Epstein-Barr Virus Hepatitis Research Articles

Acute Epstein-Barr virus Encephalitis and hepatitis without mononucleosis syndrome: a case report

Acute Epstein-Barr virus Encephalitis and hepatitis without mononucleosis syndrome: a case report

Identification of biomarkers related to sepsis diagnosis based on bioinformatics and machine learning and experimental verification.

Sepsis is a systemic inflammatory response syndrome caused by bacteria and other pathogenic microorganisms. Every year, approximately 31.5 million patients are diagnosed with sepsis, and approximately 5.3 million patients succumb to the disease. In this study, we identified biomarkers for diagnosing sepsis analyzed the relationships between genes and Immune cells that were differentially expressed in specimens from patients with sepsis compared to normal controls. Finally, We verified its effectiveness through animal experiments. Specifically, we analyzed datasets from four microarrays(GSE11755、GSE12624、GSE28750、GSE48080) that included 106 blood specimens from patients with sepsis and 69 normal human blood samples. SVM-RFE analysis and LASSO regression model were carried out to screen possible markers. The composition of 22 immune cell components in patients with sepsis were also determined using CIBERSORT. The expression level of the biomarkers in Sepsis was examined by the use of qRT-PCR and Western Blot (WB). We identified 50 differentially expressed genes between the cohorts, including 2 significantly upregulated and 48 significantly downregulated genes, and KEGG pathway analysis identified Salmonella infection, human T cell leukemia virus 1 infection, Epstein-Barr virus infection, hepatitis B, lysosome and other pathways that were significantly enriched in blood from patients with sepsis. Ultimately, we identified COMMD9, CSF3R, and NUB1 as genes that could potentially be used as biomarkers to predict sepsis, which we confirmed by ROC analysis. Further, we identified a correlation between the expression of these three genes and immune infiltrate composition. Immune cell infiltration analysis revealed that COMMD9 was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, etal. CSF3R was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, etal. NUB1 was correlated with T cells regulatory (Tregs), T cells gamma delta, T cells follicular helper, etal. Taken together, our findings identify potential new diagnostic markers for sepsis that shed light on novel mechanisms of disease pathogenesis and, therefore, may offer opportunities for therapeutic intervention.

Epstein Barr Virus Hepatitis-A Mild Clinical Symptom or a Threat?

The present study aimed to characterize pediatric patients diagnosed with hepatitis associated with primary Epstein-Barr Virus (EBV) infection. We described the changes in liver aminotransferases activity during the disease, and we analyzed the results of abdominal ultrasonography. A retrospective study was performed by analyzing the medical records of 166 immunocompetent children diagnosed with primary EBV hepatitis hospitalized at the Department of Children's Infectious Diseases, Medical University of Warsaw, Regional Hospital of Infectious Diseases in Warsaw, between August 2017 and March 2023. Elevated alanine aminotransferase (ALT) activity was noted in the first three weeks of the disease. In 46.3% of patients, ALT values exceeded five times the upper limit of the laboratory norm in the first week of illness. Aspartate aminotransferase activity increased from the first to fourth week from the onset of symptoms and showed two peaks in the first and third weeks. The changes over time of mean AST activity demonstrated significance. Transient cholestatic liver disease was the predominant type of hepatic involvement in 10.8% of children; 66.6% of them were older than 15 years. Clinical and ultrasound criteria of acute acalculous cholecystitis (AAC) were met in three female patients over 16 years of age. Hepatitis associated with primary EBV infection is usually a mild and self-limiting condition. Significantly elevated values of liver enzymes with features of cholestatic liver disease may occur in patients with a more severe course of the infection.

294 - An Unusual case of epstein-barr virus hepatitis mistaken for multisystem inflammatory syndrome in children

294 - An Unusual case of epstein-barr virus hepatitis mistaken for multisystem inflammatory syndrome in children

The influence of steroid therapy of complications of infectious mononucleosis on the course of Epstein-Barr virus hepatitis.

