When we have put these variables in multivariate logistic regression analysis (backward elimination model), we have found an independent association of complement 4 levels (OR: 0.03, [95 % CI: 0.01-0.491], p:0.04) and MRSS values (OR: 0.853, [95 % CI: 0.761-0.955], p:0.006) with significant FMD impairment in patients with SSc. Conclusion Arterial stiffness is significantly increased and endothelial functions, as assessed by FMD is significantly decreased in patients with SSc, when compared to healthy controls. Lower complement 4 levels and lower modified Rodnan skin scores seem to be independently associated with significant severe FMD impairment. Although our study included a remarkable amount of patients with SSc, an infrequent autoimmune disease, number of patients included in our study is not adequate to make more precise comments. Further prospective studies with higher amount of patients are required for certain results.

6980 A Case Report Of Severe Hypercalcemia In Acute Decompensated Liver Cirrhosis

Abstract Disclosure: M.M. Eid: None. R.M. Sargis: None. Introduction: Hypercalcemia in advanced liver disease in the absence of malignancy is a rare condition. Case: A 26 year old female with history of liver cirrhosis secondary to alcohol use disorder, presented with hematemesis and ascites. She was diagnosed with acute decompensated liver cell failure and transferred to our facility for liver transplantation. On Day 10 of her hospital course, she had an acute rise in serum calcium (Ca) to 10.8 mg/dl (N 8.7-10.5),albumin (Alb) 2.6 g/dl, corrected calcium (CCa) 11.9mg/dl. On day 13 Ca peaked to 13.5 mg/dl, CCa 14 mg/dl, ionized Ca 6.5mg/dl (N 4.2-5.4 mg/dl). Serum Ca was normal on day 9, Ca 8.7mg/dl, Alb 2.5 g/dl and CCa 9.9 mg/dl. She was not taking lithium, vitamin A or antacid. No personal or family history of bone disorder, fracture or kidney stone. On exam, blood pressure 85/45, heart rate 110 bpm, jaundiced with abdominal distension and respiratory distress. Labs: hemoglobin 8.1 g/dl, WBC 32.5K/Ul, platelet 136 K/Ul, serum creatinine 1.82 mg/dl, Na 133 mmol/l, K 3.5 mmol/l, Total/Direct bilirubin 29.9/18.1 mg/dl, alkaline phosphatase 166 U/L, AST/ALT 60/42U/l, Mag 2.3 mg/dl, Phos 5 mg/dl, INR 3, PTT 50 sec, parathyroid hormone (PTH) 12 pg/ml (N12-88), TSH 1.02 mciu/ml (N 0.34-4), 25 hydroxy vitamin D 17 ng/ml (N 20-80), parathyroid related peptide (PTHrP) 3.9 pmol/l (N<3.4), 1,25 di-hydroxy vitamin D 9.8 pg/ml (N 19.9-79.3), alpha fetoprotein 9.1 ng/ml (N <9). Normal anti smooth muscle and anti mitochondrial antibodies. Negative viral hepatitis serology. CT abdomen did not reveal hepatobiliary mass or tumor nor kidney stone. She was intubated and mechanically ventilated. Vasopressor support was initiated. One dose of calcitonin 4 units/kg and zoledronic acid 4 mg were given. Serum Ca decreased to 12 mg/dl, CCa 12.6 mg/dL then to 10.2 mg/dl, CCa 11mg/dl within hrs. Calcium normalized to 8.4mg/dl, CCa 9.2 mg/dl, ionized Ca 4.3 mg/dl within 24 hrs. Her condition deteriorated and withdrawal of care was decided. Conclusion: Our case demonstrates non PTH and non vitamin D mediated severe hypercalcemia in setting of acute decompensated cirrhosis and absence of malignancy. Previous literature has noted poor prognosis of hypercalcemia with acute decompensated cirrhosis. While hypercalcemia in cirrhosis may arise from paraneoplastic processes, in absence of malignancy it is speculated that acute hypercalcemia may arise from the inflammatory mediators inducing osteoclastic bone resorption as osteoclast activating factor, prostaglandin and immobilization. Some reports found an association between hypercalcemia and elevations in bilirubin and creatinine(1). Further research is needed to understand the pathophysiology and the management of hypercalcemia in acute decompensated cirrhosis.

