Including Liver Function Tests Research Articles

NONPRODUCTIVE COUGH AS PREAMBLE OF RESPIRATORY FAILURE IN A PATIENT WITH HYPEREOSINOPHILIC SYNDROME

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Hypereosinophilic syndrome (HES) is a rare disorder characterized by peripheral blood eosinophilia of 〖1.5 x 10〗ˆ3/μL or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. HES has an unknown prevalence, most often affects people age 20 through 50. Few patients with prolonged eosinophilia develop organ dysfunction that characterizes HES. CASE PRESENTATION: This is the case of a healthy 52-year-old man without history of significant systemic illness who presents with non-productive cough, daily febrile episodes and left upper extremity pain for a period 2 months. On physical examination, lungs are clear upon chest auscultation and left sided axillary pain is elicited upon arm abduction. Initial blood work revealed WBC 〖40.62 x 10〗ˆ3/μL; eosinophil count 〖23.56 x 10〗ˆ3/μL, elevated sedimentation rate 112 mm/hr. Initial diagnosing testing for HES was performed. Complete blood count was remarkable for increasing trend in leukocytes and eosinophils. Routine chemistries, including liver function tests were within normal limits. Quantitative serum immunoglobulin levels, including IgE were normal. Serum troponin, echocardiogram, electrocardiogram, Pulmonary function tests revealed no abnormalities. Bone marrow biopsy including cytogenetics had no myeloproliferative abnormalities. Flexible bronchoscopy with bronchoalveolar lavage revealed eosinophils count less than 3%, no evidence of bacteria, viral or fungal infection. Serology examination for diagnosis of parasitic infection, HIV testing, antineutrophil antibodies ANCA, Serum tryptase and B12 levels, PET scan, lymph node biopsy, EBV viral load were completely negative. The patient’s eosinophilia continued to rise, peaking at 56.00 x 103/μL, despite high-dose prednisone therapy (200 mg by mouth daily), he went in to respiratory failure, cardiac arrest and developed multi organ dysfunction. Hydroxyurea (1 g daily) was added. He improved after the addition of hydroxyurea, and a decrease trending of his eosinophil count was seen. Hydroxyurea was discontinued, and prednisone was tapered. DISCUSSION: HES is a rare heterogeneous disease, any organ system is vulnerable to get affected. The symptoms are common in many other medical problems, making an initial diagnosis more difficult. Sometimes no underlying cause can be found for an observed eosinophilia, even after an extensive diagnostic evaluation. In the absence of an identifiable reactive cause for the eosinophilia, a diagnosis of idiopathic HES can be established if there is evidence of organ involvement and dysfunction. CONCLUSIONS: Our case illustrates the importance of considering diagnosis in patients with significant eosinophilia. Have a high index of suspicion in the background of persistent peripheral eosinophilia; after exclusion of secondary causes. Reference #1: https://doi.org/10.1182/asheducation-2018.1.326 ASH Education Book November 30, 2018 vol. 2018 no. 1 326-331 Reference #2: Klion AD. How I treat hypereosinophilic syndromes. Blood. 2015;126(9):1069-1077. Reference #3: Khoury P, Abiodun AO, Holland-Thomas N, Fay MP, Klion AD. Hypereosinophilic syndrome subtype predicts responsiveness to glucocorticoids. J Allergy Clin Immunol Pract. 2018;6(1):190-195. DISCLOSURES: No relevant relationships by Hector Cintron-Colon, source=Web Response No relevant relationships by Ricardo Fernandez, source=Web Response No relevant relationships by Vanessa Fonseca Ferrer, source=Web Response No relevant relationships by WIlliam Marrero, source=Web Response No relevant relationships by Luis Piñeiro, source=Web Response

Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2

To investigate the potential role of alcohol use disorder (AUD) in aging processes, we employed Levine’s epigenetic clock (DNAm PhenoAge) to estimate DNA methylation age in 331 individuals with AUD and 201 healthy controls (HC). We evaluated the effects of heavy, chronic alcohol consumption on epigenetic age acceleration (EAA) using clinical biomarkers, including liver function test enzymes (LFTs) and clinical measures. To characterize potential underlying genetic variation contributing to EAA in AUD, we performed genome-wide association studies (GWAS) on EAA, including pathway analyses. We followed up on relevant top findings with in silico expression quantitative trait loci (eQTL) analyses for biological function using the BRAINEAC database. There was a 2.22-year age acceleration in AUD compared to controls after adjusting for gender and blood cell composition (p = 1.85 × 10−5). This association remained significant after adjusting for race, body mass index, and smoking status (1.38 years, p = 0.02). Secondary analyses showed more pronounced EAA in individuals with more severe AUD-associated phenotypes, including elevated gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT), and higher number of heavy drinking days (all ps < 0.05). The genome-wide meta-analysis of EAA in AUD revealed a significant single nucleotide polymorphism (SNP), rs916264 (p = 5.43 × 10−8), in apolipoprotein L2 (APOL2) at the genome-wide level. The minor allele A of rs916264 was associated with EAA and with increased mRNA expression in hippocampus (p = 0.0015). Our data demonstrate EAA in AUD and suggest that disease severity further accelerates epigenetic aging. EAA was associated with genetic variation in APOL2, suggesting potential novel biological mechanisms for age acceleration in AUD.

