Normal Total Bilirubin Research Articles

A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis

We examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with primary biliary cholangitis (PBC) at risk of disease progression (alkaline phosphatase [ALP] ≥1.67xupper limit of normal [ULN]) who were receiving or intolerant to ursodeoxycholic acid. In this 52-week, phase II, dose-ranging, open-label study, patients were randomized (1:1) to seladelpar 5mg/day (n=53) or 10mg/day (n=55) or assigned to 2mg/day (n=11; United Kingdom sites after interim analysis) for 12 weeks. Doses could then be uptitrated to 10mg/day. The primary efficacy endpoint was ALP change from baseline to Week8. Mean baseline ALP was 300, 345, and 295U/L in the 2mg, 5mg, and 10mg cohorts, respectively. Twenty-one percent of patients had cirrhosis, 71% had pruritus. At Week 8, mean±standard error ALP reductions from baseline were 26±2.8%, 33±2.6%, and 41±1.8% in the 2mg (n=11), 5mg (n=49), and 10mg (n=52) cohorts (all p≤0.005), respectively. Responses were maintained or improved at Week 52, after dose escalation in 91% and 80% of the 2mg and 5mg cohorts, respectively. At Week 52, composite response (ALP <1.67xULN, ≥15% ALP decrease, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2mg, 5mg, and 10mg cohorts, respectively. Pruritus visual analog scale score was decreased in the 5mg and 10mg cohorts. There were no treatment-related serious adverse events, and 4 patients discontinued due to adverse events. Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in patients with PBC at risk of disease progression. Seladelpar appeared safe and well tolerated and was not associated with any increase in pruritus. NCT02955602 CLINICALTRIALSREGISTER. 2016-002996-91 LAY SUMMARY: Current treatment options for patients living with primary biliary cholangitis (PBC) are not optimal due to inadequate effectiveness or undesirable side effects. Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses (2, 5, or 10mg/day) for 1 year had clinically significant, dose-dependent improvements in key liver tests. Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores.

Total Kadar Bilirubin Pada Pasien Tuberculosis (TB) Paru Setelah 5 Bulan Mengkonsumsi Obat Anti Tuberkulosis (OAT) di Rumah Sakit Tentara Kota Binjai

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis which attacks the lungs and bronchi. Anti-tuberculosis drugs consist of isoniazid, ethambutol, pyrazinamide, rifampicin and streptomycin which must be consumed for 6 months. OAT has side effects, especially disturbing liver function, one of which is bilirubin. Bilirubin is a yellow pigment derived from the heme reshuffle of hemoglobin in the process of erythrocyte breakdown by reticuloendothelial cells. This research is desktiptif. This study aims to describe the total bilirubin levels in pulmonary tuberculosis patients after 5 months of consuming anti-tuberculosis drugs in TK.IV.01.07.02 Binjai Army Hospital in May-June. This study was taken from 53 samples of total bilirubin levels in tuberculosis patients who had consumed OAT for 5 months. The results of the 53 samples found normal total bilirubin levels of (77.40%) and increased by (22.60%). Frequency distribution in male sex (56.6%) women (43.4%). Total bilirubin levels increased more in male patients (13.21%). The increase in total bilirubin occurred at&gt; 56 years of age. Total bilirubin levels increased more in female patients (9.43%).

EVALUATION OF HYPERBILIRUBINEMIA IN PATIENTS WITH APPENDICULAR PATHOLOGY

Background: The physiological obstruction of the bile flow associated with appendicular pathology leads to hyperbilirubinemia, which can be used as a predictive factor of appendicular perforation. Objective/Aim : Primary objective of this study was 1. To evaluate hyper-bilirubinemia associated with appendicular pathology. Secondary objectives of this study were 1. To evaluate elevated bilirubin level as an additional diagnostic marker for severity of acute appendicitis. 2. To evaluate whether elevated bilirubin levels have a predictive potential for the diagnosis of appendicular perforation. Methods: The study was conducted in the department of Surgery, Central Referral Hospital, associated to Sikkim Manipal Institute of Medical Sciences, Gangtok. The study was designed as a prospective observational study spanning over a time of 12 months, with enrolment of patients from 12.05.2016 to 11.05.2017. A total of 52 patients with clinical diagnosis of features of acute appendicitis or appendicular perforation admitted in the surgical ward were included. Results: Patients with appendicular perforation (n=14) were divided based on location of perforation:9(64.3%) had perforation at apex, 2(14.3%) at base and 3 (21.4%) had perforation at the body of appendix. Patient who had perforation at the apex of appendix had a mean total bilirubin of 1.84 mg/dl, 7 (77.8%) of these patients had elevated total bilirubin while an equal number had elevated direct bilirubin. Two (22.2%) had normal total bilirubin and value. Patients having perforation at base had a mean total bilirubin of 1.11 mg/dl and direct bilirubin of 0.56 mg/dl. Though one of these had elevated total bilirubin the other had normal value. On the other hand, both had elevated direct bilirubin. The patients having perforation on the body of appendix had mean total bilirubin and direct bilirubin 1.51 mg/dl and 0.57 mg/dl respectively. Both these patients had elevated total bilirubin and direct bilirubin. It was found that both total and direct bilirubin increased in cases having perforation of appendix, but these elevations was not statistically significant. Conclusions: Based on the data obtained, the bilirubin levels cannot be used as an indicator for: a) Severity of acute appendicitis b) appendicular perforation.

