Acetaminophen Levels Research Articles

AN UNUSUAL CAUSE OF TRANSAMINITIS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Elevation of liver enzymes often results from damage to the liver or biliary tract. Transaminitis may be seen in patients with sign and symptoms suggestive of liver disease or it may be an incidental finding on laboratory investigations. The initial evaluation of a patient with transaminitis includes obtaining thorough history to identify potential risk factors and performing a physical examination to look for the signs of liver disease and clues to the etiology. CASE PRESENTATION: 36 year old Caucasian male with history of type-1 diabetes mellitus presented with generalized weakness, fatigue and body aches. Hemodynamics were stable. He was noted to have sodium 123 meq/L( 135-145), potassium 6.9 meq/L( 3.7-5.2 meq/L), bicarbonate 21 meq/L( 23-30 meq/L) creatinine 2.31 mg/dL( 0.8-1.1 mg/dL), AST 2792 U/L( 5-40 U/L), ALT 1671U/L( 7-56 U/L), total bilirubin 0.7 mg/dL , blood glucose 966 mg/dL , beta-hydroxybutyrate 0.3 mmol/L( 0.4-0.5 mmol/L), CK total 109 U/L( 22-98 U/L). Patient was diagnosed with hyperglycemic-hyperosmolar state. Appropriate therapy was started including intravenous fluids and insulin. Prior blood workup did not reveal any liver function abnormality. There was no history of intravenous drug use, blood transfusions, skin tattooing or any recent travel. Salicylate and acetaminophen levels were unremarkable. Differential diagnosis including acute viral hepatitis, drug induced liver injury, infiltrative disease, autoimmune and alcoholic hepatitis were considered. Blood workup including hepatitis A, B & C serology, ANA, anti-mitochondrial and anti-smooth muscle antibody were unremarkable. Alpha-1 antitrypsin, serum ceruloplasmin and iron studies were unremarkable as well. During the course of hospitalization, transaminitis significantly improved (AST 50 U/L and ALT 317 U/L) with the treatment of hyperglycemia, hence, was attributed to severe hyperglycemia associated with poorly controlled diabetes mellitus. Later, patient had normalization of liver enzymes upon outpatient follow up. DISCUSSION: Glycogen Hepatopathy (GH) is a rare cause of transaminitis in patients with uncontrolled type 1 diabetes mellitus. It is characterized by hepatomegaly related to glycogen accumulation and elevated liver enzymes. Glycogen accumulation takes place in the liver when hyperglycemia activates glycogen synthase enzyme.The hallmark of GH is its reversibility with improved glycemic control.The correct diagnosis is important given its potential resolution after improved glycemic control. CONCLUSIONS: Hyperglycemia is a rare cause of transaminitis but should be kept in differentials particularly in patients with diabetes mellitus. Reference #1: Kumar K, Mehershahi S, Chime C, Tariq H, Nayudu SK, Chilimuri S. Glycogen Hepatopathy: A Rare and Underrecognized Cause of Recurrent Transaminitis in Patients with Uncontrolled Type 2 Diabetes Mellitus. Case Rep Gastroenterol. 2018;12(2):466-472. Published 2018 Aug 23. doi:10.1159/000492205 Reference #2: J. West, J. Brousil, A. Gazis et al., “Elevated serum alanine transaminase in patients with type 1 or type 2 diabetes mellitus,” QJM, vol. 99, no. 12, pp. 871–876, 2006. Reference #3: Kumar, Kishore MD; Mehershahi, Shehriyar MD; Nayudu, Suresh Kumar MD; Singh, Amandeep MD; Bajantri, Bharat MD; Chilimuri, Sridhar MDAuthor Information American Journal of Gastroenterology: October 2016 - Volume 111 - Issue - p S851-S852 DISCLOSURES: No relevant relationships by Muhammad Aamir, source=Web Response No relevant relationships by Muhammad Afzal, source=Web Response No relevant relationships by Saleha Dar, source=Web Response

S2468 Crigler-Najjar Syndrome Type 2 in an Adult Amish Male: A Rare Case Report of Unexplained Jaundice

INTRODUCTION: Crigler-Najjar type 2 syndrome is a rare genetic disorder caused by reduced enzyme activity of glucuronyl transferase, resulting in abnormally elevated levels of unconjugated bilirubin in blood. There are an estimated 100 known cases worldwide. We present a case of Crigler-Najjar type 2 (Arias syndrome) in an adult Amish male with new unexplained jaundice. CASE DESCRIPTION/METHODS: A 28 year old male with no medical history presented with 5 days of intermittent, right upper quadrant discomfort and jaundice. He denied any associated nausea, emesis or diarrhea. The night prior to symptom onset, he consumed several alcoholic beverages along with an unknown amount of acetaminophen. Initial laboratory work-up showed AST 10 unit/L, ALT 25 unit/L, total bilirubin 5.4 mg/dL and lipase 79 unit/L. Acetaminophen level was undetectable. Abdominal ultrasound demonstrated a heterogeneous liver measuring 15.26 cm, cholelithiasis and common bile duct of 3 mm in diameter. Endoscopic ultrasound revealed similar findings. Repeat liver testing showed uptrending total bilirubin of 8.4 mg/dL with indirect predominance (8.0 mg/dL).Viral hepatitis panel was negative. His abdominal pain resolved with simultaneous improvement of bilirubin levels without intervention. Genetic testing for UGT1A1*28 was sent and he was discharged in stable condition. Outpatient follow up revealed a single copy of the UGT1A1*28 allele, confirming Crigler-Najjar type 2. DISCUSSION: Different mutations to the coding sequence of the enzyme uridine diphosphate-glucoronyl transferase (UGT1A1) result in a spectrum of diseases known as Crigler-Najjar type 1 (CN1) and Crigler-Najjar type 2 (CN2). CN1 is diagnosed in infancy and results from absent or low levels of UGT1A1 due to abnormal protein production. CN2 typically presents later in life from point mutations that result in a single amino-acid substitution, rendering decreased enzymatic activity. Under physiologic stress, patients can develop unconjugated hyperbilirubinemia. Treatment of CN2 usually involves CYP450 induction with phenobarbital, which can also help differentiate between these 2 syndromes. While only about 100 cases of CN2 are known, studies have reported nearly 20% of these within the Pennsylvania Amish population. After thorough review of our patient’s family history, patrilineal descent of this population was discovered. Therefore, while a diagnostic challenge, specific family history can improve pretest probability for genetic testing of UGT1A1*28.

S2467 Acute Liver Failure Associated With Therapeutic Doses of Intravenous Acetaminophen

INTRODUCTION: Drug induced liver injury is an uncommon, but important phenomenon responsible for nearly half of all acute liver failure (ALF) cases in the US. The majority of these cases are due to Acetaminophen (APAP) which is hepatotoxic in a dose-dependent pattern. Current guidelines suggest that daily dosing of less than 4 grams a day is safe. However, this dose can be hepatotoxic in patients with underlying liver disease, longer duration of use or malnutrition. The following case demonstrates therapeutic acetaminophen dosing causing acute liver failure. CASE DESCRIPTION/METHODS: A 67-year-old Caucasian female with a BMI of 19.7 kg/m2.was admitted for bowel obstruction due to adenocarcinoma in the sigmoid colon. She had no history of liver disease, alcohol use, acetaminophen use and had normal aminotransferases on admission. The patient remained hemodynamically stable while a pre-surgical evaluation was conducted. She received an average of 3-4g/day of IV APAP for pain over 4 days and was on a liquid diet. On hospital day 5, laboratory evaluation showed an INR of 6.1, which was notably 1.0 before admission, and her liver chemistries were markedly elevated in a hepatocellular pattern. The patient had new psychomotor slowing meeting criteria for ALF. She was not a transplant candidate. Her acetaminophen level was 58.9 mcg/mL 2-hours after her last dose. APAP was discontinued and IV NAC was started. Evaluation of other causes of liver failure to include ultrasound of liver and serologic evaluation for EBV, CMV, HSV, HAV, HBV, HEV, AIH, and Wilson’s disease were unremarkable. Review of her medical record did not reveal any medications to explain her acute liver failure. The patient was closely monitored in the ICU and the coagulopathy, mental status and liver chemistries all improved. A presumptive diagnosis of APAP induced ALF was made. She subsequently underwent an open colectomy without complication. DISCUSSION: While generally safe in therapeutic dosing, we present a case of IV APAP causing ALF. Therapeutic dosing causing hepatoxicity has been associated with malnourishment, low BMI, advanced age, fasting, and longer duration of use. IV APAP has slightly different pharmacodynamics that may increase this risk but has been rarely described. This patient’s fasting state, age and malnutrition likely contributed to ALF. Similar to patient’s with cirrhosis, lower dosing (< 2 G/day) may be more appropriate in this patient population.Table 1.: Hospital Course with Laboratory Data.Figure 1.: Hospital Course with Laboratory Data.Figure 2.: Acetomenophen Dosing during admission.

A DANGEROUS DRUG AND HERBAL MIXTURE

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Serotonin syndrome (SS) is a life threatening disorder characterized by autonomic dysfunction, altered mental status and neuromuscular excitation (1). Muscle rigidity and hyperthermia can cause cellular damage and enzyme dysfunction leading to rhabdomyolysis, myoglobinuria, metabolic acidosis and multi-organ failure (1). SS is associated with drugs that decrease serotonin breakdown, reuptake or increase its release (1). CASE PRESENTATION: A 20-year-old male with depression, anxiety and substance abuse, presented with dyspnea for two weeks accompanied by non-productive cough and palpitations. For the past two days he reported insomnia and anorexia. His symptoms began after taking phenylethylamine (40 mg daily) and most recently Katrom (Mitragyna speciosa) for his mood. In addition, he takes perphenazine 2 mg-amitriptyline 10 mg per day prescribed by his psychiatrist for anxiety. Bupropion and sertraline were recently discontinued due to lack of symptomatic improvement. He was hemodynamically stable and afebrile, but he was tachycardic, tachypneic without hypoxemia. His neurological examination was significant for bilateral jerk nystagmus, clonus, tremor and hyperreflexia in all four extremities. Patient met Hunter criteria for serotonin syndrome and was admitted to the intensive care unit. EKG showed sinus tachycardia with normal QT interval. Laboratory showed rhabdomyolysis (creatinine phosphokinase (CK) 5068 U/L), mild transaminitis (ALT 50 U/L, AST 97 U/L) and anion gap metabolic acidosis with a bicarbonate of 8 mmol/L. Renal function was normal without electrolyte disturbances. Serum acetaminophen, alcohol, salicylate and lactic acid levels were normal. Urine drug screen was negative. However, urine organic acid panel was significant for elevated ketones and phenylacetate levels. Patient was placed on an intravenous bicarbonate infusion and benzodiazepines with resolution of neurological symptoms within 2 days. The psychotropic agents were discontinued as well. Acid-base balance and CK levels normalized. DISCUSSION: Multiple medications including herbal supplements increase the risk of SS. Phenylethylamine is an "endogenous amphetamine" metabolized by monoamine oxidase to phenylacetate (2). Additionally, Kratom is an understudied psychoactive plant, with stimulant and opiate effects (3). However, it is unclear how much this drug contributed to the development of symptoms. Literature on the acute toxicity of Kratom is confounded by the concomitant use of other drugs (3). CONCLUSIONS: Early recognition of SS is essential to initiate supportive treatment and stop all potential substances responsible for serotonin mediated toxicity. It is important to recognize herbal medications as a potential cause of SS. Reference #1: Wang RZ, Vashistha V, Kaur S et al. Serotonin Syndrome: Preventing, recognizing, and treating it. Cleveland Clinic Journal of Medicine. 2016; 83 (11): 810-817. Reference #2: Irsfeld M, Spadafore M and PruB B. β-phenylethylamine, a small molecule with a large impact. Webmedcentral. 2014; 4(9): 1-15. Reference #3: Swogger MT and Walsh Z. Kratom use and mental health: A systematic review. Drug and Alcohol Dependence. 2018; 183: 134-140. DISCLOSURES: No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Ximena Solis, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response