Spontaneous perforation of cystic duct in a 3-month-old Nigerian boy

Introduction: Biliary ascites is a rare condition in infancy and is commonly caused by the perforation of the extrahepatic bile duct. The cystic duct is the part of extrahepatic biliary tract most rarely affected. This is likely to be the first case of biliary ascites of infancy, secondary to spontaneous cystic duct perforation in our centre. Methods: Consent was obtained from the parents of the child. Ethical approval was also obtained from the research and ethics committee of Ahmadu Bello University Teaching Hospital, Shika, Zaria. The case notes of the child were summarized and the relevant literature was reviewed to give the report a context. Results: A three-month-old boy presented with ten days history of jaundice, a week history of abdominal distention, and a day’s history of fever. There was associated bilateral inguinal hernia, excessive cry, refusal to feed, and weight loss. Pregnancy history was normal. He was acutely ill-looking, irritable, febrile with an axillary temperature of 37.7°C, mildly pale, jaundiced with a greenish tinge, had a weight of 4.7kg. He had gross ascites and bilateral reducible inguinal hernia. Bedside abdominal paracentesis reveals thick yellow and foamy fluid. Abdominal ultrasound scan revealed gross ascites, clotting profile was deranged, there was hyperbilirubinaemia of 228 umol/L, other laboratory results including liver function test were normal. He was commenced on medical management for presumed sepsis with obstructive jaundice. Five days into the admission, there was no significant improvement, and the diagnosis was reviewed to a ruptured choledochal cyst and the child was prepared for an explorative laparotomy. Intra-operatively, the cystic duct was perforated. Cholecystectomy and repair of the common bile duct were performed and the child did well postoperatively. Conclusion: Perforated cystic duct should be suspected in infants presenting with jaundice abdominal distension, acholic stools with or without fever, vomiting, and inguinal hernias. Early diagnosis and prompt surgical intervention greatly reduce morbidity and mortality from the disease.

Hepatobiliary case report and literature review of hepatic reactive lymphoid hyperplasia with positive anti-smooth muscle antibody and anti-nuclear antibody tests

Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign tumor of the liver that exhibits similar imaging characteristics to those of other hepatic malignant tumors; therefore, it requires novel biomarkers to be differentiated from the other tumors. A 69-year-old female was found to have a mass in the liver and was admitted to Peking Union Medical College Hospital for further evaluation. Most laboratory tests, including liver function tests, tumor biomarkers, and autoimmune markers were within normal range, except for positive antinuclear antibody and anti-smooth muscle antibody (SMA) tests. Diagnostic imaging, including ultrasonography, computerized tomography and magnetic resonance imaging displayed a small hepatic mass suggestive of hepatocellular carcinoma (HCC). Partial hepatectomy was performed, and histological diagnosis suggested RLH. Postoperative treatments included anti-infection, nutritional enhancement and liver protection. The suspicion of autoimmune hepatitis could not be confirmed. No recurrence or autoimmune disease was observed over 6-month follow-up. Positive anti-nuclear antibody (ANA) and anti-SMA may be potential biomarkers for hepatic RLH.

Daikenchuto improved perioperative nutritional status of the patients with colorectal cancer: A prospective open-labeled randomized exploratory study.

Background and aimsThe aim of this study is to exploratively evaluate the effect of Tsumura Daikenchuto Extract Granules (DKT, TJ-100) on abdominal symptoms, body weight, and nutritional function following colorectal cancer surgery.MethodsThe subjects included 20 patients for curative resection of colorectal cancer. A TJ-100 administration group (n = 10) and non-administration group (n = 10) were randomized and compared. In the administration group, TJ-100 was administered from 2 days prior to surgery up to 12 weeks following surgery. The endpoints included body weight gain, Gastrointestinal Symptom Rating Scale (GSRS), and blood biochemical factors. For the purpose of observing safety, drug adverse events were evaluated including liver function tests.ResultsExcluding one patient, we compared 9 cases in the administration group and 10 cases in the non-administration group. No obvious adverse events were observed in any of the cases. In the comparison of body weight gain, the TJ-100 administration group showed significantly higher values at 2, 4, and 12 weeks following the surgery. There was a tendency for lower stable GSRS scores in the administration group overall, with no statistically significant difference.ConclusionIt is suggested that TJ-100 can be safely administered in the perioperative period for cases undergoing colorectal cancer surgery, potentially preventing weight loss during the early postoperative period.