Changing Features of Liver Injury in COVID-19 Patients: Impact of Infection with the SARS-CoV-2 Delta (B.1.617.2) Variants.

There is growing evidence that abnormal liver function tests (LFTs) are common in patients with coronavirus disease 2019 (COVID-19). However, it is not known whether viral involvement in the liver differs according to the strain. We investigated the impact on liver injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variants. We conducted a single-center, retrospective cohort study, including 372 patients admitted during the pre-Delta period (PDP: between February 1 and November 30, 2020) and 137 patients admitted during the Delta period (DP: between August 1 and August 31, 2021). Initial liver injury was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 × the upper limit of normal (ULN) or alkaline phosphatase (ALP) or total bilirubin ≥2 × the ULN within 3 days from admission. Of 509 patients with COVID-19 included in our study, 38 (7.5%) patients had initial liver injury. The DP group had a significantly higher rate of initial liver injury than the PDP group (PDP: 5.9% vs. DP: 11.7%, P = 0.028). The DP group (adjusted odds ratio [aOR]: 2.737, 95% confidence interval [CI]: 1.322 - 5.666) was independently associated with initial liver injury. During hospitalization, 160 (31.4%) patients had severe COVID-19. The DP group and initial liver injury had higher odds of progressing to severe COVID-19 (aOR: 2.664, 95% CI: 1.526 - 4.648, and aOR: 4.409, 95% CI: 1.816 - 10.707, respectively). The mediation analysis suggested that initial liver injury mediates the relationship between SARS-CoV-2 Delta variant infection and severe COVID-19 (unstandardized beta coefficient = 0.980, Standard error = 0.284, P = 0.001). Initial liver injury is more common in COVID-19 patients with Delta variants. Also, Delta variants and initial liver injury are associated with poor clinical outcomes.

Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study

BackgroundHyperbilirubinemia is a common complication after off-pump coronary artery bypass grafting (OPCAB), but the incidence and the risk factors are unclear. This study aimed to analyze the incidence and risk factors of postoperative hyperbilirubinemia in patients undergoing OPCAB.MethodsFrom December 2016 to March 2019, a total of 416 consecutive patients undergoing OPCAB were enrolled in this single-center retrospective study. Patients were divided into the normal serum total bilirubin group and the hyperbilirubinemia group based on the serum total bilirubin levels. Perioperative variables between the two groups were compared by univariate logistic regression analysis. Then, multivariate binary logistic regression analysis was used to analyze the independent risk factors of developing hyperbilirubinemia in patients underwent OPCAB. P < 0.05 was considered as statistically significant.ResultsThirty two of 416 (7.7%) patients developed postoperative hyperbilirubinemia. Univariate regression analysis showed significant differences in gender (73.96% vs. 93.75%, P = 0.012), preoperative total bilirubin levels (11.92 ± 4.52 vs. 18.28 ± 7.57, P < 0.001), perioperative IABP implantation (22.66% vs. 43.75%, P = 0.008), perioperative blood transfusion (37.50% vs. 56.25%, P = 0.037) between the two groups. Multivariate logistic regression analysis revealed that elevated preoperative serum total bilirubin levels (OR = 1.225, 95% CI 1.145–1.310, P < 0.001), perioperative blood transfusion (OR = 4.488, 95% CI 1.876–10.737, P = 0.001) and perioperative IABP implantation (OR = 4.016, 95% CI 1.709–9.439, P = 0.001) were independent risk factors for hyperbilirubinemia after OPCAB.ConclusionsHyperbilirubinemia is also a common complication after OPCAB. Elevated preoperative serum total bilirubin levels, perioperative blood transfusion, and perioperative IABP implantation were independent risk factors for patients developing hyperbilirubinemia after OPCAB. Further studies need to be conducted to confirm the risk factors of hyperbilirubinemia after OPCAB procedure.

