Positive Anti-smooth Muscle Antibody Research Articles

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%.

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.

Anti-synthetase syndrome with positive anti-PL-12 antibodies associated with autoimmune hepatitis: case report and literature review

Antisynthetase Syndrome (ASS) is a rare chronic autoimmune disorder, associated with interstitial lung diseases (the most important feature), such as Dermatomyositis (DM) and Polymyositis (PM). The cause of ASS is unknown. The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases (anti-ARS involved in protein synthesis). Anti -Jo1 is the most common (20% - 30%); anti-PL12 is present in 2% - 5% of SAS, associated with Interstitial Lung Disease (ILD) in 90%, mainly as Non-Specific Interstitial Pneumonia (NSIP). Autoimmune hepatitis is related to rheumatological diseases (2.7% - 20% in systemic lupus erythematosus, 6% - 47% in primary Sjögren’s syndrome), however, is rare in patients with inflammatory myopathies, and there is no previous reported association with SAS. A literature search was carried out using the PubMed and EMBASE databases in English and Spanish. Our case, a 62-year-old woman who developed polyarthritis, with progressive dyspnea, facial and lower limb edema, proximal muscle weakness, and Raynaud’s phenomenon; high-resolution chest CT, showing pulmonary interstitial disease, consistent with Nonspecific Interstitial Pneumonia (NSIP). She had elevated transaminases and a prolonged prothrombin time, with positive anti-nuclear and anti-smooth muscle antibodies, and was made a diagnosis with autoimmune hepatitis type 1 (HAI). According to this presentation and reports of the literature review, anti-PL12 patients are characteristically associated with a severe phenotype of lung inflammation, that does not necessarily require myositis manifestation. To our knowledge, there is not any case of the antisynthetase syndrome and autoimmune hepatitis reported previously in the literature.

Sjögren syndrome in childhood mimicking pediatric multiple sclerosis

Abstract The differential diagnosis of pediatric multiple sclerosis (MS) presents a wide spectrum of diseases. Sjögren syndrome (SS) is also a rare cause of this disease. Neurological involvement in SS ranges from peripheral neuropathies to the central nervous system (CNS). We report the case of a 5-year-old boy with a possible diagnosis with SS based on positive minor salivary gland biopsy findings and positive anti-smooth muscle antibodies, also fulfilling the 2017 McDonald criteria. If a patient is younger and meets the MS criteria clinically and radiologically, it is suggested to carefully examine the CNS demyelination in a patient for autoimmune diseases, particularly SS.

Клинический случай аутоиммунного гепатита 1 типа у ребенка 10 лет

Aim. To demonstrate a clinical case of autoimmune hepatitis type 1 in a patient aged 10 years. Key points. Certain infections can cause frequently asymptomatic and self-limited hepatitis, while others may result to severe acute hepatitis and/or act as a trigger for autoimmune hepatitis in young children. We present the case of a previously healthy 10-year-old girl with a syndrome of cytolysis and cholestasis who had elevated serum transaminases, Epstein — Barr virus (EBV) serology compatible with recent EBV infection, and positive anti-smooth muscle antibody characteristic of onset autoimmune hepatitis type 1. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation and interface hepatitis. Persistent EBV-related hepatitis was excluded by negative serum EBV-PCR. Conclusion. The presented clinical case suggests that in children with cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, a liver biopsy seems mandatory to achieve a correct and on-time diagnosis of a poor prognostic disease such as autoimmune hepatitis. Keywords: autoimmune hepatitis, Epstein — Barr virus, liver transaminase elevation, anti-smooth muscle antibody

S3280 A Rare Case of Isolated ALECT-2 Hepatic Amyloidosis

Introduction: Amyloidosis is a rare disease that is defined by deposition of extracellular fibrils from immunoglobulin light chains which results in organ dysfunction. Many patients with primary systemic amyloid have hepatic involvement. Hepatic amyloid deposition is characterized by mild hepatomegaly and occasional elevated liver enzymes. Ultrasound may reveal a heterogenous echogenicity of the liver and Computed Tomography (CT) may reveal decreased parenchymal attenuation. Biopsy is the gold standard for diagnosis, seen as extracellular amorphous material, and Congo red staining will reveal apple-green birefringence under polarized light. Whereas amyloidosis is most often systemic, there are rare cases of isolated hepatic amyloid deposition. Leukocyte cell-derived chemotaxin 2 (ALECT-2) is a novel amyloid subtype, previously thought to be found in renal amyloid with a predominance in Hispanic patients but has recently been reported in the liver. We present a rare case of isolated hepatic amyloidosis without systemic involvement. Case Description/Methods: A 53-year-old Hispanic female with history of diabetes mellitus, hyperlipidemia, and nonalcoholic fatty liver disease presented to hepatology clinic for liver enzyme elevation. Lab studies were significant for AST 36 U/L, ALT 67 U/L, Alkaline Phosphatase, total bilirubin 2.7 mg/dL, positive anti-smooth muscle antibody (22 U), immunoglobulin G 1049 mg/dL, normal anti-nuclear antibody screen and normal anti-mitochondrial antibody. CT showed post cholecystectomy changes, a calcified granuloma in the right hepatic lobe, but otherwise normal liver. Liver biopsy showed focal amyloid deposition, mild steatosis, mild lobular activity, and rare ballooning hepatocytes without fibrosis. Positron emission tomography-CT, bone marrow biopsy, urine and serum protein electrophoresis were unremarkable. Further amyloid testing showed leukocyte chemotactic factor-2 (ALECT-2) amyloidosis. A referral for second opinion and experimental treatment options was recommended, however the patient declined. The patient has had stable lab values over the last two years with observation. Discussion: This is a rare case of isolated hepatic amyloidosis, highlighting the need for maintaining a broad differential diagnosis in a patient presenting with elevated liver enzymes. Given the rare nature of this condition, it is important to demonstrate this patient’s presentation and two-year outcomes with observation, given lack of available treatment regimens.

S3000 Ezetimibe-Induced Autoimmune Hepatitis: An Uncommon Offender

Introduction: Drug-induced autoimmune hepatitis (DIAIH) is a subset of autoimmune hepatitis (AIH) leading to a seropositive hepatitis caused by an inciting drug. Ezetimibe is a cholesterol absorption inhibitor within the intestinal tract that very rarely causes DIAIH. The proposed mechanism of Ezetimibe-induced DIAIH is thought to be due to interactions between drug metabolites and CYP450 within hepatic cells. Statins are another class of medication known to cause hepatotoxicity that are commonly used in combination with ezetimibe for hyperlipidemia. Highlighting cases of drug-related autoimmune hepatitis can be useful as routine liver function testing for statin-induced hepatitis is currently not recommended. Case Description/Methods: This case describes a 67 year old man with hyperlipidemia and Hashimoto’s thyroiditis admitted for abdominal pain and biochemical evidence of hepatitis after starting ezetimibe 6 weeks prior. He had also been on atorvastatin but had been on a stable dose for the previous 7 years. He did not have a history of alcohol, herbal medication or Tylenol use and had entirely normal liver function tests 6 months prior to admission. Admission labs were pertinent for AST of 2159, ALT of 3011, Alkaline phosphatase of 245, total bilirubin of 2.7 (direct bilirubin 1.3), INR of 1.3, and a creatinine kinase of 497. Autoimmune serologies were notable for a positive ANA (1:320) and anti-smooth muscle antibody (1:320). An ultrasound was negative for hepatic lesions or evidence of advanced cirrhosis. Ezetimibe and atorvastatin therapy were discontinued on admission and the patient was eventually discharged after his liver function tests improved. Discussion: Ezetimibe is a common 2nd line agent used for patients with statin-refractory hyperlipidemia which has also been known to cause hepatic injury typically with a latency period of 1-2 months into treatment. When used in combination with a statin the risk of hepatic injury increases. Current guidelines recommend against regular surveillance of liver function tests during statin treatment given that significant hepatotoxicity is exceedingly rare and routine testing did not prevent these events. However, in patients taking both a statin and ezetimibe it may be beneficial to obtain pre-treatment and in-treatment liver function testing towards the end of the latency period, especially if the incidence of ezetimibe-induced autoimmune hepatitis continues to rise.

S2907 COVID-19 Vaccine-Induced Liver Injury: A Case Series

Introduction: The coronavirus 2019 (COVID-19) pandemic has caused over 248 million cases and over 5 million deaths worldwide. Given its high morbidity and mortality, there was a rapid effort to develop a vaccine within a year of the commencement of the pandemic. Although these vaccines have excellent safety profiles, there is a risk of adverse effects such as fever, fatigue, arthralgias, injection site pain, and, less commonly, anaphylactic reaction. Drug-induced hepatotoxicity (DIH) is a rare side effect of vaccines that has rarely been reported. We report a cohort of four patients who presented with DIH following COVID-19 vaccination. Case Description/Methods: Our cohort includes four patients, aged 39-70, who presented between 12 to 82 days after their second dose of Pfizer COVID-19 vaccine. Only one patient had a history of COVID-19 infection. One patient had a history of hepatic steatosis. All four patients had normal alanine transaminase [ALT] and aspartate transaminase [AST] within one year before the current presentation. All patients demonstrated a hepatocellular pattern of liver injury (peak ALT range of 57 to 904 U/L and AST range of 51 to 828 U/L). Tests for acute viral hepatitis were negative. One patient was found to have positive antinuclear antibodies and anti-smooth muscle antibodies. One patient was found to have an elevated antimitochondrial antibody. Liver stiffness measurement in three patients showed no evidence of fibrosis. Three patients underwent liver biopsy of which two suggested evidence of toxic/drug induced liver injury while the other demonstrated nonspecific inflammation. (Figure) Discussion: DIH leads to 10% of all cases of acute hepatitis and up to 50% of all cases of liver failure, making it one of the common reasons for withdrawal of medications from the market. We observed that our patients developed hepatic injury after Pfizer COVID-19 vaccination. Vaccine-induced immune-mediated hepatitis is a known phenomenon thought to be secondary to the COVID-19 spike protein triggering an auto-immune-like hepatic condition. This could explain the findings seen in our patients, raising the question of inflammatory response in patients with underlying autoimmune conditions. It is important that these patients receive pre and post vaccination laboratory monitoring, especially given the emergence of booster vaccinations. There is a need to follow these patients in the long-term to monitor for changes in clinical and laboratory studies in order to assess the risk of complications and outcomes.Figure 1.: Patient demographics and characteristics

S3170 Syphilitic Hepatitis With Cholestatic Liver Injury

Introduction: The incidence of syphilis in the United States has increased, predominantly among men who have sex with men. Very few patients with early syphilis meet the criteria for syphilitic hepatitis, but many are HIV+ and engage in high-risk sexual behavior. Case Description/Methods: A 30-year-old man who identified as a MSM presented with yellowing of his eyes and hyperbilirubinemia, preceded by one month with a rash and photosensitivity and redness of his right eye. He denied any penile lesions, history of liver disease or alcohol use. A physical examination revealed multiple hyperpigmented macular lesions over his torso, arms, palms, and the soles of his feet and scleral icterus. A slit lamp examination indicated anterior uveitis in both eyes and chorioretinitis/placoid retinitis in the right eye. CBC and iron studies showed mild anemia of chronic disease (Hb 11.7 g/dL). BMP was within normal limits. LFTs were as mentioned in Table 1. Blood tests showed positive HBsAb and T. pallidum antibody with RPR 1:128. Serum markers for viral hepatitis and HIV were negative. CSF from a lumbar puncture had an elevated WBC count (9/mm3). No biliary obstruction or masses were noted during on US and MRCP. Liver biopsy showed bland perivenular cholestasis (zone 3) (Fig. 1A) without necroinflammatory changes, mild to minimal portal inflammation (Fig. 1B), bile duct damage, and ductular reaction. The patient was treated with penicillin G for neurosyphilis, prednisolone and cyclopentolate for ocular syphilis, and ursodiol for cholestasis. Total bilirubin levels decreased to 1.7 mg/dL after 8 weeks of follow-up, and liver enzymes normalized. Discussion: This patient met the criteria for syphilitic hepatitis (elevated liver enzymes, serologic evidence of syphilis, exclusion of other etiology, and improvement following appropriate therapy). He also had bilateral anterior uveitis and placoid retinitis of the right eye, suggesting ocular syphilis. Serum chemistries, testing for T. pallidum and other serologies (including positive anti-smooth muscle antibody) supported hepatic involvement, and CSF studies were consistent with neurosyphilis. Liver biopsy showed a bland cholestatic pattern without evidence of other causes of liver disease. The biopsy results are compatible with syphilitic hepatitis, though histologic features can vary and direct staining for spirochetes has limited sensitivity. These findings, together with his rapid improvement with penicillin therapy, confirmed a diagnosis of syphilitic hepatitis.Figure 1.: (A) Liver specimen (x40 magnification, hematoxylin and eosin stain) showing bland perivenular cholestasis (zone 3 with rare apoptotic hepatocytes. No necroinflammatory activity is present. (B) Liver specimen (x40 magnification, hematoxylin and eosin stain) showing periportal inflammation and bile duct damage with mild bile ductular reaction. Table 1. - Liver function test results AST 41 IU/L ↑ (ULN < 38 IU/L) ALT 53 IU/L ↑ (ULN < 42 IU/L) ALP 210 IU/L ↑↑ (ULN < 129 IU/L) Total bilirubin 11.6 mg/dL ↑↑ (ULN < 1.3 mg/dL) Direct bilirubin 8.8 mg/dL ↑↑ (ULN < 0.4 mg/dL) GGT 53 (ULN < 61 IU/L) Albumin 3.8 g/dL INR 1.0 AST, aspartate transaminase; ALT, alanine transaminase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transferase; INR, international normalized ratio; UNL, upper limits of normal.

S3296 Acute on Chronic Liver Disease Due to Hepatic Infiltration of Chronic Lymphoproliferative Disorder of Natural Killer Cells

Introduction: We report a case of acute on chronic liver disease with a predominantly cholestatic pattern which was diagnosed as hepatic infiltration of chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) after extensive workup and an initial false-negative liver biopsy. Case Description/Methods: A 54-year-old woman with alcohol use disorder, celiac disease, and Hashimoto thyroiditis initially presented with 8-week history of night sweats, fever and jaundice. She reported taking daily naproxen for a few weeks. The physical exam was remarkable for jaundice. Labs showed bilirubin of 2.5, AST 869, ALT 543, alkaline phosphatase 966 and INR with 0.9. Right upper quadrant ultrasound showed no ductal dilation with a non-specific hypoechoic area in the superior right lobe and nodular appearance of the liver. Autoimmune workup revealed positive anti-smooth muscle antibody in a low titer but was otherwise negative. A liver biopsy showed massive hepatic necrosis with marked pan-acinar lymphocytic inflammation. The leading cause of her liver injury was thought to be drug-induced due to naproxen in a background of chronic liver disease. Her liver disease progressed, developing ascites, encephalopathy and pruritus refractory to treatment. Nine months after initial presentation she presented with a hemoglobin of 7, MCV 104, LDH 590, Haptoglobin < 10, total bilirubin 2.9, and ferritin of 4289. WBC count was noted to have an absolute increase in lymphocytes, bone marrow biopsy showed CLPD-NK. A second liver biopsy was performed showing diffuse lymphohistiocytic infiltrate and flow cytometry revealed atypical lymphocytes/NK cell population. The patient was started on chemotherapy which led to clinical and biochemical improvement of her liver disease. (Figure) Discussion: CLPD-NK is a rare and heterogeneous disorder. Unlike other NK cell disorders, CLPD-NKs is not associated with EBV infection. This disorder follows an indolent course, making it difficult to detect it in the initial stages. Hepatic abnormalities in patients with lymphoproliferative disorders can occur from direct infiltration by abnormal cells, bile duct obstruction by lymphadenopathy, paraneoplastic syndrome, hemophagocytic syndrome, and reactivation of viral hepatitis. Our patient is to our knowledge the first case reported of hepatic infiltration from CLPD-NK. Treatment is indicated in symptomatic patients. Hence, early diagnosis is essential so patients can receive timely administration of immunosuppressive therapy.Figure 1.: Liver with diffuse lymphohistiocytic infiltrate. Sections show an atypical lymphohistiocytic infiltrate of the liver and composed of small to medium-sized cells that stain CD2+, CD3+, CD4 and CD8 with down-regulation, CD3, CD5+, CD7+, CD20 focally+, CD68+, CD163+, and Granzyme B +.

P225 A case of PL-7 positive amyopathic dermatomyositis associated with autoimmune liver disease

Abstract Background/Aims Amyopathic dermatomyositis (ADM) is a variant of dermatomyositis (DM) characterized by the presence of pathognomonic skin features of dermatomyositis but without clinical muscle weakness. ADM is believed to account for about 20% of cases of DM. Methods We present the case of a 40-year-old lady who presented in May 2020 with a 6-week history of periorbital oedema and a heliotrope rash. She had a past medical history of rectosigmoiditis diagnosed on colonoscopy in 2018 managed with mesalazine 2g once a day. Blood tests revealed a transaminitis (ALT 372 u/l, AST 201 u/l). Full blood count was normal as were inflammatory markers (ESR 4 mm/hr, CRP 2 mg/dl) and renal function (creatinine 63.9 umol/l). CK was normal (72 u/l). A non-invasive liver screen including hepatitis B and C, caeruloplasmin, alpha-fetoprotein and anti-mitochondrial antibodies was negative. A liver ultrasound was reported as normal. An ANA was positive and an ENA screen revealed positive RNP-68, S/RNP and anti-smooth muscle antibodies. Atypical pANCA antibodies were also positive. A myositis antibody screen revealed a positive PL-7 antibody. A skin biopsy of the affected area around the eye demonstrated prominent dermal periadnexal and perivascular chronic inflammation composed mainly of lymphocytes and plasma cells consistent with a connective tissue disease. A liver biopsy confirmed autoimmune liver disease (AILD). Tumour markers (CEA, CA 125 and CA 19-9) were normal and a CT scan of the chest, abdomen and pelvis to rule out occult malignancy was normal. Full lung function tests including transfer factor were normal. A diagnosis of PL-7 positive ADM with associated AILD was made. Results The patient’s ADM and AILD were successfully treated with a reducing course of budesonide (6mg three times daily for 4 months reduced to 3mg twice daily for four months then 3mg daily for 3 months) and mycophenolate mofetil 720mg twice daily. Currently, 16 months after her initial presentation, the patient’s ADM and AILD are in remission and she remains on mycophenolate mofetil 720mg twice daily. Conclusion Anti-PL-7 is one of a number of anti-aminoacyl tRNA synthetase (ARS) antibodies that are associated with DM, polymyositis (PM) and ADM. Other anti-ARS antibodies include Jo-1, PL-12, EJ, OJ, KS, ZO and YRS/HA. Antibodies to PL-7 have been reported to be associated with milder muscle involvement than antibodies to Jo-1. Antibodies to PL-7 have been associated with severe interstitial lung disease (ILD). An association between AILD and inflammatory myositis has been reported in the literature but only in a handful of case reports. To the best of our knowledge however, AILD has not previously been reported in PL-7 positive DM, PM or indeed ADM. Disclosure M.A. Lee: None. V. Scott-Lang: None. K. Raja: None. S. Sahu: None.

S2792 Marked Elevation in Serum Aminotransferases in Immune-Mediated Necrotizing Myopathy

Introduction: This is an elderly female diagnosed with immune-mediated necrotizing myopathy with marked elevations in serum aminotransaminases. Case Description/Methods: A 71 year old female was admitted for progressive proximal muscle weakness and lower extremity myalgia with an initial creatinine kinase (CK) of 10,520U/L concerning for rhabdomyolysis. Gastroenterology was consulted given an elevation in liver-associated enzymes in a hepatocellular injury pattern (AST 552U/L and ALT 653U/L) thought to be due to muscle breakdown. After a few days of intravenous fluids, the myalgias continued and her CK remained elevated. Rheumatology was consulted and an MRI of the extremities was pursued revealing T2 hyper-intensity and enhancement in multiple muscle segments concerning for an inflammatory myopathy. A muscle biopsy was obtained along the right thigh confirming an inflammatory change with necrotic muscle fibers. Furthermore, an anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) returned strongly positive ( >200U). Her atorvastatin 10mg PO qHS was discontinued. Chronic liver disease serologic evaluation resulted in a positive anti-smooth muscle antibody (ASMA) and an immunoglobulin G (IgG) level of 1218mg/dL. Given the concern for a concomitant autoimmune hepatitis, an EUS-guided liver biopsy was pursued which showed centrilobular hepatocyte drop-out with associated moderate mixed inflammation, increased iron deposition (2+ out of 4), with patchy mild fibrous portal expansion with rare periportal fibrosis without features consistent with autoimmune hepatitis and were thought to be due to the underlying immune-mediated necrotizing myopathy (IMNM). She was diagnosed with anti-HMGCR myopathy and was started on a course of prednisone. After 1 month of corticosteroid therapy and one week of azathioprine, her LAEs remained elevated (AST 577U/L and ALT 645U/L) and she continued to be symptomatic with worsening weakness. Rheumatology will be initiating a course of intravenous immunoglobulin G (IVIG) given the failure to respond to corticosteroid and thiopurine combination therapy. Discussion: This is a rare example of markedly elevated liver enzymes in a hepatocellular injury pattern of greater than 20 times the upper limit of normal mimicking autoimmune hepatitis in association with IMNM refractory to corticosteroid and thiopurine combination therapy. Salvage therapy with intravenous immunoglobulin G (IVIG) will be started by rheumatology. Liver enzyme levels are expected to downtrend with improvement in CK.Figure 1.: The top of the image illustrates centrilobular hepatocyte drop-out with associated inflammation including plasma cells and ceroid laden macrophages. Contrast these changes with the normal portal tract in the bottom portion of the image. (400X magnification).

S2409 Histoplasmosis Presenting as New-Onset Ascites in a Crohn’s Disease Patient on Adalimumab

Introduction: Histoplasma capsulatum is the most frequently diagnosed endemic mycosis in the United States. The majority of cases are self-limiting but infections in immunocompromised patients may result in severe pulmonary or disseminated disease. We report a rare case of disseminated histoplasmosis presenting as new- onset ascites due to granulomatous hepatitis in a patient with perianal Crohn’s Disease on Adalimumab. Case description/methods: A 39-year-old white female with perianal but no intraluminal Crohn’s Disease currently on adalimumab and azathioprine presented with cyclical fevers and rapid onset ascites. In the preceding weeks she was noted to have uptrending alkaline phosphatase (600s) with isoenzymes consistent with liver etiology, GGT 162, mildly elevated AST (53) with normal ALT and total bilirubin. Further workup included positive anti-smooth muscle (1:160) and F-actin antibodies. Anti-nuclear and anti-mitochondrial antibodies both returned negative. MRCP demonstrated a circumferential 1.9 x 1.3cm peribiliary mass with segmental biliary duct dilation. Paracentesis with peritoneal fluid analysis demonstrated a low serum-ascites albumin gradient, lymphocytic predominance, and negative cytology, acid-fast stain, tuberculosis PCR, and adenosine deaminase. Transjugular liver biopsy revealed multiple non-necrotizing granulomas surrounded by chronic inflammation, consisting predominantly of lymphocytes and eosinophils. Grocott’s methenamine sliver stain was positive for narrow-based budding yeast, with morphology suggestive of Histoplasma species. Additionally, a quantitative serum Histoplasmosis antigen returned positive at 2.53 ng/ml. Following these findings, a course of IV Amphotericin B was started with eventual transition to PO Itraconazole for 1 year. Discussion: Histoplasmosis capsulatum is a dimorphic fungus that is endemic to the United States, specifically the Ohio and Mississippi River valleys. The majority of infections are subclinical, but when diagnosed are primarily in immunocompromised patients. A high degree of clinical suspicion is required to facilitate early treatment and prevent poor outcomes. Pulmonary histoplasmosis is by far the most common clinical presentation. Progressive disseminated disease is rare, but may involve the liver, skin, adrenals, gastrointestinal tract, central nervous system, and bone marrow. With the use of immunomodulating therapies on the rise, it is important to consider opportunistic infections in patients with atypical presentations.Figure 1.: A: H&E staining at 200x magnification of liver biopsy demonstrating non-caseating granulomas. B: Liver biopsy shows narrow-based budding yeast with positive silver stain suggestive of Histoplasma.

Real-World Management of Patients with Primary Biliary Cholangitis-A Retrospective Study from a Tertiary Medical Center in Israel.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with variation in prevalence, phenotype and prognosis across different geographical regions. Little is known about PBC in Israel. Our aim was to characterize the demography, clinical presentation, treatment patterns and prognosis in a cohort of PBC patients followed in a referral center in central Israel. Methods: Clinical, demographic and laboratory data were collected from the medical records of PBC patients followed at Tel Aviv Medical Center in the years 2003–2020. Results: We have identified 189 patients with a confirmed diagnosis of PBC; 92.6% were female and the mean age at diagnosis was 54.7 years. Thirty-nine percent were diagnosed with another autoimmune disease and 5.9% were diagnosed with a PBC-AIH (autoimmune hepatitis) variant syndrome. Ninety-six percent were treated with ursodeoxycholic acid (UDCA) at a mean dose of 13.3 mg/kg. A total of 28.1% were found with inadequate response to UDCA according to the Toronto criteria, and 53% of the UDCA non-responders were treated with bezafibrate. Younger age at diagnosis, higher baseline levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), AIH-PBC variant and positive anti-smooth muscle antibodies (ASMA) were associated with an inadequate UDCA response. In a multivariable analysis, higher ALP at diagnosis (OR = 1.92 CI 1.11–3.20 per 50-unit change, p = 0.018) and ASMA (OR = 27.6 CI 2.58–295, p = 0.006) independently predicted inadequate UDCA response. Higher alanine transaminase (ALT), ALP and GGT, lower albumin, younger age at diagnosis and pruritus conferred an increased risk for disease progression. Conclusions: Disease characteristics, treatment patterns, response to therapy and prognosis of a PBC patient cohort in a tertiary center in central Israel were revealed. The results highlight the importance of risk stratification in PBC, specifically in younger patients, those presenting with a high level of liver enzymes and in ASMA-positive patients with an assumed diagnosis of the AIH-PBC variant.

P-107 EPIDEMIOLOGICAL AND CLINICAL PROFILE OF AUTOIMMUNE HEPATITIS IN A BRAZILIAN TERTIARY HOSPITAL

Autoimmune hepatitis (IAH) is a rare inflammatory liver disease with an autoimmune nature that is characterized by predominantly affecting female patients. Variable patterns of presentation of this disease should be observed at time of diagnosis and there are few epidemiological data in Brazil in relation to this disease. Our objective was to evaluate the epidemiological profile of patients with IAH of the Gastroenterology Service of Hospital do Servidor Público Estadual “Francisco Morato de Oliveira”, HSPE-FMO, São Paulo, SP, Brazil. Descriptive, retrospective and observational study, with analysis of data from the medical records of patients, from July 2002 to July 2020. 35 patients were selected, with a female predominance (91.4%) and the average age at the diagnosis was 54.7 ± 14.2 years. The presence of extrahepatic autoimmune disease was observed in 45.7% of the cases with a predominance of thyroiditis (31.4%). Regarding the initial presentation, 59.4% of the patients presented with an acute jaundice, 31.3% with isolated elevated serum transaminases and 6.3% with decompensated liver cirrhosis. At the time of diagnosis, 50% presented with elevated gamma globulins, 79.4% with a positive standard ANA and 37.4% with positive anti-smooth muscle antibody. In relation to the initial histological evaluation, the presence of advanced fibrosis (F3 / F4) was observed in 39.2% and the most common histological finding observed was interface hepatitis in 58,3%. The present study showed a high prevalence of females among IAH patients with an average age higher than that observed in other studies already published in our country. In relation to the main form of initial clinical presentation, the acute jaundice form was predominantly similar to the other national studies and the presence of advanced fibrosis in the initial histological evaluation was seen in a considerable proportion of patients.

Autoimmune hepatitis triggered by SARS-CoV-2 vaccination

The development of autoimmune diseases has been reported after SARS-CoV-2 infection. Vaccination against SARS-CoV-2 could also trigger auto-immunity, as it has been described with other vaccines. An aberrant immune response induced by molecular mimicry and bystander activation, especially in predisposed individuals, is a potential mechanism. We report the case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-19 infection who developed severe autoimmune hepatitis (with typical features including strongly positive anti-smooth muscle antibody and markedly elevated immunoglobulins G, as well as typical histological findings) following SARS-CoV-2 vaccination (mRNA-1273 SARS-CoV-2 vaccine, Moderna®). The link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated. Although a causality relationship cannot be proven, caution may be warranted when vaccinating individuals with known autoimmune diseases.

Asymptomatic autoimmune hepatitis type 1 with normal IgG level and IgA deficiency – case report

Introduction. Autoimmune hepatitis (AIH) in children is a chronic inflammatory liver disease with a broad clinical spectrum, ranging from isolated elevated transaminases to acute liver failure. AIH is a rare condition, with an in­creased prevalence in the last years (2.4-9.9 per 100,000 chil­dren). Case report. We present the case of a young girl, 7 years old, who was admitted to our hospital for an in­crease of liver enzymes, discovered accidentally. She was asymptomatic, and no physical signs of chronic or acute liver disease were found at admission. The laboratory pa­ra­meters revealed increased transaminases without cho­les­tasis. The viral causes of hepatitis were excluded, along with alpha-1 antitrypsin deficiency and Wilson’s disease. She had a normal level of serum IgG and a low IgA level with positive antinuclear antibodies (1:80) and anti-smooth muscle antibodies (1:320), suggestive for the diagnosis of AIH type 1 and anti-liver kidney microsomal type 1 anti­bodies. The treatment with prednisone was started, and the evolution was favorable, with the normalization of la­bo­ra­tory parameters. Conclusions. This case highlights the importance of the early recognition of this pathology and the careful evaluation of any increased serum trans­ami­nases, even in asymptomatic children.

Light chain amyloidosis presenting with autoimmune hepatitis-primary sclerosing cholangitis overlap syndrome

Introduction: Light chain (AL) amyloidosis is known to affect multiple organ systems. Although it can involve the liver, biliary channel pathology is rare. Primary biliary cirrhosis or primary sclerosing cholangitis (PSC) with autoimmune hepatitis (AIH) overlap syndrome is a very unusual presentation of systemic amyloidosis and to the best of our knowledge, not reported before. We present a rare case of a 46-years-old female with systemic amyloidosis secondary to AL amyloidosis manifesting primarily as nephrotic syndrome and AIH-PSC overlap syndrome. Patient concerns: In this report, we present a 46-years-old previously healthy female who came with a 1-month history of a right upper quadrant pain and pruritis. She had hypercalcemia, deranged liver enzymes, nephrotic range proteinuria and positive Anti-smooth muscle antibody. Diagnosis: The patient was diagnosed as AIH-PSC overlap syndrome secondary to AL amyloidosis based on clinical symptoms, biochemical, and magnetic resonance cholangiopancreatography findings. She had nephrotic range proteinuria, and upon investigation, kidney biopsy revealed AL amyloidosis. A bone marrow biopsy confirmed the presence of a plasma cell neoplasm. Interventions: The patient received Ursodeoxycholic acid for pruritis. Magnetic resonance cholangiopancreatography was done to diagnose PSC. A kidney biopsy was done to diagnose amyloidosis. Bone marrow biopsy confirmed plasma cell neoplasm, for which she received bortezomib, cyclophosphamide and dexamethasone with a plan of autologous stem cell transplant. Outcomes: The patient was asymptomatic on her follow-up visit after 1 week of discharge and tolerated chemotherapy well. Her liver enzymes (Alkaline phosphatase, Alanine aminotransferase, Aspartate aminotransferase had decreased significantly. Conclusions: AL amyloidosis can very rarely present as AIH-PSC overlap syndrome, manifesting with raised liver enzymes, biliary strictures, pruritis and positive liver antibodies. Patients with amyloidosis involving multiple organ systems, especially at a young age, should be worked up to rule out malignancy. The treatment of AIH-PSC overlap syndrome should be accompanied by that of the primary amyloidosis for definitive management.

S2670 Wilson Disease Presenting With Autoimmune Hepatitis Features: A Clinical Enigma

INTRODUCTION: Wilson disease (WD) is a genetic disorder that commonly presents with neuropsychiatric and hepatic symptoms due to an inherited defect in the metabolism of copper. In some cases, the presence of autoimmune hepatitis (AIH) markers despite features of WD can result in diagnostic delays. We present the case of a 25 year old woman presenting with decompensated liver cirrhosis attributed to WD with confounding factors of AIH. CASE DESCRIPTION/METHODS: A 25 year old woman presented to the emergency department with abdominal distension and bilateral lower extremity edema. Her physical exam was remarkable for abdominal ascites and bilateral pitting leg edema. Laboratory analysis demonstrated an elevated alkaline phosphatase at 211 U/L, as well as aspartate aminotransferase and alanine aminotransferase at 97 IU/L and 62 IU/L respectively. CT abdomen demonstrated small sclerotic liver with evidence for portal hypertension. Further studies were significant for a low ceruloplasmin level, positive antinuclear antibody (ANA) and low titer positive anti-smooth muscle antibodies (ASMA). She underwent upper endoscopy that revealed Grade 2 esophageal varices (Figure 1). Patient underwent liver biopsy and pathology revealed extensive bands of bridging fibrosis consistent with cirrhosis (Figure 2). Glycogenated nuclei, iron stain and alpha-1 antitrypsin test were negative with copper stain positive for occasional deposits in hepatocytes (Figure 3). After discharge, a 24 hour urinary copper level was elevated at 595μg/and dry weight copper level was 910.3 mcg/mg confirming WD. DISCUSSION: WD is a rare genetic condition that involves hepatic and neurological dysfunctions occurring in 1 to 30,000 of the worldwide population. Intriguingly, our patient did not have any neurological or psychiatric symptoms at the moment of presentation. Of note, the patient did not undergo slit lamp examination so the presence or absence of Kayser-Fleischer rings that are present in almost every patient with neurologic disease could not be determined. We report a case of a diagnosis of WD presenting with a positive ANA and ASMA initially misdiagnosed as AIH. The confounding factor of this case was the early detection of a positive ANA and ASMA suggesting AIH as the culprit for the decompensated cirrhosis. The correct identification of the etiology for this patient’s cirrhosis is critical as treatment and prognosis differ greatly between these two entities and can prevent delays in effective interventions.Figure 1.: EGD demonstrating grade II esophageal varices.Figure 2.: Liver biopsy slide with extensive thick bands of bridging fibrosis consistent with cirrhosis.Figure 3.: Liver biopsy slide showing copper deposits in hepatocytes.

2256 A Unique Case of Concurrent Langerhans Cell Histiocytosis and Autoimmune Hepatitis Complicated by a Lower Gastrointestinal Bleed

INTRODUCTION: Autoimmune hepatitis (AIH) and Langerhans Cell Histiocytosis (LCH) are two independently rare disease processes that can have similar presentations. There have been no documented cases of concurrent AIH and LCH. We illustrate a complex case that required an interdisciplinary approach to ultimately diagnose and treat the patient. This unique presentation contributes to the medical literature of the two rare diseases. CASE DESCRIPTION/METHODS: 20-year-old male with no significant history presented with worsening jaundice, diffuse, pruritic rash, and abdominal pain over one month. On admission, the patient’s labs showed significantly elevated liver function tests (LFTs), eosinophilia, and anemia. Exam was notable for diffuse lymphadenopathy (LAD), hepatosplenomegaly, and a diffuse, non-blanching, morbilliform rash. Interdisciplinary workup was notable for positive anti smooth muscle antibody (ASMA), and anti-neutrophilic antibody (ANA). A liver biopsy was done and showed findings of severe inflammation with interface activity, consistent with AIH. A lymph node (LN) biopsy showed findings consistent with LCH, including histiocyte clusters (HC). He was started on high dose steroids with LAD/LFT improvement; yet, his hospital stay was complicated by a gastrointestinal (GI) bleed requiring a hemicolectomy. The patient was ultimately transferred to a larger referral center where he continued to improve with steroids and was ultimately discharged with close follow up. DISCUSSION: LCH tends to affect skin or bones; however, LN and GI involvement are relatively uncommon. This case was notable for a LN biopsy showing HC with reniform nuclei, nuclear grooves and eosinophils with immunohistochemical stains positive for S-100, CD1a, fascin, langerin, CD45, and CD68, consistent with LCH. The resected colon showed atypical histiocyte proliferation positive for fascin, CD4, and CD68. Key findings can help support a diagnosis of AIH, such as elevated LFTs, ASMA, and ANA, as well as a liver biopsy showing inflammation with interface activity, eosinophils, plasma cells, and characteristic fibrosis, all of which were found in this patient. In either case, steroids were indicated and ultimately helped the patient clinically improve. Such a case is distinct since the LCH appeared to be a systemic process, with findings of diffuse LAD, questionable GI involvement, and no liver involvement, but rather concurrent AIH. This case was further notable for a complication of a lower GI bleed requiring a hemicolectomy.