Acute Hepatitis A Infections among Veterans in Outbreak States, 2016-2018

ObjectiveTo conduct surveillance for acute Hepatitis A virus (HAV) infections in Veterans from states reporting outbreaks among high-risk individuals beginning in fiscal year (FY) 2017.IntroductionAlthough cases of acute HAV have declined in recent years, elevated numbers of HAV infections began to be reported by California and Michigan in the fall of 2016.1,2 Since this time, associated outbreaks have been reported in 9 additional states (Arizona, Utah, Kentucky, Missouri, Tennessee, Indiana, Ohio, Arkansas, and West Virginia).3 No common source of food, beverages or drugs have been identified and transmission appears to be primarily person-to-person with high-risk individuals including people experiencing homelessness, those who use illicit drugs and their close direct contacts. In June 2018, CDC issued a Health Alert Network Advisory providing additional guidance on identification and prevention of HAV and updates on the outbreaks.4 This prompted our office to more closely review our HAV surveillance, to identify Veterans who may be part of these outbreaks, and assess risk factors and outcomes of HAV infection.MethodsWe queried VA data sources starting in FY 2017 (October 1, 2016 – June 30, 2018) for HAV IgM laboratory tests and HAV-coded outpatient encounters and hospitalizations (ICD-10-CM: B15) to identify potential case patients. We performed a detailed chart review on all HAV IgM positive Veterans residing in or treated in an outbreak state during the identified outbreak time frame as reported by each state health department. Data elements collected included: (1) demographics; (2) risk factors, exposures and Hepatitis A vaccination status; (3) treatment locations (i.e. outpatient, Emergency Department, inpatient, intensive care unit); (4) presenting signs and symptoms; (5) laboratory data (including liver function tests (LFTs) and hepatitis testing); and (6) outcomes (i.e. deaths). County-level rates for positive HAV IgM test results were calculated using total unique users of VHA care for matching fiscal year time frames in each county as denominators.ResultsA total of 247 HAV IgM positive individuals were identified among 136,970 HAV IgM tests performed during the study period. Among these, 67 individuals resided in an outbreak state and were identified for further chart review. Additional laboratory review revealed that 5 of the 67 were positive for HAV Total Ab with no HAV IgM performed (all five patients came from a single facility and were asymptomatic at the time of testing). Based on review of clinical data for the remaining 62 HAV IgM positive patients, 22 (35%) did not meet the CSTE clinical case definition criteria5 of having signs or symptoms consistent with acute viral hepatitis plus either jaundice or elevated ALT/AST levels. These patients were either asymptomatic or had relevant symptoms that could be explained by other diagnoses. None had documented jaundice and only 4 had any LFT elevation, which was mild (ALT: 60-83 IU/L, AST: 36-103 IU/L). There was often no mention of the positive HAV IgM test result in the patient visit records. In the cases where the results were documented, it was thought to be a false positive or cross reactivity, related to recent receipt of HAV vaccination, or prolonged persistence of HAV IgM from a prior infection. Patient characteristics of the 40 patients meeting the case definition are summarized in Table 1. None of confirmed cases had documentation of HAV vaccination prior to their acute infection. The top 5 counties of residence among confirmed cases were Jefferson, KY (7, 18%), San Diego, CA (6, 15%), Wayne, MO (4, 10%), Butler, MO (3, 8%) and Macomb, MI (3, 8%). Additionally, the top three counties (Jefferson, San Diego and Wayne) were each noted to have clustering of cases of acute HAV with risk factors of homelessness, substance abuse and/or needle exposure. Incidence rates for HAV IgM+ test results were calculated for all reported outbreak counties and the 25 counties with the highest rates are shown in Figure 1.ConclusionsOccurrence of acute HAV infections among Veterans during October 2016 – June 2018 followed patterns reported by states with outbreaks during the same time frame, including high hospitalization rates. Risk factors of homelessness, substance abuse and/or needle exposures were noted in the Veteran population, similar to national HAV outbreak data. County-level clustering of cases in states with outbreaks was also observed among Veterans, with incidence rates of HAV IgM+ as high as 13 per 10,000 Veterans. Additional education of VA providers is needed regarding recognition of and appropriate testing for acute HAV infections. HAV IgM should not be ordered in asymptomatic patients with normal LFTs as the pretest probability of HAV infection is low, leading to false positives and confusion in interpreting test results. Improving Hepatitis A vaccination rates among Veterans is important, particularly among individuals who are at increased risk for infection or complications from HAV and in outbreak states to limit further spread of this outbreak.

Predicting Patients With Insufficient Liver Enhancement in the Hepatobiliary Phase Before the Injection of Gadoxetic Acid: A Practical Approach Using the Bayesian Method.

Gadoxetic acid-enhanced hepatobiliary phase (HBP) is useful in liver MRI, but sometimes shows insufficient liver enhancement. There is no established method to predict insufficient liver enhancement before the contrast injection. To reveal the utility of the Bayesian method for predicting patients with insufficient liver enhancement in the gadoxetic acid-enhanced HBP. Retrospective. In all, 576 patients with chronic liver disease. 3T/3D gradient-echo T1 -weighted imaging and MR elastography (MRE). The patients were divided into two groups: insufficient and sufficient liver enhancement in HBP according to the liver-to-portal vein signal intensity ratio. Various parameters, including liver function tests and liver stiffness by MRE, were evaluated as predictors of insufficient liver enhancement. We used Chi-square/Student's t-test/logistic regression analysis to determine independent associates, and Bayes' theorem to estimate the probability of insufficient (or sufficient) liver enhancement. The feasibility of Bayesian prediction of insufficient liver enhancement was tested by leave-one-out cross-validation to calculate sensitivity and specificity for single variables and combinations of some variables in all patients and in a subpopulation showing a confidence level of >80%. Independent associates of insufficient liver enhancement in HBP included: serum albumin (odds ratio [OR] = 4.82, P < 0.001), total bilirubin (OR = 0.30, P < 0.00), platelet count (OR = 1.54, P < 0.00), and liver stiffness by MRE (OR = 0.59, P < 0.00). The accuracy of Bayesian prediction of insufficient liver enhancement was 80.9% (466/576) for the single parameter of albumin and 79.0% (455/576) for total bilirubin, and was increased to 85.2% (487/576) for a combination of albumin, total bilirubin, and liver stiffness. In patients who showed a confidence level of >80%, the accuracy was 89.0% (439/493) for the above combination. Bayesian prediction was useful to predict patients with insufficient enhancement by combining serum liver function tests and liver stiffness by MRE. 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:62-69.

Subsequent anticancer medication following first-line lenvatinib: A posthoc responder analysis from the phase 3 REFLECT study in unresectable hepatocellular carcinoma.