The purpose of the study was to characterize the differences in the course of Epstein-Barr virus (EBV) primary infection-induced hepatitis between patients treated with steroids due to complications of infectious mononucleosis (IM) and those not receiving such therapy. We analyzed the changes in the activity of liver enzymes and differences in abdominal ultrasound results. The study was based on reviewing the medical records of children hospitalized for primary EBV infection at the Department of Children's Infectious Diseases, Medical University of Warsaw, Regional Hospital of Infectious Diseases in Warsaw, between August 2017 and March 2023. The study population was divided into two groups: patients treated with steroids (Group 1) and children not receiving steroids (Group 2). Significant differences were obtained for alanine aminotransferase activity only in the first week of IM (205.34 ±115.40 vs. 288.82 ±170.16 IU/l for Group 1 and 2, respectively; p = 0.024), and for aspartate aminotransferase in the first (170.63 ±159.47 vs. 218.85 ±128.22 IU/l for Group 1 and 2, respectively; p = 0.009) and the third week (151.09 ±138.57 vs. 235.50 ±170.27 IU/l for Group 1 and 2, respectively; p = 0.016). The analysis of the results of laboratory tests for the diagnosis of cholestasis (γ-glutamyl transferase and total serum bilirubin concentrations with fractions) did not show significant differences between the groups. Our results indicated that the two cohorts of patients may differ in the course of hepatitis associated with primary EBV infection, especially at the beginning of the disease, when the laboratory features of hepatitis were less pronounced in children treated with steroids.

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis.

Chronic active Epstein-Barr virus hepatitis (CAEBVH) is a rare and highly lethal disease characterized by hepatitis and hepatomegaly. This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH. Ten patients with confirmed Epstein-Barr virus hepatitis infection were enrolled. The clinicopathological characteristics of these patients were summarized and analyzed. Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms. Lastly, immunohistochemical staining was employed to verify pathogenic mechanisms. Clinical features observed in all Epstein-Barr virus hepatitis patients included fever (7/10), splenomegaly (10/10), hepatomegaly (9/10), abnormal liver function (8/10), and CD8+ T cell lymphopenia (6/7). Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver. Positive Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) of lymphocytes of liver tissues was noted. Whole exome sequencing indicated that cytotoxic T lymphocytes and the complement system were involved. The expression of CD8, Fas, FasL, and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls (p<0.05). Lastly, Complement 1q and complement 3d expression, were higher in CAEBVH patients relative to controls (p<0.05). CAEBVH patients developed fever, hepatosplenomegaly, and lymphadenopathy. Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity. Fas/FasL and complement activation were involved in CAEBVH patients.