S2441 Mesalamine-Induced Autoimmune Hepatitis in Patient With Ulcerative Colitis: Case Report

Introduction: Mesalamine is widely considered to be first-line therapy for patients with mild to moderate ulcerative colitis. It is generally well tolerated with usually minor side effects. Mesalamine-induced liver injury is very rarely reported, commonly in the context of multiorgan disease. Isolated mesalamine-induced autoimmune hepatitis has not been reported. Case description/methods: A 53-year-old female with one-month history of bloody diarrhea, decreased appetite, and 10-lb weight loss underwent colonoscopy that confirmed mild to moderate left-sided ulcerative colitis. Blood counts, renal function, and liver function (LFT) were normal and hepatitis B serology was negative. She was started on standard dosing of oral and rectal mesalamine and achieved clinical remission at three months. Five months later, she had abnormal LFT on routine evaluation; alanine aminotransferase (ALT) was 122 IU/L and aspartate aminotransferase (AST) was 44 IU/L, with normal total bilirubin and alkaline phosphatase. She was asymptomatic and denied personal and family history of liver disease. On repeat investigation, ALT peaked at 359 IU/L and AST at 210 IU/L (Figure 1). Serologic evaluation was notable for positive anti-nuclear antibody at 1:640 and positive anti-mitochondrial antibody of 0.5 U. Anti-smooth muscle antibody, acute viral hepatitis panel, and metabolic liver disease markers were normal. Magnetic retrograde cholangiopancreatography (MRCP) noted no abnormalities. Liver biopsy revealed inflammatory infiltrate of lymphocytes and macrophages with scattered eosinophils and plasma cells, consistent with autoimmune hepatitis. One month after discontinuation of mesalamine, liver tests normalized (AST 24 IU/L, ALT 36 IU/L). She maintained a clinical remission and normal at one year follow up after switching to adalimumab. Discussion: A recent UK audit revealed 3.2 cases of mesalamine-induced-liver-injury per million prescriptions, which included asymptomatic transaminitis, cholestatic hepatitis, and granulomatous hepatitis, mostly in the context of systemic, multiorgan disease. This is the first report, to our knowledge, of an isolated mesalamine-induced autoimmune hepatitis in a patient with ulcerative colitis. The diagnosis is strongly supported by characteristic histological findings, positive autoimmunity markers, resolution of injury with discontinuation of drug, and exclusion of other causes. It may be prudent to monitor LFT in ulcerative colitis patients treated with mesalamine.Figure 1.: Trend of transaminases following initiation and discontinuation of mesalamine.

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

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

A Hemolytic Event in a Heartmate 3 Patient in the Setting of Polycythemia

Introduction The Heartmate 3 (HM3) LVAD has significantly reduced hemocompatibility events. We present a case of a hemolytic event in a HM3 patient likely related to underling polycythemia. Case Report A 49-year-old man with multisystem sarcoidosis (pulmonary and cardiac) complicated by stage D systolic heart failure status post HeartMate 3 left ventricular assist device (LVAD) implantation and secondary polycythemia attributed to chronic hypoxic respiratory disease and pulmonary hypertension presented with symptoms of left arm numbness and tingling followed by severe substernal chest pain. Initial examination was unremarkable. EKG revealed nonspecific intraventricular conduction delay. Troponin I was elevated at 6.1. Hemoglobin was elevated to 19. LDH was elevated to LDH 568 from baseline of 300s. INR was 1.6 upon arrival. LVAD interrogation revealed speed 5600 rpm, flow 4.5 L/min, power 4.4 Watts and pulsatility index of 4.8. Heparin drip, aspirin and statin were initiated for presumed NSTEMI. LDH remained elevated to 600s. Left heart catherization revealed an acute clot in mid-circumflex associated with 50% stenosis consistent with partial resolution of thrombosis. Further workup revealed normal haptoglobin, erythropoietin and total bilirubin levels however plasma free hemoglobin was elevated to 63.1. Urine hemoglobin was not detected. A JAK2 mutation was excluded. Slow therapeutic phlebotomies with replacement of 125cc of blood with equivalent normal saline were initiated given concern for hemolytic event in the setting of worsening polycythemia. Renal imaging was negative and pretest probability for hematologic malignancies remained low. Of note, the patient reported non-compliance with home oxygen therapy used only at the time of exertion. Compliance was reinforced. Subsequently, LDH trended down to baseline following successful heparin bridge to therapeutic warfarin level. The patient was discharged in stable condition. Summary An acute hemolytic event (and possible cardioembolic NSTEMI) was seen in our patient evidenced by an elevation of LDH, plasma hemoglobin and new coronary thrombus in the setting of worsening polycythemia. Despite a remarkable low rate of pump thrombosis, HM3 recipients with acquired pro-thrombotic states such as polycythemia maybe at risk for adverse hemocompatibility events. Close surveillance is warranted for these special populations.