371 Background: Lenvatinib (LEN) was shown to be noninferior to sorafenib (SOR) for overall survival (OS) in REFLECT (median OS [mOS], 13.6 vs 12.3 months [mo]; HR 0.92; 95% CI 0.79–1.06). LEN was superior vs SOR for secondary endpoints including objective response rate (ORR) per mRECIST: 24.1% vs 9.2% by investigator and 40.6% vs 12.4% by independent review (Kudo M et al. Lancet 2018). We report a posthoc responder analysis of patients (pts) who received first-line LEN in REFLECT and subsequent anticancer medication during survival follow up. Methods: In REFLECT, pts with unresectable hepatocellular carcinoma were randomized 1:1 to receive first-line LEN or SOR. Objective response was defined as complete or partial response by mRECIST per investigator. Pts with disease progression and who discontinued treatment were followed for survival every 12 weeks; subsequent anticancer medication during survival follow up were recorded until time of death. Data cutoff: Nov 13, 2016. mOS was calculated using Kaplan-Meier estimates with 2-sided 95% CIs. Results: In REFLECT, one third of the overall study population (156/478 pts randomized to LEN and 184/476 to SOR) received subsequent anticancer medication, most commonly SOR (25% in LEN arm). ECOG performance status and laboratory assessments, including liver function tests, were comparable between arms prior to subsequent treatments. Among these pts, mOS was 21 vs 17 mo and ORR was 27.6% vs 8.7% for LEN vs SOR arms, respectively. In a subset analysis of LEN responders who received any subsequent anticancer medication (n = 43), mOS was 26 mo (95% CI 18.5–34.6). For SOR responders who received any subsequent anticancer medication (n = 16), mOS was 22 mo (95% CI, 14.6–NE). For LEN responders who subsequently received SOR (n = 35), mOS was 26 mo (95% CI 18.2–34.6). Conclusions: In REFLECT, one third of pts randomized to first-line LEN received subsequent anticancer medication, including SOR, with a mOS of 21 mo. In this exploratory, posthoc analysis of pts who responded to LEN and received any subsequent anticancer medication or SOR, mOS was 26 mo. Clinical trial information: NCT01761266.

Sedation induced by antiepileptic drugs polytherapy: A note of caution during anesthesia.

Sir, Sedation is a common complaint among patients with epilepsy taking antiepileptic drugs (AEDs). This side-effect is compounded in patients taking multiple AEDs.[123] An 18-year-old male presented with history of seizures (since day 3 of life) refractory to multiple AEDs. He was taking twice daily doses of valproate 500 mg, clonazepam 20 mg, oxcarbazepine 450 mg, and levetiracetam 1500 mg; and zonisamide 100 mg in the morning and 200 mg at bed time. He had no other co-morbidities. The patient was scheduled for vagal nerve stimulation under general anesthesia for diffuse, bilateral, non-localizing seizure foci. In the preoperative period, the patient was oriented to time, place, and person despite periods of mood swings, during which he became restless and aggressive. Baseline laboratory parameters including liver function tests were within normal limits. The patient was advised to continue AEDs on the morning of surgery. On arrival at the operating room (OR), he was deeply sedated and responded only to painful stimuli. The baseline vitals were BP 129/64 mmHg, HR 88/min, and SpO2 99% on room air. The bispectral index (BIS) value was found to be between 77 and 80. Anesthesia was induced with fentanyl 120 μg and propofol 100 mg, and tracheal intubation was facilitated with rocuronium 50 mg. The maintenance of anesthesia was done with O2: air (FiO2 0.5), sevoflurane (0.8–1 Minimum alveolar concentration [MAC]) along with continuous infusions of fentanyl (60 μg/h), and rocuronium (12 mg/h). However, the BIS value started decreasing progressively below 40 [Figure 1]. Accordingly, the sevoflurane dial concentration was tapered, and to our surprise, even at zero end-tidal concentration of sevoflurane and a MAC of 0, the BIS value consistently remained between 40 and 45 with no change in hemodynamic parameters. As a result, sevoflurane was avoided. Infusions of fentanyl and rocuronium were discontinued 45 min prior to completion of surgery. At the end of surgery (160 min), BIS value reached between 50 and 55. After confirming return of spontaneous respiration, neuromuscular reversal agent was administered. However, the patient was not able to follow the verbal commands even though gag and cough reflexes were intact, and spontaneous movement of all four limbs was present. Trachea was extubated at a BIS value of 65. The patient was shifted to the ICU and closely monitored. He showed gradual improvement in sensorium over the next 1 hour and started obeying verbal commands. On interrogation, the patient could not recall any intraoperative event.Figure 1: Shows the trend of bispectral index (BIS) during the intraoperative periodThrough this correspondence, we wish to highlight certain important issues with multiple AED therapy. First, many AEDs have sedation as an important side-effect, particularly at high doses. Our patient received five AEDs on the morning of surgery, and by the time he reached the OR, he was deeply sedated. As informed by his parents, it was a regular phenomenon, and after morning doses, he frequently slept till mid-afternoon. Second, loss of verbal responsiveness as end point of induction with propofol was not possible here. That is why a fixed dose of propofol was administered. Third, we also bring forth the importance of BIS monitoring in such cases to titrate drug doses. Had we not applied BIS monitoring, we would have unnecessarily administered higher concentrations of sevoflurane than required thereby causing further delay in anesthetic recovery. Fourth, one of the classical extubation criteria of obeying to commands by the patient at the end of the surgery was not followed. However, adequate return of spontaneous breathing and airway reflexes along with spontaneous movement of all four limbs were ensured. Moreover, the intraoperative period was uneventful, and no neurological worsening was expected. Finally, the patient could not recollect any intraoperative event in the postoperative period suggesting absence of awareness. Thus, patients taking multiple AEDs should be evaluated thoroughly during pre-anesthetic check-up. The modification of anesthetic drugs and doses should be done, accordingly. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia

BackgroundThe World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia.MethodsAt a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data.ResultsOut of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04–5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33–8.88).ConclusionsThis pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa.Trial registrationNCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.

Deficiency of Adenosine Deaminase 2 (DADA2) Presenting As Familial Hodgkin Lymphoma

Familial Hodgkin Lymphoma (HL) accounts for 4.5% of HL. Both genetic susceptibility and shared environmental factors can play a role. The usual presentation of HL is cervical lymphadenopathy/ mediastinal mass. Subdiaphragmatic presentation is rare and hepatosplenomegaly is associated with advanced HL.Adenosine deaminase 2 (ADA2) act as an outside extracellular growth factor for integrity of endothelial cells and in the development of certain immune cells. Deficiency of ADA2 (DADA2) is a recently described inborn error of immunity caused by biallelic mutations in adenosine deaminase 2 (ADA2) gene (formerly known as CECR1). It is an auto-inflammatory disorder with a spectrum of vascular, inflammatory, hematological and immunodeficiency phenotypes. The condition is inherited in an autosomal recessive pattern.The association of DADA2 with lymphoproliferation such asT-LGL like condition and ALPS like disease have been reported, however, HL has not previously been reported in DADA2.Herein we describe two siblings with DADA2 who presented with Hodgkin Lymphoma. The first patient is the third child of Saudi first degree related parents. He is known to have bronchial asthma on bronchodilators. At the age of 5 years, he was referred from primary care clinic for investigation of hepatosplenomegaly. He was otherwise well with growth along the fifth centile. His complete blood count (CBC) showed mild lymphopenia, other lab results including liver function tests were within normal. Few months later, he developed non-tender mobile cervical lymph nodes enlargement. Viral serology including EBV was negative based on PCR testing. Lymph node biopsy revealed the diagnosis of HL, mixed cellularity type, EBV negative (Figure 1). Whole exome analysis sequencing identified a homozygous variant in ADA2 gene c.1447_1451del. This variant has been confirmed by Sanger sequencing. Plasma assay of ADA2 enzyme activity revealed undetectable levels compatible with ADA2 deficiency.The patient started on prednisone 2 mg/kg/day, which showed good response in the form of being off blood support and regression of splenomegaly. Few months later, the course was complicated by recurrent infections. The patient remained stable for three years on small dose of prednisone, monthly IVIG due to hypogammaglobulinemia. Recently, etanercept was started to control disease progression.Nine months after the diagnosis of first patient, his younger brother who is known to have mild bronchial asthma on bronchodilators presented at the age of five years with hepatosplenomegaly and generalized lymphadenopathy. Lymph node biopsy revealed the diagnosis of classical HL, lymphocyte-rich subtype. Similar to his sibling, whole exome analysis identified the same mutation (a homozygous variant in ADA2 gene c.1447_1451del). This variant has been confirmed by Sanger sequencing and plasma level of ADA2 enzyme activity was undetectable. After the diagnosis of DADA2, screening for serum immunoglobulin levels showed hypogammaglobulinemia. The patient continues to be off treatment. Both patients were treated with chemotherapy with or without radiotherapy showing good response and they remained in remission at respectively and months after cessation of chemotherapy.This study is important for several reasons. First, this is the first report of HL in the context of DADA2. This again widens the clinical spectrum of DADA2. Interestingly, the boys presented two different forms of HL at the cellular level with no evidence of viral infection. The reported siblings presented with subdiaphragmatic diseases, which is uncommon in HL but in line with the sites of lymphoproliferation in DADA2. In addition, the age of presentation in the two siblings is uncommon in HL (less than 10 years).Second, we report an novel mutation in ADA2 gene. It creates a shift in the reading frame starting at codon Ser483. The new reading frame ends in a stop codon 4 positions downstream. This description and the description of the HL occurrence further expands the spectrum of DADA2. Our data, call for judicious exclusion of ADA2 deficiency in the HL patient with an aberrant course and additional symptoms / signs.In summary, we report familial HL in two patients with a novel deleterious mutation in ADA2 gene. This expands the spectrum of this disease to include cancer and should alert the hemato-oncologist to the possibility of DADA2 as an underlying diagnosis in HL. DisclosuresNo relevant conflicts of interest to declare.

Effects of tenofovir and telbivudine on HBV RNA in pregnant women with different genotypes of HBeAg-positive hepatitis B in Guizhou Province

Objective: To investigate whether HBV genotype influences HBV DNA and RNA responses to tenofovir(TDF) and telbivudine(LDT) in pregnant women with HBeAg-positive in Guizhou. Methods: This was a retrospective analysis of 75 pregnant women hepatitis B with HBsAg and HBeAg double-positive(19-38 years old, median age 26 years old), who were enrolled in the Department of Infectious Diseases and Obstetrics Clinic of the Affiliated Hospital of Guizhou Medical University from May 2016 to July 2017.Blood samples were collected at 12-24, 28-32 and 36-40 weeks of pregnancy for analyses of genotype, including hepatitis B surface antigen(HBsAg), hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA and liver function, alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBiL), total bile acids(TBA), cholinesterase(CHE), alkaline phosphatase (ALP). Continuous variable was adopted by means of mean±standard deviation, and categorical variables were used for statistical analysis. Results: The HBV genotype was B in 64.0%(48/75)and C in 36.0%(27/75). The TDF and LDT groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)HBV DNA and log(10)HBV RNA.TDF groups, pre-treatment: HBV DNA (4.8±2.0), HBV RNA (6.4±1.1); at 4 weeks of treatment: HBV DNA (4.0±0.8), HBV RNA (6.0±0.9); at the end of treatment: HBV DNA (3.1±0.7), HBV RNA (5.5±0.8). LDT groups, pre-treatment HBV DNA (5.1±2.0), HBV RNA(6.5±0.9); at 4 weeks of treatment: HBV DNA (4.4±1.2), HBV RNA(6.5±0.8); at the end of treatment: HBV DNA(3.5±1.2), HBV RNA (6.1±0.7). Compared with pre-treatment (12-24 weeks), the TDF and LDT group showed significant reductions in log(10)(HBV DNA) and log(10)(HBV RNA) at 36-40 weeks ( P<0.05). Under the influence of excluding other variables, the genotype had a certain influence on the HBV RNA load.That was, HBV RNA in patients with the C genome decreased by 0.54 units(log(10)) at the end of the treatment compared to patients with the B genome, and the P value was less than 0.05. Conclusion: B and C genotypes are predominant in pregnant women with hepatitis B in Guizhou Province. B-type viruses are more easily controlled when different genotypes are treated with nucleotide analogues.

Agenesis of the Gallbladder: A Phantom Menace

Objective: Gallbladder agenesis (GBA) is a rare congenital disorder with an estimated incidence of about 0.06%. Despite the absence of a gallbladder, these patients may present with symptoms mimicking biliary colic or cholecystitis. Ultrasound findings and liver function tests are often misleading. Some of these patients undergo laparoscopy without successful identification of gallbladder and paradoxically report symptom relief.&#x0D; Case: We present a case of GBA in a 54 year-old female, who presented with right-sided abdominal pain. The clinical history and examination were consistent with biliary colic. Initial investigations, including liver function tests, upper endoscopy and ultrasound did not demonstrate upper gastrointestinal pathology and did not clearly identify a gallbladder. Subsequent HIDA scan and CT of the abdomen did not visualize a gallbladder. An MRCP confirmed gallbladder agenesis. The patient was managed conservatively and was symptom free on discharge and follow-up.&#x0D; Discussion: We wish to highlight four learning points: 1. Patients with gallbladder agenesis often present with biliary symptoms. 2. Ultrasound and CT of the liver may not always identify this anomaly. 3. MRCP is the gold standard for making a diagnosis of gall- bladder agenesis. 4. Surgeons must have a high index of suspicion of GBA when the gallbladder is poorly visualized or not identified on ultrasound.

Biochemical and clinical variations among severe Plasmodium Vivax malaria cases: A prospective study

Context: Plasmodium vivax is geographically widely distributed with up to 2.5 billion people at risk and an estimated 70-80 million cases every year. India contributes 77% of the total malaria in Southeast Asia. Retrospective analysis of burden of malaria showed that disability adjusted life years due to malaria were 1.86 million years. According to recent study, West Bengal contributes 11% of total malaria cases in country and is one of states where falciparum resistance to chloroquine has been confirmed. Aims: The aim of this study was to evaluate the biochemical and clinical profile of severe and non-severe Plasmodium vivax malaria and the complications and outcome of P. vivax malaria infections as there is very limited information on age and sex specific seasonal prevalence of malaria in different paradigms in the country. Materials and Methods: A hospital based prospective study was conducted in Medical College, Kolkata comprising of 138 patients with fever (≥37.5˚C), peripheral smear and/or rapid diagnostic tests positive for P. vivax. Previously established cases of CKD, hematological abnormalities, chronic liver diseases and neuro-psychiatric disorders were excluded from our study. Demographical, clinical and laboratory parameters including liver function test, renal function test were documented and were presented in tabular and statistical means. Results: Jaundice was present in 22% of patients and vomiting in 32% of the patients. Hepatomegaly was seen in 16 % cases and 33% cases had splenomegaly. ARDS was seen in 16% of severe malaria cases. Acute kidney injury was seen in 8% and cerebral malaria was seen in 12% of severe malaria cases. Multi organ dysfunction was seen in12 %cases. There was 1 death in the study due to multi organ dysfunction. Conclusion: Life threatening complications such as ARDS, AKI, cerebral malaria and MODS can be seen in P. vivax mono infections.

Intraductal Papillary Mucinous Neoplasm of the Duct of Santorini in the Absence of Pancreatic Divisum

Introduction: Intraductal Papillary Mucinous Neoplasm (IPMN) is a mucin-producing cystic neoplasm of the pancreas that arises from the main pancreatic duct or one of the branch ducts. The literature has described a small number of IPMNs arising from the accessory duct of Santorini, with the majority of these cases in the setting of pancreatic divisum. We report a case of IPMN of the accessory duct of Santorini in a transgendered male patient without pancreatic divisum. We provide an endoscopic image of the fish-mouth appearance of the minor papilla, which has not been previously reported in the literature. Case Report: A 59-year-old transgender male presented with right-sided abdominal pain. Abdominal KUB revealed a severely enlarged liver silhouette. History revealed the patient to be transgendered, on estradiol, conjugated estrogens, and medroxyprogesterone acetate. Physical exam revealed no abnormalities and all labs, including liver function tests (LFTs) were within normal limits. CT showed hepatomegaly and a 5.5 X 5.5 X 21 mm cystic structure in the head and uncinate process, which was not contiguous with the extrahepatic common bile duct or main pancreatic duct with several enlarged retroperitoneal lymph nodes. On MRI/MRCP a tubular markedly hyperintense T2 lesion measuring 27 X 11 X 9 mm was present. This lesion appeared in continuity with the distal accessory pancreatic duct, which appeared mildly dilated with communication to the main pancreatic duct. On endoscopy, the major papilla appeared normal. The minor papilla had a fish-mouth appearance exuding mucoid material. EUS revealed tubulocystic dilation of the duct of Santorini measuring 1.3 X 0.6 cm. There was also dilation of a side-branch towards the communication between the accessory duct and the main pancreatic duct. The pancreatic duct was normal in contour and caliber through the remainder of the gland. Fine needle aspiration (FNA) was done and fluid analysis revealed amylase of 14780 Units/L and carcinoembryonic antigen (CEA) of 89.1. Cytological analysis of the fluid was nondiagnostic. Patient referred for Whipple, but declined surgical intervention.1257_A.tif Figure 1: No Caption available.1257_B.tif Figure 2: No Caption available.1257_C.tif Figure 3: No Caption available.Discussion: IPMNs are generally found incidentally on imaging. While guidelines for managmenent of MD- and BD-IPMNs are clear, an IPMN of the duct of Santorini is a rare entity with no diagnostic recommendations currently in place, though one study suggests surgical resection. Our patient has done well with endoscopic monitoring for 7 years.

AN UNUSUAL CASE OF MARIJUANA-INDUCED ACUTE PANCREATITIS

SESSION TITLE: Critical Care 6 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Cannabis (marijuana) is the most frequently consumed illicit drug in the world. Pancreatitis is one of the least reported adverse effects of cannabis with the literature merely limited to a few anecdotal case reports. Given the increasing illicit and medical use of marijuana globally, the goal of this case report is to increase the awareness on an unusual yet potential adverse effect, namely, acute pancreatitis. CASE PRESENTATION: A 23-year-old African-American male with no significant past medical history presented with sudden onset of epigastric pain. It was associated with nausea and vomiting. Vomitus was non-bloody and non-bilious. He was former social drinker until he quit five months ago. He did admit using marijuana regularly. On examination, vital signs were within normal limits. Examination of the abdomen and other systems were otherwise unremarkable except for epigastric tenderness. He had elevated serum lipase measuring 1387 units/liter. Metabolic parameters including liver function test, serum calcium and triglyceride levels were within normal limits. Abdominal imaging with plain radiograph was unremarkable, ultrasound was negative for cholelithiasis. Computed tomography of abdomen did not reveal a pancreatic edema or necrosis. Urine drug screen was positive for cannabinoids. He was diagnosed with acute pancreatitis likely triggered by cannabis use. He was treated conservatively with bowel rest, acid suppression along with supportive measures. He had an uneventful recovery and was discharged home. At discharge, he was counseled against of marijuana use and was enrolled in a drug rehabilitation program. DISCUSSION: Cannabis contains tetrahydrocannabinol and cannabidiol that acts on CB1 and CB2 receptors. CB1 receptors are present in pancreatic tissue and are thought to be responsible for pancreatic breakdown, although a detail of pathologic mechanism remains a mystery. Cannabis is the world’s most popular illicit drug with over 4% of the word population using it each year. Despite this, acute pancreatitis is a rarely reported adverse effect of cannabis. Reporting drug-induced acute pancreatitis is challenging as it has no distinguishing clinical features. The diagnosis gets further challenged by frequent use of polypharmacy making it difficult to pinpoint the specific offending agent. Thus, the true incidence of cannabis-induced pancreatitis may therefore be underestimated. A high index of clinical suspicion and detailed drug history may therefore be essential in identifying the causality. CONCLUSIONS: Considering, the universally increasing medical and illicit use of cannabis clinicians should be well aware of acute pancreatitis as an uncommon yet potential adverse effect of cannabis. Reference #1: Barkin, J.A., Nemeth, Z., Saluja, A.K. and Barkin, J.S., 2017. Cannabis-Induced Acute Pancreatitis: A Systematic Review. Pancreas, 46(8), pp.1035-1038. DISCLOSURES: No relevant relationships by Soney Basnyat, source=Web Response no disclosure on file for Hira Irfan; no disclosure on file for Banathally Nandish; No relevant relationships by Milan Patel, source=Web Response No relevant relationships by David Steinberger, source=Web Response

Optimizing diagnostic approach to drug-induced liver injury

Drug-induced liver injury (DILI) is often a trial even to expert clinicians, because sometimes diagnosis is not easy to be made. Guidelines of the American College of Gastroenterology (ACG) yielded in 2014, help to better understand the problem. The diagnosis of DILI is made through a detailed evaluation of clinical, serological, radiological and histological aspects. Biochemical data include liver function tests that allow to assess the pattern of damage, such as hepatocellular, cholestatic and mixed liver injury; serological data include testing for major and possibly minor hepatotropic viruses, non-organ specific autoantibodies. Clinical scenario might include jaundice, nausea, vomiting and extra-hepatic manifestations such as fever, pruritus, rash and eosinophilia. Investigation of the potential culprit drugs should involve firstly the temporal relationship between intake of the medication and onset of symptoms, thus the improvement after drug withdrawal. Overall, to complete the diagnostic evaluation, an abdominal ultrasound can be performed, as well as measurement of liver stiffness by transient elastography, and finally liver biopsy, which still represents the most accurate method to definitely assess liver damage. Sometimes, in such cases, computed tomography scan and magnetic resonance could help in the diagnosis of cases presenting with focal lesions of the liver, with cholestatic-like disease or vascular alterations, such as veno-occlusive disease. DILI diagnostic criteria help clinicians thinking of liver injury induced by drug, excluding other causes of liver disease. According to severity of liver damage and type of drug, it is possible to carefully predict the patient’s outcome.

Contemporary approaches to the prevention and management of paediatric obesity: an Australian focus.

Of the 34 member countries of the Organisation for Economic Co-operation and Development, obesity prevalence is highest in the United States, with Australia ranking fifth for girls and eighth for boys. Curbing the problem is achievable and can be realised through a combination of smart governance across many sectors, community initiatives, the support of individual efforts, and clinical leadership. At 5 years of age, one in five Australian children are already affected by overweight or obesity; obesity prevention strategies must therefore start before this age. There is strong evidence that reducing screen time and promoting breastfeeding in 0-2-year-olds are effective interventions in the early years. The main behavioural risk factors for obesity are overconsumption of energy-dense, nutrient-poor foods and a lack of physical activity. Emerging evidence suggests poor sleep quality and duration and high amounts of sedentary time also play a role. Systems-based policy actions may change long term obesity prevalence in children by targeting the food environment through nutrition labelling, healthy foods in schools, restricted unhealthy food marketing to children, and fiscal policies to reduce consumption of harmful foods and sugar-sweetened beverages. Macro-environmental factors influence obesity risk. Public transport policy and the built environment (proximity to parks, bike paths, green space, schools and shops) influence play time spent outdoors, walking and cycling. Greater access to parks and playgrounds and active commuting are associated with lower body mass index. Australian interventions have largely employed individual level approaches. These are important, but of limited effectiveness unless priority is also given to policies that reduce obesity-conducive environments. Clinicians can provide anticipatory guidance to support healthy weight and weight-related behaviours, including weight monitoring, early feeding and children's diets, physical activity opportunities, and limited sedentary and screen time. Investigations in children with obesity usually include liver function tests and measuring fasting glucose, lipid and possibly insulin levels. As obesity can be associated with micronutrient deficiencies, it may be prudent to check full blood count and iron, vitamin B12 and vitamin D levels. Endocrinological assessment is usually not needed. Second line investigations may include liver ultrasound, oral glucose tolerance testing and sleep study. Traditional treatment of child and adolescent obesity has focused on family-based, multicomponent (diet, physical activity and behaviour change) interventions, although these lead to small and often short term weight reductions (mean, - 1.45 kg; 95% CI, 1.88 to - 1.02). Nevertheless, these principles remain core interventions in children and adolescents with obesity. A very low energy diet should be considered in adolescents with severe obesity or obesity-related comorbidities, and for adolescents who have not achieved weight loss following a more conventional dietary approach. Pharmacotherapy confers only small reductions in weight; for example, effect size for metformin is - 3.90 kg (95% CI, - 5.86 to - 1.94). Bariatric surgery should be considered in adolescents over 15 years of age with severe obesity (body mass index > 40 kg/m2, or > 35 kg/m2 in the presence of severe complications).

Alcohol Consumption and Subclinical Findings on Cognitive Function, Biochemical Indexes, and Cortical Anatomy in Cognitively Normal Aging Han Chinese Population.

Background: Binge drinking of alcohol is associated with brain damage, but less is known about relationship of light-to-moderate alcohol consumption with cognitive function, biochemical indexes, and cortical anatomy. Previous findings have debated on whether light-to-moderate drinking has any health benefits. We investigated cortical thickness and its association with alcohol consumption and cognitive functions in a non-dementia aging Han Chinese population.Methods: 940 non-dementia aging subjects were included in our study (alcohol n = 149; non-alcohol n = 791). Among them, 572 received blood biochemical tests including liver function and lipid metabolism (alcohol n = 100; non-alcohol n = 472) and 141 had brain magnetic resonance imaging (alcohol n = 27; non-alcohol n = 114). The Beijing version of the Montreal Cognitive Assessment and the Chinese version of the neuropsychological test battery were used to assess cognitive functions.Results: There was no significant difference in cognitive functions between alcohol and non-alcohol groups in the overall database. Similarly, there was no significant difference in liver function and lipid metabolism between two groups in the sub-database. The left superiortemporal gyrus was one of age sensitive regions and alcohol consumption was significantly associated with thinner cortex of the left superiotemporal cluster in the sub-database.Conclusion: Alcohol consumption was not significantly associated with better or worse cognitive function and biochemical indexes abnormality, however, significantly associated with thinner cortex of the left superiortemporal gyrus in cognitively normal aging Han Chinese population.

The Prevalence of Gallstone Disease Is Significantly Lower in Natives than in Migrants of Jeju Island.

BackgroundThe eating habits of Jeju Island natives are quite different from those of the mainland people because of geographic isolation. Diet is a main factor affecting gallstone disease. We investigated the prevalence of gallstone disease in both Jeju Island natives and migrants and studied the risk factors affecting gallstone disease in the Jeju Island people.MethodsA total of 20,763 subjects who underwent medical checkups at the Health Promotion Center of Jeju National University Hospital in Korea from January 2003 to December 2015 were enrolled in the study. Ultrasonography was used to determine the presence of gallbladder stones. Body mass index and biochemical parameters, including liver function test results, lipid profiles, and fasting blood glucose levels, were verified, and data on age, birthplace, and sex were collected from medical records. Univariate and multivariate analyses were performed to identify risk factors affecting gallstone disease.ResultsThe prevalence of gallstone disease in the Jeju Island people was 4.0%: Jeju Island natives, 3.8% and migrants, 4.4% (P=0.047). After multivariate logistic regression analysis, the independent risk factors were older age, Jeju migrants, higher fasting blood glucose and alanine aminotransferase levels, and lower high-density lipoprotein cholesterol levels.ConclusionThe prevalence of gallstone disease was significantly lower in natives than in migrants from Jeju Island. Older age, Jeju migrants, higher fasting blood glucose and alanine aminotransferase levels, and lower highdensity lipoprotein cholesterol levels contributed to gallstone disease prevalence in the Jeju Island people.