S1928 Seeing the Forest for the Trees: Not All Colitis Is IBD

Introduction: Gastrointestinal involvement by Epstein-Barr virus (EBV) infection is rare, and almost always occurs in states of immunodeficiency or chronic inflammation. We present a case of EBV colitis in a healthy immunocompetent patient. Case description/methods: A 33-year-old man presented with 3 weeks of bloody diarrhea, fatigue, malaise, and weight loss. On exam, he had tender cervical lymphadenopathy. Labs showed leukocytosis of 19.2 K/UL (64% lymphocytes), hemoglobin of 11.5 g/dL, and elevated CRP of 23.8 mg/L. Liver enzymes were elevated, with ALT of 156 U/L, AST of 125 U/L, and alkaline phosphatase of 220 U/L. Albumin (4 g/dL) and platelets (221 K/UL) were normal. Tests for HIV, viral hepatitis, and stool bacteria, ova, and parasites were negative. Computed tomography showed splenomegaly, enlarged intraabdominal lymph nodes, and diffuse colon wall thickening with hyperemia. Colonoscopy revealed patchy ulcers, friability, and erythema in the colon, with normal intervening mucosa and terminal ileum. He was referred to the Inflammatory Bowel Disease (IBD) service, and initial pathology showed mild active chronic pancolitis. Due to symptom severity, he was started on IV methylprednisolone 20 mg twice daily and rapidly improved in 2 days. Final pathology showed positive EBV-encoded small RNA (EBER) in situ hybridization (50 cells/hpf) without evidence of an underlying lymphoproliferative disorder. Serologies showed acute EBV infection (IgM+, IgG-, PCR viral load 341 IU/mL), and liver biopsy showed EBV hepatitis. Infectious Disease (ID) agreed with supportive therapy. He was discharged on 5 days of prednisone 40 mg daily. On 1-week follow up, he was asymptomatic off steroids. Repeat colonoscopy will be performed in 3 months. Discussion: Acute EBV infection classically presents with lymphadenopathy, splenomegaly, and constitutional symptoms. EBV colitis is exceedingly rare in immunocompetent patients, especially in the absence of lymphoma, with only 3 published case reports. Our case highlights the importance of maintaining a holistic approach to arrive at a unifying diagnosis. EBV in colon biopsies is not always pathologic; serologies are needed to determine active or latent infection. Coordinating with ID is prudent. Management is typically supportive, given the self-limited course; the role of corticosteroids and antivirals remains unclear. Repeat colonoscopy with biopsies to evaluate mucosal healing and to rule out underlying IBD is recommended.Figure 1.: Figure 1A. 4.3 x 3.5 cm mass anterior to a large sigmoid diverticulum with Hounsfield units of 22-36 (red arrow). Hounsfield units of lipomas range from 30 to 70. Figure 1B. 4 cm pedunculated polyp 20 cm from the anal verge. Figure 1C. Microscopy depicting submucosal mass with mature white adipose tissue (red arrow).

Protein Arginine Methyltransferase 5 Functions via Interacting Proteins.

The protein arginine methyltransferases (PRMTs) are involved in such biological processes as transcription regulation, DNA repair, RNA splicing, and signal transduction, etc. In this study, we mainly focused on PRMT5, a member of the type II PRMTs, which functions mainly alongside other interacting proteins. PRMT5 has been shown to be overexpressed in a wide variety of cancers and other diseases, and is involved in the regulation of Epstein-Barr virus infection, viral carcinogenesis, spliceosome, hepatitis B, cell cycles, and various signaling pathways. We analyzed the regulatory roles of PRMT5 and interacting proteins in various biological processes above-mentioned, to elucidate for the first time the interaction between PRMT5 and its interacting proteins. This systemic analysis will enrich the biological theory and contribute to the development of novel therapies.

S3540 A Youthful Old Man – A Rare Case of EBV Hepatitis Presenting in the Elderly Population

INTRODUCTION: Epstein- Barr virus (EBV) is a herpes virus with a majority of its primary presentations being sub-clinical. It is estimated that 90%-95% of adults are positive for infection with studies suggesting that primary infection occurs by the age of 20. EBV presentation of hepatitis accounted for < 1% of the final diagnosis compared to hepatic injury. This rare case presents the uncommon clinical and laboratory manifestations of acute EBV hepatitis. CASE DESCRIPTION/METHODS: An 83-year-old male presented with weakness and loss of appetite with 10 lb weight loss over the last month. He states 3/10 diffuse epigastric pain and nausea for one week prior to admission. He denied exposure to sick contacts, recent travel with last sexual encounter 4 years ago. He denies history of hepatitis or intravenous drug use with occasional use of Tylenol and fish oil supplements. Physical examination revealed a grossly jaundiced male with a normal abdomen without hepatomegaly or splenomegaly. Laboratory findings on admission showed elevated transaminases with ALT 1,028U/L, AST 718U/L, alkaline phosphatase (ALP) 1,185 U/L, total bilirubin 4.2mg/dL, and INR 1.1. During the patient’s hospital stay, the transaminases continued to decrease but ALP rose to 1,378U/L over the next two days before trending down and total bilirubin to 14.7 mg/dL (direct bilirubin >10 mg/dL). Ultrasound revealed a 13.7cm heterogeneous textured liver without biliary or common ductal dilation. Multiple echogenic lesions were seen, likely hemangiomas. All viral panels were negative aside from the EBV panel, which was positive for IgM and IgG. Patient was diagnosed with EBV hepatitis and was provided supportive treatment with NAC therapy. During the patient’s hospital course, his weakness and nausea persisted but pain resolved as LFTs started to trended down. The total bilirubin remained elevated at discharge. INR was stable throughout his stay. AST/ALT had decreased to 190/195 and with improvement, he was discharged home with hepatology clinic follow up. DISCUSSION: EBV hepatitis typically presents with fever, lymphadenopathy, sore throat, lymphocytosis, and splenomegaly with auto resolution over 8 weeks. Our patient did not have the typical symptoms, but presented with jaundice, cholestatic liver injury with significant elevations in liver panels. Treatment is supportive care. Our patient completed NAC therapy and with improvement was discharged home with close with close monitoring but was unfortunately lost to follow up due to the Covid pandemic.