Incidental biliary dilation in the era of the opiate epidemic: High prevalence of biliary dilation in opiate users evaluated in the Emergency Department.

BACKGROUNDBiliary dilation is frequently related to obstruction; however, non-obstructive factors such as age and previous cholecystectomy have also been reported. In the past two decades there has been a dramatic increase in opiate use/dependence and utilization of cross-sectional abdominal imaging, with increased detection of biliary dilation, particularly in patients who use opiates.AIMTo evaluate associations between opiate use, age, cholecystectomy status, ethnicity, gender, and body mass index utilizing our institution’s integrated informatics platform. METHODSOne thousand six hundred and eighty-five patients (20% sample) presenting to our Emergency Department for all causes over a 5-year period (2011-2016) who had undergone cross-sectional abdominal imaging and had normal total bilirubin were included and analyzed.RESULTSCommon bile duct (CBD) diameter was significantly higher in opiate users compared to non-opiate users (8.67 mm vs 7.24 mm, P < 0.001) and in patients with a history of cholecystectomy compared to those with an intact gallbladder (8.98 vs 6.72, P < 0.001). For patients with an intact gallbladder who did not use opiates (n = 432), increasing age did not predict CBD diameter (r2 = 0.159, P = 0.873). Height weakly predicted CBD diameter (r2 = 0.561, P = 0.018), but weight, body mass index, ethnicity and gender did not.CONCLUSIONOpiate use and a history of cholecystectomy are associated with CBD dilation in the absence of an obstructive process. Age alone is not associated with increased CBD diameter. These findings suggest that factors such as opiate use and history of cholecystectomy may underlie the previously-reported association of advancing age with increased CBD diameter. Further prospective study is warranted.

Dogs with biliary rupture based on ultrasound findings may have normal total serum bilirubin values.

The absence of hyperbilirubinemia can lead to decreased suspicion of biliary rupture in dogs. This delay of suspicion and treatment can result in increased mortality rates. The objective of this retrospective, observational study was to describe ultrasound and serum bilirubin findings in a group of dogs with an ultrasonographic diagnosis of suspected biliary rupture. The records of a single institution were searched over the period of 2007-2019 for cases having ultrasound reports describing suspicion of biliary rupture. Clinical findings for each of the cases were recorded. A total of 35 dogs met inclusion criteria and, of these, 30 dogs had confirmed ruptured biliary tracts. It was found that 40% (12/30) of dogs with confirmed ruptured biliary tracts had a serum bilirubin values within the normal reference range. No statistical difference was found in serum bilirubin values between the ruptured and nonruptured biliary tracts. Leukocytosis and neutrophilia were found to be statistically significant between ruptured and nonruptured biliary tracts. Mucinous material, similar to "white bile" found in human literature, was found within the peritoneal effusion of six dogs with biliary rupture, three of which also lacked bile pigment. Findings from this study indicated that normobilirubinemia may be present in some dogs with biliary rupture, and therefore should not be used as a reason for excluding this differential diagnosis.

S1459 Immune Checkpoint Inhibitor-Induced Pancreatic Injury: An Atypical Presentation