S2737 When the Student Becomes the Patient: A Case of Epstein-Barr Virus-Induced Acute Liver Injury

INTRODUCTION: Viral hepatitis is a diagnosis that can lead to acute liver injury and commonly occurs following an acute Hepatitis A or B infection. Epstein-Barr virus (EBV) is a rare cause of acute viral hepatitis. We present a case of acute liver injury secondary to acute EBV infection. CASE DESCRIPTION/METHODS: A 25-year-old female medical student with no significant past medical history presented with five days of fever, sore throat, nausea, and left upper quadrant abdominal pain while on her Pediatric rotation. She was afebrile, tachycardic to 106 beats/min, and demonstrated tender cervical lymphadenopathy, exudative tonsillar enlargement, and splenomegaly on physical exam. Heterophile antibody was negative three days prior to presentation. Initial studies revealed a leukocytosis of 12,600/mm3 and elevated liver enzymes (AST 421 U/L, ALT 788 U/L, alkaline phosphatase 404 U/L, total bilirubin 1.4 mg/dL, and INR 1.3). CT abdomen revealed hepatosplenomegaly. Hepatic vasculature was patent on doppler ultrasound with an unremarkable gallbladder and biliary tree. Subsequent studies were pertinent for an undetectable serum acetaminophen level, negative Hepatitis A-C serologies, and negative cytomegalovirus PCR. EBV serologies were positive for acute infection including an elevated viral capsid antibody, IgM, IgG, and negative nuclear antigen antibody. The patient was discharged with supportive treatment and followed ten days later in clinic with liver enzymes improved to near normal levels. DISCUSSION: Infectious mononucleosis from EBV infection is associated with development of acute hepatitis in 80% of cases. Diagnosis may be delayed due to high rate of false negative heterophile antibodies early in the disease course. Most cases are subclinical with hepatomegaly occurring in only 14% of cases. The pattern of liver injury is typically hepatocellular. Serum aminotransferases exhibit a transitory rise to three-fold the upper limit of normal, peak in the second or third week of illness, and normalize within thirty days. Treatment is typically supportive, though steroids and antivirals have been used in severe cases. Viral hepatitis is a common cause of acute liver injury, second to drug-induced liver injury, and accounts for 10% of acute liver failure. This case highlights the importance of including uncommon causes of viral hepatitis in the differential for acute liver injury, particularly in patients without traditional risk factors for hepatitis.

S2400 Typhoid Fever: An Unusual Cause of Acute Hepatitis

INTRODUCTION: Typhoid fever, a disease highest in incidence in South Asia, is due to Salmonellae ingestion via feces-contaminated food or water. While hepatic involvement is not rare given colonization of reticuloendothelial tissues, an acute hepatitis picture, as seen here, is unusual. CASE DESCRIPTION/METHODS: A 25 year old female without past medical history presented febrile, tachycardic, and hypotensive after 8 days of fatigue, fevers, chills, myalgias, headaches, nausea, and emesis following a trip to Miami. She had taken daily Acetaminophen since onset and denied other medication, herbal, and alcohol consumption. Of note, the patient emigrated to the United States 9 months prior and made a 3 month trip home to the Indian subcontinent 3 weeks before presentation. While there, she took Acetaminophen and a course of Amoxicillin. She and multiple family members also experienced fever, nausea, emesis, and diarrhea after consuming raw vegetables. Notable labs include leukopenia at 4.1, AST 593, ALT 560, and ALP 148. Urgent care labs 2 days prior were significant for AST 68, ALT 59, ALP 106, and negative hepatitis serologies. She received Ceftriaxone, IV fluids, and NAC, though plasma Acetaminophen level resulted as < 5 mcg. After blood cultures yielded gram negative rod bacteremia, antibiotics were changed to Piperacillin/Tazobactam. Abdominal ultrasound was unremarkable and triple phase CT showed mild hepatic heterogeneity. Repeat hepatitis serologies, CMV, EBV, autoimmune markers, malarial smears, and HIV were among tests ordered to determine acute transaminitis etiology. Blood cultures eventually revealed Salmonella enterica susceptible to Amoxicillin. Transaminases continued to downtrend after 5 days of hospitalization and she was successfully discharged home. DISCUSSION: Acute febrile illness in a patient recently abroad prompts investigation into diseases endemic to the region from which a patient has travelled. For the Indian subcontinent, typhoid fever may be a culprit, but its nonspecific presentation renders suspicion difficult especially when complicated by acute transaminitis and DILI concerns. As with our patient, diseases such as malaria, hepatitis, and HIV should also be considered. Depending on individual inoculum as well as host immunocompetence, incubation may be 5-21 days with prolonged fever for up to 1 month if the disease goes untreated. Interestingly, leukopenia is noted in 15-25% of cases. Blood cultures, integral to the work-up of recurrent fever, ultimately led to our diagnosis.

Sphingolipid metabolism as a marker of hepatotoxicity in drug-induced liver injury

Drug-induced liver injury (DILI) has a substantial impact on human health and is a major monetary burden on the drug development process. Presently, there is a lack of robust and analytically validated markers for predicting and early diagnosis of DILI. Sphingolipid metabolism and subsequent disruption of sphingolipid homeostasis has been documented to play a key role contributing to hepatocellular death and subsequent liver injury. A more comprehensive understanding of sphingolipid metabolism in response to liver toxicity has great potential to gain mechanistic insight into hepatotoxicity and define molecular markers that are responsible for hepatocyte dysfunction. Here, we present an analytical platform that provides multidimensional mass spectrometry-based datasets for comprehensive structure characterization of sphingolipids extracted from human primary hepatocytes (HPH) exposed to toxic levels of acetaminophen (APAP). Sphingolipid metabolism as measured by characterization of individual sphingolipid structure was sensitive to APAP toxicity displaying a concentration-dependent response. A number of sphingolipid structures were differentially expressed across varying APAP exposures highlighting the unique role sphingolipid metabolism has in response to hepatotoxicity and its potential use as a molecular marker in DILI.

Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity

Despite evidence of an association between prenatal acetaminophen exposure and attention-deficit/hyperactivity disorder (ADHD) in offspring, the drug is not contraindicated during pregnancy, possibly because prior studies have relied on maternal self-report, failed to quantify acetaminophen dose, and lacked mechanistic insight. To examine the association between prenatal acetaminophen exposure measured in meconium (hereinafter referred to as meconium acetaminophen) and ADHD in children aged 6 to 7 years, along with the potential for mediation by functional brain connectivity. This prospective birth cohort study from the Centre Hospitalier Université de Sherbrooke in Sherbrooke, Québec, Canada, included 394 eligible children, of whom 345 had meconium samples collected at delivery and information on ADHD diagnosis. Mothers were enrolled from September 25, 2007, to September 10, 2009, at their first prenatal care visit or delivery and were followed up when children were aged 6 to 7 years. When children were aged 9 to 11 years, resting-state brain connectivity was assessed with magnetic resonance imaging. Data for the present study were collected from September 25, 2007, to January 18, 2020, and analyzed from January 7, 2019, to January 22, 2020. Acetaminophen levels measured in meconium. Physician diagnosis of ADHD was determined at follow-up when children were aged 6 to 7 years or from medical records. Resting-state brain connectivity was assessed with magnetic resonance imaging; attention problems and hyperactivity were assessed with the Behavioral Assessment System for Children Parent Report Scale. Associations between meconium acetaminophen levels and outcomes were estimated with linear and logistic regressions weighted on the inverse probability of treatment to account for potential confounders. Causal mediation analysis was used to test for mediation of the association between prenatal acetaminophen exposure and hyperactivity by resting-state brain connectivity. Among the 345 children included in the analysis (177 boys [51.3%]; mean [SD] age, 6.58 [0.54] years), acetaminophen was detected in 199 meconium samples (57.7%), and ADHD was diagnosed in 33 children (9.6%). Compared with no acetaminophen, detection of acetaminophen in meconium was associated with increased odds of ADHD (odds ratio [OR], 2.43; 95% CI, 1.41-4.21). A dose-response association was detected; each doubling of exposure increased the odds of ADHD by 10% (OR, 1.10; 95% CI, 1.02-1.19). Children with acetaminophen detected in meconium showed increased negative connectivity between frontoparietal and default mode network nodes to clusters in the sensorimotor cortices, which mediated an indirect effect on increased child hyperactivity (14%; 95% CI, 1%-26%). Together with the multitude of other cohort studies showing adverse neurodevelopment associated with prenatal acetaminophen exposure, this work suggests caution should be used in administering acetaminophen during pregnancy. Research into alternative pain management strategies for pregnant women could be beneficial.

Bioavailability of rectal acetaminophen in children following anorectal surgery

BackgroundAcetaminophen is widely used as an analgesic and antipyretic agent in pediatrics.Although bioavailability of rectal acetaminophen is unpredictable, rectal route is a usual and acceptable method of prescription. Major anorectal surgery may alter the normal structure of the surgical site, especially the vascular elements and the normal connections between port and systemic vessels. As a result the pharmacokinetics of rectal medications might also be altered.Based on this hypothesis, we decided to study acetaminophen plasma concentration among children who underwent these types of surgeries to determine the pharmacokinetic of absorption, plasma concentration, safety, and efficacy of rectal acetaminophen. Materials and methodsThe study included 20 cases with previous history of pull-through procedure owing to Hirschsprung's disease (HD), 20 cases with imperforate anus (IA) reconstructive surgeries who were admitted for colostomy closure, and 20 otherwise healthy cases of inguinal herniotomy. Venus blood sampling was done 4, 8 and 12 hrs after a single loading dose of rectal acetaminophen (40 mg/kg), and plasma acetaminophen concentration was compared between groups. ResultsMean serum acetaminophen levels of the HD group were significantly higher than those of the herniotomy group (36.3 ± 6.79, 27.4 ± 8.42, 16.8 ± 7.62 versus 25.9 ± 9.12, 16.7 ± 6.74, 8.1 ± 5.79 (μg/ml) at 4, 8 and 12 hrs after drug administration and P < 0.05). The IA group had higher concentrations of plasma acetaminophen compared to the herniotomy group; however, the p values were not statistically significant. (31.4 ± 10.39, 21.5 ± 9.12, 13.3 ± 6.79 versus 25.9 ± 9.12, 16.7 ± 6.74, 8.1 ± 5.79 (μg/ml) at 4, 8 and 12 hrs after drug administration). Serum concentrations of acetaminophen in IA and HD patients were above the therapeutic range four hours after administering the loading dose (31.4 ± 10.39 and 36.3 ± 6.79 versus 5–20 μg/ml). ConclusionBioavailability of rectal acetaminophen might get altered after major anorectal surgery in children. Rectal acetaminophen should be administered with special caution among infants with history of anorectal operations. Repeated dose of rectal acetaminophen may cause the drug blood concentration to reach toxic levels in these patients. Type of studyProspective comparative study. Level of evidenceLevel II.

Pharmaceuticals and personal care products in a Brazilian wetland of international importance: Occurrence and environmental risk assessment

Despite the fact that the occurrence of emerging contaminants in the environment has become frequent in recent decades, the seasonal dynamics of contaminants in different environmental compartments are little studied in protected areas influenced by effluent discharges. In this study, the seasonal and spatial occurrence of 33 pharmaceuticals and personal care products (PPCPs) was investigated in surface waters and sediments from Anil and Bacanga rivers (northeast of Brazil). The studied area is located within a Wetland of International Importance by Ramsar Convention (Amazon Estuary and its Mangroves). Sample preparation was carried out using solid-phase extraction and QuEChERS, for water and sediment samples, respectively and all determinations were performed by liquid chromatography tandem mass spectrometry. Eleven PPCPs were detected in water samples and 14 in sediments. In aqueous samples, caffeine was the most occurring compound reaching 13,798 ng L−1. In addition, high levels of acetaminophen, ibuprofen, sulfamethoxazole, carbamazepine and diclofenac were also observed. In the sediment samples, triclocarban, benzophenone-3, ketoconazole and methylparaben were also detected. The spatial and temporal distribution of the assessed molecules indicates urbanization and anthropic activities as relevant sources of PPCPs in the region. Moreover, the levels of acetaminophen, caffeine, diclofenac, ibuprofen, benzophenone-3, triclosan and triclocarban measured within the Ramsar site pose a high risk to aquatic and terrestrial organisms. These findings indicate potential threats to the allegedly protected biodiversity and, therefore, urgent actions are needed to effectively protect this unique and vulnerable area.

Acetaminophen interference with Nova StatStrip® Glucose Meter: case report with bench top confirmation

Context: Point-of-care glucose meters are an integral part in the assessment of patients with altered mental status. For this reason, glucose meters are checked for interference from commonly encountered substances, including acetaminophen. The Nova StatStrip® glucose meter has previously been reported to be resistant to interference. We report a case of a very high acetaminophen concentration causing interference with this point-of-care glucose meter.Case report: A 25-year-old female presented after an overdose of acetaminophen and diphenhydramine combination product. Patient was minimally responsive, so a point-of-care glucose check was attempted using the Nova StatStrip® glucose meter. Five different meters were attempted, and each showed an error message. Laboratory analysis using Beckman Coulter® Unicel DxC 800 revealed a glucose of 180 mg/dL and an acetaminophen concentration of 465 mg/L. Serum spiked with acetaminophen at different concentrations revealed interference with the Nova StatStrip® glucose meter at a concentration of 399 mg/L and above. To our knowledge, this interference with the Nova StatStrip® glucose meter has not been reported in the medical literature.Conclusion: Very high levels of acetaminophen can interfere with point-of-care glucose meters, even those that have previously been reported to be robust such as the Nova StatStrip® glucose meter. Clinicians should be aware of this possible interference when treating patients with acetaminophen overdose.

Sonochemical synthesis of polyoxometalate-stabilized gold nanoparticles for point-of-care determination of acetaminophen levels: preclinical study in an animal model.

The aim of this study is the accurate and rapid detection of acetaminophen (AP) for point-of-care (POC) clinical diagnosis. Acetaminophen overdose causes acute liver failure and currently there is a lack of rapid quantitative detection methods for this drug in the emergency room. Here, low-frequency sonication (20 kHz) in the presence of phosphomolybdic acid (PMo12) was used to reduce Au3+ to Au0 and stabilize the resulting spherical Au0 nanoparticles (herein AuNPs). These AuNPs@PMo12 were used as nano-probes for the selective detection of acetaminophen in the presence of other commercial drugs. The optical sensing method we describe is based on the aggregation of AuNPs@PMo12 in the presence of acetaminophen, which produces a red-shift in the absorption spectrum of the AuNPs@PMo12, which is characterised by a color change from red to purple that is visible to the naked eye. Furthermore, the quantitative determination of acetaminophen concentrations can be carried out using the eyedropper function in Microsoft's PowerPoint or open access ImageJ software, using RGB (red, green, and blue) values. To prove the feasibility of this novel nanosensor, the concentration of acetaminophen was measured in over-the-counter pharmaceutical tablets and in serum samples taken from mice. This simple sensing approach offers high stability, selectivity, rapid detection time, and cost saving compared to other detection methods, which therefore opens the way for the development of quantitative POC acetaminophen detection using polyoxometalate-stabilized metal nanoparticles.

Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood

Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report. To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood. This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018. Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth. Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records. Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD. Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.

2214 Acetaminophen-Induced Liver Toxicity in a Patient With Undetectable Acetaminophen Levels

INTRODUCTION: Acetaminophen is a common cause of overdose related acute liver injury (ALI). However, patients using acetaminophen chronically may have undetectable levels on presentation. It is important to recognize acetaminophen induced ALI early during clinical presentation and treat it promptly to prevent acute liver failure (ALF). CASE DESCRIPTION/METHODS: 72-year-old female with a history of osteoarthritis relieved by acetaminophen presented with severe right upper quadrant (RUQ) pain. On admission, temperature 38°C, blood pressure 119/73, and heart rate 111. Physical exam shows tenderness to palpation in RUQ, no guarding or rebound tenderness, negative murphy sign, complete alertness and orientation, and no asterixis. Laboratory findings show total bilirubin 1.6, direct bilirubin 1.0, ALT 2,133, AST 36,600, alkaline phosphatase (AP) 92, albumin 3.7, INR 1.6, ferritin 77,183, acetaminophen level &lt; 5, alcohol levels undetectable. RUQ ultrasound showed reduced liver echogenicity. Given history of chronic acetaminophen use, patient started on n-acetylcysteine (NAC) protocol for 72 hours. During hospitalization, diagnostic testing showed: Iron, TIBC, and transferrin all within normal limits, hemochromatosis DNA testing negative, alpha-1 antitrypsin within normal limits, ceruloplasmin within normal limits, IgG serum within normal limits, ANA Ab screen negative, hepatitis A Ab IgM negative, Hepatitis B Core IgM, Surface Ag, Surface Ab all negative, Hepatitis C Ab negative, EBV and CMV negative, HSV IgM negative, anti-liver kidney microsomal antibody negative, anti-smooth Muscle Ab negative, AMA negative, MRI of liver not concerning for iron overload. While on NAC therapy, liver enzymes and function tests trended to normal limits and RUQ pain and fevers resolved. On discharge, bilirubin and AP were within normal limits, ALT 305, AST 61, albumin 3.6, ferritin 8002 (Figures 1 and 2). 2-week post discharge follow up with primary care provider showed liver enzymes within normal limits. DISCUSSION: In this case, although acetaminophen levels were undetectable, careful elicitation of patient history gave clinicians more reason to suspect acetaminophen related liver toxicity. This led to prompt initiation of NAC therapy and prevention of ALF. This case demonstrates the importance of not excluding acetaminophen toxicity because of undetectable levels, especially in patients who use acetaminophen chronically, and initiating NAC therapy early for patients with ALI or ALF when acetaminophen toxicity is suspected.

2449 The Great Mimicker Syphilis and a Case of Hepatitis

INTRODUCTION: Early syphilitic hepatitis during the stage of secondary syphilis is often an overlooked presentation of syphilis. Liver involvement occurs in 0.2–3% of patients with syphilis. 1 CASE DESCRIPTION/METHODS: Here, we present the case of a 31 yr old male with type 1 diabetes and hyperlipidemia who presented with epigastric abdominal pain that began on morning of admission. Patient denied any change in bowel movements and, on initial exam, was found to be tachycardic and hypotensive. On physical exam, patient had tenderness in the epigastrium without any skin changes noted. On evaluation of lab work, patient was found to be in DKA with moderately elevated LFTs, ALP 273, AST 400 and ALT 200, Bilirubin 0.2. Hepatitis panel and Acetaminophen level were negative. A right upper quadrant ultrasound was performed that did not show any evidence of cholelithiasis or passed stone. Patients DKA resolved one day into admission, however AST/ALT more than doubled from admission to 4000/1000 respectively, with rising ALP of 320. Bilirubin remained normal. Given elevated liver enzymes, there was concern for possible passed stone and therefore MRCP was pursued. MRCP showed incidental finding of hepatomegaly without any evidence of cholelithiasis. Acute hepatitis panel was also found to be negative. On further history, patient reported that he did engage in unprotected sexual intercourse approximately 1 month prior, with another male. Patient's abdominal pain resolved and he was discharged with HIV, HSV, RPR, GC Chlamydia studies pending. Lab workup revealed RPR to be reactive, 1:16 TU with reactive Treponema pallidum particle agglutination assay (TPPA), and negative HIV testing. Patient was diagnosed with secondary syphilis with hepatitis and treated with Benzathine Penicillin 2.4 MU IM in 2 divided doses. AST/ALT trended down to 116/43 and ALP 242. DISCUSSION: This case highlights the critical importance of a broad differential in workup of hepatitis.

2471 UnDRESSing Elevated Liver Enzymes

INTRODUCTION: The differential diagnosis for liver transaminases over 1000 units/liters typically includes liver ischemia, acute viral hepatitis, acetaminophen-induced liver toxicity, autoimmune hepatitis, Wilsonian crisis, or acute Budd-Chiari. Prompt evaluation and exclusion of these causes must be completed as many of these etiologies can ultimately lead to fulminant liver failure. We present a case of liver transaminases over 1000 units/liter from an atypical etiology. CASE DESCRIPTION/METHODS: A 52-year-old male with hypertension, CKD stage 5, gastroesophageal reflux disease, and gout presented with intermittent fevers of 39C. He was recently hospitalized for Clostridium difficile colitis and treated with oral vancomycin. During this hospitalization he was started on allopurinol for an acute gout flare. Soon after starting allopurinol, he developed a diffuse morbilliform rash. On initial exam, vitals were within normal limits and temperature was 39C. Laboratory data revealed white blood cell count within normal limits, hemoglobin 7.9 gm/dL, platelet count 71 K/mcl, INR 1.1, AST 878 unit/L, ALT 1,117 unit/L, AKI, and peripheral eosinophilia. Viral hepatitis serologies, autoimmunity studies, as well as viral markers for EBV, CMV, HSV, and varicella were negative. Ceruloplasmin, Alpha 1 antitrypsin, and acetaminophen levels were within normal limits. N-acetylcysteine was administered due to suspicion for drug-induced liver injury. Given that he had taken allopurinol two weeks before presentation, presented with fevers, rash, and renal impairment and now developed peripheral eosinophilia, DRESS syndrome secondary to allopurinol was diagnosed. DISCUSSION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening, drug-induced hypersensitivity reaction. Diagnosis is suspected in a patient who received a drug treatment in the previous two to six weeks and subsequently presents with characteristic symptoms including skin rash, liver involvement, hypereosinophilia, and lymphadenopathy. Dress typically causes transaminase elevations, but usually not in the 1000s, as was seen in our patient. The pathogenesis is hypothesized to involve a genetically deficient detoxifying enzyme resulting in an accumulation of drug metabolites. Supportive therapy and prompt withdrawal of the offending agent is the primary treatment for drug hypersensitivity reactions. Additionally, N-acetylcysteine has been shown to significantly increase survival in cases of drug-induced liver failure.

2480 Nivolumab-Induced Hepatitis and Vesiculopustular Skin Rash in a Patient With Metastatic Melanoma

INTRODUCTION: The advent of immunotherapy has been hailed as a breakthrough in cancer treatment. However, it comes with a multitude of immune mediated adverse effects. Gastrointestinal adverse effects include hepatitis and colitis. Immunotherapy related hepatitis can range from asymptomatic elevation of liver enzymes (grade 1) to decompensated liver failure (grade 4). CASE DESCRIPTION/METHODS: 82 years old male with stage IIC Malignant Melanoma of right posterior diagnosed in 2014, treated with wide excision. In December 2016, PET scan revealed right chest wall lesion, treated with re-excision. c-kit and BRAF were negative. In June 2017, PET scan showed metastatic disease involving lung, pancreas, gluteus maximus and left flank. The patient was started on Nivolumab. After 7 cycles, the PET scan became negative for any metastatic lesions. After 8 cycles, he had a severe morbilliform, vesiculopustular rash secondary to Nivolumab. Skin Biopsy showed a lymphocytic infiltrate with scattered eosinophils and numerous neutrophils. High dose prednisone was started with tapering for 3 months. Nivolumab was temporarily held and resumed after a good response to steroids. After 14 cycles, the patient developed malaise, fatigue, nausea and mild abdominal pain. ALT was 393, AST 302, ALK 164. Bilirubin was 1.1. Hepatitis A, B, and C testing were negative, anti-liver kidney microsomal antibody and anti-mitochondrial antibody was negative, acetaminophen level was normal, CT and Ultrasound of the liver were negative for metastatic lesions or other hepatic pathology. No recent change in medication or alcohol use was reported. As per ASCO guidelines, hepatitis was classified as Grade III (ALT and AST &gt;5-20 times the upper limit of normal). The patient was started on 100 mg prednisone daily with tapering for 2 months. Liver enzymes normalized and symptoms resolved. Nivolumab was discontinued. PET scan 6 months from the last cycle showed disease in remission. DISCUSSION: Treatment of immunotherapy induced hepatitis depends on severity. Immunotherapy can be continued in grade 1, temporarily held in grade 2, and permanently discontinued in grade 3 and 4 as per guidelines. High dose steroids (prednisone 1-2 mg/kg) with tapering serve as the mainstay of treatment. Mycophenolate or azathioprine can be considered in refractory cases. However, it needs further research whether immunotherapy can be re-trialed in patients with grade 3 toxicity, who have responded well to the steroids, and would potentially benefit from a repeat trial.

2217 Silent Propafenone-Induced Liver Injury: Case Report

INTRODUCTION: Propafenone is a class Ic antiarrhythmic. It is metabolized primarily by hepatic cytochrome P-450 2D6 and rarely associated with liver toxicity. We report a case of silent propafenone-induced liver injury. CASE DESCRIPTION/METHODS: An 82-year-old man with DM, HTN, COPD, moderate mitral valve regurgitation, CABG, and aortic valve replacement, presented with progressive SOB and orthopnea of 2-week duration. Two weeks prior, he had atrial fibrillation treated with ablation, apixaban, and propafenone. Other medications were losartan, amlodipine, and furosemide. He denied alcohol/illicit drug use. He was alert, oriented, in moderate respiratory distress, and non-icteric. Temperature was 37.4 C, BP 155/67, HR 112, and RR 18. He had shallow breath sounds with bilateral diffuse crackles, bilateral lower extremity pitting edema, and unremarkable abdominal exam. EKG showed atrial fibrillation. He was treated with IV diltiazem and furosemide with improvement of SOB. However, on routine investigations, AST was 2182 IU/L, ALT 1805 IU/L, alkaline phosphatase 210 IU/L, total/direct bilirubin 4.6/1.0 mg/dL, and INR 3.4. Urine and serum toxicology, IgM hepatitis A virus, IgM hepatitis B core, hepatitis B surface antigen, hepatitis C virus Ab, Epstein-Barr virus, and cytomegalovirus were negative. ANA, smooth muscle Ab, LKM Ab, celiac serology, ceruloplasmin, alpha 1 antitrypsin, iron studies, and acetaminophen levels were all normal. Ultrasounography showed normal common bile duct and no intrahepatic biliary dilatation and was consistent with hepatocellular disease. Hepatic vessels doppler was unremarkable. Propafenone was discontinued and 5 days later, AST was 148, ALT 581, alkaline phosphatase 132, total/direct bilirubin 1.1/0.5; all tests normalized within 2 weeks. DISCUSSION: Hepatotoxicity secondary to propafenone is rare; only 9 cases have been previously reported. Our patient developed hepatotoxicity 2 weeks after starting propafenone, had immediate improvement after its withdrawal, and work up was otherwise negative, strongly suggesting propafenone as the cause. Similar to previous cases, hepatotoxicity had a cholestatic pattern and was completely reversible. Unlike previous cases where jaundice, pruritis, and abdominal pain were presenting symptoms; hepatotoxicity was incidentally discovered in our patient. Although very rare, clinicians should be aware of propafenone-associated hepatotoxicity and routine monitoring of hepatic function may be warranted.

2419 Fatal Outcome Associated With Herbal Supplements

INTRODUCTION: Herbal and dietary supplements are widely used without prescription and used by the public as harmless remedies for a variety of ailments. It is difficult to determine causal relationships between herbal preparations and hepatotoxicity. We present a case of fulminant hepatic failure from over-the-counter hair regrowth supplements containing Polygonum multiflorum. CASE DESCRIPTION/METHODS: A 71-year-old male presented to the ER with complaints of abdominal discomfort and jaundice, associated with nausea and vomiting. He went to the ER ten days prior for abdominal discomfort and nausea, labs showed total bilirubin 1.8, ALP 141, AST 267, ALT 85, platelet 70, BUN 31 and Creatinine 1.2. CT abdomen showed duodenitis and was discharged with Metoclopramide. His symptoms continued to worsen. 12 weeks prior, he started a hair regrowth supplement which contained Polygonum multiflorum. Pertinent labs were-Total Bilirubin 9.8, AP 280, AST 445, ALT 156, platelet 49, BUN 85, creatinine 3.4 and INR 1.82. CT abdomen showed mild hepatic steatosis, mild peripancreatic and periduodenal inflammatory changes. Ultrasound of the gallbladder showed no gallstones or cholecystitis. Normal CBD and common hepatic duct. Hepatitis A, B, C, Anti-smooth muscle antibodies, anti-mitochondrial antibodies, smear for parasites and tick borne were negative, IgG, IgM, IgA – normal, Ceruloplasmin 45. Acetaminophen level &lt;10. He was getting supportive treatment. Day 3 labs showed AST 556, ALT 151, AP 278, total bilirubin 15.1, direct bilirubin 14.6, PT 23.7, INR 2.03. platelets 24, BUN 97, creatinine 2.5. He was started on Acetylcysteine and Lactulose, then transferred to a hospital with a liver transplant facility, where toxicology screening was positive for P multiflorum. He was not a candidate for liver transplant and labs continued to worsen. Shortly thereafter he coded while getting an HD catheter for dialysis and expired. Liver biopsy after autopsy showed diffuse necrosis of hepatic cells. DISCUSSION: The mechanism of hepatotoxicity of P multiflorum is unknown but it is known to have anthraquinones including chrysophanol, emodin, and rhein which can induce hepatotoxicity. The pattern of enzyme elevations is typically hepatocellular or mixed and the clinically resembles acute viral hepatitis. The latency to onset ranges from a few days to as long as 6 months. Liver biopsies show changes typical of acute hepatitis. The course is usually self-limited but there are also a small number of patients with liver failure and even death.

2421 A Case of Acute Liver Injury Caused by an Herbal Supplement Containing Saw Palmetto: “Good for the Prostate but Not for the Liver”

INTRODUCTION: Saw palmetto (Serenoa repens), an herbal product used for benign prostatic hyperplasia, is a part of many herbal and dietary supplements (HDS) used for bodybuilding. It is associated with a hepatocellular pattern of acute liver injury. We present a case of liver injury secondary to supplement containing saw palmetto, which improved upon discontinuation. CASE DESCRIPTION/METHODS: A 36-year-old man with history of gastric bypass surgery was admitted with vomiting and diarrhea for the last 2 days. Abdominal examination was unremarkable. Labs revealed ALT of 2200 U/L, AST of 800 U/L with normal bilirubin, alkaline phosphatase and INR. Abdominal ultrasound revealed gallstones with a normal bile duct. Work up for infectious diarrhea was unremarkable. The symptoms were attributed to acute viral gastroenteritis. A diagnosis of acute liver injury was made, and further tests were performed to establish the etiology. Viral markers for Hepatitis A, B, C, E, Epstein Barr, Herpes simplex and Cytomegalovirus were all negative. The ANA, ASMA, ceruloplasmin and acetaminophen levels were unremarkable. He denied any alcohol use. Further history revealed that he had been using an over the counter herbal product to boost the testosterone levels to increase the muscle mass for the last one month. The ingredients of the product included saw palmetto and other herbal constituents. Review of the literature showed an association between saw palmetto and hepatocellular type of liver injury. The liver injury was attributed to the supplement and the cessation was advised. Follow up 4 weeks later showed normalization of the liver profile. DISCUSSION: HDS induced liver injury accounts for 20% cases of hepatotoxicity and 13% cases of acute liver failure in America. Many such cases are due to MINS (multi ingredient nutritional supplements), and the component responsible for the toxicity is usually unknown or can only be suspected. One of such ingredients used in these products is sawPalmetto which may cause supplement-induced liver injury. The latency to onset is within 1 to 2 weeks, and the clinical features resemble acute viral hepatitis with a hepatocellular pattern of liver enzyme elevations. Liver injury is probably an idiosyncratic phenomenon and usually resolves in 1 to 3 months. HDS-induced liver injury presents many challenges in diagnosis, identification of the responsible constituents, treatment and prevention. The regulation of non-prescription products to guarantee public safety is very important.