S2582 Acute Hepatitis Secondary to Asymptomatic Epstein-Barr Virus (EBV) Infection

INTRODUCTION: Symptomatic EBV infection usually presents with fever, sore throat, lymphadenopathy, termed as infectious mononucleosis syndrome. Marginal elevation of liver enzymes may be seen however, acute symptomatic hepatitis without mononucleosis syndrome is rare. We present a case of a female with acute cholestatic hepatitis with laboratory-confirmed EBV infection without mononucleosis syndrome. CASE DESCRIPTION/METHODS: A 36-year-old female, underweight, with past history of alcohol use (sober for 60+ days), seizure disorder, sub-clinical hypothyroidism presented with intermittent nausea followed by non-bloody, non-bilious vomiting for 5 days without melena or blood in the stool. She didn’t report any fever, chills, night sweats, sick contacts, recent travel history. On clinical exam, her vital signs were blood pressure 112/78 mm Hg, pulse 104/min, oral temperature of 36.7 deg C and breathing comfortably on room air. Inspection notable scleral icterus without periorbital skin involvement, no buccal mucosa changes, enlarged tonsil, no spider nevi, or scratch mark on inspection, no lymphadenopathy on palpation. The abdomen was soft and protuberant on the exam with liver just palpable below costal margin but non-tender to palpation. Her home medicine includes oral vitamin B12, folic acid, zonisamide (no changes to regimen in 2 years). Initial laboratory evaluation revealed a normal white cell count with an elevated liver enzymes, bilirubin, and alkaline phosphatase (R factor: 1.2). An ultrasonography of abdomen showed a common bile duct diameter of 3 mm without any dilation of extra or intrahepatic ducts, visualized portion of the portal vein was patent and showed hepatopetal flow. Unremarkable pancreas with cholelithiasis without cholecystitis. To rule in/out additional causes of cholestatic jaundice, viral, and antibody panel were sent which were positive for EBV infection. Additionally, ANA was positive reflecting cross-reactivity between EBV proteins and autoantigens. Her symptoms improved with conservative management which included hydration and low-fat diet. DISCUSSION: EBV is an important cause of cholestatic hepatitis resulting in elevated liver enzymes and bilirubin, however, the presentation is usually associated with mononucleosis syndrome. EBV hepatitis as a differential in patients with cholestatic hepatitis but without demonstrable biliary obstruction, prompt identification would avoid costly and/or invasive diagnostic procedures. No effective treatment is available for EBV hepatitis.Table 1.: Laboratory profile on admission and 8 weeks later

Acute Epstein-Barr virus hepatitis presenting clinically as ascending cholangitis in an immunocompetent patient

Symptomatic acute Epstein-Barr virus (EBV) hepatitis, without associated infectious mononucleosis syndrome, is exceptionally rare. A 30-year-old female presented to hospital with jaundice, fevers, and right upper quadrant abdominal pain. Her blood tests demonstrated marked hyperbilirubinemia and mild global liver function test abnormalities consistent with obstructive jaundice. Preliminary imaging with ultrasound showed gallbladder wall thickening and cholelithiasis, suggestive of potential cholecystitis. Authors were concerned for potential ascending cholangitis in the setting of her hyperbilirubinemia. The diagnosis was refuted after magnetic resonance cholangiopancreatography demonstrated no choledocholithiasis. A hepatic panel was performed which revealed positive EBV IgM serology. This case highlights the importance of considering EBV hepatitis as a potential differential diagnosis in patients with right upper quadrant pain, fevers and jaundice in the absence of an obstructing cause.

Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial

Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60–7·60]; p=0·0016). At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9–23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9–25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2–29·2) versus 31·3% (21·9–40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5–35·1) in the anti-thymocyte globulin group and 41·3% (31·3–51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 70·6% (95% CI 60·6–78·6) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 53·3% (42·8–62·8) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35–0·90]; p=0·017). Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient in the anti-thymocyte globulin plus GVHD prophylaxis group died of Epstein-Barr virus hepatitis, but no deaths were attributable to anti-thymocyte globulin. The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including decreases in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin should be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. Canadian Institutes of Health Research and Sanofi.

Reactivation of Epstein-Barr Virus Hepatitis in T/Natural Killer (NK) Cells Mimicking Liver T/NK-Cell Lymphoma

Diagnosis of Epstein-Barr virus (EBV)-associated hepatitis, chronic active EBV infection, and EBV-associated lymphoproliferative diseases, is always challenging due to the overlapping symptoms and lack of diagnostic criteria. We report such a case of a 40-year-old man with unremarkable past medical history. He presented with fever of unknown origin for 1 month with jaundice for 2 days. Physical exams were unremarkable with body temperature at 98.6 °F. His liver function tests were elevated with alanine transaminase (ALT) 559 U/L, aspartate transaminase (AST) 892 U/L, alkaline phosphatase 319 U/L and total bilirubin 4.4 mg/dL. Computed tomography of his chest, abdomen and pelvis did not show lymphadenopathy or hepatosplenomegaly. A liver biopsy showed moderately acute hepatitis with hemophagocytosis, positive Epstein-Barr virus encoding RNA (EBER) in situ hybridization in CD3 and CD4-positive T cells and CD56-positive natural killer (NK) cells. CD20 was negative. The pathology diagnosis was consistent with reactivation of EBV hepatitis but NK-cell lymphoma needs to be excluded. Steatohepatitis with mild activity was present. His blood EBV DNA was 846,000 copies/mL and continued to increase to 2,000,000 copies/mL. Flow cytometric analysis of his bone marrow revealed an increased NK-cell activity but no T/NK-cell lymphoma was identified. Initial treatment with rituxan, etoposide and/or ruxolitinib/acyclovir failed or only had limited effect. However, subsequent valganciclovir greatly improved his conditions. In his 3 months follow-up, the patient was doing well with almost normal liver function tests except mildly elevated ALT (95 U/L) that was due to mild steatohepatitis. EBV DNA PCR was 2,009 copies/mL. To the best of our knowledge, this is the first documented case with reactivation of EBV hepatitis mimicking NK-cell lymphoma in the English literature. With appropriate anti-EBV viral treatments, the patient eventually became asymptomatic and was able to return to his routine life.