Detection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis

ObjectiveThe detection of autoantibodies is essential to diagnose autoimmune hepatitis (AIH). Particularly in children, specificity of autoantibodies decreases due to lower titers being diagnostic and being present not only in AIH but also in other liver diseases. Recently, quantification of polyreactive IgG (pIgG) for detection of adult AIH showed the highest overall accuracy compared to antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), anti-liver kidney microsomal antibodies (anti-LKM) and anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP). We aimed to evaluate the diagnostic value of pIgG for pediatric AIH.DesignpIgG, quantified using HIP1R/BSA coated ELISA, and immunofluorescence on rodent tissue sections were performed centrally. The diagnostic fidelity to diagnose AIH was compared to conventional autoantibodies of AIH in training and validation cohorts from a retrospective, European multi-center cohort from nine centers from eight European countries composed of existing biorepositories from expert centers (n = 285).ResultsIgG from pediatric AIH patients exhibited increased polyreactivity to multiple protein and non-protein substrates compared to non-AIH liver diseases and healthy children. pIgG had an AUC of 0.900 to distinguish AIH from non-AIH liver diseases. pIgG had a 31–73% higher specificity than ANA and anti-SMA and comparable sensitivity that was 6–20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM. pIgG had a 21–34% higher accuracy than conventional autoantibodies, was positive in 43–75% of children with AIH and normal IgG and independent from treatment response.ConclusionDetecting pIgG improves the diagnostic evaluation of pediatric AIH compared to conventional autoantibodies, primarily owing to higher accuracy and specificity.Graphical

Association between Autoimmune Hepatitis and Celiac Disease among Egyptian Children and Adolescents

Abstract Background Celiac disease (CD) is an immune-mediated intolerance to gluten .CD has been recognized as a multisystem disorder which may affect other extra intestinal organs, such as the skin, thyroid, heart, nervous system, pancreas and liver. Individuals with CD are at increased risk of liver disease namely cryptogenic liver disorder and autoimmune liver disorder. However, until now, it remains unknown whether these two forms of liver disease are really different entities or only different severities of the same disorder. Objective To evaluate the association of CD with autoimmune hepatitis in pediatrics. Subjects and Methods This was a cross-sectional study that was conducted at the Pediatric Hepatology Clinic and Pediatric Gastroenterology Clinic, Children’s Hospital, Ain Shams University. The study included 2 groups of patients each comprised 20 children and adolescents as follow: Group I: Patients with established diagnosis of autoimmune hepatitis (AIH). All patients were receiving corticosteroids and azathioprine Group II: Patients with established diagnosis of CD. In group I patients with AIH, CD was screened for using anti-tissue transglutaminase (tTG) IgA in addition to measuring serum IgA to determine the need to measure anti-tTG IgG. Immunological markers (ANA, anti-smooth muscle antibody (ASMA) and liver and kidney microsomal (LKM) antibodies in addition to protein electrophoresis were done for group II patients with CD to screen for AIH. Results All patients in group I with AIH had normal serum IgA levels and were found negative for anti-tTG IgA. Also, group II patients with CD were negative for ANA, ASMA and LKM antibodies with normal protein electrophoresis. Conclusion The current study showed that CD does not seem to have significant association with AIH, however, the small sample size is a study limitation. Further wider scale studies are needed to evaluate the risk of AIH in CD.

Acute Presentation of Autoimmune Hepatitis: Case Report

This case report describes the clinical presentation, diagnostic evaluation, and treatment outcome of a 38-year-old female patient presenting with yellow discoloration of eyes and urine, along with associated symptoms such as nausea, poor appetite, abdominal pain, extreme fatigue, and mild joint pain. The patient had a history of amenorrhea for three months and no family history of autoimmune disease or drug-induced liver injury. Upon examination, the patient exhibited deep icterus and mild tender hepatomegaly, but without signs of acute liver failure. Laboratory investigations revealed elevated liver function markers and positive autoimmune antibodies, including antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA), while ruling out other possible etiologies such as viral hepatitis, Wilson's disease, and hemochromatosis. Imaging studies showed features of acute hepatitis, and liver biopsy could not be performed due to prolonged prothrombin time. The patient was diagnosed with probable autoimmune hepatitis (AIH) and initiated on a treatment regimen consisting of prednisolone 40 mg daily, which was gradually tapered over time and added azathioprine 100 mg daily. The patient demonstrated significant improvement in liver function tests with this treatment approach. However, she discontinued treatment on her own accord but continued to have normal liver function during subsequent follow-up visits. During the consultation, the patient and healthcare provider engaged in a comprehensive discussion concerning the significance of sustained treatment over an extended period and the inherent possibility of relapse.

Different course and management of khat-induced autoimmune hepatitis: report on three cases

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).

A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.

Non-A-E hepatitis (NAEH) not leading to acute liver failure (ALF) is poorly documented. The objective was to compare clinical and laboratory features of uncomplicated acute NAEH with acute viral (AVH) and autoimmune hepatitis (AIH) and histopathology in NAEH and AIH. Cases of hepatocellular jaundice were included. These were grouped into AVH, AIH and NAEH based on clinical, laboratory and, when indicated, liver biopsy findings. NAEH and AIH were followed up at three months. Of 336 patients with hepatocellular jaundice, 15 (5%) were NAEH, 25 (7%) acute AIH and 45(14%) AVH. Among NAEH patients, seven (46.7%) were males with a mean age of presentation 39 years. Jaundice (100%) was the most common presentation of NAEH. Peak bilirubin was 10.7 mg/dL. Peak aspartate and alanine aminotransferase (AST, ALT) were 512 and 670 U/L. Five (33.3%) patients had positive anti-nuclear antibody and one had anti-smooth muscle antibody. Mean immunoglobulin G (IgG) levels were 1829. On liver biopsy, all had ballooning degeneration, four (26.7%) had mild and three (20%) moderate interface hepatitis, four (26.7%) mild lymphoplasmacytic infiltrate, one (6.7%) rosette formation, bridging necrosis in none and stage 1 fibrosis in one. Comparing NAEH with AIH, AIH showed significantly older age at presentation, female predisposition, past history of jaundice, lower ALT, more autoantibodies, higher IgG, higher grade interface hepatitis, lymphoplasmacytic infiltrate, rosette formation and higher bilirubin, AST at three months. NAEH and viral hepatitis had similar features. Etiology of NAEH is unlikely to be autoimmune and is probably viral, unidentified as yet. Uncomplicated NAEH likely has self-limiting course even without specific treatment.

Evaluating Clinical Presentations and Diagnostic Procedures in Pediatric Autoimmune Hepatitis

Background: The aim of the current research was to assess the clinical manifestations and diagnostic methods used in juvenile cases of Autoimmune Hepatitis (AIH). Methods: This study employed a retrospective cross-sectional design to investigate pediatric patients diagnosed with AIH at Children’s Medical Center Hospital, which is affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. The study included patients who received routine examinations, treatments, and follow-ups during the period from 2018 to 2021. Results: The present investigation encompassed the evaluation of 52 pediatric patients, mostly female, with a mean age of 7.76 years. The vast majority of patients have encountered the occurrence of acute AIH. Positive findings for the Anti-Smooth Muscle Antibodies (ASMA) test were seen in 50% of the patients. The mean score for fibrosis in the observed individuals was 2.56, whereas the mean value for the Hepatitis Activity Index (HAI) in a subset of 29 patients was found to be 7.34. One patient succumbed to the condition, one case underwent transplantation, and another individual was identified as a candidate for liver transplantation. Conclusion: Patients with AIH saw a decrease in long-term survival. There was no observed disparity in prognosis based on gender; nevertheless, it was noted that males had a shorter lifespan, perhaps attributable to an earlier beginning of the illness. The presence of cirrhosis at the time of diagnosis constituted a significant risk factor for unfavorable prognosis, as it was associated with an elevated overall risk of mortality owing to liver dysfunction.

Exploring autoantibodies as predictors of severe fibrosis or cirrhosis in metabolic dysfunction associated with steatotic liver disease.

Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH) are rapidly growing public health concerns. Identifying predictive markers for advanced liver disease in MASLD patients is crucial for early intervention. This study investigates the association between autoantibody positivity and risk for severe fibrosis or cirrhosis across various subgroups. We conducted a retrospective study of adult patients diagnosed with MASLD between 1994 and 2019. Autoantibody status (anti-nuclear and anti-smooth muscle antibodies) was assessed using laboratory studies. Hepatic fibrosis or cirrhosis was determined histologically or through accepted non-invasive measures. Logistic regression analyses were employed to evaluate the association between autoantibody positivity and severe fibrosis or cirrhosis. Patients with comorbid viral and alcohol liver disease were assessed separately. Among 2,749 MASLD patients, 1,425 (51.8%) were male and 1,324 (48.2%) were female, with a mean age of 58.7 years. A total of 541 (19.7%) patients tested positive for autoantibodies. Autoantibody positivity was associated with a higher risk of severe fibrosis or cirrhosis in MASLD patients (odds ratio 1.28, 95% CI [1.0-1.6]). This association persisted across various subgroups, including those with concurrent hepatitis B and C virus infections. In contrast, in alcohol liver disease, autoantibody-positive patients exhibited a lower risk. Autoantibody positivity emerges as a potential predictive marker for advanced liver disease in MASLD patients, facilitating risk stratification and tailored interventions. This study highlights the clinical relevance of autoantibodies in MASLD and underscores the need for prospective validation and mechanistic investigations to refine risk assessment and management strategies.

