Anti-smooth Muscle Antibodies Research Articles

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%.

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.

The onset of de novo autoantibodies in healthcare workers after mRNA based anti-SARS-CoV-2 vaccines: a single centre prospective follow-up study

Nowadays, data concerning the risk of autoimmune disease after SARS-CoV-2 (COVID-19) vaccination is controversial. The aim of this single centre prospective follow-up study was to evaluate whether healthcare workers (HCWs) vaccinated with BNT162b2 mRNA and mRNA-1273 will show a development and/or a persistence of autoantibodies, focussing on the detection of antibodies against nuclear antigens (antinuclear antibodies, ANA). We enrolled 155 HCWs, however only 108 of them received the third dose and were considered for further analysis. Blood samples were collected before vaccine inoculation (T0), at 3 (T1) and 12 months (T2) after the first dose. All samples were analysed for the presence of a) ANA using indirect Immunofluorescence [IIF] (dilutions of 1:80, 1:160. 1:320 and 1:640), and anti-smooth muscle antibodies (ASMA); b) anti-myeloperoxidase (anti-MPO), anti-proteinase 3 (anti-PR3) and anti-citrullinated peptide antibodies (aCCP) [FEIA]; c) anti-phospholipid antibodies (anticardiolipin [aCL], anti-beta-2- glycoprotein I [anti-ß-2GPI] (Chemiluminescence). Line-blot technology was performed using the following kit: EUROLINE ANA profile 3 plus DFS70 (IgG). Our research suggests that mRNA based anti-SARSCoV-2 vaccines can induce the production of de novo ANA in 22/77(28,57%) of subjects and that the percentage of positivity seems to be directly correlated to the number of vaccine expositions: 6/77 (7,79%) after 2 doses; 16/77 (20,78%) after 3 doses. Since it is known that hyperstimulation of the immune system could lead to autoimmunity, these preliminary results seem to further sustain the idea that the hyperstimulation of the immune system might lead to an autoinflammatory mechanism and eventually to autoimmune disorders. However, the link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated.

Estimating autoimmune hepatitis in patients with hepatic dysfunction

Autoimmune Hepatitis (AIH) is a chronic inflammatory disease of the liver of unknown aetiology characterized by polyclonal hypergammaglobulinemia and circulating autoantibodies. Objective of the study is to find out the prevalence of autoimmune hepatitis and its causative autoantibody (Anti-nuclear, anti-smooth muscle, anti-liver kidney microsomes-1) following comprehensive diagnostic criteria given by International Autoimmune Hepatitis Group. Material and methods250 patients with raised aminotransferase but, negative for the commonest three clinical conditions viz, viral hepatitis, drug induced liver injury and alcohol induced liver injury were suspected to be a case of autoimmune hepatitis. Recent IAIHG criteria was followed in making diagnosis of autoimmune hepatitis. We did the investigation for viral hepatitis (acute/chronic), drug induced liver injury and alcohol induced liver injury and then measured serum IgG. Indirect Immunofluorescence (IIF) was done for Anti-nuclear antibody and was also done for anti-smooth muscle antibody and anti-liver kidney microsomes-1 antibody simultaneously. ResultAs per IAIHG criteria, out of 250 patients, Ig “G” was elevated in 88 patients with significant titres for Anti-nuclear antibody (50 patients), anti-smooth muscle antibody (65 patients), anti-liver kidney microsomes-1 antibody (7 patients) and Anti-mitochondrial antibody (18 patients) were found. As per International Autoimmune Hepatitis Group Comprehensive scoring system, probable diagnosis was made in 83 patients (33.2%) and 12 were confirmed for autoimmune hepatitis (4.8%). ConclusionFemale preponderance was observed and type 1 Autoimmune Hepatitis was most common whereas type 2 Autoimmune Hepatitis was found in few cases. Most patients had anti-smooth muscle antibody and anti-nuclear antibody positivity indicating the type, but no significant difference was seen in clinical symptoms or biochemical parameters between the different types. 162 patients couldn't be evaluated for autoimmune hepatitis because of serum IgG cut-off criteria >1500 ​mg/l.

Molecular Idiosyncratic Toxicology of Drugs in the Human Liver Compared with Animals: Basic Considerations

Drug induced liver injury (DILI) occurs in patients exposed to drugs at recommended doses that leads to idiosyncratic DILI and provides an excellent human model with well described clinical features, liver injury pattern, and diagnostic criteria, based on patients assessed for causality using RUCAM (Roussel Uclaf Causality Assessment Method) as original method of 1993 or its update of 2016. Overall, 81,856 RUCAM based DILI cases have been published until mid of 2020, allowing now for an analysis of mechanistic issues of the disease. From selected DILI cases with verified diagnosis by using RUCAM, direct evidence was provided for the involvement of the innate and adapted immune system as well as genetic HLA (Human Leucocyte Antigen) genotypes. Direct evidence for a role of hepatic immune systems was substantiated by (1) the detection of anti-CYP (Cytochrome P450) isoforms in the plasma of affected patients, in line with the observation that 65% of the drugs most implicated in DILI are metabolized by a range of CYP isoforms, (2) the DIAIH (drug induced autoimmune hepatitis), a subgroup of idiosyncratic DILI, which is characterized by high RUCAM causality gradings and the detection of plasma antibodies such as positive serum anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), rarely also anti-mitochondrial antibodies (AMA), (3) the effective treatment with glucocorticoids in part of an unselected RUCAM based DILI group, and (4) its rare association with the immune-triggered Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) caused by a small group of drugs. Direct evidence of a genetic basis of idiosyncratic DILI was shown by the association of several HLA genotypes for DILI caused by selected drugs. Finally, animal models of idiosyncratic DILI mimicking human immune and genetic features are not available and further search likely will be unsuccessful. In essence and based on cases of DILI with verified diagnosis using RUCAM for causality evaluation, there is now substantial direct evidence that immune mechanisms and genetics can account for idiosyncratic DILI by many but not all implicated drugs, which may help understand the mechanistic background of the disease and contribute to new approaches of therapy and prevention.

Hepatitis E-associated neuralgic amyotrophy: a rare respiratory presentation.

Hepatitis E-associated neuralgic amyotrophy: a rare respiratory presentation.

The frequency of co-positivity of anti-smooth muscle antibody and anti-nuclear antibodies and their contribution to the diagnosis of autoimmune hepatitis

Aim: Autoimmune hepatitis (AIH) is a chronic disease observed especially in women. The International Autoimmune Hepatitis Group recommends scoring systems for diagnosis using clinical and laboratory data. All scoring systems gave points to autoantibodies as anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) positivity. This study investigates the impact of the co-positivity of the ANA and SMA antibodies on the autoimmune hepatitis diagnosis.&#x0D; Material and Method: We monitored 78 autoimmune liver disease (autoimmune hepatitis, AIH) suspected patients with positive SMA antibody and then further tested for ANA between 2014 and2021. SMA test was screened at 1/40 and 1/100 titers and patients who were positive were taken to further dilution. The ANA test was screened at a titer of 1/40 and 1/160, a positive result was found to be repeated with advanced dilutions. All patients’ autoantibody scores of simplified AIH diagnostic system were calculated.&#x0D; Results: Seventy eight patients with positive SMA antibodies screened for ANA test with 1/40 and 1/160 titer, only 2 patients was found to be negative. The most frequently observed ANA pattern is cytoplasmic linear fibrils (68% ). The 95% ANA positive results was examined at a screening titer of 1/160. The 95% SMA positive results was found at a screening titer of 1/100. The autoantibody scores of 76 patients were +2, patient’s scores were +1.&#x0D; Conclusion: SMA antibody positivity is accompanied by a high rate of ANA antibody positivity but the co-positivity didn’t effect diagnostic score systems. On the other the co-positivity could be a sign of another associated autoimmune diseases.

Autoantibody Positivity Has No Impact on Histological Parameters in Nonalcoholic Fatty Liver Diseases

Previous reports on association of autoantibodies with histological severity in nonalcoholic fatty liver disease (NAFLD) have revealed inconsistent results. Therefore, this study was undertaken to find the impact of autoantibodies on histological severity of NAFLD. All cases with histological diagnosis of NAFLD during January 2016 to January 2021 were included in the study. Laboratory parameters were recorded, and histological assessment was done. The positivity of autoimmune markers was defined as presence of either antinuclear antibody (ANA; titer >1:80), anti-smooth muscle antibodies (ASMA), or anti-liver-kidney-microsomal antibodies (LKM-1; titer >1:40). Serum levels of CK18 - M30 and PIIINP were evaluated to assess the subtle changes in necroinflammatory activity and fibrosis in the liver. Autoantibodies were present in 281/683 (41.1%, 95% CI 37.4-44.9) patients. ANA, ASMA, ANA+ASMA was seen in 20.9% (95% CI 17.9-24.2); 14.5% (95% CI 11.9-17.4); and 5.7% (95% CI 4.1-7.7) cases, respectively. No significant difference was noted between the two groups in terms of age and metabolic tests. No significant difference was noted in the histological parameters between groups with autoantibodies positivity and no-positivity. Mean value of CK18-M30 between cases with negative autoantibody; ANA positivity; ASMA positivity; and combined positivity of autoantibody were 178.2±81.8, 161.6±63.7, 153.2±70.3 and 169.8±42.9, respectively (P= 0.57). However, CK18-M30 and PIIINP showed a rising trend with NAFL, NASH, NASH+AIH (P < 0.001). Autoantibodies noted in 41% NAFLD cases. No significant necroinflammatory activity or fibrosis associated with presence of antibodies in NAFLD cases. However, CK-18-M30 showed a rising trend from NAFL to NASH to NASH+AIH.