2464 A Case of Acute Icteric Hepatitis Caused by Epstein Barr Virus in an Immunocompetent Adult

INTRODUCTION: Epstein Barr Virus (EBV) is a viral infection that can often remain asymptomatic but is also a major cause of infectious mononucleosis. Patients often present with sore throat, fever, lymphadenopathy and can develop splenomegaly. EBV-associated hepatitis is uncommon and cases with clinical jaundice are rare. CASE DESCRIPTION/METHODS: A 23-year old male without significant past medical history presented with one week of flu-like symptoms and acute onset of a generalized pruritic rash, right upper quadrant (RUQ) abdominal pain and dizziness. He denied any recent alcohol consumption, IV drug use or new medication initiation. On arrival to the emergency department the patient was afebrile with a blood pressure 130/84. Physical exam revealed scleral icterus and cutaneous jaundice, a diffuse macular rash was across his face, chest and arms and he had tender hepatomegaly. He was alert and oriented without confusion. Laboratory examination revealed a leukocytosis of 11.8, a total bilirubin of 15.8, direct bilirubin of 13.3, an INR of 1.2, ammonia of 26, an alkaline phosphatase of 499, and an ALT of 615 with AST of 405 signifying acute hepatitis. A urine drug screen was negative. A RUQ ultrasound with doppler showed no evidence of Budd-Chiari or portal vein thrombus; fatty infiltration of the liver was seen with no evidence of cholelithiasis or common bile duct obstruction. Hepatitis A, B and C viral screen was negative, acetaminophen level was within normal limits, HIV antibody test was negative, herpes virus IgM negative, CMV IgM negative, anti-smooth muscle antibody negative for autoimmune hepatitis. Ceruloplasmin and alpha-1 antitrypsin levels were not suggestive of Wilson's disease or alpha-1 antitrypsin deficiency. A peripheral smear showed reactive lymphocytosis. There was significant elevation in EBV IgM and heterophile antibody suggesting systemic Epstein Barr viral infection as the cause of acute hepatitis. Over the next 3 days, his liver enzymes began trending down slowly with symptomatic management and he was determined stable for discharge with plans for 2 and 4 week follow ups to monitor for resolving acute EBV hepatitis. DISCUSSION: It is important to remember that, although rare, EBV can cause hepatitis with diffuse jaundice and significant hyperbilirubinemia along with AST and ALT levels over 10 times the upper limit of normal. Such presentation could easily be misconstrued as an alternative diagnosis and patient safety compromised with unnecessary treatment.

2325 Severe Cholestatic Hepatitis: An Atypical Presentation of Epstein-Barr Virus Infection

INTRODUCTION: Infectious mononucleosis (IM) is a benign lymphoproliferative disease caused by Epstein-Barr Virus (EBV). In adults, EBV infection can cause an acute hepatitis with elevation of transaminases, usually resolving spontaneously. We report a rare case of a severe cholestatic hepatitis following an acute EBV infection. CASE DESCRIPTION/METHODS: A 24-year-old previously healthy Caucasian woman presented with fever, body aches, headache, odynophagia and dry cough for 5 days. Initially CBC was normal but she had significant liver test abnormalities: aspartate transaminase (AST) 723 IU/L, alanine transaminase (ALT) 647 IU/L, alkaline phosphatase (ALP) 708 IU/L, and normal total bilirubin (TB) 1.2 mg/dl (Figure 1). Patient took acetaminophen (&lt;2 g/day) at home for fever for 5 days. She had no prior history of hepatitis, blood transfusions, intravenous drug use, high-risk sexual activity, or significant alcohol use. Monospot test was positive. Chest x-ray showed left lower lobe pneumonia, azithromycin was prescribed for 5 days. The fever subsided, but she became jaundiced (TB 9.2 mg/dl) on day 11 and the patient was admitted. RUQ ultrasound showed no evidence of biliary obstruction, masses or gallstones. CBC showed profound lymphocytosis. Hepatitis A, B, C and E serologies were negative. EBV VCA IgM Ab was positive, CMV and EBV PCR were negative. Autoimmune markers revealed mildly elevated ANA (1:160). Liver biopsy was done revealing sinusoidal lymphocytic infiltration typical of EBV hepatitis (Figure 2). Cholestasis worsened after admission with peak TB of 9.6 mg/dl and ALP 2080 IU/L. Follow-up lab work a month later showed a normal TB with mild elevation of ALP, GGT, AST and ALT. At 4-month follow up, all liver tests normalized with positive EBV serology (VCA IgG and EBNA), which confirmed the patient’s recent EBV infection. DISCUSSION: Acute cholestatic hepatitis is an extremely rare presentation of EBV infection, with few cases reported in the medical literature. To the best of our knowledge, our patient had the highest ALP elevation reported in association with EBV infection. It is essential for physicians to recognize this unusual EBV infection presentation in patients with fever and progressive cholestasis in the absence of biliary obstruction, to avoid prolonged hospitalization and invasive procedures.