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%.

Patients With Autoimmune Hepatitis and Nonalcoholic Fatty Liver Disease: Characteristics, Treatment, and Outcomes.

The objective of this study was to characterize an autoimmune hepatitis (AIH)/nonalcoholic fatty liver disease (NAFLD) overlap cohort, determine if they received standard of care treatment, and delineate their outcomes in comparison with patients with AIH or NAFLD alone. AIH is a relatively rare and heterogeneously presenting liver disease of unknown etiology. NAFLD is a leading cause of liver disease worldwide. AIH treatment includes steroids, which have adverse metabolic effects that can worsen NAFLD. No treatment guidelines are available to mitigate this side on AIH/NAFLD overlap patients. Few studies to date have examined these patients' characteristics, management practices, and outcomes. A single-center, retrospective chart review study examining biopsy-proven AIH/NAFLD, AIH, and NAFLD patients. Characteristics, treatment, and 1- and 3-year outcomes (all-cause mortality, need for liver transplantation, or decompensated cirrhosis) were evaluated. A total of 72 patients (36.1% AIH/NAFLD, 34.7% AIH, and 29.2% NAFLD) were included. AIH/NAFLD patients were found to be more often Hispanic/Latino, female, and with lower liver aminotransaminases, immunoglobulin G, and anti-smooth muscle antibody positivity. AIH/NAFLD patients were less likely to receive standard of care treatment. No significant differences in outcomes were seen between AIH/NAFLD and either AIH or NAFLD. Our study demonstrated that AIH/NAFLD patients have unique characteristics and are less likely to receive standard of care treatment compared with patients with AIH alone. Despite this, no difference in outcomes (all-cause mortality, need for liver transplantation, or decompensated cirrhosis) was seen. Given NAFLD's rising prevalence, AIH/NAFLD cases will likely increase, and may benefit from alternative treatment guidelines to prevent worsening of NAFLD.

Peculiarity of Autoimmune Hepatitis Triggered by SARS-CoV-2 Infection.

Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Up until now, a few reports have described autoimmune hepatitis (AIH) triggered by SARS-CoV-2 infection, but no data are available about the specific liver inflammatory infiltrate and cluster of differentiation. We report a case of AIH triggered by SARS-CoV-2 infection, with a particular focus on its histological and mainly immunohistochemical features. A 60-year-old man, with a history of paucisymptomatic SARS-CoV-2 infection that occurred one month earlier, was admitted for alterations of hepatocellular necrosis and cholestasis indexes. He completed vaccination for SARS-CoV-2 a year earlier. The serologies for hepatotropic viruses were negative. The anti- smooth muscle antibodies (ASMA) and antinuclear antibodies (ANA) results were positive. Anti-liver kidney microsome (anti-LKM) antibodies and antimitochondrial (AMA) were negative. By liver biopsy, haematoxylin-eosin staining highlighted severe portal inflammation with a rich CD38+ plasma cell component, while immunohistochemical staining showed low cell CD4+ count and prevalence of CD8+ and CD3+. After biopsy, the patient started an immunosuppressant regimen, with benefit. We can conclude that the patient developed a type 1 AIH triggered by SARS-CoV-2 infection. The presence of CD8 T-cells at immunohistochemical examination suggests different mechanisms from classic AIH. Similar cases are described after AIH triggered by SARS-CoV-2 vaccination. The AIH after SARS-CoV-2 infection developed by the patient showed a histological picture similar to a classic AIH for the abundant presence of plasma cells, and immunohistochemical features similar to those described after SARS-CoV-2-vaccination. Recently, medical interest has been growing in SARS-CoV-2 infection and its multiorgan involvement, including the liver. Underlying mechanisms are not still clear, more likely consisting of an inflammatory and immune mediated process rather than a direct cytopathic damage.Our report describes a rare case of type 1 AIH triggered by SARS-CoV-2 infection, showing a peculiar histological pattern, different from classic AIH, conversely similar to AIH triggered by SARS-CoV-2 vaccination.The mechanisms underlying liver involvement in SARS-CoV-2 infection are still under investigation. Further studies should be encouraged to improve understanding on this focus and to support physicians in its management.

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.

Immune-mediated cholangiopathies in children: the need to better understand the pathophysiology for finding the future possible treatment targets.

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.

FRI088 Vanishing Bile Duct Syndrome?

Abstract Disclosure: C.T. Malvar: None. D. Bleich: None. H. Moran: None. Background: Dyslipidemia is a common metabolic disorder in the US, but only a few conditions can cause a total cholesterol greater than 1000 mg/dl. We present a suspected case of vanishing bile duct syndrome in a patient referred to the emergency department due to transaminitis. Case Report: A 41-year-old female with type 2 diabetes mellitus and alcohol use disorder was found to have abnormal liver function tests. She had jaundice, pruritus, and bipedal edema for 2 weeks, but had quit drinking approximately 2 years ago. She denied any recent travel, sick contacts, prior history of hyperlipidemia, family history of premature CAD or lipid abnormalities. On chart review, she received Azithromycin 2 months before presentation for a presumed upper respiratory tract infection. On evaluation, she had scleral icterus and jaundice. Initial labs revealed Na 117 (133 - 145 meq/l), Cl 84 (97 - 110 meq/l), glucose of 542 (70 - 109 mg/dl), total bilirubin 20.9 (<=1.0 mg/dl), 218 (0 - 33 U/L), AST 133 (0 - 32 U/L), GGTP 778 (5 - 36 u/l), Alkaline phosphatase 2,327 (35 - 105 u/l), Lipase 252 (13 - 60 U/L), Total cholesterol 1329 (100 - 200 mg/dl), LDL 1282 (0 - 99 mg/dl), HDL 13, and Triglycerides 172 (0 - 200 mg/dL). Alpha 1 antitrypsin, Liver Kidney Microsomal (LKM-1) Antibody, ANA, Antimitochondrial antibody, Anti-smooth muscle antibody, Ceruloplasmin, CMV, EBV, HSV, and HIV were all within normal limits. An abdominal CT revealed a right pleural effusion and cholelithiasis without gallbladder wall thickening. A right upper quadrant ultrasound demonstrated hepatic steatosis. Magnetic resonance cholangiopancreatography (MRCP) showed no focal lesions, fatty infiltrations, or ductal dilatation. Ursodeoxycholic acid and cholestyramine were started for pruritus. Pseudohyponatremia was due to the increased lipid fraction in blood. Lipoprotein phenotyping revealed type IIb hypercholesterolemia with elevated triglycerides. An apo-lipoprotein B level was 147 mg/dl at the upper limit of normal (range 50-150 mg/dL). Cholestasis-induced hypercholesteremia was considered as a diagnosis. Endoscopy esophageal ultrasound with liver biopsy revealed a smooth liver with non-cirrhotic appearance, severe cholestatic pattern of injury, including bile duct infarcts, and marked bile ductular reaction. Ezetimibe was started instead of a statin due to elevated liver enzymes. Discussion: Vanishing bile duct syndrome is an extremely rare condition unknown to many clinicians. Patients present after drug-induced liver injury. Treatment focuses on symptomatic relief and supportive care. Hyperlipidemia in these patients minimally respond to statins and are thus avoided. The prognosis of these patients can vary from slow recovery to eventual cirrhosis with end-stage liver disease requiring transplant. Increasing awareness among physicians is essential to facilitate its diagnosis and management. Presentation: Friday, June 16, 2023

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.

Incidentally Discovered Cryptogenic Cirrhosis in a Patient with Untreated Celiac Disease

Celiac disease is a common gastrointestinal disorder that primarily manifests its effects on the small bowel. However, the systemic nature of this condition, especially regarding the liver, has been gaining some recognition in the literature. Mild liver disease is common, but few cases progress to cirrhosis. We present a case of an asymptomatic 78-year-old male with a past medical history of longstanding celiac disease, atrial fibrillation, heart failure with preserved ejection fraction, type 2 diabetes mellitus (DM), and chronic kidney disease stage III who underwent a computed tomography (CT) scan for thoracic aortic aneurysm surveillance. Incidentally, on a CT scan, cirrhotic liver morphology was discovered. Right upper quadrant ultrasound confirmed heterogenous echotexture of the liver, consistent with a diagnosis of cirrhosis. Laboratory work-up demonstrated elevated alkaline phosphatase of 171, tissue transglutaminase (TTG) significantly elevated at > 100, and a negative panel of other chronic liver disease labs, including negative anti-smooth muscle antibody, antimitochondrial antibody, liver kidney microsomal antibody, HFE gene, ceruloplasmin, alpha-1-antitrypsin, and alpha-fetoprotein < 2 ng/mL. The patient was not taking any hepatotoxic medications. Although the patient did have type 2 DM, his hemoglobin A1c was well-controlled at 5.9%, and he had no hyperlipidemia and a normal body mass index, making a metabolic etiology of liver disease less likely. The patient had no significant alcohol use, either. The only patient’s major risk factor for liver disease was his untreated celiac disease, diagnosed in infancy. The patient was instructed to avoid any gluten, alcohol, and other hepatotoxic substances and was subsequently followed by a gastroenterologist. The following case report explores the pathogenesis of celiac-associated liver disease and the effect a gluten-free diet can have on the small bowel and the liver.