INTRODUCTION: Immune checkpoint inhibitors (ICI) are effective in the treatment of several advanced cancer types. ICI-pancreatic injury (ICI-PI) is uncommon and often asymptomatic with incidentally elevated pancreatic enzymes. We present a case of ICI-PI mimicking autoimmune pancreatitis (AIP) with obstructive jaundice. CASE DESCRIPTION/METHODS: A 60-year-old male with acral melanoma metastatic to the liver was treated with four cycles of nivolumab and ipilimumab. After three cycles of maintenance nivolumab, surveillance positron emission tomography (PET) revealed diffuse fluorodeoxyglucose (FDG)-avidity of the pancreas with peripancreatic fat stranding (Image 1). He endorsed mild abdominal discomfort with an elevated lipase 10x the upper limit of normal (Table 1). He had no gallstones on imaging and socially drank alcohol. ANA was negative with normal IgG4. He was given a diagnosis of ICI-PI and treated with intravenous fluids and discharged on a 14-day steroid taper and lab monitoring. Three weeks after completing the steroid taper, he presented with worsening abdominal pain and gray colored stool. Labs showed elevated liver tests consistent with a cholestatic obstructive pattern. Computed tomography (CT) revealed diffuse mild enlargement of the pancreas. MRCP showed dilated extrahepatic bile duct up to 11mm with an intrapancreatic stricture. Endoscopic ultrasound (EUS) showed diffusely lobular pancreas with hypoechoic areas and intervening hyperechoic standing. The pancreatic duct was not dilated. The bile duct was dilated and abruptly narrowed as it entered the pancreatic head. Fine needle aspiration (FNA) of the pancreatic head with 25G needle revealed pancreatic acini and focal findings suggestive of chronic pancreatitis without metastatic melanoma (Image 2). A diagnosis of ICI-PI mimicking AIP was made. He received high dose oral steroids with a long taper. His liver enzymes normalized. Repeat PET showed interval resolution of pancreatic FDG-avidity and peripancreatic fat stranding with continued remission of melanoma. DISCUSSION: This is a unique case of ICI-PI evolving into obstructive jaundice and resolving with steroids. Although he had negative serologies, his imaging and clinical course mimicked AIP. Both ICI related adverse events and AIP are T-cell driven processes suggesting a possible similar pathogenesis. The incidence of ICI-PI will likely rise with the increasing use of ICIs; thus, awareness of ICI-PI and its variable presentation are clinically salient.Table 1.: Liver enzymes, total bilirubin and lipase from the last cycle of nivolumab therapy through both hospitalizations. Normal aspartate aminotransferase (AST) is 0–40 IU/L. Normal alanine aminotransferase (ALT) is 0-32 IU/L. Normal alkaline phosphatase (ALP) is 39-117 IU/L. Normal total bilirubin is 0–1.2 mg/dL. Upper limit of normal lipase is 51 U/LFigure 1.: Image 1. Positron emission tomography (PET) imaging. A. Prior to nivolumab therapy. B. After three cycles of maintenance nivolumab. C. After high dose oral steroids and normalization of liver enzymes.Figure 2.: Image 2. Biopsy obtained during endoscopic ultrasound (EUS). A. Benign pancreatic acini and focal findings suggestive of chronic pancreatitis on hematoxylin and eosin (H&E) stain. B. SOX10 stain with control. SOX10 is a melanoma marker and thus no metastatic melanoma identified.

S2692 Fulminant Hepatic Failure Caused by Primary Herpes Simplex Virus Infection

INTRODUCTION: Herpes simplex virus (HSV) types 1 and 2 are common lifelong infections. Disseminated HSV is a rare but fatal complication of HSV infection, traditionally affecting immunocompromised individuals. Here we present a case of an immunocompetent 72-year old male with primary disseminated HSV-2 whose clinical picture rapidly progressed from abdominal pain to fulminant hepatic failure and death. CASE DESCRIPTION/METHODS: A 72-year-old Caucasian man presented to the ER for abdominal pain and sore throat. His only chronic medical conditions were BPH and hypertension. On presentation he was febrile (38.9oC) and tachycardic (117). Physical exam was remarkable for pharyngeal erythema with white ulcerative lesions and diffuse abdominal tenderness. Laboratory evaluation revealed an elevated WBC count (14.6), transaminitis (AST 336 U/L, ALT 486 U/L, ALP 153 U/L), and normal total bilirubin. CT abdomen revealed hepatomegaly, and the patient was admitted for treatment of sepsis. Blood serological studies at time of admission were negative for Hepatitis A/B/C, HSV 1/2, CMV, and EBV (immunoglobulin (Ig)M). He continued to be febrile despite broad spectrum antibiotics and LFTs trended up into the 1,000s so a liver biopsy was performed on day 8. On day 9, he developed a few small blisters on his right thigh and abdomen. These were biopsied and the patient was placed on empiric acyclovir with new studies ordered. On day 14 biopsy results from both the leg and liver showed disseminated HSV. Repeat serologies then confirmed disseminated HSV with high titers for HSV-2 IgM. Despite 2 weeks of IV acyclovir the patient declined rapidly, was transferred to hospice on day 21, and died shortly after. DISCUSSION: The diagnosis of disseminated HSV is typically made via serological studies demonstrating high titers of IgM HSV antibodies. However, this method of diagnosis is flawed in that it misses early primary infections, as was the case in our patient. Based on literature review by Levitsky et al. early empiric treatment of HSV hepatitis with acyclovir leads to a significant decrease in mortality. Because HSV hepatitis is difficult to diagnose, treatment is often delayed and the infection progresses to acute liver failure in 74% of cases, with a 90% mortality rate. This case highlights two key barriers to achieving better outcomes in HSV hepatitis management: lack of sensitive screening tests and lack of standard guidelines on the use of empiric antivirals in cases of fulminant hepatic failure of unclear etiology.Figure 1.: Liver immunohistochemical staining for HSV-2.Figure 2.: Skin lesions right lower extremity.

S2671 Chest Wall Metastasis as the First Clinical Manifestation of Hepatocellular Carcinoma: A Rare Case Report

INTRODUCTION: Hepatocellular carcinoma (HCC) is a highly malignant tumor that is mostly diagnosed at an advanced stage. Here, we report a metastatic HCC in an elderly man with hepatitis C virus (HCV) and alcoholic cirrhosis. Literature is sparse on chest wall metastasis. CASE DESCRIPTION/METHODS: A 69-year-old Caucasian man presented because of a growing left chest wall mass, back pain, and weight loss for three months. He had never visited a physician before; history was pertinent for tobacco smoking and alcohol dependence. He was hemodynamically stable, cachectic on examination with a >10 cm large left upper chest wall non-erythematous firm, fixed palpable mass. Labs were pertinent for elevated liver enzymes, with ALT of 141, AST of 374, ALP of 675, normal total bilirubin, and HCV antibody positive, with an elevated viral PCR of 6.1 log IU/ml. A CT chest, abdomen, and pelvis showed a left extrapleural chest wall mass measuring 10.8 × 15.5 × 11.0 cm with erosions of adjacent ribs, destructive lytic bony lesions, and liver cirrhosis; features suspicions of metastatic HCC. Subsequent chest wall mass biopsy confirmed a moderately differentiated metastatic HCC with Immunostain positive for CAM 5.2, Hep Par, glutamine synthetase, and glypican-3. A serum AFP was elevated at 2376.15 ng/ml. Abdominal MRI demonstrated a total of five large enhancing masses with the largest measuring 4.1 × 3.5 cm with arterial enhancement, washout, diffusion restriction, and internal hemorrhage consistent with biopsy-proven HCC (LR-5). A brain and spine MRI were unremarkable except for the previously reported bony metastases. Consequently, he received localized spine and left chest wall radiotherapy, and upon completion, he was discharged home, and currently, he is on systemic chemotherapy with Lenvatinib. DISCUSSION: HCC is the second most lethal neoplasm with an 18% five-year survival. Common etiologies are HBV, HCV, alcoholic cirrhosis, and NAFLD. The most frequent metastatic locations include bones, lymphatics, and adrenals. Spread occurs heterogeneously or via a lymphatic route or by direct invasion. Extrahepatic metastasis is rare and even rarer, with poorer prognosis when the first presentation is a mass at the metastatic site. This should be in the differential of rapidly growing chest wall masses, particularly in alcoholic and/or treatment-naïve hepatitis virus-infected patients. Timely recognition of risk factors can prevent and aid early diagnosis of such aggressive tumors.Figure 1.: Chest Wall Metastasis.Figure 2.: MRI Abdomen showing the Primary Liver Lesion.Figure 3.: Pathology Slide: H & E stain showing features suggestive of HCC on a liver biopsy.

Su1441 PRIMARY NEEDLE KNIFE SPHINCTEROTOMY FOR BILIARY ACCESS IN SELECTED PATIENTS WITH HIGH RISK FOR POST-ERCP PANCREATITIS: A PROSPECTIVE PRELIMINARY FEASIBILITY STUDY

Needle knife fistulotomy may be useful as the first line of procedure for biliary access to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) based on recent clinical data. We aimed to evaluate the safety, effectiveness, and feasibility of primary needle knife sphincterotomy (NKS) for biliary cannulation in patients with a high risk of PEP. A total of 40 patients who need ERCP using primary NKS for biliary disease in our institution between June 2018 and November 2019 were prospectively enrolled in this study. The procedures were conducted by two expert biliary endoscopists (S.J. and J.S.P.) who had experience of ERCPs. They had one or more of the following risk factors of PEP; young age (<50 years), female gender, normal common bile duct (CBD) diameter (≤9 mm), normal serum total bilirubin level (0.2-1.2 mg/dL), obesity (body mass index: >30), or history of pancreatitis. The success rate of biliary cannulation, time to biliary cannulation, and the occurrence rate of PEP, as well as other post-ERCP complications, were assessed. Of 40 patients enrolled, 34 patients underwent primary NKS. Nine patients had 1 risk factor of PEP, seven had 2, eight had 3, seven had 4, and three had 5. The success rate of CBD cannulation using NKS was 94.1% (32/34). The median time for biliary cannulation was 243 seconds (range, 32-1,514 seconds). None of the patients experienced post-ERCP pancreatitis, cholangitis, and perforation. One case of minor bleeding (2.9%, 1/34) and 1 asymptomatic hyperamylasemia (2.9%, 1/34) occurred. Primary NKS might be safe, effective and feasible for biliary access in patients with high risk for PEP if the procedure is performed by expert hands.

Role of Hyperbilirubinemia as a Diagnostic Tool to Predict Gangrenous/Perforated Appendicitis: An Observational Study

Background: Elevation in serum bilirubin was reported recently, but the importance of the raised total bilirubin has not been stressed in acute appendicitis and appendicular perforation. The aim of the study was to establish the role of hyperbilirubinemia as a new diagnostic tool to predict gangrenous/perforated appendicitis. Subjects and Methods: This was a prospective observational study, which was conducted at the Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India. A total of 100 patients clinically diagnosed as appendicitis from August 2018 to August 2019 at Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India. Patients were clinically evaluated by detailed history, routine examination on initial contact with patients and the routine investigations as per surgery and anesthesia requirements with inclusion of serum total bilirubin. Based on histopathological examination patients will be categorized as positive (acute appendicitis with perforation and/or gangrene) and negative (acute appendicitis without perforation or gangrene). Results: Out of 100 patients, 20 were managed conservatively (mass formation) and was called for interval appendectomy after 6 weeks. In acute catarrhal appendicitis group 47 patients showed normal total bilirubin levels, whereas 8 patients showed increase in levels of total bilirubin. In gangrenous appendicitis group all 10 patients showed elevated serum total bilirubin levels In perforated appendicitis group consisted of 15, 11 patients showed elevated serum bilirubin levels and 4 patients showed normal total bilirubin levels. Conclusion: Serum bilirubin is easily available test and cheap and can be estimated from the sample of blood drawn for routine blood investigations.

SUN-495 Rapid Resolution of Hyperthyroidism Induced Hepatic Dysfunction with Methimazole

Background:Hepatic dysfunction in the setting of hyperthyroidism is difficult to diagnose and poses a challenge in therapy, since the classic medications used are potentially hepatotoxic.Clinical case:A 51-year-old female patient presented with fatigue, palpitations and tremors. BP 146/65 mmHg, HR 111 bpm and Temp 97.8 F. She was severely thyrotoxic with 3 + DTRs, tremors, enlarged thyroid gland with bruit on auscultation, clear lungs and no lower extremities edema. Blood tests showed TSH <0.003 IU/ml (0.450-5.330 IU/ml), Free T4 5.33 ng/dL (0.45-1.80 ng/dL), Free T3 > 30.0 pg/mL (2.3-4.2 pg/mL). Liver enzymes showed elevation in transaminases with ALT 319 IU/L (7-40 IU/L), AST 330 IU/L (7-40 IU/L) normal total Bilirubin 0.7 mg/dL (0.1-1.5 mg/dL) and Alkaline phosphatase 65 IU/L (40-200 IU/L). Transaminases were also elevated 3 weeks prior to presentation and this was extensively worked up with no identifiable etiology to explain the liver dysfunction. She was started on beta blocker therapy and admitted to the ICU. She had no clinical or echocardiographic evidence of cardiac dysfunction and remained hemodynamically stable. She was started on Methimazole 45 mg daily. The patient improved clinically and a pronounced decline in transaminase levels was documented in the first 72 hours. She was discharged home on day 3 of admission. On follow up visit her transaminases were found to have completely normalized within 14 days.Discussion:The diagnosis of elevated transaminases in hyperthyroidism is a challenge. This is due to the possibility of multiple etiologies including decreased cardiac output and/or liver congestion, concomitant primary liver disease or more specifically autoimmune hepatic disease such as primary biliary cirrhosis. (1-2). Incidentally Methimazole has been associated with transient asymptomatic transaminitis typically during the first three months of therapy (3). Our case indicates, that methimazole can be used in patients with a presumed diagnosis of hyperthyroidism induced hepatotoxicity after all possible etiologies are ruled out. Hyperthyroidism as the cause of liver dysfunction can only be entertained after all those etiologies are ruled out and upon resolution of transaminase elevation in conjunction with improvement in the hyperthyroid state itself, as was demonstrated in this case.Conclusion:Methimazole can be safely used in patients with severe hyperthyroidism and elevated liver enzymes when all other etiologies of liver dysfunction have been ruled out.

Liver Injury in Patients With Cholestatic Liver Disease Treated With Obeticholic Acid.

Obeticholic acid (OCA) was approved for the treatment of primary biliary cholangitis (PBC) based on studies in patients with an alkaline phosphatase (ALP) level of at least 1.67 times the upper limit of normal (ULN) or elevated total bilirubin less than 2 times ULN.1 Postmarket reports of serious liver injury in patients receiving OCA prompted a boxed warning by the Food and Drug Administration (FDA). Drug-induced liver injury (DILI) in patients with PBC can put them at risk for acute on chronic liver failure (ACLF) and increased mortality.2 We describe in this report worsening of liver disease or ACLF after starting OCA among a cohort of patients with PBC and primary sclerosing cholangitis (PSC).

An Unusual Finding During Endoscopic Ultrasound-Guided Gallbladder Drainage

Question: A 39-year-old man with stage III adenocarcinoma of the pancreas presented with right upper quadrant abdominal pain. Five months earlier, the patient was hospitalized for acute calculous cholecystitis complicated by gallbladder perforation, requiring antimicrobials and percutaneous drain placement, with eventual clinical resolution. Physical examination revealed right upper quadrant tenderness to palpation. Laboratory tests were notable for normal white blood cell count (4.9 × 103/μL) and normal total bilirubin (0.3 mg/dL).

Transjugular Intrahepatic Portosystemic Shunt (TIPS) for Very Severe Veno-Occlusive Disease after Unmanipulated Haploidentical HSCT with Post-Transplant Cyclophosphamide

Background: The use of unmanipulated Haploidentical HSCT (Haplo-HSCT) with post-transplant Cyclophosphamide (PT-Cy) as GVHD prophylaxis has widely extended. Veno-occlusive disease (VOD) is a threatening complication after both autologous and allogeneic HSCT, with high mortality rates despite early medical treatment, including the use of defibrotide. The objective of this study was to describe characteristics and outcomes of patients with refractory very severe VOD after Haplo-HSCT with PT-Cy, treated with TIPS as salvage procedure. Methods: We retrospectively analysed 176 Haplo-HSCT with Cy-post consecutively performed between 2011 and May 2019 in a single centre. VOD was defined according to modified Seattle, Baltimore or revised EBMT criteria. Severity was retrospectively graded according to revised EBMT severity criteria into four categories: mild, moderate, severe and very severe. Complete response (CR) was defined as a normal total bilirubin level (&lt;2 mg/dL) or, in patients with normal bilirubin or alternative causes of hyperbilirubinemia, as normalized renal function, reduction of elevated transaminase level &lt;50%, tense ascites resolution, and no need for oxygen supplement in the absence of alternative hypoxemia causes. Results: Sixteen patients (9.1%) met the modified Seattle, Baltimore or revised EBMT diagnostic criteria for VOD. Ultrasound with Doppler ultrasonography was performed in all patients, and at least indirect signs of VOD were found in all cases. Based on revised EBMT severity criteria, there were 2 mild (12.5%), 2 moderate (12.5%), 2 severe (12.5%) and 10 very severe (62.5%) grade VOD. Twelve patients (75%) were treated with defibrotide, including all patients with very severe VOD, except one with CNS hemorrhage (Patient 1). Six patients with very severe VOD, were treated with TIPS due to rapid clinical or analytical deterioration or refractory hepatorenal syndrome, despite medical treatment including defibrotide (Table 1). All were male patients, with a median age of 31 years (range 22-36), all transplanted with myeloablative conditioning regimen. TIPS insertion was performed on a median time since VOD diagnosis of 5 days (range 1-28) without technical complications in any case. Median total bilirubin, ALT, creatinine and INR the day of procedure were 3 mg/dL (range 2.2-11.2), 1120 UI/L (range 10-2595), 2.45 mg/dL (range 2.06-3.58) and 1.96 (range 1.1-4) respectively. Median hepatic venous pressure gradient (HVPG) prior to and after TIPS was 22.5 (range 14-29) and 6.5 (range 2-10) mmHg respectively, with a median drop of 16.5 mmHg (range 9-19). Following TIPS, all patients showed clinical improvement with hepatomegaly, ascites and renal failure resolution, and all showed analytical improvement with bilirubin, creatinine and ALT values reduction, except for patient 2, whose TIPS indication was refractory hepatorenal syndrome with normal ALT levels (Figure 1). The 5 patients who had iniciated defibrotide before TIPS, completed 21 days of treatment. All patients met criteria for CR in a median of 8 days after TIPS insertion (range 2-82). The 100-day overall survival (OS) was 100%. Five patients were alive with normal liver and renal function at last follow up, and one patient died due to infection 7 months after Haplo-HSCT, with VOD in complete resolution. Conclusions: Incidence of VOD after Haplo-HSCT with PT-Cy is comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe VOD according to revised EBMT severity criteria. For patients with rapid progressive VOD, early TIPS insertion allowed completion of defibrotide therapy. The use of TIPS together with defibrotide resulted in complete response and no associated complications with a 0% of VOD associated mortality in spite of high severity. ALT values may be the best predictor of CR after TIPS procedure. In our experience, timely and individualized use of TIPS significantly improves outcome of very severe VOD after Haplo-HSCT. Therefore, TIPS should be promptly considered in rapid progressive cases. Disclosures No relevant conflicts of interest to declare.

How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy.

To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM). Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging. Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46kPa for ≥ F2, 10.94kPa for ≥ F3, and 15.88kPa for F4, than those with normal TB (7.62kPa, 8.26kPa, and 11.01kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage. Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage. • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve.