Elevated Liver Chemistries Research Articles

Biliary Duct Dilatation: AJR Expert Panel Narrative Review.

Biliary duct dilatation is a common incidental finding in practice, but it is unlikely to indicate biliary obstruction in the absence of clinical symptoms or elevated levels on liver function tests (LFTs). However, the clinical presentation may be nonspecific, and LFTs may either be unavailable or difficult to interpret. The goal of this AJR Expert Panel Narrative Review is to highlight a series of topics fundamental to the management of biliary duct dilatation, providing consensus recommendations in a question-and-answer format. We start by covering a basic approach to interpreting LFT results, the strengths and weaknesses of the biliary imaging modalities, and how and where to measure the extrahepatic bile duct. Next, we define the criteria for biliary duct dilatation, including patients with prior cholecystectomy and advanced age, and discuss when and whether biliary duct dilatation can be attributed to papillary stenosis or sphincter of Oddi dysfunction. Subsequently, we discuss two conditions in which the duct is pathologically dilated but not obstructed: congenital cystic dilatation (i.e., choledochal cyst) and intraductal papillary neoplasm of the bile duct. Finally, we provide guidance regarding when to recommend obtaining additional imaging or testing, such as endoscopic ultrasound or ERCP, and include a discussion of future directions in biliary imaging.

S3185 The Great Imitator Spares No Organ: A Case of Syphilitic Hepatitis in an Immunocompetent Patient

Introduction: Syphilis, infamously known as the “great imitator,” is an infectious disease caused by the spirochete Treponema pallidum and can affect many organs. Though uncommon, syphilis can also affect the liver, often manifesting as elevated liver enzymes. Herein we describe the case of a 48-year-old immunocompetent male who was found to have a syphilis-induced acute liver injury. Case Description/Methods: A 48-year-old male presented with a two-week history of dry cough, fever, anorexia, and sore throat. He initially presented to an outside hospital where he was diagnosed with community-acquired pneumonia and discharged on amoxicillin-clavulanate. Given poor improvement in symptoms, he presented to our emergency department several days later and noted additional symptoms of headache, blurry vision, and rash. On admission, liver enzymes were elevated (Table 1), and a mild maculopapular rash was noted on his trunk and extremities. Clinical findings and liver injury were attributed to a drug injury in the setting of recent amoxicillin-clavulanate use. However, the liver injury persisted, prompting additional evaluation. Acute and chronic liver serology tests were unrevealing except for a positive anti-mitochondrial antibody, 44 units, and anti-nuclear antibodies, titers of 1:160. Syphilis screen with rapid plasma reagin was reactive with a titer of 1:32. Given neurological symptoms, a lumbar puncture was performed and revealed a reactive fluorescent treponemal antibody test absorption test. The patient was diagnosed with secondary syphilis complicated by neurosyphilis and syphilitic hepatitis. The patient completed a two-week course of intravenous penicillin with complete resolution in symptoms. After initiation of penicillin, the patient's liver chemistries downtrended and normalized after treatment, confirming the diagnosis of syphilitic hepatitis. Discussion: Syphilitic hepatitis is an uncommon manifestation of syphilis. Suspicion should be raised in patients with elevated liver chemistries, in particular cholestatic pattern, who also have manifestations such as maculopapular rash, low grade fever, arthralgias, headache, and changes in vision. This case highlights the importance of maintaining a broad differential and avoiding anchoring bias when approaching elevated liver chemistries. Table 1. - Liver Function Tests Baseline Outside Hospital Presentation Week 1 Week 3 Alkaline phosphatase (IU/L) 78 1126 1118 997 437 ALT (IU/L) 14 225 231 224 53 AST (IU/L) 19 130 154 139 37 Total bilirubin (mg/dL) 0.8 1.9 4.3 2.0 0.9

S3531 A Rare Cause of Obstructive Jaundice: Afferent Limb Syndrome

Introduction: Afferent limb syndrome (ALS) is a rare but potentially life-threatening complication of upper gastrointestinal (GI) surgery and reconstruction causing distal obstruction of the biliopancreatic limb with subsequent accumulation of bile, pancreatic fluid, and other small bowel secretions upstream afferent limb dilation. It is imperative to recognize this complication postoperatively as buildup in the small bowel can result in bowel perforation requiring emergency surgery. We present a patient who developed ALS after upper gastrointestinal reconstruction with esophagojejunostomy for the treatment of gastric adenocarcinoma. Case Description/Methods: An 84 year-old female with a past medical history of gastric adenocarcinoma with total gastrectomy and esophagojejunostomy presented to the emergency department with a subacute history of upper abdominal pain and new-onset jaundice. Initial labs were notable for elevated liver chemistries including alkaline phosphate level of 435 U/L (normal 39-117 U/L), alanine transaminase of 62 U/L (normal 6-45 U/L), and aspartate transaminase of 36 U/L (normal 10-25 U/L). Abdominal ultrasound demonstrated markedly dilated common bile and intrahepatic ducts and gallbladder distention without stones. CT scan of the abdomen confirmed the ultrasound findings, but also identified a dilated duodenum with an abrupt transition point in the proximal jejunum suggestive of ALS shown in Figure A. The patient underwent open laparotomy which demonstrated multiple tumor implants. A large implant at the site of the previous jejunojejunostomy was identified as the cause of afferent limb obstruction. A palliative bypass was performed. The patient had a complicated post-operative course. Ultimately, due to the extensive disease burden and ongoing patient discomfort, the patient and their family decided to pursue hospice care. Discussion: ALS is a post-operative complication of upper GI tract surgery that involves mechanical obstruction of the biliopancreatic limb. Patients often present with jaundice. CT scan is the preferred diagnostic modality. First-line treatment involves surgery to relieve the obstruction with revision of the prior anastomosis. Although rare, this diagnosis should be considered in appropriate patients.Figure 1.: A: CT scan with markedly dilated intrahepatic and extrahepatic biliary ductal dilation, distended gallbladder, and markedly dilated duodenum with abrupt transition point in proximal jejunum.

S3275 A Peculiar Case of Limb-Girdle Muscular Dystrophy Masquerading as Elevated Transaminases

Introduction: A disproportional elevation in aspartate transaminase (AST) and alanine transaminase (ALT) is considered a marker of hepatocellular injury. Guidance on the work up of chronically elevated liver chemistry suggests an algorithmic approach to testing of common causes of liver injury based on the degree of elevation and even mentions consideration of nonhepatic etiologies such as skeletal muscle damage. We present a unique case of asymptomatic elevation in liver chemistries as the herald finding in a patient with limb-girdle muscular dystrophy (LGMD). Case Description/Methods: Our patient is a 19-year-old adopted male who was referred to outpatient gastroenterology clinic for asymptomatic elevation in transaminases. AST was 133 IU/L and ALT was 223 IU/L. Total bilirubin and alkaline phosphatase were normal. He denied alcohol use, prescribed medications, herbal supplements, or weightlifting supplements. BMI was normal. Workup for viral hepatitis, hemochromatosis, autoimmune hepatitis, Wilson’s disease, alpha-1 antitrypsin, celiac disease, and thyroid disease were normal. Liver biopsy revealed reticulin collapse with complete regeneration without inflammation. Subsequent follow-up over years demonstrated persistently elevated but stable elevations. At the age of 24, he began to endorse proximal lower extremity muscle pain and weakness. Creatine kinase (CK) was elevated at 11,937 U/L; aldolase was elevated at 31.4 U/L; myositis workup was normal. Right thigh biopsy revealed a myopathic process. Genetic testing confirmed mutation in the CAPN3 gene consistent with calpainopathy, a subtype of LGMD. Discussion: LGMD is a rare, genetic disorder resulting in loss of ambulation within 20 years after disease onset. Concurrent liver disease is rare in LGMD, but elevations in transaminases can be found because of severe elevations in CK. Our patient was found to have calpainopathy, a subtype associated with a recessive mutation in the CAPN3 gene. Our case demonstrates that beyond the recommended algorithmic evaluation of abnormal liver chemistries, inconclusive evaluation of abnormal liver chemistries in children and young adults should include a CK level to further investigate nonhepatic causes, specifically a myopathic process. Although there is no cure for LGMD, interventions focused on muscle conditioning are more beneficial with early detection to mitigate the devastating effects of this disorder.

Early detection of COVID-19 cholangiopathy using cholangioscopy-acase report of two critically ill patients.

BackgroundThe coronavirus disease 2019 (COVID-19) crisis caused by the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) rapidly led to a pandemic. While the majority of SARS-CoV-2-infected patients present with fever and respiratory symptoms, gastrointestinal symptoms may also occur. In addition, serious hepatic manifestations like cholangiopathy and liver failure have been described.Patients and methodsWe identified two critically ill patients suffering from SARS-CoV‑2 infection in our intensive care unit (ICU). In both patients, laboratory testing revealed elevated liver chemistries weeks after initial diagnosis with COVID-19.ResultsDuring repeated endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy, a severely destructed biliary mucosa with ischemia and epithelial roughness was seen in both patients. Due to the prolonged course of COVID-19 and chronic liver damage with ongoing sepsis, both patients succumbed to the disease.ConclusionIn our opinion, a COVID-19 infection can lead to development of cholangiopathy in critically ill patients. Cholangioscopy performed early can confirm the diagnosis of COVID-19-associated cholangioscopy.

Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients.

BACKGROUNDAbnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understoodAIMWe aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality.METHODSThis retrospective, observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System (Baltimore, MD, United States). Demographic data, clinical characteristics, laboratory findings, treatment measures, and outcome data were collected. Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosisRESULTSA total of 2698 (70.4%) had abnormal alanine aminotransferase (ALT) at the time of admission. Other more prevalent abnormal liver chemistries were aspartate aminotransferase (AST) (44.4%), alkaline phosphatase (ALP) (16.1%), and total bilirubin (T-Bil) (5.9%). Factors associated with liver injury were older age, Asian ethnicity, other race, being overweight, and obesity. Higher ALT, AST, T-Bil, and ALP levels were more commonly associated with disease severity. Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization. Abnormal AST, T-Bil, and ALP were associated with a need for vasopressor drugs, whereas higher levels of AST, T-Bil, and a decreased albumin levels were associated with mechanical ventilationCONCLUSIONAbnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient’s severity and prognosis. Elevated liver chemistries, specifically ALT, AST, ALP, and T-Bil levels, can be used to stratify risk and predict the need for advanced therapies in these patients.

Dress syndrome following carbamazepine exposure: A very early onset

IntroductionDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction characterised by both systemic and cutaneous clinical manifestation with a mean latency period of 3.9 weeks.ObjectivesTo underline the importance of an early diagnosis of DRESS SYNDROME.MethodsWe reported a case of carbamazepine induced DRESS syndrome with atypical chronology of manifestations.ResultsA 43-year-old man with no previous known medical history was admitted in psychiatry. He experienced a relapse of schizoaffective symptoms. In the last three years, the patient was treated by Valproic acid as a mood stabilizer. Because of the unavailability of this molecule, carbamazepine was prescribed in combination with antipsychotics. Three days later, the patient developed a high fever, hypotension, a pruritus, a facial oedema, a skin rash associated to lymphadenopathy. Laboratory findings showed a lymphopenia, eosinophilia and elevated liver chemistries. In order to define the case, RegiSCAR scoring system was used, and our case is categorized as probable with a score of five. Carbamazepine was discontinued upon clinical manifestationsand the patient was treated with systemic antihistaminic treatment associated to methylprednisolone with a good outcome. After 3 weeks, clinical and biological improvement were noted.ConclusionsDespite the absence of a delayed onset, typically between 3 weeks and 3months, we can diagnose dress syndrome 3 days after carbamazepine intake. This case highlights that psychiatrists should be aware of the risk of early onset dress syndrome associated with carbamazepine and they should monitor for warning symptoms from treatment initiation.DisclosureNo significant relationships.

S2621 A Case of Hepatic Infarction Following Transjugular Intrahepatic Portosystemic Shunt Placement

INTRODUCTION: Transjugular intrahepatic portosystemic shunt (TIPS) is a therapeutic modality used to manage complications of portal hypertension including refractory ascites and esophageal varices. Post-TIPS complications include hemorrhage, acute hepatic encephalopathy (HE), stent migration, and acute liver failure (ALF). Herein we present a patient with decompensated cirrhosis complicated by hepatic infarction following TIPS placement.1,2 CASE DESCRIPTION/METHODS: A 56-year-old man with decompensated cirrhosis secondary to primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) overlap underwent TIPS for refractory ascites. Post-TIPS, he developed severe epigastric pain. Imaging revealed known hepatomegaly with cirrhotic morphology and new hypodense areas in the right lobe of the liver suggestive of infarction (Figures 1 and 2). He improved with medical management and was discharged home. Over two years, he required TIPS revisions due to stent malfunction and stent thrombosis with eventual need for orthotropic liver transplant. Native liver histopathology showed focal necrosis (Figure 3) as noted on imaging following the initial TIPS. DISCUSSION: With TIPS, a metal stent creates a low-resistance channel between the hepatic vein and the intrahepatic portion of the portal vein and decreases portal pressure allowing for blood return to systemic circulation. Hepatic infarction is rare, with a post-TIPS complication rate of 0.5%.3 Proposed pathogenesis of hepatic infarction include direct arterial injury, hepatic artery occlusion, hypotension and shock with decreased hepatic arterial flow, and extrinsic compression of a branch of the hepatic artery after stent deployment.2,4 Portal flow diversion and inadequate compensation of hepatic arterial blood flow may lead to hepatic ischemia resulting in ALF and infarction.2 The Child-Pugh score negatively correlates with the arterial buffer reserve that is integral in facilitating hepatic perfusion following TIPS.5 Manifestations of hepatic infarction include right upper quadrant pain, HE, and elevated liver chemistries, with worsening hyperbilirubinemia suggestive of ALF.5 CT and MRI demonstrate the ischemic insult if present. In our case, we believe the patient did not immediately progress to ALF as his extensive hepatomegaly compensated for the ischemic injury by maintaining steady state as evidenced by clinical improvement without intervention. While rare, this case demonstrates the importance of recognizing hepatic infarction as a post-TIPS complication.Figure 1.: Coronal slice of CT-abdomen and pelvis with IV contrast demonstrating hepatomegaly with cirrhotic morphology and hypodense areas in the right hepatic lobe suggestive of infarction.Figure 2.: Axial slice of CT-abdomen and pelvis with IV contrast demonstrating hepatomegaly with cirrhotic morphology and hypodense area in the right hepatic lobe suggestive of infarction.Figure 3.: Histopathology contrasting necrotic liver parenchyma (top) with non-necrotic liver parenchyma (bottom). (Magnification 40x).

S2550 Liver Transplantation in a Patient With Refractory Pruritus From Follicular Cholangitis

INTRODUCTION: Follicular cholangitis is rare and can present as a mimicker of cholangiocarcinoma. Surgical intervention is considered on follicular cholangitis patients for suspicion of rapidly progressive cholangiocarcinoma. Here we present the case of a 43-year-old female who initially underwent a Whipple procedure due to concern for a cholangiocarcinoma. Pathology showed follicular cholangitis. She continued with intractable pruritus and a liver transplant was pursued for that indication. CASE DESCRIPTION/METHODS: A 43-year-old previously healthy female presented with progressive fatigue and pruritus. Laboratory evaluation was significant for elevated liver chemistries, filamentous-actin of 121 and a positive antinuclear antibody. A liver biopsy showed dense portal inflammation, mostly lymphocytes, rare plasma cells, mild interface hepatitis, paucity of bile ducts, but no florid duct lesion or fibrosis. Initially, she was started on immunosuppression with no improvement in labs. A magnetic resonance cholangiopancreatography (MRCP) was obtained to rule out bile duct obstruction. MRCP was significant for common bile duct (CBD) stones. Endoscopic retrograde cholangio-pancreatography (ERCP) showed CBD stricture with cytology concerning for cholangiocarcinoma. At this time, she underwent a Whipple procedure. Surgical pathology was suggestive of follicular cholangitis and no malignant cells were identified. Post operatively, she continued to have pruritus and fatigue. Immunosuppression was resumed with no change in symptoms. Repeat MRCP showed right hepatic lobe strictures, but subsequent ERCP was unsuccessful due to post-whipple anatomy. Percutaneous cholangiogram was pursued and did not show any obvious lesion. She was then trialed on multiple pruritus medications including naltrexone, rifampin and sertraline without any improvement in symptoms as well as numerous side effects. She was ultimately maintained on ursodiol with minimal improvement. Liver transplant was considered due to quality of life concerns from pruritus. At that time her MELD was 6. She recently received a liver transplant, and is now pruritus free for months, maintained on standard immunosuppression. DISCUSSION: Clinicians should consider follicular cholangitis in the differential for obstructive jaundice. Review of the literature showed 11 cases of follicular cholangitis and one liver transplant due to cirrhosis. This is the first reported liver transplant case for refractory pruritus due to follicular cholangitis.

S2475 The Buck Stops Here: A Case of Deer Antler Extract-Induced Liver Injury

INTRODUCTION: Liver injury secondary to prescription or over the counter drugs and supplements is an ongoing public health concern, especially with the growing marketplace of unregulated supplements. Drug induced liver injury (DILI) has been reported as the most common reason for regulatory actions instituted by the US FDA against medications and supplements. Deer antlers are the only mammalian organs that can entirely grow back once lost and their extract contains insulin-like growth factor. Many athletes admit using deer antler extract as a performance-enhancing supplement, but its safety is unknown. The following is the first reported case of a deer antler supplement induced liver injury. CASE DESCRIPTION/METHODS: A 38 YO male presented with fatigue and elevated liver chemistry tests: AST 360, ALT 1297, ALP 78 (U/L) and bilirubin 2.9 mg/dL. He was not on any medications but did note recent use of a supplement called “Bucked Up” consisting of deer antler velvet extracts, ginseng, caffeine, taurine and Himalayan rock salt. He denied any concurrent supplement, herb, drug, or alcohol use, and noted improved symptoms following stopping using the supplement 5 days prior to presentation. The patient underwent a thorough work-up which ruled out infectious causes such as viral hepatitis, CMV, HSV, EBV, biliary obstruction, genetic diseases and autoimmune hepatitis. Liver biopsy showed moderate acute lobular cholestatic hepatitis. Patient was followed for total of 150 days after the liver injury. Figure 1 shows the peaks of Alk Phos, T bili, AST and ALT throughout the follow-up period. Alk Phos and T bili peaked around day 25 after the injury, while ALT and AST peaked at the first day and decreased to normal level at day 10. Another peak in AST and ALT was noted at around day 30. At day 50, all the labs started to return to the normal level. DILI resolved spontaneously without any treatment. DISCUSSION: The updated RUCAM Causality Assessment was used to evaluate the probability of DILI secondary to the deer antler velvet blend. The R ratio was consistent with hepatocellular type injury. It showed a probable correlation with a 7-point score, which along with the patient’s clinical course confirms the diagnosis of DILI secondary to the supplement. This report represents the first case of a deer antler-based supplement leading to hepatotoxicity, highlighting the need for public awareness regarding the hepatotoxicity of deer antler extract containing supplements.Figure 1.: Lab measurements from day 0 to day 150.Table 1.: The R ratio score

Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19.

SummaryBackgroundThe incidence of elevated liver chemistries and the presence of pre‐existing chronic liver disease (CLD) have been variably reported in COVID‐19.AimsTo assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID‐19.MethodsA comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID‐19.Results107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5‐5.1) among the 15 407 COVID‐19 patients. The pooled incidence of elevated liver chemistries in COVID‐19 was 23.1% (19.3‐27.3) at initial presentation. Additionally, 24.4% (13.5‐40) developed elevated liver chemistries during the illness. The pooled incidence of drug‐induced liver injury was 25.4% (14.2‐41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%‐5.2%). The odds of developing severe COVID‐19 in CLD patients was 0.81 (0.31‐2.09; P = 0.67) compared to non‐CLD patients. COVID‐19 patients with elevated liver chemistries had increased risk of mortality (OR‐3.46 [2.42‐4.95, P < 0.001]) and severe disease (OR‐2.87 [95% CI, 2.29‐3.6, P < 0.001]) compared to patients without elevated liver chemistries.ConclusionsElevated liver chemistries are common at presentation and during COVID‐19. The severity of elevated liver chemistries correlates with the outcome of COVID‐19. The presence of CLD does not alter the outcome of COVID‐19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.

Highlights From the AASLD/EASL ALD Endpoints Conference 2019.

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2390 Trenbolone-Induced Liver Injury

INTRODUCTION: Anabolic-androgenic steroid abuse has been steadily increasing in the general population. According to a 2014 study, approximately 1 in 50 students in the 12th grade reported using anabolic steroids. Trenbelone acetate is a synthetic anabolic androgen which is an agonist of the androgen receptor and most often used in cattle. CASE DESCRIPTION/METHODS: A 23 year old male with no significant past medical history presented with complaints of jaundice and generalized weakness which began 10 days prior to presentation. Patient endorsed weekly IM trenbelone 1000 mg weekly over the last 8 weeks. Physical examination was remarkable for icterus and appropriate mentation. Initial investigations reflected a total bilirubin of 13.44 mg/dL, AST 159 IU/L, ALT 425 IU/L, PT 11.0, INR 1.0, and Alk Phos of 142. Serologies were negative for viral hepatitis, anti-mitochondrial antibody, anti-smooth muscle antibody and ANA of 1:40. A liver ultrasound reported normal liver size without biliary obstruction. Patient's liver chemistries improved over the next three days and he was discharged with total bilirubin of 12.54 mg/dL, AST 135 IU/L, ALT 320 IU/L, PT 11.0, INR 1.0 and Alk Phos of 121. Patient advised to abstain from any future use of trenbelone. On repeat labs in 10 days, his total bilirubin of 29.50 mg/dL, AST 78, ALT 123, PT 20.1, INR 1.85 and Alk Phos 242. Physical examination noted worsening jaundice overall along with icterus but mentation remained appropriate. Patient denied any new medications and no further use of trenbelone since discharge. Patient's liver chemistries remained stable and he underwent MRI abdomen which was unremarkable. Patient was discharged home on ursodiol 300 mg BID. Patient's liver chemistry improved in one week and returned to baseline in one month. DISCUSSION: Anabolic steroids have been linked to four different forms of liver injury including an acute cholestatic syndrome such as in our patient, elevation in serum enzymes, chronic vascular injury and hepatic tumors including adenomas and hepatocellular carcinoma. Mechanism of cholestatic syndrome is not well defined in this type of injury. Urosdiol has been used in the past for treatment however efficacy has not been shown in a study. Healthcare provides managing patients with elevated liver chemistries should able to recognize anabolic induced liver injury given increasing use and ease of availability of such performance enhancing drugs.

30-Year-Old Woman With Intractable Vomiting

30-Year-Old Woman With Intractable Vomiting

3185 An Unusual Cause of Abdominal Pain and Elevated Liver Chemistries

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a spectrum ranging from simple steatosis to cirrhosis. It is present in 33% of the general adult population and is more prevalent in overweight and diabetic patients. This can be explained by abnormal lipid metabolism with stressed conditions such as Cushing's disease (CD). In CD, glucocorticoids act synergistically with insulin to increase lipid accumulation. The incidence of NAFLD in CD is not well described but is thought to be greater than the general population. CD is less commonly labelled as a culprit of elevated liver chemistries. Here, we present a case of a young woman with uncharacteristically elevated liver tests found to be due to CD. CASE DESCRIPTION/METHODS: A 35-year-old woman was admitted for abdominal pain, nausea, and vomiting. Her medical history included a pituitary adenoma with subsequent CD status post three resections, diabetes insipidus, diabetes mellitus type 2, bipolar disorder, and symptomatic cholelithiasis status post cholecystectomy. Admission labs showed total bilirubin 3.70 mg/dL, ALP 480 U/L, AST 681 U/L, ALT 992 U/L, lipase 25 U/L. Workup was negative including viral hepatitis including hepatitis E, autoimmune hepatitis, hemochromatosis, alpha-1 anti-trypsin deficiency were negative. Abdominal ultrasound and MRCP showed hepatic steatosis. Liver biopsy revealed 70-80% macrovesicular hepatic steatosis and prominent cholestasis. Her liver function tests transitioned to a cholestatic pattern with total bilirubin 7.07 mg/dL, ALP 1019 U/L, AST 273 U/L, and ALT 519 U/L. She was started on ursodiol 15 mg/kg resulting in immediate symptomatic improvement. One month following hospitalization while on treatment, labs were AST 21 U/L and ALT 30 U/L. DISCUSSION: NAFLD is diagnosed by adiposity within the liver on imaging or histopathology and remains the most common cause of abnormal liver chemistries. Patients with CD have been shown to have a higher incidence of NAFLD, as much as 20%. This is thought due to an increase in visceral fat rather than a direct effect of cortisol, as often the BMI is not particularly elevated. While a majority of patients with NALFD may have normal transaminases, a study by Shirin et al found that patients with higher elevations in cholestatic enzymes were more likely to have advanced liver disease. Thus, clinicians should have a high suspicion when a patient has comorbidities predisposing them to hepatic steatosis, including metabolic syndromes such as CD.

1418 A Troublesome Remnant

INTRODUCTION: Postcholecystectomy syndrome (PCS) is the persistence of symptoms of biliary colic after cholecystectomy. Although PCS is relatively common with multiple etiologies, a remnant cystic duct is a rare etiology accounting for only 2.5% of cases. Mirizzi's syndrome is a rare cause of PCS due to a remnant cystic duct stone. CASE DESCRIPTION/METHODS: A 34-year-old female with a history of choledocholithiasis status-post cholecystectomy 6 years prior presented with severe, constant, sharp right upper quadrant pain with nausea and vomiting for 1 day. She had abdominal tenderness with a negative Murphy sign. She was found to have elevated liver chemistries. Patient had two hospitalizations within the past year with similar presentations with the finding of choledocholithiasis requiring endoscopic retrograde cholangiopancreatography (ERCP) on both occasions. Magnetic retrograde cholangiopancreatography (MRCP) showed a dilated, remnant cystic duct with filling defect indicative of obstruction caused by the stone. ERCP was done with removal of one stone followed by surgical resection of the remnant cystic duct with an endoluminal stone. DISCUSSION: The cystic duct typically measures 2-4 cm in length, and formation of stone in the structure leads to symptoms of dyspepsia, nausea, vomiting, and possibly jaundice. Cholecystectomy provides symptom relief to 85% of patients. After cholecystectomy, an incomplete surgery can leave a residual duct of greater than 1 cm in length, defined as a cystic duct or gallbladder remnant. Formation of calculi in this structure can lead to PCS. PCS can present as continuation of symptoms after the operation or after an interval of 2 days to 25 years after disease free period. PCS has been reported in 5 to 40% of patients post-cholecystectomy. Most common causes are extrabiliary, however, biliary etiologies are not uncommon. The incidence of PCS due to remnant cystic duct has been reported to be less than 2.5%. Identifying and promptly treating the underlying etiology are important to minimize morbidity. Cystic duct remnant stones may predispose a patient to postcholecystectomy Mirizzi's syndrome. While difficult to diagnose with different imaging studies, this can be effectively diagnosed with MRCP and treated with ERCP. One study showed that ERCP/MRCP failed to identify 2 out of 3 patients with a remnant cystic duct. While endoscopic therapy is an effective and safe alternative to surgery for postcholecystectomy Mirizzi's syndrome, surgical intervention is a definite treatment.

2278 Rapidly Progressive Hepatitis C After Liver Transplantation Treated With Glecaprevir/Pibrentasvir

INTRODUCTION: Hepatitis C recurrence following liver transplantation occurs in all patients with chronic HCV infection who have detectable serum HCV RNA levels prior to transplant. Less than 10% of these patients develop an acute and severe phenotype called fibrosing cholestatic hepatitis, which often involves fibrosis, rapid graft loss and decreased survival. The introduction of direct-acting antiviral agents (DAAs) have changed the paradigm of treatment of these patients. CASE DESCRIPTION/METHODS: A 62-year-old woman with a medical history of hepatitis C infection, hepatocellular carcinoma status post orthotropic liver transplantation, diabetes mellitus and hypertension who was hospitalized for fatigue and elevated liver chemistries following her liver transplantation. Laboratory tests showed a white cell count 6.67 × 103/μL, creatinine 1.1 mg/dL, aspartate aminotransferase 592 U/L, alanine aminotransferase 504U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL, albumin 2.9 g/dL. Acute hepatitis work up showed a positive hepatitis C virus antibodies with genotype 1B, with a viral load of 80 million IU/mL HCV RNA. HBsAg, HBc IgG, HBc IgM, and hepatitis A virus IgM were negative. Evaluation for Epstein-Barr virus, cytomegalovirus and herpes simplex virus were negative. Ultrasound of the abdomen revealed that the liver is normal in size, echotexture and contours. No focal hepatic lesions. Normal hepatic blood flow. The patient underwent liver biopsy that showed lymphocytic portal inflammation with frequent lobular apoptosis consistent with active chronic hepatitis C (MHAI: 5-6/18). Mild portal fibrosis (ISHAK FIBROSIS STAGE: 1/6) and minimal evidence of acute t cell-mediated rejection (rejection activity index: 1/9). During the patient hospitalization her liver chemistries significantly worsened and peaked to aspartate aminotransferase 740 U/L, alanine aminotransferase 511U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL. We decided to start the patient on Glecaprevir/Pibrentasvir for acute and severe hepatitis. Fourteen days after starting Glecaprevir/Pibrentasvir, the patient viral load decreased to 782 IU/mL HCV RNA and normalized liver chemistries with AST19 and ALT 27. The patient denied any adverse events due to the treatment. DISCUSSION: To our knowledge, this is the first case report of treating early and aggressive form of HCV recurrence with Glecaprevir/Pibrentasvir. The dramatic improvement of the patient suggest that DAA might be safe and effective in this situation.

2216 Toxic Epidermal Necrolysis and Drug-Induced Liver Injury Secondary to Oseltamivir

INTRODUCTION: Multiple antibiotics have the well documented adverse reactions of Stevens-Johnson syndrome, toxic epidermal necrolysis, and liver injury. Oseltamivir is not known to cause any of the above reactions. We present a patient who suffered both toxic epidermal necrolysis and drug induced liver injury (DILI) secondary to oseltamivir. CASE DESCRIPTION/METHODS: A 40-year-old female with systemic lupus erythematosus (SLE) on hydroxychloroquine and azathioprine for several years presented with community acquired pneumonia and rash concerning for Stevens-Johnson syndrome (SJS). She was also found to have newly elevated liver chemistries in a hepatocellular pattern. Her only new medication was oseltamivir which had been started 48 hours prior to presentation for empiric treatment of influenza. She was transferred to our tertiary care academic medical center burn unit for further management of SJS which eventually progressed to toxic epidermal necrolysis (TEN) (confirmed via dermatopathology). On arrival to our institution, her pattern of abnormal liver chemistries evolved into that of a cholestatic hepatitis with a peak conjugated hyperbilirubinemia of 16.7mg/dL, alkaline phosphatase of 1087 U/L, AST of 400 U/L, and ALT of 708 U/L. Her TEN started to improve with supportive care and cessation of oseltamivir. She underwent MRCP which revealed possible bile duct stricturing without biliary ductal dilatation. Her ANA was positive with a titer of 1:640, anti-smooth muscle antibody was negative, anti-mitochondrial antibody was negative, and IgG level was within normal limits. She underwent liver biopsy which was consistent with drug induced liver injury. Her liver chemistries eventually started to improve and she was discharged from the hospital with continued improvement on follow up. DISCUSSION: Oseltamivir is an antiviral sometimes used for influenza infection. Very few reports exist regarding oseltamivir’s association with SJS/TEN, and even less on its association with liver injury. Our case is unique in that a patient developed both TEN as well as drug induced liver injury secondary to oseltamivir which are rare but important differential diagnoses to be aware of for patients who develop rash or elevated liver enzymes while being treated with oseltamivir.

2503 Cholestasis in a Patient With HNF-1B Mutation

INTRODUCTION: Maturity Onset Diabetes of the Young, MODY5, is a syndrome characterized primarily by renal cysts, renal dysfunction and early onset diabetes caused by pancreatic atrophy and hepatic insulin resistance. Hepatocyte nuclear factor 1b (HNF1b) plays a key regulatory role in the organogenesis of tubular epithelia within the renal, pancreatic and biliary systems. CASE DESCRIPTION/METHODS: 33-year-old woman presented to hepatology clinic with chronically elevated liver chemistries in a mixed hepatocellular/cholestatic pattern (Table 1). Abnormalities were first noted in her teens with symptoms of fatigue and pruritus. No history of liver-toxic medications. Medical history: pre-diabetes, polycystic ovarian syndrome with associated infertility issues, renal cysts. Surgical history: bladder/ureteral surgery as a child. Unremarkable social history. Father with ulcerative colitis. Work up included negative hepatitis panel, anti-smooth muscle ab, anti-mitochondrial ab, and ANA. Normal ceruloplasmin, copper, and ferritin. Sonogram with a 15.6 cm homogenous liver, cholelithiasis (resolved on repeat study), and bilateral renal cysts. Liver biopsy was essentially normal with minimal focal lobular chronic inflammation and mild sinusoidal congestion. Her medical history prompted genetic testing for HNF1B mutation, positive for heterozygous disease. MRI/MRCP revealed normal appearing bile ducts and pancreatic atrophy, consistent with the diagnosis. DISCUSSION: HNF1b deficiency compromises the functional integrity of human cholangiocytes by altering the structure of primary cilia. Roelandtet al. were the first to demonstrate aberrant cholangiocytes at the structural level in patients with HNF1b heterozygosity (Figures 1 and 2). The defects do not affect the structure of intra and extrahepatic ducts themselves, so patients may present with normal hepatic and biliary architecture. More overt biliary anomalies have been noted in HNF1b associated MODY5, with many carriers of the mutation demonstrating choledochal cysts. HNF-1b mutations should be considered in patients with cholestasis, late onset diabetes and renal cysts, particularly when standard work up does not reveal a cause for abnormal liver chemistries. While morbidity is associated with pancreatic and renal dysfunction, symptomatic management of cholestasis should be addressed. Further studies are needed to determine if surveillance is necessary to assess the development and potential malignant transformation of choledochal cysts.

MON-333 Failure of Medical Therapy to Control Marked Hypercortisolemia by a Metastatic ACTH Producing Neuroendocrine Tumor

Objective: We present a young woman with rapidly progressive Cushing’s syndrome due to ectopic ACTH production from a pancreatic NET. We describe severe neurological and immunosuppressive sequalae of marked hypercortisolemia associated with chemotherapy and reconsider our therapeutic strategy. Case: A previously active and healthy 28 year old woman was admitted with weakness and leg swelling. Two months prior she noticed a petechial rash on her face, back and arms. One week prior she was found to have DM and elevated liver chemistries prompting an abdominal US showing abnormal liver architecture. An outpatient CT showed a 3.7 cm pancreatic mass with liver lesions. Pertinent findings: BP 118/74, rounded facies, acneiform rash and leg edema, WBC 9400/ul, Glucose 173mg/dl, A1C 8.1%, K 2.3meql/L, random cortisol 114ug/dl, ACTH 830pg/ml, Calcitonin 1135 pg/mL, Chromogranin A 1482 ng/mL and Glucagon 276 pg/mL. After a 2 mg DST, 8 AM cortisol was 123 mcg/dL. We planned to reduce her ectopic ACTH production and hypercortisolemia with ketoconazole and chemotherapy followed by bilateral adrenalectomy. FOLFOX protocol reduced ACTH to 76 pg/mL and Cortisol to 73 mcg/dL but she clinically deteriorated, delaying adrenal surgery. She began having muscle weakness, aphasia, and other polyneuropathies. Blood cultures were positive for K. pneuomoniae and she received antibiotics. Cultures were negative for fungemia. Brain MRI showed extensive subcortical changes suggestive of PRES. Cortisol levels increased to 635 mcg/dL! In addition to ketoconazole and spironolactone, mifepristone was started with improvements in her hypokalemia and glucose. Mental status did not improve and repeat MRI showed findings suggestive of multiple abscesses. She was no longer a candidate for further chemotherapy or surgery and died within 40 days of admission. Discussion: Autopsy showed NET with hepatic metastases and multiple organs with fungal hyphae indicating Aspergillus. Both hypercortisolemia and chemotherapy predisposes to opportunistic infections. This patient’s remarkably elevated cortisol levels raised the consideration of urgent adrenalectomy prior to chemotherapy to limit steroid related complications and the polypharmacy required to control this. Both cortisol and chemotherapy impair cell mediated immunity and down regulate pro-inflammatory cytokines providing the opportunity for fungal and other uncommon infections to develop. This patient’s outcome could not have been worse if we elected adrenalectomy as the first therapeutic option to preclude the marked immunosuppressant effects of persisting hypercortisolemia together with chemotherapy. Otherwise, in a patient so profoundly immunosuppressed by endogenous steroids, a multitude of fungi and other atypical infections which are difficult to detect, need be considered when sepsis develops in association with chemotherapy.