Normal Bilirubin Research Articles

Phase 2, Randomized, Open-Label Trial of Bitopertin in Erythropoietic Protoporphyria: Beacon Trial Design

Background: Erythropoietic protoporphyria (EPP) caused by FECH and ALAS2 mutations results in toxic accumulation of photoreactive protoporphyrin IX (PPIX). High levels of PPIX result in excruciating phototoxic reactions and hepatopathy caused by biliary stasis. Reduction of PPIX is associated with amelioration of disease in the settings of hematopoietic stem cell transplant, pregnancy and extracorporeal photoinactivation. Bitopertin is a small molecule inhibitor of glycine transporter 1 (GlyT1), which imports large amounts of extracellular glycine into erythropoietic precursors. GlyT1 is needed to supply adequate amounts of substrate for the heme synthesis pathway to enable the large amounts of hemoglobin needed for normal red blood cell production. Treatment of EPP mouse models with FECH and ALAS2 mutations resulted in 45-73% reduction in PPIX, as compared to controls (Hong et al. 2021). These data, combined with a well-defined safety profile that has previously been established in over 4,000 patients and healthy volunteers motivates the current study to evaluate this potentially disease-modifying treatment. Study Design and Methods: This is a Phase 2, randomized, open-label, parallel arm trial of 20 and 60 mg bitopertin daily for 24 weeks in EPP patients. The trial is being conducted at 2 sites in Australia. The primary endpoint is percent change in metal-free PPIX. Secondary endpoints include patient reported outcomes of light tolerance, safety and tolerability, and PK parameters. Eligibility criteria include: age ≥18 years with EPP by FECH/ALAS2 genotyping or porphyrin analysis, AST/ALT <2x upper limit of normal, normal bilirubin, and hemoglobin ≥10 g/dL. Up to 22 participants will be randomized and stratified by baseline daily light tolerance (< or ≥ 30 minutes) and study site. Study sample size calculations were not performed for this first in EPP study. Endpoints will be summarized using descriptive statistics. Results: Subject enrollment began July 2022. Initial data will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Trial-in-Progress: A Phase 2 Study of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Acute Myeloid Leukemia That Persisted after the 1st Induction Regimen

Background Acute myeloid leukemia (AML) is a disease characterized by a clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elements. The standard treatment for newly diagnosed AML has not changed appreciably over the last few decades and consists primarily of an anthracycline combined with a nucleoside analogue. Complete remission (CR) rates of 65-80% can be expected in younger patients but decrease with older age. There is no agreed standard of care for AML patients that do not respond to initial first line induction therapy. Although remission after second-line therapy may occur, the CR rate is lower. A few chemotherapy regimens have been used in patients with resistant disease with overall CR rates of 20-40%. Gemtuzumab ozogamicin (GO) is an antibody drug conjugate consisting of a recombinant humanized antibody to CD33 which is linked to calicheamicin. Although GO is currently approved for induction therapy in combination with "7+3", its benefit is mostly evident in favorable risk disease (Hills et al Lancet Onc 2014) and thus its use is mostly limited in this setting. Pre-clinical data suggest that GO is most effective when it saturates CD33 which happens in low-burden disease (Van der Velden et al Leukemia 2004). Thus, we decided to proceed with a trial that incorporates gemtuzumab ozogamicin on the 2nd induction regimen for patients that did not achieve complete remission with the first. Methods This is a phase II, singe-center clinical trial of GO in combination with mitoxantrone and etoposide in patients with AML that persisted after their 1st induction regimen. The patients are eligible if they have at least 10% of blasts in their day 14 bone marrow biopsy and CD33 expression in at least 30% of leukemic blasts in the bone marrow. Patients with repeat bone marrows after day 14 showing progression of AML (>5% blasts) were also eligible. Patients also need to have ECOG performance status 0-2, left ventricular ejection fraction (LVEF) >50%, GFR > 30 ml/min, AST/ALT < 2.5 x upper normal limits and total bilirubin <2 x upper normal limit. Patients that received CPX-531 for induction are excluded due to concerns for prolonged thrombocytopenia. The standard of care for our center for this patient population is 10mg/m2 of mitoxantrone on days 1-5 and 100mg/m2 of etoposide on days 1-5. Trial patients receive the same regimen and a single dose of GO 3mg/m2 (capped at 4.5mg) on day 6. The primary endpoint of the trial is complete remission rate (CR). The hypothesis is that addition of GO to mitoxantrone, and etoposide will increase our historical CR rate of 35% to 50%. The trial has a Simon's two-stage design, with an interim analysis planned after 16 evaluable patients have been enrolled. The trial plans to accrue 44 evaluable patients. This design has an alpha of 0.15 and 80% power. Secondary objectives include progression-free survival, overall survival, and treatment-related mortality. To-date we have enrolled 15 patients, 13 of them evaluable. 2 patients died from sepsis before the administration of GO. We have not recorded any episodes of VOD so far. Recruitment is continuing and this trial is registered on clinicaltrials.gov; NCT03839446.

Sustained Complement C1s Inhibition with Sutimlimab in Patients with Cold Agglutinin Disease Results in Continued Efficacy during Part B of the Randomized Placebo-Controlled Phase 3 Cadenza Study (NCT03347422)

Background: Cold agglutinin disease (CAD) is a rare chronic autoimmune hemolytic anemia characterized by classical complement pathway (CP)-mediated hemolysis. Sutimlimab (SUT) is a first-in-class humanized monoclonal antibody that prevents CP activation by selectively inhibiting C1s; both the alternative and lectin pathways remain intact. In the randomized, double-blind, placebo-controlled Part A (26 weeks) of Phase 3 CADENZA, SUT treatment resulted in rapid and sustained improvements in hemoglobin (Hb), hemolytic markers and quality of life (QoL). Aims: To report the long-term safety and efficacy of SUT treatment in patients with CAD from the open-label Part B extension of CADENZA. Methods: In Part A, eligible patients with CAD without a history of recent blood transfusion (≤1 during previous 12 months; 0 during last 6 months), received SUT or placebo (PBO) through intravenous infusions on Days 0 and 7, then biweekly. All patients completing Part A were eligible to enter Part B and receive biweekly SUT for ≥1 year after the last patient completed Part A. Efficacy data up to Week 79 as well as the last available patients' values are reported. Efficacy endpoints included change from baseline (BL) in Hb, hemolytic and pharmacodynamic markers, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, and blood transfusions. Safety data was recorded throughout the study; treatment emergent adverse event (TEAE) and serious TEAE (TESAE). Results: Of the 42 patients enrolled in Part A, 39 completed Part A and entered Part B, with 32 (82.1%) completing Part B; 7 (17.9%) patients discontinued the study prematurely, due to TESAE (n=1), lack of efficacy (n=3), withdrawal of consent (n=2) and withdrawal by sponsor (n=1). SUT treatment rapidly improved Hb levels; mean (SE) Hb at the end of Part A was 11.51 (0.40) g/dL and 9.43 (0.40) g/dL for SUT and PBO groups, respectively. In Part B, improvements in Hb were sustained in the SUT group and the ex-PBO group saw rapid and comparable increases in Hb upon initiation of SUT; at Week 79 mean (SE) Hb levels were 11.86 (0.54) g/dL and 11.76 (0.58) g/dL in the SUT only and ex-PBO groups, respectively (Panel A). Mean total bilirubin was normalized with SUT treatment in Part A and sustained in Part B; similar decreases were observed for patients in the ex-PBO group when they started receiving SUT in Part B (Panel B). Improvements in mean [SE] FACIT-Fatigue scores (BL: 32.96 [1.79]) observed in Part A were sustained in Part B in the SUT only group (44.31 [2.19] at Week 87); the mean FACIT-Fatigue score increased to comparable levels in the ex-PBO group (41.40 [2.71] at Week 87). Improvements in Hb, bilirubin, and FACIT-Fatigue correlated with normalization of C4 and near-complete inhibition of CP activity, that was maintained through the end of treatment. Reductions in mean absolute reticulocyte count and increases in haptoglobin levels observed with SUT treatment in Part A were maintained in Part B, and upon initiation of SUT in Part B, the ex-PBO group reached comparable levels. In Part B, 9 (23.1%) patients received a ≥1 transfusion. Thirty-six (92.3%) patients experienced ≥1 TEAE in Part B. Seven (17.9%) patients experienced a total of 11 TESAEs; one TESAE of hypertension was assessed as related to SUT by the investigator. Thromboembolic events (transient ischemic attack [n=1]; deep vein thrombosis [n=1]) were observed in 2 (5.1%) patients with underlying risk factors for thromboembolism. Both events were assessed as non-serious and unrelated to SUT by the Investigator. One TESAE of infection (urinary tract infection Grade ≥3) was reported. No meningococcal infections, serious events of hypersensitivity, anaphylaxis or systemic lupus erythematosus were reported. One patient with a history of tobacco use (received PBO in Part A) experienced a TESAE of squamous cell carcinoma of the lung with fatal outcome. SUT was withdrawn due to this TESAE prior to the patient's death. Conclusion: Long-term treatment with SUT, an anti-C1s CP inhibitor, maintained mean Hb levels >11 g/dL, achieved sustained normalization of bilirubin and led to clinically meaningful improvements of FACIT-Fatigue scores, while maintaining a favourable safety profile. Improvements in anemia, inhibition of hemolysis and favourable effects on QoL were rapidly achieved and sustained to a similar extent in those patients administered SUT throughout the study and those who switched to SUT treatment in Part B. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Rare Cause of Abdominal Pain After Transjugular Intrahepatic Portosystemic Shunt

Question: A 77-year-old woman presented with progressive dyspnea for 4 months. The patient was diagnosed with primary biliary cirrhosis more than 1 years ago and was ever since on ursodeoxycholic acid medication. Recurrent ascites occurred at least 6 months before diagnosis and was responsive to diuretics. Beyond these, she did not experience any onset of gastrointestinal bleeding or hepatic encephalopathy. Laboratory examination indicated the decreased hemoglobin (10.7 g/dL, normal value [nv]: 11.5–15 g/dL), leukocyte (2.85 × 103/μL, nv: [3.5–9.5] × 103/μL), and platelet counts (53 × 103/μL, nv: [100–300] × 103 /μL), increased alkaline phosphatase (195 IU/L, nv: 50–135 IU/L) and glutamyl transpeptidase (149 IU/L, nv: <45 IU/L), and normal aminotransferase and total bilirubin levels. Chest computerized tomography showed a large amount of right-sided pleural effusion. Pleural fluid tests revealed an uncomplicated hepatic hydrothorax with serum-pleural fluid albumin gradient >1.1 g/dL and polymorphonuclear cell count <500 cells/μL. However, the patient did not show significant improvement of symptoms with dietary sodium restriction and adequate-dose diuretics. Considering the existence of hepatic hydrothorax refractory, transjugular intrahepatic portosystemic shunt (TIPS) was performed thereafter. The portal pressure gradient decreased from 18 mm Hg–7 mm Hg after stent implantation. The interventional procedure was uneventful and no complication occurred during the processes. Postoperatively, the patient experienced slight dull pain in the right upper abdomen, and the symptom intensified gradually despite giving analgesic medication in the following 36 hours. Abdominal examination showed tenderness in the right upper quadrant and percussion pain in the liver area. Liver function tests revealed obviously elevated alanine aminotransferase (1147 IU/L, nv: <50 IU/L) and aspartate aminotransferase (1582 IU/L, nv: <40 IU/L), mildly elevated total bilirubin (1.73 mg/dL, nv: 0.29–1.64 mg/dL). Blood routine showed the change of hemoglobin (11.4 g/dL) and leukocyte (6.67 × 103 /μL). Abdominal computerized tomography showed multiple strips of low-density shadows along the blood vessels and scattered low-density nodules in the liver parenchyma (Figure A, white arrowheads). What is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Abdominal contrast-enhanced computerized tomography (CECT) showed diffuse linear hypodensity around portal vein branches and multiple low-density nodules in the liver, but no obvious enhancement was observed (Figures B and C, white arrowheads). These imaging findings were absent from hepatic vein and intrahepatic inferior vena cava (Figure D). According to the history of hepatic invasive procedure, laboratory findings, and CECT presentation, intrahepatic lymphangiectasia was suspected. After a short course of nonsteroidal anti-inflammatory drug therapy, her symptoms completely resolved and transaminases gradually returned to normal levels. Follow-up CECT scans at 30 days showed complete resolution of the periportal low-density areas (Figures E and F). Intrahepatic lymphangiectasia (IHL), manifested as dilated hepatic lymphatics and related lymphedema, is caused by either increased lymph flow or lymphatic obstruction.1Pupulim L.F. Vilgrain V. Ronot M. et al.Hepatic lymphatics: anatomy and related diseases.Abdom Imaging. 2015; 40: 1997-2011Crossref PubMed Scopus (26) Google Scholar Liver transplantation, blunt abdominal trauma, hepatic malignant neoplasms, and congestive hepatomegaly due to cardiac decompensation are the most common underlying etiology of IHL.2Koslin D.B. Stanley R.J. Berland L.L. et al.Hepatic perivascular lymphedema: CT appearance.AJR Am J Roentgenol. 1988; 150: 111-113Crossref PubMed Google Scholar “Periportal halo,” characterized by hypodense appearance on computed tomography and hyperintense appearance on T2-weighted magnetic resonance images, has important clinical significance in the diagnosis of IHL.3Karcaaltincaba M. Haliloglu M. Akpinar E. et al.Multidetector CT and MRI findings in periportal space pathologies.Eur J Radiol. 2007; 61: 3-10Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Presence of hypodense appearance on both sides of the portal venous system can allow differentiation from biliary dilatation.3Karcaaltincaba M. Haliloglu M. Akpinar E. et al.Multidetector CT and MRI findings in periportal space pathologies.Eur J Radiol. 2007; 61: 3-10Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar In fact, IHL could be an overlooked complication of TIPS that has never been previously reported. Iatrogenic injury during a TIPS procedure may interrupt lymphatic vessels and initiate coagulation at the injury site, and thrombus/microthrombus provisionally compresses and blocks the hepatic lymphatic system. Once the thrombus/microthrombus dissolves, the occluded lymphatics are recanalized and IHL could be spontaneously resolved. In conclusion, IHL is a procedure-related complication of TIPS that should not be neglected. Periportal halo by CECT provides valuable evidence for both diagnosis and differential diagnosis. Further studies with a larger sample size are necessary to investigate the morbidity and natural course of IHL after TIPS.

Spectrum of Autoimmune Liver Disease and Real-World Treatment Experience from a Tertiary Care Hospital

Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000-1.003], P= 0.034), high albumin (OR 1.91 [1.05-3.48], P= 0.034) and low fibrosis on biopsy (OR 0.54 [0.33-0.91], P= 0.020) predicted complete response. AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response.

Evaluation of Liver Function Tests in Normal Pregnancy-An Observational Epidemiological Study-Kumbakonam Urban Rural Epidemiological Study-KURES 10

Early interpretation of liver function tests (LFTs) can result in timely management and it may decrease the incidence of complications in both the mother and the foetus. Normal LFTs don't always imply a normal liver. A number of drawbacks can occur when interpreting basic blood LFTs. Abnormal Liver Function Tests (LFTs) in pregnancy must be properly interpreted to avoid diagnostic pitfalls. we did a routine testing in 498 asymptomatic antenatal mothers in the third trimester. Ninety-seven percentage of mothers had normal bilirubin while 93 % had normal enzyme levels. The other abnormal values were also within 1 to 1.5 % above the normal. No mother had any symptoms. Only two patients had gallstones whose LFTs were normal. Two mothers had tattoo marks while the other two were HbSAg positive. All the 498 mothers had an uneventful progress towards delivery. Cross consultation done on a few cases with abnormal values were non-contributory. Pregnancy-related disorders are the most common reason for unusual liver function tests during pregnancy, especially in the third trimester. We omitted such cases to support our hypotheses of avoiding undue testing. The most prevalent is pre-eclampsia-related disorder. This is the first such study on a huge sample size. We suggest a routine testing of LFTs is not needed in otherwise healthy antenatal mothers.

CT-282 Case Report: Successful Management of Severe Veno-Occlusive Disease after Allogeneic Stem Cell Transplantation Using a Transjugular Intrahepatic Portosystemic Shunt

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (VOD/SOS), of the liver is a complication of allogeneic bone marrow or peripheral stem cell transplantation and is known to be an unpredictable, life-threatening complication with high mortality. We report here a case of a 24-year-old male patient who was diagnosed in 2019 at Gustave Roussy institute with AML. The patient was treated with the AML protocol 3+7 in December 2019 with a complete cytologic response and a positive MRD. Leukemia relapse was observed in September 2020, treated by gemtuzumab ozogomycin and cytarabine with a negative MRD. A successful allogeneic bone marrow transplantation from an HLA-matched pheno-identical related donor was conducted on December 22, 2020, using a myeloablative conditioning regimen. The patient was always controlled by a daily blood test and controlled blood transfusions, and a weekly repeated Doppler ultrasound examination did not indicate a high-risk profile of VOD. However, 12 days post transplant, the patient's condition deteriorated with the appearance of abdominal ascites, weight gain of 6 kg (per base 76 kg), and liver cytolysis with ASAT 72 UI/L, ALAT 86 UI/L, and normal bilirubin. Worsening cytolysis was observed, with ASAT 659 UI/L, ALAT 557 UI/L, and normal bilirubin. A Doppler ultrasound found 5 positive criteria of VOD (hepatomegaly, portal dilation, enlargement of the gall bladder wall, splenomegaly, ascites, decrease in the diameter of the subhepatic veins). Defibrotide was initiated. The patient's condition worsened and was refractory to medical therapy. Transjugular intrahepatic portosystemic shunting (TIPS) was performed 13 days after transplantation without technical complications in any case. The median hepatic venous pressure gradient prior to the procedure was 20 mmHg with a drop to 12 mmHg. An abdominal CT scan showed an under hepatic hematoma with hemorrhagic syndrome. Ascites puncture with abdominal drain installation was done. In summary, following TIPS, the patient showed clinical improvement, and VOD resolved subsequently with a complete remission post allogeneic transplant.

S2919 Bile Duct Injury Due to Ketamine Use

Introduction: Ketamine is used routinely in the hospital for anesthesia, but is also used recreationally for its hallucinogenic and dissociative side effects. Chronic recreational use has been linked to bile duct damage and ulcerative cystitis. We report a case of ketamine induced sclerosing cholangiopathy. Case Description/Methods: A 42-year-old Cantonese woman with past medical history of bilateral hydronephrosis with stents leading to chronic kidney disease presented with abdominal pain associated with abnormal transaminases. Alkaline phosphatase was high at 1,017 IU/L with gamma glutamyl transferase of 2,310 IU/L with normal bilirubin. Abdominal imaging showed diffuse dilatation of the common bile duct. Viral serologies and anti-mitochondrial antibody were negative. She reported chronically elevated liver tests of unknown etiology. Social history was notable for prior alcohol abuse. She denied family history of liver diseases. Her pain resolved and plan was for outpatient follow-up, but she re-presented with sepsis with a rise in bilirubin to 2.9 mg/dL (Table 1). Given prior abnormal imaging, a magnetic resonance cholangiopancreatography was obtained, which showed increased intra- and extrahepatic bile duct dilation with irregular appearance of the central intrahepatic ducts with possible stricture. Differential diagnoses were recurrent pyogenic cholangitis, sclerosing cholangitis, and IgG4 disease. Her IgG level was high at 2,779 mg/dL with IgG4 elevated at 213 mg/dL. Liver biopsy showed chronic cholestatic liver injury consistent with sclerosing cholangitis (Image 1). IgG4 stain was negative. Upon further investigation, patient admitted to at least a decade of daily ketamine use, which was likely the culprit of both her kidney and liver diseases. Discussion: Due to her age, race, gender and rarity of ketamine induced cholangiopathy, she was not directly asked about ketamine use. Since the early 2000s, ketamine has emerged as the illicit drug of choice in Hong Kong and has seen increased use throughout Asia. The biliary damage from ketamine has been studied by a Chinese group that found 62% of the 257 chronic ketamine users had biliary tract anomalies. The greater the alkaline phosphatase, the higher the likelihood of finding biliary tract anomalies on imaging. Ketamine cessation has resulted in normalization of liver tests and imaging, however worsening cholangiopathy has been seen despite abstinence. In patients who present with unexplained cholangiopathy, chronic ketamine use should be considered.Figure 1.: Liver biopsy: A mild lymphoplasmacytic inflammation is noted in some triads with focal and mild interface activity. The bile ducts are injured (irregular contour, unevenly distributed nuclei, intracytoplasmic vacuoles) with focal periportal cholestasis. Immunohistochemical stain for keratin 7 confirms predominantly periportal cholestatic hepatocytes. Keratin 19 shows widespread loss of canals of Hering and focal bile duct loss. Rhodanine stain confirms periportal hepatocellular copper accumulation compatible with a chronic cholestatic process. Table 1. - Patient's hepatic function panels during initial encounter, subsequent encounter, and at least 6 months after subsequent encounter Liver Tests Reference Range & Units Initial Hospitalization Subsequent Hospitalization Most Recent Liver Tests Total bilirubin 0.2 – 1.2 mg/dL 0.8 2.9 4.5 Direct bilirubin 0 – 0.5 mg/dL 0.7 1.8 3.3 Aspartate aminotransferase 5 – 34 IU/L 75 104 88 Alanine transaminase 0 – 37 IU/L 74 129 91 Alkaline phosphatase 40 – 150 IU/L 1017 1106 845 Gamma glutamyl transferase 12 – 43 IU/L 2310 2516 1897

S3158 Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient’s improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion: DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient’s supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent liver transplantation. Our patient’s unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. Table 1. - The patient’s laboratory values, including total bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) improved after stopping Artemisinin/Bioperine Total bilirubin (mg/dL) ALP (U/L) AST (U/L) ALT (U/L) Initial labs with PCP 11 293 170 196 Repeat labs with PCP 5.6 143 75 98 3 weeks after stopping supplement 2.4 85 34 41

S3261 A Case of Rheumatoid Nodules in the Liver

Introduction: Rheumatoid arthritis (RA) has a prevalence of 0.5-1%. Extra-articular manifestations, including rheumatoid nodules (RNs), can be present in up to 40% of individuals. Rarely, RNs can manifest in the gastrointestinal system. We present a case of a 52-year old female with RA who presented with hepatic nodules and fever. Case Description/Methods: A 52-year-old woman with seronegative RA on sulfasalazine 1000mg BID presented with three weeks of fevers ranging from 101 – 103 F. She had been on adalimumab until one year ago, which was stopped after she developed a psoriatic rash. Six months ago she diagnosed with an incidental left upper lobe pulmonary nodule but IR biopsy was non-diagnostic. On admission, the patient was afebrile with stable vital signs, and the following labs: WBC 25, CRP 6.44, ESR 70, and ALP 179, with normal ALT, AST, and bilirubin. A chest, abdomen and pelvis contrast CT scan showed reduced size of the previous lung nodule but multiple new hypodensities within the liver, with the largest lesion 2cm in diameter (Figure 1a). Liver MRI confirmed numerous hepatic lesions (Figure 1b). After admission, she remained afebrile and her WBC resolved without antibiotics. Infectious, malignancy, and autoimmune workup were negative. The patient underwent a colonoscopy with no concerning signs for malignancy. She then underwent an IR liver biopsy and pathology revealed multiple necrotizing granulomas with plasma cells, most concerning for RNs. Rheumatology and hepatology were consulted and planned to increase her sulfasalazine and get repeat abdominal imaging at her next visit. Discussion: Although extra-articular disease is evident in RA, RNs in the liver are rare. A postmortem analysis of a patient from 1986 identified multiple nodules up to 5mm. In 2019, a 62 year-old female had abdominal pain and was found to have a 5cm RN in the liver. A 61 year-old male in 2020 had a 4cm liver mass resected with histology revealing a necrotizing granulomatous inflammation suggestive of a RN. Additionally, prior studies have shown that cells in RNs produce similar proinflammatory cytokines as those in synovial membranes. This could suggest cytokine release due to RNs as a cause of our patient's fevers. Although she had well controlled RA, she was also previously treated with TNF inhibitors which have been noted to cause RNs in the lungs. This may have led to her pulmonary and hepatic nodules. Overall, our case adds to the data highlighting uncommon gastrointestinal manifestations of RA.Figure 1.: Figures 1a and 1b. CT and MRI Studies Revealing Multiple Hepatic Hypodensities.

S1729 Drug-Induced Pancreatitis: Meth, Cannabis, or Meth-Laced Cannabis?,

Introduction: Drug-induced pancreatitis (DIP) is a rare entity with a 0.1 to 2% incidence of acute pancreatitis cases. Methamphetamine is a serotonergic drug used as a stimulant. It has infrequently been observed to cause pancreatic and hepatic damage due to its keen vasoconstrictive properties. Cannabis in its recreational form has also been linked with drug-induced pancreatitis. We report a 36-year-old female who presented with findings of acute pancreatitis revealing a drug-induced etiology. Case Description/Methods: The patient is a 36-year-old previously healthy female who presented with diffuse, sudden in onset abdominal pain, radiating to the back, aggravated with food without alleviating factors of 3 days duration. She reported nausea on the first day of her pain along with a single episode of nonbilious vomiting that had self-subsided. Social history was remarkable for smoking marijuana since her teenage years unremarkable for alcohol and tobacco use. She reported resorting to street, methamphetamine laced marijuana, the past month. The patient was vitally stable with a physical exam remarkable for epigastric and left lower quadrant tenderness with negative peritoneal signs. Laboratory tests showed elevated lipase, amylase, and CRP with normal liver function tests, hematocrit, BUN, bilirubin, triglycerides, and phosphocalcium balances. Ultrasound was done corroborating the absence of obstruction. Computed tomography (CT) abdomen was subsequently performed showing irregular contour of the pancreatic margins, blurring of peripancreatic fat planes, soft-tissue stranding, and trace-free fluid at the pancreatic body and tail without bile duct dilatation. Serological survey for mumps virus, cytomegalovirus (CMV), epstein barr virus (EBV), and human immunodeficiency virus (HIV) was negative. Anti-nuclear antibodies (ANA), neutrophil anti-cytoplasmic antibody (ANCA), and serum Ig G4 were also negative. She was diagnosed with mild acute pancreatitis with the culprit agent being methamphetamine-laced cannabis. The patient was followed up 3 months after agent cessation with marked symptomatic improvement and unremarkable lab work. Discussion: This case highlights that methamphetamine might also be the precipitating cause of pancreatitis in street marijuana-associated pancreatitis cases. Drug-induced pancreatitis is often challenging because there are no unique clinical characteristics to distinguish drugs from other etiologies, let alone the possibility of identifying one potential drug versus another.

S3157 Respiratory Syncytial Virus-Associated Hepatitis in Pregnancy

Introduction: Respiratory syncytial virus (RSV) predominantly affects children and typically manifests as an upper respiratory tract infection. Primary RSV infection in immunosuppressed adults may increase risks of disseminated infection manifesting as RSV hepatitis. RSV hepatitis may present with fever, abdominal pain, nausea, vomiting, jaundice, coagulopathy, and elevation of transaminases. Case Description/Methods: A 29-year-old woman with 10 weeks of pregnancy, history of anemia and vitamin B12 deficiency was admitted to the hospital for fatigue, intractable nausea, vomiting and inability to tolerate oral intake. She denied respiratory symptoms. She was taking prenatal multivitamins but denied starting new medications or supplements. At presentation, her vital signs and clinical exam were unremarkable with uterine fundus palpable just above the pubic bone. Initial laboratory work up revealed elevated liver enzymes with AST 497 U/L, ALT 712 U/L, normal total bilirubin and ALP. Abdominal ultrasound (US) demonstrated cholelithiasis without evidence of cholecystitis or common bile duct dilation. Subsequent workup including an acute hepatitis panel; CMV, EBV serology; stool H. pylori testing; and autoimmune workup was negative. HSV IgM serology was indeterminant. A respiratory viral molecular panel by PCR was positive for RSV. Abdominal US with doppler showed normal hepatic and portal vessel blood flow and magnetic resonance cholangiopancreatography was negative for choledocholithiasis. She was treated supportively with intravenous fluids, antiemetics and close fetal monitoring. Her liver enzymes peaked on hospital day 4 with AST 863 U/L, ALT 1214 U/L, total bilirubin 1.1 mg/dL. By hospital day 5, her symptoms improved, and she was discharged. At 5 week follow up, AST and ALT improved to 62 U/L and 82 U/L, respectively. Her elective laparoscopic cholecystectomy was deferred until after delivery due to symptom resolution and absence of acute cholecystitis. Discussion: Disseminated RSV a rare manifestation in immunocompromised individuals. Clinical presentation may be atypical, creating diagnostic challenges. Liver biopsy is rarely required to establish the diagnosis. RSV hepatitis is typically self-limited and can be treated with supportive care as antiviral agents have no proven efficacy. A high index of suspicion is required for early identification of RSV hepatitis as timely supportive care may prevent progression to acute liver failure. Table 1. - Laboratory Testing Done to Investigate Emesis Etiology Caption Laboratory Test Reference Range and Units Results Liver Function Tests Alanine aminotransferase (ALT) 0-34 U/L 990 (H) Aspartate aminotransferase (AST) 15-46 U/L 750 (H) Alkaline phosphatase (ALP) 38-126 U/L 89 (N) Total bilirubin 0.2-1.3 mg/dL 1.4 (H) Total Protein 6.3-8.2 g/dL 6.4 (N) Albumin 3.5-5.0 g/dL 3.6 (N) Coagulation Studies Prothrombin time (PT) 9.0-12.0 10.9 (N) International normalized ratio (INR) 0.9-1.1 1.0 (N) Viral Serologies Hepatitis A, IgM Non-reactive Non-reactive Hepatitis B, core IgM Non-reactive Non-reactive Hepatitis B, surface antigen Non-reactive Non-reactive Hepatitis C antibody Non-reactive Non-reactive Hepatitis E antibody Non-reactive Non-reactive Human immunodeficiency virus 1 and 2 antibody/antigen Non-reactive Non-reactive Herpes simplex virus 1 and 2 IgM < =0.89 0.96 (intermediate) Cytomegalovirus quantitative PCR Non-reactive Not detected Epstein Barr virus, IgM Not detected Not detected Influenza A, antigen Not detected Not detected Influenza B, antigen Not detected Not detected Respiratory Syncytial Virus Not detected Detected Autoimmune liver disease panel Liver-Kidney Microsome-1 Antibody IgG (Anti-LMK) 0.0 - 24.9 U 0.8 (N) Antinuclear antibody (ANA) titer < 1:80 < 1:80 (N) Anti-smooth muscle antibody (ASMA) 0-19 Units 6 (N) Antimitochondrial antibody (AMA) 0.0-24.9 Units 2.4 (N) Miscellaneous Rapid plasma regain (RPR) Negative Negative Total Creatinine Kinase (CK) 30-170 U/L < 20 (L) H. pylori antigen Negative Negative - H: High; N: Normal; L: Low.

S3509 A Case of Diffuse Malignant Peritoneal Mesothelioma

Introduction: Malignant Mesothelioma occurs most commonly in the pleural space but can also occur in the peritoneum in those with an extensive history of asbestos exposure. Peritoneal mesothelioma (MPeM) is relatively rare accounting for 15% of all mesotheliomas. Most patients are asymptomatic until advanced stages but will present with nonspecific abdominal symptoms. We present a case of MPeM in a male who worked in a wire hanger factory for 20 years. Case Description/Methods: An 81-year-old Arabic male presented with nausea, vomiting, abdominal distention and diarrhea lasting three weeks. His vitals were remarkable for hypertension (192/102 mmHg), and he had diffuse abdominal tenderness without peritonitis on physical exam. CT A/P with contrast showed fluid distending the small and large bowel and mild fat stranding and wall thickness of the ascending and descending colon. Ascites was also noted. Laboratory studies revealed elevated ALT (54 unit/L) with otherwise normal AST, ALP and bilirubin. CRP (87 mg/L), ESR (30 mm/hr) and WBC’s (12.9 x10^3/mm3) were all elevated. A repeat CT A/P was suggestive of small bowel obstruction and he underwent a diagnostic laparoscopy with right hemicolectomy, ileocolonic anastomosis and omentectomy. The resected obstructing mass was diffuse MPeM, epithelioid type extensively involving the small bowel muscularis propria and submucosa and focally involving the lower mucosa of the ileocecal region (T0N0). Immunohistochemical analysis showed strong positive reactions with calretinin, CK 5/6, WT-1 and D2-40. Negative reaction was present with CK20, synaptophysin, chromogranin, and prostatic markers. He received 12 cycles of nivolumab, 7 cycles of ipilibumab and palliative radiation due to increasing tumor burden but was ultimately transferred to hospice approximately 2 years after initial diagnosis. Discussion: MPeM as the primary source of mesothelioma is uncommon. Asbestos exposure confers a lower risk of MPeM in males. Patients with MPeM are typically younger at the time of diagnosis than those with pleural involvement and are usually women. Females have prolonged survival due to less aggressive histological subtypes, such as epithelial. The 3- year survival rate for MPeM after treatment is 39% for males. Our patient was 81 years-old at time of diagnosis and was a male who was likely exposed to asbestos for over 20 years. He outlived his life expectancy given his age, gender, location of mesothelioma, etiology and histological subtype.

S3125 Overlapping Hepatotoxicity and Colitis Associated With Immune Checkpoint Inhibitors

Introduction: Immunotherapy with immune checkpoint inhibitors (ICIs) has become the standard of care for many solid-organ and hematologic malignancies. Gastrointestinal toxicities are common side effects that typically occur 6 weeks after starting ICI therapy. Overlapping hepatotoxicity and colitis associated with ICIs is rare and may be overlooked, resulting in high mortality. Case Description/Methods: A 73-year-old man with metastatic squamous cell carcinoma (SCC) of the head and neck presented with intermittent, diffuse abdominal discomfort, bloating and painless non-bloody diarrhea (up to 6 episodes daily) triggered by meals. Symptom onset was 6 weeks after starting pembrolizumab for head and neck SCC. Pembrolizumab therapy was held, and supportive therapy with proton pump inhibitors, antacids and antidiarrheals provided partial symptom relief. Laboratory work up showed elevated AST 132 U/L, ALT 220 U/L, ALP 851 U/L and normal total bilirubin. ANA was elevated with titer 1:80, with normal total IgG (699.5 mg/dL) and negative serologies for anti-smooth muscle antibody, CMV, EBV, and HSV. Abdominal CT with contrast showed a dilated common bile duct (CBD) of 11 mm and a new curvilinear filling defect in the distal CBD, without choledocholithiasis. MRCP revealed mildly dilated intrahepatic biliary ducts, CBD dilation (13 mm), and an ovoid 8mm soft tissue nodule in the periampullary duodenum. Upper endoscopy was nondiagnostic. At this time, the patient’s symptoms improved, but there was high suspicion of grade-2 ICI-associated hepatitis (ICIH). Percutaneous liver biopsy showed interlobular bile duct injury with intraepithelial lymphocytes and neutrophils and a neutrophilic ductular reaction consistent with ICIH. Serial lab work demonstrated improvement of liver enzymes, with AST 77 U/L, ALT 69 U/L and ALP 667 U/L at 60 days after initial labs. Diarrhea resumed, up to 6 episodes per day, consistent with the Common Terminology Criteria for Adverse Events diagnosis of ICI-related colitis (ICIC). Initial supportive therapy failed to improve diarrhea; thus, a prednisone taper was started, resolving the colitis. He declined the option to resume immunotherapy and transitioned to comfort care (Figure 1). Discussion: Overlapping ICIH and ICIC is rare and may have discordance between symptomatology and lab findings. Early recognition of overlapping ICIH and ICIC, supportive treatment, permanent cessation of the inciting ICI and switching it with alternative immunosuppressive therapy may improve patient outcomes and quality of life.Figure 1.: Panel A - CT chest/abdomen with contrast (coronal view) showing common bile duct dilation of 1.2 cm (yellow calipers) status post cholecystectomy. Panel B. Upper endoscopy showing prominent ampulla with free-flowing bile. Panel C. Histology of percutaneous, ultrasound-guided liver biopsy with H&E staining (10×) shows preserved lobular hepatic architecture with mixed inflammatory infiltrate including lymphocytes, histiocytes, and scattered eosinophils expanding the portal tracts. Table 1. - Immune Checkpoint Inhibitor Associated Hepatitis Grades, adapted from the American Society of Clinical Oncology, 2021 Grade Criteria 1 Asymptomatic (AST or ALT > ULN to 3.0 X ULN and/or total bilirubin > ULN to 1.5 X ULN) 2 Asymptomatic (AST or ALT > 3.0 to ≤ 5 X ULN and/or total bilirubin > 1.5 to ≤ 3 X ULN) 3 AST or ALT 5-20 X ULN and/or total bilirubin 3-10 X ULN, OR symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis; and reactivation of chronic hepatitis 4 AST or ALT > 20 X ULN and/or total bilirubin > 10 X ULN OR decompensated liver function (e.g., ascites, coagulopathy, encephalopathy, and coma) Abbreviations: AST, aspartate transferase; ALT, alanine transaminase; ULN, upper limit of normal.

EFFICACY AND SAFETY OF NIPOCALIMAB, AN FCRN BLOCKER, IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA): ENERGY PHASE 2/3 STUDY DESIGN

Warm autoimmune hemolytic anemia (wAIHA) is characterized by the destruction of red blood cells (RBCs) by pathogenic autoantibodies which bind to RBCs and lead to their clearance in the spleen and liver. Patients with wAIHA can experience acute worsening of anemia, which can be a medical emergency, and have an increased risk of thromboembolic events and premature death. Nipocalimab is a fully human, aglycosylated, effectorless IgG1 monoclonal antibody that blocks the IgG binding site on the neonatal Fc receptor (FcRn) with high affinity. FcRn, which is expressed in endothelial cells, is responsible for recycling IgG into the circulation and for the relatively long half-life of IgG antibodies compared to other Igs. It is expected that nipocalimab, by blocking IgG binding to FcRn, will prevent IgG recycling and lower pathogenic IgG autoantibodies that cause many autoantibody diseases, including wAIHA. Nipocalimab has been studied in multiple phase 1 studies in healthy subjects and in a completed phase 2 study in subjects with Generalized Myasthenia Gravis (gMG). Treatment with nipocalimab was associated with rapid and durable total serum IgG and pathogenic IgG autoantibody reduction and meaningful clinical response. Here we share the rationale and study design for an adaptive, phase 2/3 multicenter, randomized, double-blind, placebo-controlled study in patients with wAIHA whose aim is to evaluate the efficacy, safety, tolerability, PK, and PD of nipocalimab compared with placebo (NCT04119050). Male or female subjects ≥18 years of age who have been diagnosed with primary or secondary wAIHA and have not experienced a sufficient response or have not tolerated currently available treatments will be included in the study. Subjects with cold antibody AIHA, cold agglutinin syndrome, mixed type (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria will be excluded. Participants will be randomized 1:1:1 to receive nipocalimab at two different dose schedules or placebo. Following completion of 24 weeks of double-blind treatment, participants may enter an open-label extension period to receive nipocalimab. The primary endpoint is percentage of participants achieving durable response of improvement in hemoglobin (Hgb). The main secondary endpoints are change from baseline in the total score from the FACIT-Fatigue Scale, number of participants who attain normal lactate dehydrogenase, normal haptoglobin, and normal indirect bilirubin levels at a minimum of 3 consecutive visits after baseline. ENERGY is a phase 2/3 study that will evaluate the efficacy and safety of nipocalimab in wAIHA. ENERGY is currently enrolling globally. IM received research support from Alexion, Annexon, Incyte, Kezar, Momenta, Rigel, and Sanofi; and served as a consultant for Apellis, Janssen, Momenta, Novartis, Rigel, and Sanofi. BF is a consultant of Alexion, Amgen, Janssen, Momenta, and Novartis. DC is an employee of Janssen Global Services, LLC, which is a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson; was an employee of Momenta. AMBP is an employee of Janssen Latin America, which is a wholly owned subsidiary of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson. MHJ was an employee of Momenta.

S1708 Combination of Pancreatic and Hepatic Pseudocyst in a Patient With Pancreatitis: A Case Report

Introduction: Pancreatic pseudocysts are common occurrences after episodes of acute pancreatitis. Up to 20% of pseudocysts are extra-pancreatic throughout the abdomen including intrahepatic. There are only a few cases of hepatic pseudocysts reported in the literature. We report this unique case with both pancreatic and intrahepatic pseudocysts occurring at the same time in a patient with pancreatitis. Case Description/Methods: A 56-year-old White woman with history of alcoholism and chronic pancreatitis, presented with epigastric and left upper quadrant abdominal pain radiating to the left shoulder. Examination revealed tenderness in the epigastric and left upper quadrant of the abdomen. Labs showed an elevated lipase of 217 IU/L (13-60), normal total bilirubin and transaminases, hemoglobin of 9.1 g/dL(11.5-15), and slight leukocytosis 12.6 K/uL (3.7-10.4). She was admitted 3 times in the last 4 months. Prior computerized tomography (CT) scan showed pseudocysts in the head and tail of the pancreas. CT scan this admission showed a decreased size of pseudocyst in the pancreatic head from 2.5 cm to 2.2 cm and pancreatic tail from 4.2 cm to 3.7 cm (Figure). It also showed 2 subcapsular fluid collections in the left lobe of the liver measuring 9X5X2cm and 9X7X3 cm. Percutaneous drainage of the hepatic cysts with the placement of a drainage catheter was performed by interventional radiology. 50 mL of bilious appearing fluid was drained with negative gram stain and cultures with an elevated fluid amylase level of 1,765 U/L. The patient’s pain improved and a subsequent CT a few weeks after discharge showed a decrease in the size of the hepatic cysts. Discussion: This is the first documented case of combined pancreatic and intrahepatic pseudocyst formation. Elevated amylase level in the hepatic fluid analysis confirmed the diagnosis of a hepatic pseudocyst. The interesting fact is that the size of the pancreatic pseudocyst decreased as the hepatic pseudocyst increased because of fluid tracking likely in the pre-renal space or along the hepato-gastric ligament. The diagnosis of hepatic pseudocyst needs to be considered in a patient with new hepatic fluid collection with a recent history of pancreatitis and pancreatic pseudocyst.Figure 1.: A – Axial CT showing previous pancreatic pseudocyst prior to admission B – Axial CT showing new hepatic pseudocyst adjacent to falciform ligament during admission C – Axial CT showing drain in hepatic pseudocyst.

S3194 The Search for Chest Pain and Shortness of Breath: Drug-Induced Liver Injury

Introduction: Patients with drug-induced liver injury (DILI) are often asymptomatic and have undetected increases in their liver function tests (LFTs). Symptoms of DILI, if present, are vague, mimic a host of diseases, and are attributable to other etiologies before DILI is considered. In our case, we present a series of overlapping and vague symptoms that ultimately were attributed to DILI. Case Description/Methods: We describe the case of a 43-year-old male who presented to his cardiologist office with complaints of chest pain followed by shortness of breath (SOB). The patient has a past history for coronary artery disease and two kidney transplants on tacrolimus. Due to the patient's cardiac history, cardiac catheterization was performed which did not show any signs of re-stenosis or obstructive disease. He underwent evaluation for possible pulmonary cause as well including pulmonary function testing and diagnostic imaging which were normal. Laboratories drawn showed elevated liver enzymes (ALT 154, AST 56) and gamma-glutamyl transferase (GGT) of 382 with a normal total bilirubin. Abdominal ultrasound showed no evidence of biliary dilation, choledocholithiasis, or structural abnormality. On further review, patient had recently started a second immunosuppressant, mycophenolate, around the time he started to experience these unexplained symptoms. Additionally, on thorough physical exam, it was noted that the patient’s subjectively stated chest pain was isolated to the epigastrium on palpation. Liver enzymes were continually monitored with eventual return to normal ranges with resolution of reported pain and SOB without having to hold any immunosuppressant agents. Discussion: This case illustrates the unusual clinical presentation of hepatic injury secondary to an unusual cause of DILI. It was surmised that the mild transient elevation in liver enzymes and GGT was due to the initiation of mycophenolate. Mycophenolate is known to cause liver injury in rare cases and in the setting of inflamed liver tissue irritating Glisson’s capsule, abdominal tenderness can develop. It is important to perform an encompassing physical examination to correlate patients’ subjective complaints with objective findings. For patients taking hepatotoxic medications, widening one’s differential diagnosis to include DILI can ensure minimalization of liver damage.

S1764 Localized Truncal Xanthoderma Secondary to Bile Leakage Post Laparoscopic Cholecystectomy

Introduction: Xanthoderma is a yellow to yellow-orange discoloration of the skin. The 2 main pathologies leading to xanthoderma are jaundice and carotenoderma. Although the most common mechanism for jaundice is the elevation of serum bilirubin, localized jaundice can rarely occur in the settings of bile leakage into the retroperitoneal space. Case Description/Methods: A 40-year-old female patient presented with biliary pain. Examination showed right upper quadrant tenderness. Initial labs revealed total bilirubin of 49 µmol/L, with a direct bilirubin of 47µmol/L (Table). The US abdomen showed cholelithiasis. MRCP showed a small distal CBD stone; CBD diameter was 9 mm. She underwent laparoscopic cholecystectomy with an intraoperative cholangiogram. The small distal CBD stone was pushed to the duodenum. Repeated IOC showed a smooth passage of contrast. Her clinical status didn’t improve postoperatively, and her bilirubin was persistently elevated. Localized yellowish discoloration of the right side of the abdominal wall and the suprapubic area was observed 5 days after the surgery (Figure A). Repeated MRCP showed suspicious distal CBD stone with gall bladder bed collection and diffuse inflammatory change of the right abdominal wall. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a bile leak at the site of the cystic stump (Figure A) and a small filling defect in the distal CBD. Sphincterotomy and CBD stenting were performed. The bilirubin improved gradually after ERCP, but the abdominal pain persisted. CT abdomen showed large perihepatic and perisplenic fluid collection measuring 10x 17.6x 20 cm, necessitating US-guided percutaneous drainage. Turbid yellow fluid was drained, confirming that the collection was a biloma related to the bile leak. Four weeks later, the percutaneous drain was removed after the collection resolved. Repeated ERCP showed no biliary leak. Discussion: In our patient, the localized xanthoderma post laparoscopic cholecystectomy was secondary to bile leakage from the cystic duct stump. In a similar case report, the authors explained that the localized xanthoderma occurred as a result of bile staining of the tissues deep to the membranous layer of the superficial fascia (fascia of Scarpa) after the bile has leaked from the cystic duct through the hepatoduodenal ligament. The management of our patient involved sphincterotomy and bile duct stenting combined with percutaneous drainage of the collections.Figure 1.: A: Localized yellowish discoloration of the anterior abdominal wall. B: An ERCP fluoroscopic image showing contrast leakage near the cystic stump. Table 1. - Laboratory investigations Laboratory test Patient's value Normal range Total bilirubin 49 µmol/L 0-21 Direct bilirubin 47 µmol/L 0-9 AST 287 U/L 0-32 ALT 249 U/L 0-33 Alkaline phosphatase 264 U/L 35-104