Histology and clinical correlations in autoimmune hepatitis, primary biliary cholangitis, and autoimmune hepatitis-primary biliary cholangitis overlap syndrome

ObjectivesThe diagnosis of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and AIH-PBC overlap syndrome (OS) relies on their histologic features and clinical findings. In this study, we aimed to identify specific morphologic features of these diseases and evaluate their clinical correlation. MethodsWe included initial biopsies from untreated patients with AIH (n = 14), PBC (n = 10), and OS (n = 7). Histologic features of the portal tract, portal-lobular interface, and hepatic lobule, fibrosis, as well as clinical data including serology, autoantibodies, treatment, and prognosis were reviewed and analyzed. ResultsOur results showed that several histologic features differed significantly between AIH and PBC (p < 0.05). Among these features, OS cases were more likely to present with bile duct-centered processes (presence of bile duct damage while absence of inflammation gradient from bile duct to interface, plasma cell cluster and pericentral inflammation) unlike those seen in AIH (p < 0.05), and interface-centered processes (unequivocal interface hepatitis, ductular reaction, and periportal fibrosis) which were not seen in PBC (p < 0.05). We observed a significant correlation between transaminase levels and lobular inflammation, including numbers of lymphocyte, plasma cell and eosinophil. Our study also found that anti-smooth muscle antibody positivity was associated with interface hepatitis (p < 0.01), while antimitochondrial antibody positivity was associated with duct damage (including ductopenia) and granulomas (p < 0.05). ConclusionOur results highlight distinctive morphological features between AIH and PBC. The possibility of overlap syndrome should be considered when encountering AIH with bile duct-centered processes or PBC with interface-centered processes in morphology and correlation with autoantibodies.

Chronic non-bacterial osteomyelitis with autoimmune hepatitis: a case report and literature review

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

Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use

Clinical and mechanistic considerations in idiosyncratic drug-induced liver injury (iDILI) remain challenging topics when they are derived from mere case narratives or iDILI cases without valid diagnosis. To overcome these issues, attempts should be made on pathogenetic aspects based on published clinical iDILI cases firmly diagnosed by the original RUCAM (Roussel Uclaf Causality Assessment Method) or the RUCAM version updated in 2016. Analysis of RUCAM-based iDILI cases allowed for evaluating immune and genetic data obtained from the serum and the liver of affected patients. For instance, strong evidence for immune reactions in the liver of patients with RUCAM-based iDILI was provided by the detection of serum anti-CYP 2E1 due to drugs like volatile anesthetics sevoflurane and desflurane, partially associated with the formation of trifluoroacetyl (TFA) halide as toxic intermediates that form protein adducts and may generate reactive oxygen species (ROS). This is accompanied by production of anti-TFA antibodies detected in the serum of these patients. Other RUCAM-based studies on serum ANA (anti-nuclear antibodies) and SMA (anti-smooth muscle antibodies) associated with AIDILI (autoimmune DILI) syn DIAIH (drug-induced autoimmune hepatitis) provide additional evidence of immunological reactions with monocytes as one of several promoting immune cells. In addition, in the blood plasma of patients, mediators like the cytokines IL-22, IL-22 binding protein (IL-22BP), IL-6, IL-10, IL 12p70, IL-17A, IL-23, IP-10, or chemokines such as CD206 and sCD163 were found in DILI due to anti-tuberculosis drugs as ascertained by the prospective updated RUCAM, which scored a high causality. RUCAM-based analysis also provided compelling evidence of genetic factors such as HLA (human leucocyte antigen) alleles contributing to initiate iDILI by a few drugs. In conclusion, analysis of published RUCAM-based iDILI cases provided firm evidence of immune and genetic processes involved in iDILI caused by specific drugs.