Infectious mononucleosis (Epstein-Barr virus infection) and chronic hepatitis.

Aim To describe a case of an eight-year-old boy with chronic Epstein-Barr virus (EBV) hepatitis with incipient cirrhosis, rarely found in practice. Methods The diagnosis was based on findings of specific IgG serum antibodies and EBV positive liver biopsy. Other etiologies of hepatitis were excluded: autoimmune hepatitis, viral hepatitis A, B, or C, cytomegalovirus (CMV), herpes simplex virus (HSV), adenovirus infection, toxoplasma infection. Results A mild form of infectious mononucleosis with acute hepatitis without icterus was found in the boy first time at the age of three. He got sick again in april 2018 with fever, minor loss of appetite and weakness, skin and sclera were anicteric, no enlarged neck lymph nodes. Ultrasonography of the spleen revealed a spleen diameter of 10.7 cm, while the liver was 11.8 cm. Laboratory findings, sedimentation, blood count, C reactive protein (CRP) were all normal. Ten days and a month later an increase of aminotransferase was noticed. The liver biopsy and PCR EBV DNA were performed six months of disease onset. The disease had lasted for about one more year with loss of strength and an increase of aminotransferase with maximum value of 3-4 times higher than normal one. The therapy was supportive. Conclusion Chronic EBV hepatitis is very rare. In differential diagnosis of hepatitis and unclear febrile conditions, EBV infection should not be forgotten.

A Retrospective Cohort Study of Nasopharyngeal Carcinoma Screening and Hepatocellular Carcinoma Screening in Zhongshang City

Background: Nasopharyngeal carcinoma (NPC) and hepatocellular carcinoma (HCC) have remained a major burden of public health in Southern China. The screening for early disease in asymptomatic individuals has potentially been the most promising tool to improve cancer treatment outcomes. The present study aims to evaluate the compliance rates and characteristics of cancer incidence in the population of NPC and HCC screening.Methods: Enzyme-linked immunsorbent assay (ELISA) for Epstein-Barr virus (EBV) antibodies and Hepatitis B surface antigen (HBsAg) was performed in this population. NPC high/medium risk and HCC high risk individuals were followed-up for a number of years. The compliance rate, cancer incidence and early diagnosis rate of the screened population were statistically analyzed.Results: (1) In the preliminary screening, the compliance rate for NPC screening was significantly higher than that for HCC screening (29.3% vs. 26.2%; P<0.05). The compliance rates for screening were positively associated with age in these two screenings (P<0.01). (2) In the NPC screening, the compliance rates for the first year follow-up among NPC high/medium risk individuals were 74.9%, which was higher than that (60.2%) for the second year follow-up (P<0.05). The compliance rates for fiberoptic endoscopy among high risk individuals decreased along with the frequency of screening (P<0.016). The rates of missed diagnosis by non-compliance and the poor diagnostic accuracy of indicators were 3.3% and 3.3%, respectively. The average annual incidence and early diagnosis rate of the compliers were higher than those of the non-compliers (94.3 per 100,000 vs. 29.0 per 100,000; P<0.05 and 77.8% vs. 18.5%; P<0.05). (3) In the preliminary HCC screening, the compliance rate for ultrasonography among high risk individuals was 61.8%. The compliance rates for the follow-up were unsatisfactory. The rates of missed diagnosis by non-compliance and the poor diagnostic accuracy of indicators were 12.3% and 24.6%, respectively. There was no significant differences in average annual incidence and the rate of early diagnosis between compliers and non-compliers (79.4 per 100,000 vs. 54.6 per 100,000, P>0.05; 49.1% vs. 38.5%, P>0.05).Conclusion: The compliance rates for NPC and HCC screening needs to be improved. In particular, public health policies for HCC should be implemented. The present NPC screening could be the preferred strategy. However, the efficiency of HCC screening remains substantially unsatisfactory and needs to be further discussed.

