Acetaminophen Levels Research Articles

SHOCK FROM NADOLOL OVERDOSE: THE FIRST REPORTED CASE OF SUCCESSFULLY TREATED WITH CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT)

SHOCK FROM NADOLOL OVERDOSE: THE FIRST REPORTED CASE OF SUCCESSFULLY TREATED WITH CONTINUOUS RENAL REPLACEMENT THERAPY (CRRT)

SEVERE COLCHICINE TOXICITY IN A SUICIDE ATTEMPT CAUSING MULTIORGAN FAILURE: A SURVIVAL STORY

SEVERE COLCHICINE TOXICITY IN A SUICIDE ATTEMPT CAUSING MULTIORGAN FAILURE: A SURVIVAL STORY

S2939 Ashwagandha Toxicity: A Rare Case of Drug Induced Liver Injury (DILI)

Introduction: The pursuance of natural and herbal remedies by many has brought with it further knowledge of the many causes of Drug Induced Liver Injury (DILI). Many of these "natural" over-the-counter (OTC) supplements may not be benign due to the lack of scientific analysis and unregulated production. Ashwagandha is a supplement used for memory enhancement, management of anxiety, and general increase in vitality. We present a case of Ashwagandha DILI in a healthy 36-year-old man. Case Description/Methods: A 36-year-old male presented to our institution with 1 week of fatigue, jaundice, nausea and subjective fevers. Upon presentation he was hemodynamically stable and afebrile. Physical exam was notable for jaundice without other stigmata of liver disease or mental status changes. He was found to have acute liver injury with lab chemistries remarkable for AST= 1482 U/L, ALT= 1375 U/L, Tbili= 22.3 mg/dL, alkaline phosphatase= 202 U/L and an INR of 1.6. He denied alcohol and drug use, recent travel or sick contacts. Medications list was notable for cetirizine, diphenhydramine (both taken as needed), OTC testosterone supplements, OTC apple cider vinegar gummies BID and OTC ashwagandha gummies BID. Workup was negative for autoimmune, infectious, metabolic, obstructive and vascular causes of liver injury. Acetaminophen level and urine drug screen were negative. Trans-jugular liver biopsy revealed evidence of acute portal and lobular hepatitis and cholestasis, suggestive of DILI. Patient's liver enzymes continued to downtrend (AST=929, ALT=765, Tbili=22.5) after withdrawal of his supplements and was discharged (Figure). Discussion: Ashwagandha causing DILI has been infrequently reported in the literature. One case series of 5 patients in Iceland and a single case in Japan reported that ashwagandha is an uncommon culprit linked to acute liver injury. None of the reported cases necessitated liver transplant. Average time to resolution and normalization of LFTs was 3.5 months and R values usually ranged in the mixed range (R value 2-5). The case series also revealed that ashwagandha's toxicity could be dose dependent, as higher peaks in LFT's were tied to recent increases in ashwagandha dosing. Although ashwagandha has been a rarely reported cause of DILI, a thorough history of medication and OTC supplements in patients with undifferentiated acute liver injury may yield more cases. Further study and reporting of DILI in the ever-growing supplement market appears to be required to minimize potential injury.Figure 1.: Tranjugular Liver Biopsy Findings.

S3107 Successfully Treated Acute Liver Injury in Acute Hepatitis C With N-Acetyl Cysteine: A Case Report

Introduction: Significant liver injury related to acetaminophen overdose is more common in patients with preexisting liver disease. We present a patient with newly diagnosed acute hepatitis C infection with acute liver injury treated successfully with N-acetylcysteine despite negative acetaminophen levels. Case Description/Methods: A 29-year-old male with history of spontaneously cleared HCV two years ago and polysubstance use presented with abdominal pain, anorexia, and jaundice. He admitted to taking less than 2 g of acetaminophen for tooth ache and chronic back pain along with recent IV drug use, alcohol use, and marijuana use. Examination revealed scleral icterus and right upper quadrant tenderness. Labs revealed normal acetaminophen level, elevated bilirubin 9.4, transaminases AST 1,023; ALT 1,941; alkaline phosphatase (ALP) 202, and INR of 1.4. Hepatitis C antibody returned positive. Hepatitis C genotype was 1a or 1b with an HCV RNA level of 10,917. Evaluation for other etiologies for acute liver injury including alpha-1 antitrypsin, ceruloplasmin, autoimmune, and other infectious work up was negative. MRCP was normal without biliary pathology. He was given 140 mg/kg oral N-acetylcysteine for suspected acetaminophen overdose as the etiology for liver injury. His symptoms improved and liver tests showed an improvement in the next few days (total bilirubin 5.1, mg/dL, AST 100, ALT 731, ALKP 218). The patient was prescribed Sofosbuvir-Velpatasvir at discharge for the treatment of acute hepatitis C. Discussion: In patients with hepatitis C infection the rate of liver injury with acute or chronic infection is about 16.7%. This case highlights the importance of having a low threshold for treating patients for acetaminophen toxicity in acute hepatitis C patients based on history. This case also highlights further studies are needed to determine the incidence and implications of acute liver injury in acute hepatitis C patients as there are no studies in this group of patients so far. Table 1. - Liver Function Tests During Admission Liver Function Tests Initial Repeat Total Bilirubin (mg/dL) 9.4 5.1 ALT (IU/L) 1,941 731 AST (IU/L) 1,023 100 ALKP (IU/L) 202 218 INR 1.4 1.2

S2994 Fulminant Liver Failure Due to Budd-Chiari Syndrome Triggered by Strenuous Exercise

Introduction: This case illustrates the complexity of diagnosis of Budd-Chiari syndrome especially with an atypical presentation. Case Description/Methods: A 27-year-old man in his usual good state of health attended an all-day police academy fitness test. That evening he developed abdominal pain, nausea, vomiting, and diarrhea. He left work the next day due to these symptoms and progressive confusion. His family called EMS and he was transported to a local emergency department where he was found to be hypothermic, tachycardic, and hypoxemic. Labs were notable for acute kidney injury with creatinine 1.7, lactate 11.8, total bilirubin 1, AST 116, and ALT 95. He was begun on 2 vasopressors and empiric antibiotics. CT Abdomen noted a possible mesenteric thrombus; he was taken emergently to the operating room, but no bowel ischemia was found. His laboratory tests increased over the next 3 days reaching total bilirubin 3.0, AST 8560, ALT 5880, alkaline phosphatase 92, albumin 2.7, creatinine 3.1, INR 5.06, WBC 34.5, and ferritin 18,724. He was subsequently transferred to a tertiary center where his mental status worsened, and he was intubated. A transjugular liver biopsy demonstrated perivenular coagulative necrosis involving 80% of the hepatic parenchyma, and a hepatic venogram noted extensive portal vein thrombus. He had no history of taking any medications on a regular basis and did not take acetaminophen. An acetaminophen level was negative. Orthotopic liver transplantation was performed on the sixth day after his initial hospital presentation. During the surgery the patient was noted to have extensive thrombus involving the portal system including the main portal vein as well as the superior mesenteric vein, and thrombus in the hepatic veins. Testing for hypercoagulable state was positive for JAK2 V617F mutation, and he was begun on treatment with hydroxyurea. Discussion: His development of Budd-Chiari syndrome is felt to be due to this hypercoagulable state combined with dehydration from strenuous exertion. There was no hepatomegaly noted on imaging which had led to confusion regarding the diagnosis of Budd-Chiari syndrome, but the occlusion of the portal vein in this patient resulted in decreased blood flow to the liver and prevented the development of hepatomegaly. His initial development of lactic acidosis, leukocytosis, and elevated ferritin is felt to be the result of marked hepatic necrosis from the Budd-Chiari syndrome but had led to confusion over the possibility of septic shock or bowel ischemia.

S3204 Turmeric-Induced Liver Injury: A Rare Case of DILI

Introduction: Turmeric, a plant prevalent in South Asia, is often marketed to be safe, with many benefits including antioxidant and anti-inflammatory effects. Hepatotoxicity, a rare adverse effect, has only been documented in a few case reports. Here we present a case of turmeric Drug Induced Liver Injury (DILI) with normalization of liver function tests after its cessation. Case Description/Methods: A 62-year-old female with a history of hypertension presented with nausea and generalized abdominal pain for five days. She denied taking medications other than hydrochlorothiazide. Further interview noted that she initiated turmeric tea over the preceding three weeks. On physical exam, she had scleral icterus and right upper quadrant tenderness. Laboratory workup showed AST 1510 U/L, ALT 1889 U/L, total bilirubin 13.9 mg/dL, direct bilirubin 8.1 mg/dL, ALP 134 U/L, LDH 542 U/L, with an ALT/LDH ratio of 3.49. INR was normal. Ultrasound revealed findings consistent with acute hepatitis. Ferritin, ceruloplasmin, and acetaminophen levels were normal. Alpha-1-antitrypsin, anti-mitochondrial, and anti-smooth muscle antibodies were unremarkable. Viral serologies were normal. The patient improved with turmeric cessation, with complete resolution of abnormal liver enzymes on follow-up. Discussion: Turmeric, previously considered safe, has now been reported to be associated with DILI in a few case reports. Our case adds to the growing body of evidence supporting turmeric induced DILI. Although we could not uncover the exact dose, we do establish a high probability of adverse effects from turmeric using the validated Roussel Uclaf Causality Method (RUCAM) scoring system. Our patient scored 9, with a score >8 representing a high probability. Turmeric induced DILI is thought to be both dose dependent and associated with formulations that contain supplements or nanoparticles that increase turmeric’s bioavailability. Lombardi et al. and Sohal et al. for example both report several cases of acute hepatitis associated with turmeric preparations developed with piperine (black pepper), which has been shown to increase the absorption of turmeric by 2000%. In our case, the patient’s turmeric tea also included black pepper, which likely explains the hepatotoxicity. This case underscores the importance of supplement history, with an emphasis on turmeric, when evaluating for potential causes of DILI.

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.

S3114 Painless Jaundice With a Significantly Elevated CA 19-9: It Is Not Always Pancreaticobiliary Cancer

Introduction: Carbohydrate antigen 19-9 (CA 19-9) is often very high in pancreaticobiliary cancers but can be substantially elevated in benign diseases too. We present a case of painless jaundice with a significantly elevated CA 19-9 from vanishing bile duct syndrome (VBDS). Case Description/Methods: 65-year-old white male with history of obesity, hypertension, hyperlipidemia, prior cholecystectomy and no family history of pancreatic cancer presented with two weeks of painless jaundice and 10 pounds unintentional weight loss. Physical exam noted scleral icterus and jaundice with a T.Bili of 23 mg/dL (Table 1). CT scan showed intrahepatic bile duct dilation and a 10 mm common bile duct without a discrete mass. CA 19-9 was elevated to 1,480 U/mL, concerning for malignancy. ERCP found a low-grade main bile duct stricture which was stented. Bile duct brushings and fine needle aspiration of the pancreas were negative for malignancy. Biliary dilation was resolved on follow-up MRCP but his bilirubin remained high. Infectious and autoimmune workup was unremarkable. Repeat cholangiography and brushings confirmed no obstruction or malignancy (Fig. 1a). An infiltrative versus drug induced liver injury was suspected. EUS-guided liver biopsies revealed cholestasis with dilated bile canaliculi, hepatocytes with ballooning degeneration and a paucity of bile ductules. Cytokeratin-7 immunostaining demonstrated >50% ductopenia, confirming VBDS (Fig. 1b and c). Follow up at hepatology clinic determined triamterene-HCTZ, atorvastatin or omeprazole stopped during hospitalization to be the likely culprit. His CA 19-9, LFTs and symptoms improved over the following weeks (Table 1). Discussion: VBDS is an acquired cholestatic liver disease that may mimic the presentation of pancreatic cancer. CA 19-9 can be substantially elevated through T-cell mediated destruction of small bile ducts causing impaired excretion, inflammatory production, and decreased clearance. Severity of liver damage depends on the duration of injury and degree of bile duct loss at the time of diagnosis. Prompt diagnosis is important to prevent cirrhotic progression, improve outcomes, and avoid unnecessary treatments. Recognizing its association with an elevated CA 19-9 may help with this, but is scarcely reported in the literature. CA 19-9 is not typically checked in cases of VBDS but is likely commonly elevated. Providers should be aware of this association when faced with a patient with painless jaundice and a significantly elevated CA 19-9 but no obvious malignancy. Table 1. - LFT Trends During the Course of Presentation Normal Range Hospital Admission * 2 weeks 3 weeks ** 4 weeks *** 7 weeks 13 weeks Total bilirubin 0.2-1.3 mg/dL 23 22.7 22 19.7 4.7 1.3 Direct bilirubin 0.0-0.2 mg/dL >13 n/a 14.9 14.6 4.2 0.6 AST 0-45 U/L 107 134 172 200 121 27 ALT 0-50 U/L 190 130 163 182 120 35 ALP 40-150 U/L 267 179 187 168 132 109 CA 19-9 0-35 U/mL 1480 n/a n/a 85 49 n/a AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CA19-9, carbohydrate antigen 19-9; n/a, not available. * ANA, anti-AMA, anti-SMA, anti-mitochondrial, anti-TTG, anti-LKM 1/2 IgG, and EBV IgG antibodies were negative. Serum IgA, A1AT, ceruloplasmin, TSH, iron levels, hepatitis panel, serum protein electrophoresis and acetaminophen levels were normal. Acetaminophen, multivitamin, iron, triamterene- HCTZ, omeprazole and atorvastatin were stopped on discharge. ** Three weeks post hospitalization. Repeat EUS/ERCP showed biliary decompression. VBDS diagnosed on liver biopsies. *** Seen in liver clinic. Started ursodiol 2000mg daily. Figure 1.: (A) ERCP with cholangiogram showing a low-grade distal biliary stricture without significant upstream dilation. (B) Liver biopsy with H&E stain, 500 μm magnification showing small portal tracts with no bile ducts (red circle); note marked cholestasis (arrows) in dilated canaliculi and lack of ductular reaction. Also visible at this magnification is the ballooning degeneration of hepatocytes. (C) Liver biopsy with cytokeratin 7 immunostain, 500 μm magnification. Small portal tracts with no terminal/small bile ducts. Early signs of ductular reaction seen by hepatocytes taking up CK7 stain (arrows).

S3300 Acetaminophen Toxicity Amplified: Drug-Induced Liver Injury in a Malnourished Patient

Introduction: Acetaminophen toxicity is a leading cause of acute liver injury and failure in the U.S. Excess acetaminophen results in formation of N-acetyl-p-benzoquinoneimine (NAPQI) which causes irreversible oxidative hepatocyte injury and cell necrosis. Treatment with N-acetylcysteine (NAC) replenishes glutathione stores which inactivate NAPQI. In a healthy adult, acetaminophen doses less than 4 g per 24 hours are considered safe. Toxicity from therapeutic doses of acetaminophen, in the setting of malnourishment, has been rarely reported and is presented here. Case Description/Methods: A 37-year-old female with a history of gastroparesis and chronic malnutrition was admitted for elevated liver enzymes on routine blood work. She reported symptoms of fatigue, nausea, and poor oral intake from suspected gastroparesis. She also admitted to taking 1300 mg of acetaminophen intermittently during the past week for myalgias. Exam revealed normal mentation without evidence of hepatic encephalopathy (HE), cachexia with a BMI of 15.2, and mild epigastric and left upper quadrant tenderness. Laboratory data (36 hours after last ingestion of acetaminophen) revealed an ALT of 1180 u/L, AST of 1950 u/L, ALP of 121 u/L, total bilirubin of 2.7 mg/dL, direct bilirubin of 2.5 mg/dL and INR of 1.6. Her acetaminophen level was 15.8 mcg/mL. A liver ultrasound was unremarkable. NAC was subsequently administered as per protocol 21 hour infusion. She was ruled out for other etiologies of acute liver injury. She never developed HE and her liver enzymes, along with INR, normalized at discharge. Discussion: This case highlights the lower threshold for toxicity of acetaminophen in a malnourished patient. In previous case reports, acetaminophen doses less than 2 g per 24 hours are listed as being safe in a nutritionally deficient patient. Our case questions this assertion given our patient ingested 65% of this amount. Evidence in the relatively limited pool of literature suggests that malnourished patients generally have low stores of glutathione, thereby limiting the metabolic clearance of acetaminophen ingested even at normal dosages, amplifying total acetaminophen levels, and leading to increased NAPQI. Prospective study is limited to rat models and single case reports. Fortunately, our patient was promptly treated with NAC and did not progress to liver failure. This case highlights the narrow therapeutic window of acetaminophen in malnourished patients, one that warrants close observation by clinicians.

S3278 A Rare Case of Gabapentin-Induced Hepatotoxicity

Introduction: Gabapentin is an anti-convulsant that is also used off-label to treat neuropathic pain. It is not metabolized by the liver, and there have been few reports of hepatotoxity associated with it. We present a rare case of gabapentin-induced hepatotoxicity occurring in a young male. Case Description/Methods: A 41-year-old male with an extensive past medical history including type 1 diabetes, end stage renal disease on hemodialysis, TIA, hypertension, and hyperlipidemia was admitted for severe hyperkalemia with K 8.2 and peaked T waves on EKG, and hyperglycemia with glucose 561. He was admitted to the intensive care unit for urgent dialysis. Lab work revealed abnormal liver function tests, with ALP 1,232 IU/L, AST 291 IU/L, and ALT 188 IU/L, and normal total bilirubin of .8 mg/dL. Prior records revealed completely normal liver function tests 6 months prior to presentation. Ultrasound of the RUQ revealed small volume of ascites but was otherwise unremarkable with no abnormality of hepatic parenchyma or biliary ducts noted. Patient reported having a below-knee amputation 3 months prior to presentation, after which he started taking gabapentin 300 mg three times per day. He denied any other medication changes. He reported taking acetaminophen occasionally, and acetaminophen level was < 10 mcg/mL. A full hepatitis panel was negative. An autoimmune workup was planned including Anti-LKM, ASMA, AMA but patient insisted on leaving prior to those labs being drawn. Gabapentin was held and patient’s liver function tests improved, with ALP 1058 IU/L, AST 158 IU/L, and ALT 149 IU/L, and remained stable. Patient discontinued gabapentin and was advised to follow up outpatient, unfortunately he was lost to follow-up. Discussion: Although the exact mechanism of gabapentin is unknown, it is structurally related to GABA and high-affinity binding sites for gabapentin which modulate the release of excitatory neurotransmitters which participate in epileptogenesis have been found throughout the brain. Gabapentin is not hepatically metabolized, and therefore was not studied in patients with hepatic impairment during the FDA approval process. There have been very few cases of gabapentin induced liver injury. In our patient there was a clear temporal association of liver injury occurring after our patient began gabapentin therapy, and slight improvement after a few days of discontinuation. Although further studies on this topic are needed, gabapentin should be considered as a cause of drug induced liver injury.

S2940 Bupivacaine-Induced Hepatotoxicity in a Healthy Patient Without Chronic Liver Disease After Shoulder Arthroscopy

Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient’s health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion: Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity; and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.

S3020 Hepatitis From a Sexually Transmitted Bacterial Infection

Introduction: Syphilis is a multisystemic, sexually transmitted infection (STI) that is caused by the spirochete Treponema pallidum. Hepatic involvement is rare. We present a patient who was diagnosed with syphilitic hepatitis (SH). Case Description/Methods: A 54-year-old male presented to the hospital with one week of sharp upper abdominal pain, jaundice, poor appetite, and a 25-lb. weight loss. He also reported multiple sexual partners and a rash that developed 2 months ago. Vital signs were within normal range. Physical examination revealed scleral icterus, a soft, non-tender abdomen, a plaque-like penile lesion and small, circular lesions on his palms and soles of feet. Laboratory studies revealed aspartate aminotransferase (AST) 164 U/L, alanine aminotransferase (ALT) 207 U/L, alkaline phosphatase (ALP) 1395 U/L, total bilirubin 5.6 mg/dL, gamma-glutamyl transferase 782 U/L. Hepatitis panel, acetaminophen and alcohol levels were negative. Chronic liver disease work-up was unremarkable. Treponemal antibody and rapid plasma reagin test were both positive. HIV test and cerebrospinal fluid venereal disease research laboratory (VDRL) test were negative. Abdominal ultrasound and CT scan of the abdomen were unremarkable. Magnetic resonance cholangiopancreatography was notable for hepatomegaly and hepatitis. Patient received 1 dose of penicillin G 2.4 million units intramuscularly with remarkable improvement in his symptoms and liver function tests. He was discharged home with close follow-up with gastroenterology and infectious disease. Discussion: SH occurs in 0.2-9.7% of patients with syphilis and is most commonly seen in the primary and secondary disease stages. Clinical manifestations include a maculopapular rash (involving the trunk, palms and/or soles of feet), fatigue, poor appetite, hepatomegaly and icterus. Liver function tests (LFTs) may reveal a marked increase in ALP and GGT in comparison to ALT and AST. SH is diagnosed with abnormal LFTs, serological evidence of syphilis, exclusion of other liver diseases and LFTs returning to normal after antibiotic therapy as in our patient. The histological features of SH include inflammatory infiltration of the bile duct and hepatic granulomas. Spirochetes are often difficult to identify in liver tissue. Penicillin is the mainstay of treatment. Clinicians should consider syphilitic hepatitis in a patient with abnormal LFTs (especially ALP) and a rash involving the palms and soles of feet in the appropriate clinical context.

S3014 Hepatotoxic Effects of Whey Protein Supplementation

Introduction: Currently, more than 50% of Americans take dietary supplements. Whey is a commonly used protein supplement that is often viewed as safe, with only rare reports of drug-induced liver injury (DILI). Here, we report an unusual case of severe liver injury following whey protein consumption. Case Description/Methods: A 40-year-old female with obesity and well-controlled hypothyroidism presented with 3 days of nausea and painless jaundice. Her only home medication was levothyroxine. Two months prior, she began drinking whey protein shakes (each containing 20 grams of protein) twice daily to aid with weight loss. She denied use of alcohol, recreational drugs, herbal supplements, and recent medication changes. On physical exam, she was alert and oriented x4, with jaundice and scleral icterus present. Lab work was significant for ALT 2,502, AST 1,434, total bilirubin 11.0, INR 1.42, and platelets 217,000. Acetaminophen and salicylate levels were unremarkable. Her whey protein supplementation was immediately stopped and a workup for transaminitis was initiated. RUQ ultrasound was unremarkable. Evaluation for other causes of acute liver injury, including viral hepatitis (A, B, C, E), EBV, CMV, HIV, hemochromatosis, Wilson’s disease, and autoimmune hepatitis was unremarkable. A liver biopsy was performed, with pathology showing diffuse ballooning degeneration of hepatic parenchyma, numerous acidophil bodies, and dominant pericentral hepatocyte drop-out. A diagnosis of DILI (with predominant hepatocellular injury) was made. Following discontinuation of whey protein supplementation, the patient’s labs and clinical symptoms improved, and she was discharged home on hospital day 8. Discussion: This case highlights a rare occurrence of DILI secondary to whey protein consumption and emphasizes the importance of taking a thorough history when working up liver injury. Furthermore, in the treatment of DILI, we recommend cessation of all possible offending agents that were recently started, including supplements that are reputably marketed to be safe for consumption.

S3340 An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion: Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient’s use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

S3248 A Case of Drug-Induced Liver Injury Secondary to Clobenzorex Use

Introduction: Drug-induced liver injury (DILI) is a cause of both acute and chronic liver disease and is often a challenging condition for clinicians. It is a diagnosis of exclusion that requires a detailed history and workup to ensure other potential causes have been ruled out before affirming the diagnosis. There are numerous offending agents with varied presentations, often idiosyncratic in nature, with the additional challenge being a lack of specific testing or biomarkers to aid diagnosis. Case Description/Methods: We present a case of a 25-year-old male who immigrated from Mexico 4 months ago, with no reported past medical history, who presented to the emergency department for a two-day history of postprandial non-radiating right upper quadrant and epigastric pain. Associated symptoms include subjective fevers, chills, decreased appetite, nausea, one episode of blood-tinged emesis, night sweats and dyspnea. The patient worked as a driver in Mexico and was taking two different formulations of 30mg Clobenzorex, an amphetamine pro-drug, daily for two years to help him stay awake for work. These medications were available over the counter. He had not taken it since he moved to the US. He denies the use of illicit drugs, contact with any inmates or Tuberculosis patients. At the time of his presentation, he works in a wooden floor-making company. Labs revealed a markedly elevated total bilirubin of 4.4 mg/dL, INR 1.1, AST 1325 IU/L, ALT 3151 IU/L, LDH 745 IU/L and a mildly elevated ALP 220 IU/L. Acute hepatitis and autoimmune panels were not reactive. Serum acetaminophen level was also within normal limits. Ultrasound of the abdomen and MRCP noted gallbladder wall thickening but no biliary dilatation or pathology. The patient subsequently underwent a core-needle liver biopsy that displayed lobular infiltrates of inflammatory cells of predominantly lymphocytes (Figure 1). Given the absence of positive viral serology, a diagnosis of drug-induced hepatitis was concluded. Discussion: This case report documents a unique instance of drug-induced liver injury secondary to Clobenzorex use. This case highlights the importance of a detailed social history and should encourage clinicians not to neglect to ask about over-the-counter medications to help elucidate potential causes of liver injury. This is an important consideration, especially in the subset of patients from countries outside the United States who have access to a variety of OTC medications that are potentially hepatotoxic.Figure 1.: Core needle liver biopsy showing lobular infiltrates of inflammatory cells consisting of predominantly lymphocytes.

Transplacental transfer of acetaminophen in pregnant rats

Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUCtissue/AUCblood) was approximately 11–23 % after acetaminophen (100 and 300 mg/kg) administration. However, the transporter of multidrug resistance-associated protein (MRP) inhibitor MK-571 did not significantly change the transplacental transfer ratio. This basic study provides constructive information for the clinical application of acetaminophen in pregnant women.

Characterization and Quantification of Oxidized High Mobility Group Box 1 Proteoforms Secreted from Hepatocytes by Toxic Levels of Acetaminophen.

The high mobility group box 1 (HMGB1), which is released during acute acetaminophen (APAP) overdose, is thought to mediate a subsequent immune response, particularly hepatic infiltration of macrophages. The redox behavior of HMGB1 and the proteoforms of HMGB1 present in oxidative environments has been the subject of a number of confusing and contradictory studies. Therefore, a stable isotope dilution two-dimensional nanoultrahigh-performance liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry method was developed in order to characterize and quantify oxidative modifications to the cysteine (Cys) residues (Cys-23, Cys-45, and Cys-106) that are present in HMGB1. Disulfide linkages were determined using carbamidoethyl derivatization before and after reduction as well as by direct analysis of disulfide cross-linked peptides. A stable isotope labeled form of HMGB1 was used as an internal standard to correct for sample to sample differences in immunoaffinity precipitation, derivatization, and electrospray ionization. Four discrete HMGB1 proteoforms were found to be released from a hepatocarcinoma cell model of APAP overdose after 24 h. Fully reduced HMGB1 with all three Cys-residues in their free thiol state accounted for 18% of the secreted HMGB1. The proteoform with disulfide between Cys-23 and Cys-45 accounted for 24% of the HMGB1. No evidence was obtained for a disulfide cross-link between Cys-106 and the other two Cys-residues. However, 45% of the HMGB1 formed a cross-link with unidentified intracellular proteins via an intermolecular disulfide bond, and 12% was present as the terminally oxidized cysteic acid. Surprisingly, there was no evidence for the formation of HMGB1 disulfides with GSH or other low molecular weight thiols. Secreted plasma HMGB1 Cys-23/Cys45 disulfide proteoform together with the Cys-106/protein disulfide proteoforms could potentially serve as early biomarkers of hepatoxicity after APAP overdose as well as biomarkers of drug-induced liver injury.

Design of electrochemical sensor based on N-doped reduced graphene oxide/copper oxide nanocomposite and ionic liquid for the simultaneous determination of 4-aminophenol and acetaminophen

The present effort was made to design a facile, fast and sensitive electrochemical method to detect 4-aminophenol via the appreciable properties of N-doped reduced graphene oxide/copper oxide (N-rGO/CuO) nanocomposite and ionic liquid (IL). The modification of carbon paste electrode (CPE) with N-rGO/CuO/IL (N-rGO/CuO/ILCPE) exhibited an excellent electrochemical sensing performance to 4-aminophenol compared with bare CPE, ILCPE and N-rGO/CuO/CPE. The N-rGO/CuO/ILCPE exhibited the linear dynamic ranging between 0.1 and 800.0 μM with a detection limit of 0.027 μM to determine 4-aminophenol. Also, as-prepared N-rGO/CuO/ILCPE was also employed to detect 4-aminophenol and acetaminophen simultaneously. In a system consisting of 4-aminophenol and acetaminophen concurrently, there were two distinct oxidation peaks and the potential separation of oxidation peaks of 4-aminophenol and acetaminophene was 310 mV, owing to the synergistic impact of CuO/N-rGO nanocomposite and IL. Furthermore, the 4-aminophenol and acetaminophen levels in acetaminophen tablets and river water samples were accurately detected by the prepared sensor.

Nomogramın Uygulanamadığı Durumlarda Parasetamol Zehirlenmesi Riskinin Belirlenmesi

The Rumack-Matthew nomogram for acetaminophen toxicity was prepared using the acetaminophen levels of untreated patients and published in 1975. In order to determine the risk, the authors aimed to determine the acetaminophen levels that cause the aminotransferase level to increase to 1,000 IU/L and above (1). Thus, the line presenting the values above 200 was created. In the study published by Rumack et al. in 1981, the line representing values above 150 was suggested as a safer value (2). On the other hand, the nomogram was designed on the known intake times of single dose, immediate-release acetaminophen preparations. This causes significant limitations in clinical practice.

COMPARISON OF N-ACETYLENE CYSTEINE AND RESVERATROL TREATMENTS IN ACETAMINOPHEN TOXICITY MODEL IN RABBITS

Purpose: Acetaminophen is safe drug but it may cause hepatic failure in high doses. N-acetyl cysteine (NAC) is used in treatment of acetaminophen intoxication. Resveratrol may be used in experimental acetaminophen intoxication models. Purpose, compare the efficacy of NAC and resveratrol treatments in acetaminophen intoxication.&#x0D; Materials and Methods: We used 34 rabbits. 6 rabbits were included in control group and 7 rabbits were enrolled in other groups APAP group, animals administered 2 g/kg of acetaminophen by orogastric tube. APAP + NAC group, 150 mg/kg NAC was administered intramusculer (i.m) to animals at 1st hour following 2 g/kg of acetaminophen administration by orogastric tube. APAP + RES group, animals received 100 mg/kg resveratrol by orogastric tube at 1st hour following oral administration of 2 g/kg of acetaminophen by orogastric tube. APAP + NAC + RES group, animals received 100 mg/kg resveratrol by orogastric tube and 150 mg/kg NAC i.m at 1st hour following oral administration of 2 g/kg of acetaminophen by orogastric tube. ALT, AST, GSH and acetaminophen levels were measured. Animals were sacrificed at 24th hour Liver samples were obtained for histopathological examination.&#x0D; Results: According to our results, GSH level at 12th hour was significantly different between APAP + NAC group and APAP + RES group (p = 0.007). In histopathological examination, HSCORE level we used for apoptosis was statistically significantly lower in control group than in APAP group (p = 0.007). Its supports that acetaminophen toxicity triggers apoptosis in liver cells.&#x0D; Conclusion: Our results support that resveratrol is option for acetaminophen toxicity.