S3188 The Tale of an Ancient Herb: A Stress Reliever or a Liver Stressor

Introduction: Ashwagandha is found in several herbal products today. However, there is a paucity of literature regarding its safety. Our case serves to remind physicians about the potential liver toxicity of Ashwagandha and to illustrate how early recognition of drug-induced liver injury (DILI) and discontinuation of the offending substance can be lifesaving. Case Description/Methods: A 58-year-old man with a remote history of hepatitis B and C presented with nausea, vomiting, and right upper quadrant abdominal pain of one day duration. He reported using an herbal supplement called “Primal Male,” which contained Ashwagandha as a main ingredient, over the past two weeks. He was normotensive, tachycardic up to 120 beats per minute (bpm), and febrile. The initial laboratory studies were notable for elevated AST level of 954 U/L, ALT level of 860 U/L, and a normal alkaline phosphatase level of 101 U/L. He had a normal total bilirubin level and an international normalized ratio of 1.3. His complete blood count and renal function were unremarkable. His creatinine kinase (CK) level was also within the normal range. His drug test, alcohol level, and acetaminophen level were unremarkable. The viral panel did not suggest active viral infections. His autoimmune panel was negative. An abdominal CT scan did not reveal any acute abnormality. In the following days, his symptoms worsened, and he became more encephalopathic. His AST, ALT, total bilirubin, and INR levels continued to rise. He developed hypotension and received intravenous fluids and midodrine. He also completed a course of N-acetylcysteine treatment. On the fifth day of admission, he underwent a transjugular liver biopsy. Liver histology showed active lymphocytic hepatitis with moderate inflammation (primarily lymphocytes, abundant neutrophils, and occasionally eosinophils) around the portal tract. On the sixth day of hospitalization, he reported decreasing pain and was more hemodynamically stable. His liver enzymes also showed improvement. The cause of acute liver injury was suspected to be drug-induced liver injury from Ashwagandha use. He was counseled to avoid the use of the herbal supplement and other hepatotoxic products. One month later, his liver enzymes were in normal range. Discussion: DILI is a less common form of liver injury but is a leading cause of acute liver failure in the United States. Ashwagandha has been reported in a few cases of DILI. It is important to have an early suspicion of the offending agent and avoid further substance exposure.

S2895 A Rare Case of Inferior Pancreaticoduodenal Artery Pseudoaneurysm Rupture Following Endoscopic Retrograde Cholangiopancreatography

Introduction: Hemorrhage is a known potential complication of endoscopic retrograde cholangiopancreatography (ERCP), often occurring at the site of sphincterotomy. Less commonly, intra- and retroperitoneal hemorrhage can occur secondary to splenic, hepatic, or vascular injury. Here we present a rare case of inferior pancreaticoduodenal artery (IPDA) pseudoaneurysm (PSA) rupture following ERCP in a patient with a large diaphragmatic hernia. Case Description/Methods: The patient is a 68 year old man with a history of hypertension, chronic kidney disease, and splenectomy. He presented with jaundice, fatigue, and labs notable for hypoglycemia, acidemia, acute kidney injury, normal transaminase levels, alkaline phosphatase (129 IU/L), total bilirubin (4.2 mg/dL), direct bilirubin (2.5 mg/dL), and lipase (157 IU/L). Computed tomography (CT) with contrast revealed choledocholithiasis with a 1.2 cm stone in the head of the pancreas associated with pneumobilia, intra- and extrahepatic ductal dilation, and pancreatic ductal dilation. A large left diaphragmatic hernia with protrusion of nonobstructed loops of large and small bowel into the left hemithorax was also noted. He underwent ERCP with biliary sphincterotomy and removal of one stone. One large stone remained. A plastic stent was placed in the common bile duct with plans to repeat ERCP in 4-6 weeks with cholangioscopy and electrohydrolic lithotripsy. Following ERCP, the patient developed acutely worsening anemia without overt evidence of lumenal gastrointestinal bleeding. CT angiography revealed active extravasation and a PSA within an intra-abdominal hematoma (18.4 x 8.5 cm). The patient then underwent mesenteric angiography which showed one multilobulated (2 x 1.8 cm) and one smaller PSA arising from an IPDA branch. Coil embolization of the dominant PSA was performed, achieving hemostasis. (Figure, Table) Discussion: Visceral artery aneurysm (VAA) rupture is an exceedingly rare complication of ERCP with IPDA pseudoaneurysms accounting for just 2% of VAA. Although there is a known association of VAA with pancreatitis, the mechanism for PSA formation following ERCP is unclear. It is thought to be associated with sphincterotomy with rupture caused by direct mechanical injury related to pancreaticobiliary manipulation. Mortality related to VAA rupture and hemorrhage can be as high as 19%. A high index of suspicion and early detection followed by angioembolization are critical for reducing mortality.Figure 1.: (A) CT with contrast showing choledocholithiasis with a 1.2 cm stone in the head of the pancreas. (B) CT angiography showing active extravasation and a pseudoaneurysm (PSA) within an intra-abdominal hematoma (18.4 x 8.5 cm). (C) Mesenteric angiography which showed one multilobulated (2 x 1.8 cm) and one smaller PSA arising from an inferior pancreaticoduodenal artery branch. Table 1 - Summary of currently available case reports of inferior pancreaticoduodenal artery (IPDA) pseudoaneurysm (PSA) development following endoscopic retrograde cholangiopancreatography (ERCP) Age/Sex Comorbidities ERCP Indication Interventions Symptom Diagnosis Treatment Al-Jeroudi et al 2001 76 F None Palliation of pancreatic carcinoma Precut sphincterotomy, biliary stent Abdominal pain IPDA PSA Embolization Rim et al 2021 27 M Sickle cell disease Choledocholithiasis Sphincterotomy, stone extraction, biliary stent, pancreatic duct stent Abdominal pain, acute anemia IPDA PSA rupture Embolization Current Case 68 M Hypertension, chronic kidney disease, diaphragmatic hernia Choledocholithiasis Sphincterotomy, stone extraction, biliary stent Abdominal pain, acute anemia IPDA PSA rupture Embolization