Epstein-Barr Virus Hepatitis: A Review of Clinicopathologic Features and Differential Diagnosis.

The liver is frequently affected by Epstein-Barr virus (EBV) infection, but involvement is commonly subclinical and self-limited. Severe and potentially fatal EBV hepatitis has also been occasionally reported in immunocompromised patients and, even more rarely, in immunocompetent individuals. To provide a review of the clinicopathologic findings of EBV hepatitis, with a focus on microscopic features and ancillary testing with a brief discussion of the differential diagnosis. Analysis of the pertinent literature (PubMed) and clinical practice experience based on institutional materials. Characteristic microscopic findings in EBV hepatitis include a diffuse lymphocytic sinusoidal infiltrate in a "string of beads" pattern, expansion of portal tracts by a predominantly lymphocytic infiltrate, and intact lobular architecture. In situ hybridization of EBV-encoded RNA is a helpful ancillary test. Correlation of clinical history, laboratory findings, and histopathologic features is essential to distinguish EBV hepatitis from autoimmune liver diseases, transplant rejection, lymphomas, and drug-induced liver injury.

Focal Nodular Hyperplasia: An Eluding Liver Lesion in a Background of EBV Hepatitis

A 25 year old female presented with flank pain, lower abdomen pain and daily subjective fevers for one week. The pain was relieved with NSAID use. She also had chills, sweats, malaise and weakness. She denied weight loss. She denied any acetaminophen use, new medications or herbal supplements. On exam, she had no scleral icterus, but was tender to palpation of in the right upper quadrant. Labs were remarkable for elevated liver function tests, leukopenia and thrombocytopenia without anemia. CT revealed an 11 cm right hepatic lobe lobulated partially exophytic mass. HIV, Influenza A and B, acute viral hepatitis panel, AFP, ANA, ASMA, AMA, ferritin, and iron studies were all negative. MRI revealed an 11 cm irregular mass arising from the right hepatic lobe with heterogeneous arterial phase enhancement and delayed washout. Hematology was consulted given leukopenia and thrombocytopenia. Bone marrow biopsy revealed atypical lymphocytes consistent with CMV and EBV but no evidence of malignancy. EBV PCR showed active viremia. Due to concern of malignancy (especially lymphoma), the patient underwent liver biopsy of both the mass and random liver with both being consistent with Epstein-Barr hepatitis. PET/CT showed no significant uptake in the liver. The exact nature of the patient's liver mass remained unclear in the setting of acute Epstein-Barr virus hepatitis. Per Infectious Disease consultation, no specific treatment for the EBV hepatitis was necessary as patients liver function tests were improving. She returned for follow up 2 weeks later. Repeat MRI showed a large right hepatic lobe mass with heterogeneous enhancement persisting in the hepatobiliary phase, a large central scar with increased signal on T2-weighted images and a significant fibrous component. A repeat liver biopsy of the mass was consistent with focal nodular hyperplasia. Repeat MRI 6 months later demonstrated stability of the tumor size. Focal nodular hyperplasia (FNH) is the most common non-malignant hepatic tumor that is not of vascular origin. It is predominately seen in women between the ages of 20-50 years. Only 3% of cases are larger than 10cm. Our case is interesting given that the patient came in with nonspecific complaints and initial biopsies showed evidence of EBV hepatitis. But with continued clinical suspicion repeat MRI of the liver and repeat liver biopsy did eventually provide the diagnosis of FNH.

Hepatitis due to Epstein–Barr virus and cytomegalovirus: clinical features and outcomes

Objective: To determine the frequency of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes.Methods: A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006–2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records.Result: Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain–Barré syndrome following the infection.Conclusion: A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis.