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1
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Li Y, Tang J, Ma Y, Yan Y, Cheng F, Wang K. Clinical significance and pathogenesis of GBP5 in infectious mononucleosis associated liver injury. Ital J Pediatr 2025; 51:72. [PMID: 40075517 PMCID: PMC11905478 DOI: 10.1186/s13052-025-01907-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Accepted: 02/16/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Infectious mononucleosis (IM) is a common disease in children; however, liver injury is its most common complication. However, the pathogenesis of IM complicated with liver injury is ambiguous. Thus, this study aimed to explore the potential mechanism of IM-associated liver injury. METHODS This study was conducted at the Children's Hospital of Soochow University by collecting peripheral blood of 70 hospitalized children with IM. These patients were categorized into the liver injury (LIG, n = 35) and the non-liver injury groups (NLIG, n = 35), respectively. Subsequently, PBMCs and plasma were separated and obtained. PBMCs transcriptome sequencing was performed in two groups (5 cases in each group), and significantly differentially expressed genes (DEGs) were screened. Additionally, GO function enrichment, KEGG enrichment and GSEA analyses were performed. RT-PCR helped to detect the relative GBP5, NLRP3 and caspase-1 expressions in two groups (30 cases in each group) while the two groups' caspase-1, IL-1β and IL-18 in plasma levels were measured by ELISA. Thus, clinical and laboratory datas of 60 hospitalized children with IM were evaluated. RESULTS Transcriptome sequencing results showed that 171 DEGs were screened in the NLIG group, compared with the LIG. Among them, 154 DEGs were up-regulated, and 17 were down-regulated, respectively. KEGG and GSEA analyses showed that IM-associated liver injury is correlated with a NOD-like receptor signaling pathway. Statistically significant differences were observed in the white blood cell and lymphocyte counts, CD3+CD4+ T cells, CD3+CD8+T cells, alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) of the two groups (p < 0.05). Compared with NLIG, GBP5, NLRP3 and caspase-1 expressions in PBMCs, as well as the caspase-1, IL-1β and IL-18 in plasma levels, were significantly higher in LIG (p < 0.001). A correlation analysis revealed a positive correlation of GBP5 with LDH, ALT, AST, CD3+CD8+T cells and NLRP3 (p < 0.05). CONCLUSIONS Our findings demonstrate that GBP5 contributes to liver injury in IM children through the NLRP3-dependent pathway.
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Affiliation(s)
- Yan Li
- Department of Infectious Diseases, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310000, China
| | - Jiamei Tang
- Department of Infectious Diseases, Children's Hospital of Soochow University, Suzhou, 215000, China
| | - Yulan Ma
- Department of Infectious Diseases, Children's Hospital of Soochow University, Suzhou, 215000, China
| | - Yujuan Yan
- Department of Infectious Diseases, Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, 215000, China
| | - Fangfang Cheng
- Department of Infectious Diseases, Children's Hospital of Soochow University, Suzhou, 215000, China.
| | - Kun Wang
- Department of Infectious Diseases, Children's Hospital of Soochow University, Suzhou, 215000, China.
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Tahvildar P, Atalla M, Tahir R, Cheung A. Newest "Co-Members" of the 1000s Club: A Case of Severe Transaminitis Secondary to Epstein-Barr and Dengue Virus Co-Infection in a Returning Traveler. Eur J Case Rep Intern Med 2024; 11:004748. [PMID: 39525451 PMCID: PMC11542953 DOI: 10.12890/2024_004748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/09/2024] [Indexed: 11/16/2024] Open
Abstract
Background Timely identification of the etiology of transaminitis is critical in informing subsequent management as strategies can vary from supportive care to urgent transplant assessment. This is especially important in returning travelers as there may be multiple causes of injury that need to be addressed. Case report We present a case of severe transaminitis secondary to non-hepatitis viral co-infections. A 28-year-old south Asian male returning traveler presented with an acute liver injury (aspartate aminotransferase/alanine aminotransaminase levels of ≥4000 IU/l) and marked jaundice. A thorough and expanded work-up of acute hepatitis was negative aside from positive mononucleosis spot testing and positive dengue fever serologies. This atypical presentation of mononucleosis and dengue fever was managed conservatively, and the patient was discharged with outpatient follow-up after an eight-day admission. Conclusions Usually, non-hepatitis viruses typically do not present with severe transaminitis or hyperbilirubinemia. These viruses, such as infectious mononucleosis and dengue fever, may work synergistically to cause an elevated inflammatory response, resulting in severe transaminitis in returning travelers. In the absence of a classic clinical presentation, clinicians should be aware of co-infections in returning travelers and test for them based on a thorough history and physical examination. LEARNING POINTS The differential diagnosis for severe transaminitis is narrow and commonly includes viral hepatitis (A-E), drug-induced liver injury, vascular and autoimmune causes; however other causes exist, and greater clinical awareness is needed.This case study demonstrates that even in the absence of a classic clinical presentation; in returning travelers, clinicians should have a low index of suspicion to order appropriate screening serologies based on a thorough history and physical examination as they can be sensitive diagnostic tools in detecting the etiology of severe transaminitis.In rare cases, non-hepatitis virus may act synergistically to cause severe transaminitis and should be considered in returning travelers when viral hepatitis serologies are negative.
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Affiliation(s)
- Parsa Tahvildar
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Marina Atalla
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Rabia Tahir
- Department of Health Sciences, McMaster University, Hamilton, Canada
| | - Andrew Cheung
- Department of Medicine, McMaster University, Hamilton, Canada
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3
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Kramarov S, Yevtushenko V, Seriakova I, Voronov O, Kyrytsia N, Zakordonets LV, Shadrin V, Shatrova C, Savostikova N, Zhezhera V. A Case Report of Acute Liver Failure in a Child with Hepatitis a Virus and Epstein-Barr Virus Coinfection on the Background of Autoimmune Sclerosing Cholangitis. Int Med Case Rep J 2024; 17:801-807. [PMID: 39355258 PMCID: PMC11444069 DOI: 10.2147/imcrj.s477802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 09/23/2024] [Indexed: 10/03/2024] Open
Abstract
Background Fulminant hepatitis is a rare and severe form of acute liver failure (ALF) characterized by rapid and massive destruction of liver cells and associated with a high mortality rate. Infectious factors, in particular viral hepatitis, take a prominent place in the etiology of ALF, however, the presence of chronic liver pathology can play a significant role in the disease progression and development of ALF. Case Presentation A 2-year-old child was hospitalized on the 4th day of the disease with manifestations of jaundice and general intoxication. The examination revealed markers of active hepatitis A virus infection and Epstein-Barr virus infection. From the seventh day of the disease, the child's condition began to progressively deteriorate due to manifestations of ALF. Despite the use of immunomodulatory and replacement therapy, the disease ended fatally on the 9th day. Pathohistological examination revealed manifestations of viral necrotic hepatitis on the background of autoimmune sclerosing cholangitis. Conclusion The case is novel as regards the occurrence of two viral hepatitis with different modes of transmission on a background of unidentified liver disease.
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Affiliation(s)
- Sergiy Kramarov
- Department of Pediatric Infectious Diseases, Bogomolets National Medical University, Kyiv, Ukraine
| | - Vitalii Yevtushenko
- Department of Pediatric Infectious Diseases, Bogomolets National Medical University, Kyiv, Ukraine
| | - Iryna Seriakova
- Department of Pediatric Infectious Diseases, Bogomolets National Medical University, Kyiv, Ukraine
| | - Oleksandr Voronov
- Department of Pediatric Infectious Diseases, Bogomolets National Medical University, Kyiv, Ukraine
| | - Nataliia Kyrytsia
- Department of Pediatric Infectious Diseases, Bogomolets National Medical University, Kyiv, Ukraine
| | | | - Valerii Shadrin
- Department of Pediatric Infectious Diseases, Bogomolets National Medical University, Kyiv, Ukraine
| | - Claudia Shatrova
- Department of Morphology, Clinical Pathology and Forensic Medicine, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine
| | - Nataliia Savostikova
- Сhildren’s Pathology Department, National Specialized Children’s Hospital Ministry of Health of Ukraine, Kyiv, Ukraine
| | - Volodymyr Zhezhera
- Сhildren’s Pathology Department, National Specialized Children’s Hospital Ministry of Health of Ukraine, Kyiv, Ukraine
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4
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McSteen BW, Ying XH, Lucero C, Jesudian AB. Viral etiologies of acute liver failure. World J Virol 2024; 13:97973. [PMID: 39323454 PMCID: PMC11401000 DOI: 10.5501/wjv.v13.i3.97973] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/07/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.
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Affiliation(s)
- Brian W McSteen
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Xiao-Han Ying
- Department of Medicine, New York-Presbyterian/Weill Cornell Campus, New York, NY 10021, United States
| | - Catherine Lucero
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
| | - Arun B Jesudian
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10021, United States
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5
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Joshi A, Jha D, Wari E, Saeed M, Hussain M, Hiatt TK. Cholestatic hepatitis in acute Epstein-Barr virus infection: A case report. Clin Case Rep 2024; 12:e9357. [PMID: 39176101 PMCID: PMC11338836 DOI: 10.1002/ccr3.9357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/01/2024] [Accepted: 08/13/2024] [Indexed: 08/24/2024] Open
Abstract
Cholestatic hepatitis is a rare complication of Epstein-Barr virus infection and is often self-limiting. Systemic signs, including viral prodrome and lymphadenopathy, can provide crucial diagnostic cues and avoid unnecessary invasive investigations or aggressive medical therapy unless indicated.
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Affiliation(s)
- Amey Joshi
- Department of Internal MedicineSparrow Hospital—Michigan State UniversityEast LansingMichiganUSA
| | - Divij Jha
- Department of Internal MedicineSparrow Hospital—Michigan State UniversityEast LansingMichiganUSA
| | - Eki Wari
- Department of Internal MedicineSparrow Hospital—Michigan State UniversityEast LansingMichiganUSA
| | - Moiz Saeed
- Department of Internal MedicineSparrow Hospital—Michigan State UniversityEast LansingMichiganUSA
| | - Murtaza Hussain
- Department of GastroenterologySparrow Hospital‐University of MichiganEast LansingMichiganUSA
| | - Tadd Kaeo Hiatt
- Department of GastroenterologySparrow Hospital‐University of MichiganEast LansingMichiganUSA
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6
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Mitra S, Hanumanthappa MK, Sarkar S, Bhalla A, Minz R, Ratho RK. Epstein Barr Virus-Related Acute Liver Failure and Hemophagocytosis in an Immunocompetent Individual: An Autopsy Report. Int J Surg Pathol 2024; 32:838-844. [PMID: 37723947 DOI: 10.1177/10668969231195068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2023]
Abstract
Epstein-Barr virus (EBV) is a nonhepatotropic virus. It causes mild self-limiting illness characterized by fever, oral ulcer, diarrhea, lymphadenopathy, and hepatosplenomegaly. Rarely it causes acute liver failure (ALF). EBV-related ALF (EBV-ALF) accounts for 0.2% of all ALF cases. The prognosis of EBV-ALF is dismal, and it can affect both immunocompromised and immunocompetent individuals. We performed a partial autopsy on a 30-year-old immunocompetent individual with infectious mononucleosis and ALF. The autopsy showed characteristic histomorphology of EBV-ALF in the form of centrizonal confluent hepatocytic necrosis, portal mixed inflammatory infiltrate, sinusoidal lymphocytosis, numerous hemophagocytic figures, and tissue Epstein-Barr encoded RNA-in situ hybridization (EBER-ISH) positivity. Extensive hemophagocytosis was noted in the liver, spleen, lymph node, and bone marrow. Other features include T-zone expansion of lymph nodes and spleen, interstitial pneumonia pattern in the lungs, and exanthematous skin changes. EBV-DNA polymerase chain reaction from the postmortem blood sample yielded 70,200 copies/µL. The index case highlights the uncommon occurrence of EBV-ALF, its histomorphological features, and its putative pathogenesis.
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Affiliation(s)
| | | | | | - Ashish Bhalla
- Department of Internal Medicine, PGIMER, Chandigarh, India
| | - Ranjana Minz
- Department of Immunopathology, PGIMER, Chandigarh, India
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7
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Sehrawat SS, Premkumar M. Critical care management of acute liver failure. Indian J Gastroenterol 2024; 43:361-376. [PMID: 38578565 DOI: 10.1007/s12664-024-01556-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/12/2024] [Indexed: 04/06/2024]
Abstract
The management of acute liver failure (ALF) in modern hepatology intensive care units (ICU) has improved patient outcomes. Critical care management of hepatic encephalopathy, cerebral edema, fluid and electrolytes; prevention of infections and organ support are central to improved outcomes of ALF. In particular, the pathogenesis of encephalopathy is multifactorial, with ammonia, elevated intra-cranial pressure and systemic inflammation playing a central role. Although ALF remains associated with high mortality, the availability of supportive care, including organ failure support such as plasma exchange, timely mechanical ventilation or continuous renal replacement therapy, either conservatively manages patients with ALF or offers bridging therapy until liver transplantation. Thus, appropriate critical care management has improved the likelihood of patient recovery in ALF. ICU care interventions such as monitoring of cerebral edema, fluid status assessment and interventions for sepsis prevention, nutritional support and management of electrolytes can salvage a substantial proportion of patients. In this review, we discuss the key aspects of critical care management of ALF.
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Affiliation(s)
- Surender Singh Sehrawat
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
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8
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Biswas S, Kumar R, Shalimar, Acharya SK. Viral hepatitis-induced acute liver failure. Indian J Gastroenterol 2024; 43:312-324. [PMID: 38451383 DOI: 10.1007/s12664-024-01538-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 01/18/2024] [Indexed: 03/08/2024]
Abstract
Viral hepatitis-induced acute liver failure (ALF) is a preventable cause for liver-related mortality worldwide. Viruses are the most common cause for ALF in developing nations in contrast to the west, where acetaminophen is largely responsible. Viruses may be hepatotropic or affect the liver secondary to a systemic infection. In tropical countries, infections such as leptospirosis, scrub typhus and malaria can mimic the symptoms of ALF. Differentiating these ALF mimics is crucial because they require etiology-specific therapy. Treatment of viral hepatitis-induced ALF is two-pronged and directed towards providing supportive care to prevent organ failures and antiviral drugs for some viruses. Liver transplantation (LT) is an effective modality for patients deteriorating despite adequate supportive care. Early referral and correct identification of patients who require a transplant are important. Liver support devices and plasma exchange have evolved into "bridging modalities" for LT. Preventive strategies such as hand hygiene, use of clean and potable water and inclusion of vaccines against viral hepatitis in the national program are simple yet very effective methods focusing on the preventive aspect of this disease.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, 801 507, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India.
| | - Subrat Kumar Acharya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India
- KIIT University, Bhubaneswar, 751 024, India
- Fortis Escorts Digestive and Liver Institute, Okhla, New Delhi, 110 025, India
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9
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Servellita V, Sotomayor Gonzalez A, Lamson DM, Foresythe A, Huh HJ, Bazinet AL, Bergman NH, Bull RL, Garcia KY, Goodrich JS, Lovett SP, Parker K, Radune D, Hatada A, Pan CY, Rizzo K, Bertumen JB, Morales C, Oluniyi PE, Nguyen J, Tan J, Stryke D, Jaber R, Leslie MT, Lyons Z, Hedman HD, Parashar U, Sullivan M, Wroblewski K, Oberste MS, Tate JE, Baker JM, Sugerman D, Potts C, Lu X, Chhabra P, Ingram LA, Shiau H, Britt W, Gutierrez Sanchez LH, Ciric C, Rostad CA, Vinjé J, Kirking HL, Wadford DA, Raborn RT, St George K, Chiu CY. Adeno-associated virus type 2 in US children with acute severe hepatitis. Nature 2023; 617:574-580. [PMID: 36996871 PMCID: PMC10170441 DOI: 10.1038/s41586-023-05949-1] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 03/10/2023] [Indexed: 04/01/2023]
Abstract
As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P < 0.001) and to 0 of 30 patients with hepatitis of defined aetiology (P < 0.001). In controls, HAdV type 41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P < 0.001). Co-infections by Epstein-Barr virus, human herpesvirus 6 and/or enterovirus A71 were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P < 0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.
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Affiliation(s)
- Venice Servellita
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
| | | | - Daryl M Lamson
- Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, NY, USA
| | - Abiodun Foresythe
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Hee Jae Huh
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Adam L Bazinet
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Nicholas H Bergman
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Robert L Bull
- Federal Bureau of Investigation Laboratory Division/Scientific Response and Analysis Unit, Quantico, VA, USA
| | - Karla Y Garcia
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Jennifer S Goodrich
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Sean P Lovett
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Kisha Parker
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Diana Radune
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - April Hatada
- California Department of Public Health, Richmond, CA, USA
| | - Chao-Yang Pan
- California Department of Public Health, Richmond, CA, USA
| | - Kyle Rizzo
- California Department of Public Health, Richmond, CA, USA
| | - J Bradford Bertumen
- California Department of Public Health, Richmond, CA, USA
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | | | - Paul E Oluniyi
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Jenny Nguyen
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Jessica Tan
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Doug Stryke
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Rayah Jaber
- Florida Department of Health, Tallahassee, FL, USA
| | | | - Zin Lyons
- North Carolina Department of Health and Human Services, Raleigh, NC, USA
| | - Hayden D Hedman
- Centers for Disease Control and Prevention, Atlanta, CA, USA
- South Dakota Department of Health, Pierre, SD, USA
| | - Umesh Parashar
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | - Maureen Sullivan
- Association for Public Health Laboratories, Silver Spring, MD, USA
| | - Kelly Wroblewski
- Association for Public Health Laboratories, Silver Spring, MD, USA
| | | | | | - Julia M Baker
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | - David Sugerman
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | - Caelin Potts
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | - Xiaoyan Lu
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | - Preeti Chhabra
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | | | - Henry Shiau
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - William Britt
- University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Caroline Ciric
- Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Christina A Rostad
- Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Jan Vinjé
- Centers for Disease Control and Prevention, Atlanta, CA, USA
| | | | | | - R Taylor Raborn
- National Biodefense Analysis and Countermeasures Center (NBACC), Frederick, MD, USA
| | - Kirsten St George
- Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, NY, USA
- Department of Biomedical Science, University at Albany, SUNY, Albany, NY, USA
| | - Charles Y Chiu
- Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
- Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA.
- Chan-Zuckerberg Biohub, San Francisco, CA, USA.
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10
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Abstract
In addition to being the primary target of infections such as viral hepatitis, the liver may also be affected by systemic disease. These include bacterial, mycotic, and viral infections, as well as autoimmune and infiltrative diseases. These conditions generally manifest as abnormal liver biochemistries, often with a cholestatic profile, and may present with additional signs/symptoms such as jaundice and fever. A high index of suspicion and familiarity with potential causal entities is necessary to guide appropriate testing, diagnosis, and treatment.
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Affiliation(s)
- Humberto C Gonzalez
- Division of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA.
| | - Stuart C Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA
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11
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Prognostic Scores in Acute Liver Failure Due to Viral Hepatitis. Diagnostics (Basel) 2023; 13:diagnostics13061035. [PMID: 36980341 PMCID: PMC10047191 DOI: 10.3390/diagnostics13061035] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023] Open
Abstract
Viral infections are among the major causes of acute liver failure (ALF) worldwide. While the role of agents such as hepatitis A, B, C, D and E viruses in precipitating ALF are well known, improvements in serological assays have led to the detection of viral agents such as Epstein Barr virus, cytomegalovirus etc. as atypical causes of ALF. Despite the plethora of literature available on viral hepatitis and ALF, there is very limited large-scale epidemiologic data on the prevalence, risk factors of progression and outcomes in ALF of viral causes. This is important as viral infections remain the leading cause of ALF in the East and in developing countries, while the impact of viral ALF in the West has largely been ameliorated by effective vaccination and sanitization programs. This review focuses specifically on the available prognostic scores that aid in the management of ALF of viral etiologies while also briefly reviewing the current literature on newer viral agents known to cause ALF, risk factors of progression, outcomes and how management algorithms can be developed by incorporation of prognostic scoring systems for referral and transplant listing.
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12
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Infectious mononucleosis - should we routinely assess liver function in acute presentation and follow up? J Laryngol Otol 2023; 137:319-322. [PMID: 35465858 DOI: 10.1017/s0022215122000639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Infectious mononucleosis is a relatively common acute presentation to the ENT department. There is an expected derangement in the liver function test results in most patients. There is no guidance regarding follow up, and practice varies. This study aimed to evaluate the utility of liver function tests and abdominal ultrasound in infectious mononucleosis. METHODS This was a retrospective study of all adult patients admitted under ENT with infectious mononucleosis over a five-year period. RESULTS A total of 153 patients were included; 80 per cent had abnormal liver function test results at presentation. Around 50 per cent had at least one liver function test assessment following discharge. Median (interquartile range) time to resolution of liver function test results was 32 days (20-50 days); maximum time was 10 months. Six patients had in-patient abdominal ultrasound: all showed a normal liver and biliary tree. No patient developed any liver disease sequelae. CONCLUSION The findings suggest that serial assessment of liver function is not required in immunocompetent adults with subclinical derangement in liver function.
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13
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Varga NI, Mateescu DM, Negrean RA, Horhat FG, Bagiu IC, Kodimala SC, Bandi SSS, Horhat RM, Horhat DI, Mot IC, Miutescu B. Diagnosis and Management of a Triple Infection with Leptospira spp., Hepatitis A Virus, and Epstein-Barr Virus: A Rare Occurrence with High Hepatotoxic Effect. Healthcare (Basel) 2023; 11:healthcare11040597. [PMID: 36833132 PMCID: PMC9956391 DOI: 10.3390/healthcare11040597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/09/2023] [Accepted: 02/14/2023] [Indexed: 02/19/2023] Open
Abstract
The etiology of acute hepatic cytolysis is complex, and a thorough laboratory investigation is needed to find the causative agent and guide the clinician toward a specific treatment. Viral hepatitis A is a well-known cause of acute hepatitis, but other viruses and bacteria can lead to or contribute to liver damage. We report the case of a young male patient with triple infection with hepatitis A virus, Epstein-Barr virus, and Leptospira spp. To our knowledge, this is the first case of an HAV, EBV, and Leptospira triple infection, and it aims to bring awareness about the possibility of double or triple infection with such pathogens that are highly cytotoxic for the liver tissue since all three pathogens are known to cause or contribute to the onset of acute hepatitis. It was deduced that the source of the infection likely happened during a two-week visit to the countryside in Romania, returning 16 days before the onset of symptoms. The evolution was favorable receiving treatment with amoxicillin/clavulanic acid (1200 mg/8 h); glucose 5% 500 mL/day; 0.9% saline 500 mL/day; phenobarbital 1 tablet/day (200 mg); vitamins B1 and B6 and a complex of vitamin C and D3 and zinc. Lactulose syrup was also administered when the patient had no bowel movement for more than 24 h to prevent the onset of hepatic encephalopathy, and the patient was discharged after 20 days. This case suggests that a detailed anamnesis can raise suspicion about more uncommon causes of hepatic cytolysis and lead to a broader and more complex laboratory investigation, thus improving the quality of patient care. Yet, this is the only case previously reported to compare different management options and patient outcomes.
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Affiliation(s)
- Norberth-Istvan Varga
- Department of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
| | - Diana-Maria Mateescu
- Department of Infectious Diseases, Victor Babes University of Medicine and Pharmacy Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
| | | | - Florin George Horhat
- Multidisciplinary Research Center on Antimicrobial Resistance (MULTI-REZ), Microbiology Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
- Correspondence:
| | - Iulia-Cristina Bagiu
- Multidisciplinary Research Center on Antimicrobial Resistance (MULTI-REZ), Microbiology Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Shiva Charana Kodimala
- MediCiti Institute of Medical Sciences, NTR University of Health Sciences, Hyderabad 501401, India
| | - Satya Sai Sri Bandi
- Malla Reddy Institute of Medical Sciences, Suraram Main Road 138, Hyderabad 500055, India
| | - Razvan Mihai Horhat
- Department of Conservative Dentistry and Endodontics, Faculty of Dental Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Delia Ioana Horhat
- Ear-Nose-Throat Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq, 300041 Timisoara, Romania
| | - Ion Cristian Mot
- Ear-Nose-Throat Department, “Victor Babes” University of Medicine and Pharmacy Timisoara, 2 Eftimie Murgu Sq, 300041 Timisoara, Romania
| | - Bogdan Miutescu
- Department of Gastroenterology and Hepatology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
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Li B, Hong C, Fan Z, Cai S, He Q, Lan X, Lai Q, Ji Y, Luo W, Li J, Cheng X, Liu M, Gu Y, Lu G, Li S, Wang Y, Weng X, Niu X, Liu Q, Jalan R, Chen J. Prognostic and therapeutic significance of microbial cell-free DNA in plasma of people with acute decompensation of cirrhosis. J Hepatol 2023; 78:322-332. [PMID: 36309130 DOI: 10.1016/j.jhep.2022.10.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 09/13/2022] [Accepted: 10/11/2022] [Indexed: 11/14/2022]
Abstract
BACKGROUND & AIMS Although the effect of bacterial infection on cirrhosis has been well-described, the effect of non-hepatotropic virus (NHV) infection is unknown. This study evaluated the genome fragments of circulating microorganisms using metagenomic next-generation sequencing (mNGS) in individuals with acute decompensation (AD) of cirrhosis, focusing on NHVs, and related the findings to clinical outcomes. METHODS Plasma mNGS was performed in 129 individuals with AD of cirrhosis in the study cohort. Ten healthy volunteers and 20, 39, and 81 individuals with stable cirrhosis, severe sepsis and hematological malignancies, respectively, were enrolled as controls. Validation assays for human cytomegalovirus (CMV) reactivation were performed in a validation cohort (n = 58) and exploratory treatment was instituted. RESULTS In the study cohort, 188 microorganisms were detected in 74.4% (96/129) of patients, including viruses (58.0%), bacteria (34.1%), fungi (7.4%) and chlamydia (0.5%). A NHV signature was identified in individuals with AD, and CMV was the most frequent NHV, which correlated with the clinical effect of empirical antibiotic treatment, progression to acute-on-chronic liver failure, and 90-day mortality. The NHV signature in individuals with acute-on-chronic liver failure was similar to that in those with sepsis and hematological malignancies. CMV was detected in 24.1% (14/58) of patients in the validation cohort. Of the 14 cases with detectable CMV by mNGS, nine were further validated by real-time PCR or pp65 antigenemia testing. Three patients with CMV reactivation received ganciclovir therapy in an exploratory manner and experienced clinical resolutions. CONCLUSIONS The results of this study suggest that NHVs may play a pathogenic role in complicating the course of AD. Further validation is needed to define whether this should be incorporated into the routine management of individuals with AD of cirrhosis. IMPACT AND IMPLICATIONS A non-hepatotropic virus (NHV) signature, which was similar to that in individuals with sepsis and hematological malignancies, was identified in individuals with acute decompensation of cirrhosis. The detected viral signature had clinical correlates, including clinical efficacy of empirical antibiotic treatment, progression to acute-on-chronic liver failure and short-term mortality. Cytomegalovirus reactivation, which is treatable, may adversely affect clinical outcomes in some individuals with decompensated cirrhosis. Routine screening for NHVs, especially cytomegalovirus, may be useful for the management of individuals with acute decompensation of cirrhosis.
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Affiliation(s)
- Beiling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Changze Hong
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhiping Fan
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shumin Cai
- Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qinjun He
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaoqin Lan
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Qintao Lai
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yali Ji
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wenfan Luo
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junying Li
- Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiao Cheng
- Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Miaoxia Liu
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yixiu Gu
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guanting Lu
- Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shaochuan Li
- Realmeta Technology Co.,Ltd, Guangzhou, China; Goodwill Clinical Laboratories Co.,Ltd, Guangzhou, China
| | - Yali Wang
- BGI Infection Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China
| | - Xing Weng
- BGI Infection Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China
| | - Xiaoyun Niu
- Realmeta Technology Co.,Ltd, Guangzhou, China; Goodwill Clinical Laboratories Co.,Ltd, Guangzhou, China
| | - Qifa Liu
- Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rajiv Jalan
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Liver Failure Group, Institute for Liver and Digestive Health, UCL Medical School, London, UK; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.
| | - Jinjun Chen
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, China.
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15
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Shen R, Zhou Y, Zhang L, Yang S. The value of bile acid spectrum in the evaluation of hepatic injury in children with infectious mononucleosis caused by Epstein Barr virus infection. Front Pediatr 2023; 11:1109762. [PMID: 37025296 PMCID: PMC10070945 DOI: 10.3389/fped.2023.1109762] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 03/06/2023] [Indexed: 04/08/2023] Open
Abstract
Background Infectious mononucleosis (IM) is an acute infectious disease, caused by Epstein-Barr virus (EBV) infection, which can invade various systemic systems, among which hepatic injury is the most common. In this study, ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to detect serum bile acid spectrum in IM children quantitatively, and to investigate its role in the early assessment of hepatic injury. Methods This case-control study was conducted at Yuhuan People's Hospital. A total of 60 IM children and 30 healthy children were included in the study. Among 60 children with IM, 30 had hepatic injury, and 30 without hepatic injury. The clinical and laboratory data were analyzed, and the serum bile acid spectrum and lymphocyte subsets were evaluated in the three groups. Results There were statistically significant differences in cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid(GDCA), glycolithocholic acid (GLCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), ursodeoxycholic acid (UDCA), glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid(TUDCA), percentage of NK cells, CD4+ and CD8+ in IM hepatic injury group, without hepatic injury group, and the healthy control group (P < 0.05). The percentage of NK cells was positively correlated with TCA (P < 0.05); it was negatively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA, TUDCA (P < 0.05). CD4+ was positively correlated with CA, TCA and TCDCA (P < 0.05); it was negatively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA and TUDCA (P < 0.05). CD8+ was positively correlated with CDCA, DCA, LCA, GCDCA, GDCA, GLCA, TDCA, UDCA, GUDCA and TUDCA (P < 0.05); it was negatively correlated with CA, TCA and TCDCA (P < 0.05). ROC curve analysis showed that CD8+, GDCA and GLCA had high predictive value for hepatic injury in IM patients. Conclusions UPLC-MS/MS method can sensitively detect the changes in serum bile acid spectrum before hepatic injury in children with IM, which is helpful for early assessment of hepatic injury in children with IM. The changes in lymphocyte subsets in IM children are related to some bile acid subfractions, which may be related to IM hepatic injury.
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Aronova ES, Belov BS, Gridneva GI. Viral mixed infection complicated by acute hepatitis and allergic toxic dermatitis (clinical case). MODERN RHEUMATOLOGY JOURNAL 2022. [DOI: 10.14412/1996-7012-2022-5-71-74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Epstein-Barr virus (EBV) belongs to the family of herpesviruses (herpes type 4) and is one of the most common and highly contagious. During the pandemic of a new coronavirus disease, it was found that in patients previously infected with EBV, COVID-19 can cause its reactivation, which is often manifested by the clinic of acute hepatitis. The article presents a clinical case of the development of acute hepatitis in a patient with mixed infection with EBV and SARS-CoV-2 in combination with allergic toxic reaction while taking sulfasalazine prescribed for spondyloarthritis. A feature of this case was the development of severe hepatitis of mixed genesis with a favorable outcome. The importance of adherence to drug monitoring rules for newly prescribed drugs for COVID-19 was emphasized. In severe cases of the disease, the possibility of mixed infection should be taken into account.
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Affiliation(s)
| | - B. S. Belov
- V.A. Nasonova Research Institute of Rheumatology
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17
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Gao Y, Li L, Hu X, Zhang W, Li Y. Interleukin-35 has a Protective Role in Infectious Mononucleosis-Induced Liver Inflammation Probably by Inhibiting CD8 + T Cell Function. Arch Immunol Ther Exp (Warsz) 2022; 70:25. [PMID: 36219249 DOI: 10.1007/s00005-022-00663-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 09/15/2022] [Indexed: 11/26/2022]
Abstract
Interleukin (IL)-35 plays an immunosuppressive role in infectious diseases, autoimmune disorders, and cancers. However, IL-35 expression and its regulation of CD8+ T cells in infectious mononucleosis (IM) are not fully understood. In this study, three groups of participants were compared, including twenty-three patients of IM without liver inflammation, twenty-eight patients of IM with liver inflammation, and twenty-one controls. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. CD8+ T cells were purified. Plasma IL-35 was measured by ELISA. PBMCs and CD8+ T cells were stimulated with recombinant human IL-35 in vitro. Perforin and granzyme B secretion was assessed by ELISPOT. Immune checkpoint molecule expression was investigated by flow cytometry. CD8+ T cells were co-cultured with HepG2 cells in direct contact and indirect contact manner. The cytotoxicity of CD8+ T cells was calculated by measuring lactate dehydrogenase release and proinflammatory cytokine expression. There was no significant difference in plasma IL-35 levels between patients with IM without liver inflammation and the controls, but the IL-35 level was notably increased in patients with IM who presented with liver inflammation and negatively correlated with aminotransferase. CD8+ T cells in patients with IM with liver inflammation showed stronger cytotoxicity. IL-35 stimulation inhibited CD8+ T cell-induced target cell death in patients with IM, mainly through suppression of IFN-γ/TNF-α secretion and elevation of immune checkpoint molecule expression, but did not affect perforin or granzyme B secretion. The current data indicated that IL-35 dampened the cytotoxicity of CD8+ T cells in patients with IM probably via repression of cytokine secretion. Elevated IL-35 may protect against CD8+ T cell-induced liver inflammation in patients with IM.
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Affiliation(s)
- Ying Gao
- Department of Hematology, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, Xi'an, 710068, Shaanxi Province, China
| | - Lan Li
- Department of Hematology, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, Xi'an, 710068, Shaanxi Province, China
| | - Xingxing Hu
- Department of Hematology, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, Xi'an, 710068, Shaanxi Province, China
| | - Weihua Zhang
- Department of Hematology, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, Xi'an, 710068, Shaanxi Province, China
| | - Yu Li
- Department of Infectious Diseases, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, 256 West Youyi Rd, Xi'an, 710068, Shaanxi Province, China.
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18
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He HC, Han R, Xu BH, Huang C, Li MM, He CY, Lin WQ. Circulating Epstein-Barr virus DNA associated with hepatic impairment and its diagnostic and prognostic role in patients with gastric cancer. Front Med (Lausanne) 2022; 9:1028033. [PMID: 36275793 PMCID: PMC9583533 DOI: 10.3389/fmed.2022.1028033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/16/2022] [Indexed: 11/23/2022] Open
Abstract
Epstein–Barr virus (EBV) infection may affect all tissues and organs of the body. Little is known about the impact of this entity on its systematic incorporation in patients with gastric cancer (GC). This study enrolled a total of 113 GC patients with EBV infection (EBVaGC) and 167 GC patients without EBV infection (EBVnGC). It was found that the CRP levels (indicative of inflammatory status) were significantly increased in EBVaGC compared with those in EBVnGC (12.11 mg/L vs. 5.72 mg/L, P = 0.008), but WBC and neutrophils counts were similar in both groups (P > 0.05). Consistent elevations in the levels of liver enzymes, ALP and GGT, with incompatible alterations in ALT or AST were observed in EBVaGC. Slightly prolonged coagulation indices, PT and INR, and decreased albumin consistently suggested impaired synthesis capability of the liver in EBVaGC (all P < 0.05). The level of circulating EBV DNA was positively correlated with the level of GGT, tumor marker CA72-4 and the lymphocyte infiltration in tumor tissues (all P < 0.05). Of note, the EBV associated high-lymphocyte infiltrated tissues presented rich CD8 + T cells. Circulating EBV DNA further showed a predictive role in distinguishing EBVaGC from EBVnGC (AUC 0.79, 95% CI 0.73 to 0.85, P < 0.001), and was associated closely with better overall survival (HR 0.45, 95% CI 0.21 to 0.96, P = 0.039). EBV infection in patients with gastric cancer may be linked to hepatic impairment and immune response. Circulating cell-free EBV DNA is not only a biomarker for the screening of an EBV-related GC subtype but is also an independently prognosis factor for the long-term survival benefit in GC patients.
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Affiliation(s)
- Hui-Chan He
- State Key Laboratory of Oncology in South China, Department of Blood Transfusion, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Center for Clinical Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Rui Han
- State Key Laboratory of Oncology in South China, Department of Blood Transfusion, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Bo-Heng Xu
- State Key Laboratory of Oncology in South China, Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Chan Huang
- State Key Laboratory of Oncology in South China, Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Min-Min Li
- Center for Clinical Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, China,*Correspondence: Min-Min Li,
| | - Cai-Yun He
- State Key Laboratory of Oncology in South China, Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Cai-Yun He,
| | - Wen-Qian Lin
- State Key Laboratory of Oncology in South China, Department of Blood Transfusion, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Wen-Qian Lin,
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19
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Chen WJ, Wolff E, Varma CR, Shoela R. Biliary Intraepithelial Neoplasia With Gallbladder Adenoma and Cirrhosis: A Case Report. Cureus 2022; 14:e27780. [PMID: 36106242 PMCID: PMC9449331 DOI: 10.7759/cureus.27780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2022] [Indexed: 11/17/2022] Open
Abstract
Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of cholangiocarcinoma that has been rarely reported. The present study reports a 56-year-old male with low-grade BilIN of the bile ducts and the cystic duct margin. Stent exchange endoscopy demonstrated an irregular, intraductal mass extending along the common bile duct, common hepatic duct, and hepatic duct bifurcation. The peribiliary mass was found to abut the right portal vein, inferior vena cava, and pancreatic head, and replaced the right hepatic artery. In addition, there was evidence of gallbladder adenoma managed with cholecystectomy and a right-lobed liver lesion and cirrhosis, which prompted the discussion of prophylactic liver transplantation. We emphasize the radiological features of BilIN and associated pathological findings through multiple imaging modalities. Consideration of this diagnosis is indicated in western countries and requires timely management based on available guidelines.
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Tan ET, Wilkinson D, Edafe O. The utility of liver function tests and abdominal ultrasound in infectious mononucleosis - A systematic review. Clin Otolaryngol 2022; 47:611-619. [PMID: 35834363 DOI: 10.1111/coa.13965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/12/2022] [Accepted: 06/26/2022] [Indexed: 11/30/2022]
Abstract
INTRODUCTION A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal ultrasound (US). METHODS A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done. RESULTS A total of 3924 patients were included from 32 studies, of which LFT values were reported on 2779 patients. A combination of typical clinical features, heterophile antibodies and EBV-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFTs: AST (57%); ALT (62%); ALP (65%); Bilirubin (16%); GGT (41%). Reported median (i.q.r.) time to resolution of LFT was 8 (6-12) weeks (n = 438). Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients respectively. Enlarged liver and spleen on US were seen in 16/29 and 38/38 of patients respectively. There were no reports of decompensated liver disease. CONCLUSION Current evidence questions the need for routine assessment of LFTs in immunocompetent patients presenting with IM; serial LFT assessments following initial abnormalities are not required in immunocompetent patients with subclinical derangement of LFTs; routine US abdomen in IM to evaluate for derangement of LFTs is not required.
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Affiliation(s)
- E Tian Tan
- Barnsley Hospital NHS Foundation Trust, UK
| | | | - Ovie Edafe
- Oncology & Metabolism, University of Sheffield, UK
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21
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Abstract
Pediatric acute liver failure (PALF) is a life-threatening disorder characterized by acute hepatocellular injury occurring in children without recognized underlying liver disease. The clinicopathologic evaluation of PALF requires a different approach from that in adults. The diagnostic considerations differ depending on the age, personal and family history, geographical region, and clinical presentation. Distinct entities such as gestational alloimmune liver disease, herpes simplex virus infection, and metabolic disorders should be considered in neonates with acute liver failure, while acetaminophen toxicity and autoimmune hepatitis are more frequently seen in older children and adolescents. An identified cause for PALF despite a negative complete evaluation (indeterminate) is lacking in 30 to 50% of cases. Although not routinely performed in the setting of PALF, liver biopsy may be helpful in assessing the etiology, potential mechanisms of injury, determining the appropriateness of liver transplantation, and prognostication of the patients. In this article, we review the clinicopathologic characteristics of PALF with an emphasis on general approach of pathologic evaluation and histopathologic characteristic of selected entities.
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Affiliation(s)
- Juan Putra
- Division of Pathology, Department of Paediatric Laboratory Medicine, 7979The Hospital for Sick Children, Toronto, ON, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Vicky L Ng
- Division of Gastroenterology, Hepatology, and Nutrition, 7979The Hospital for Sick Children, Toronto, ON, Canada
| | - Antonio R Perez-Atayde
- Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
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22
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Shi T, Li J, Miao Y, Huang L, Tian J. Adenosine deaminase as a marker for the severity of infectious mononucleosis secondary to EBV in children. BMC Infect Dis 2022; 22:164. [PMID: 35189820 PMCID: PMC8862226 DOI: 10.1186/s12879-022-07150-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 02/12/2022] [Indexed: 11/10/2022] Open
Abstract
Background Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels. Methods This case-control study was conducted at the Children’s Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children’s clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups. Results The adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3+CD8+ T cells (%), CD4+/CD8+ ratio, and CD3−CD19+ (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis. Conclusions Adenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.
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Affiliation(s)
- Ting Shi
- Children's Hospital of Soochow University, 303 Jingde Road, Suzhou, 215000, Jiangsu, China
| | - Jungen Li
- The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, Jiangsu, 215000, China
| | - Yuzhu Miao
- The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, Jiangsu, 215000, China
| | - Linlin Huang
- Pediatric intensive care unit, Children's Hospital of Soochow University, 303 Jingde Road, Suzhou, 215000, Jiangsu, China.
| | - Jianmei Tian
- Pediatric intensive care unit, Children's Hospital of Soochow University, 303 Jingde Road, Suzhou, 215000, Jiangsu, China. .,Department of Infectious Diseases, Children's Hospital of Soochow University, 303 Jingde Road, Suzhou, 215000, Jiangsu, China.
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23
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Gupta M, Manek G, Dombrowski K, Maiwall R. Newer developments in viral hepatitis: Looking beyond hepatotropic viruses. World J Meta-Anal 2021; 9:522-542. [DOI: 10.13105/wjma.v9.i6.522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/09/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis in the entirety of its clinical spectrum is vast and most discussion are often restricted to hepatotropic viral infections, including hepatitis virus (A to E). With the advent of more advanced diagnostic techniques, it has now become possible to diagnose patients with non-hepatotropic viral infection in patients with hepatitis. Majority of these viruses belong to the Herpes family, with characteristic feature of latency. With the increase in the rate of liver transplantation globally, especially for the indication of acute hepatitis, it becomes even more relevant to identify non hepatotropic viral infection as the primary hepatic insult. Immunosuppression post-transplant is an established cause of reactivation of a number of viral infections that could then indirectly cause hepatic injury. Antiviral agents may be utilized for treatment of most of these infections, although data supporting their role is derived primarily from case reports. There are no current guidelines to manage patients suspected to have viral hepatitis secondary to non-hepatotropic viral infection, a gap that needs to be addressed. In this review article, the authors analyze the common non hepatotropic viral infections contributing to viral hepatitis, with emphasis on recent advances on diagnosis, management and role of liver transplantation.
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Affiliation(s)
- Manasvi Gupta
- Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, United States
| | - Gaurav Manek
- Department of Pulmonology and Critical Care, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Kaitlyn Dombrowski
- Department of Internal Medicine, University of Connecticut, Farmington, CT 06030, United States
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110070, India
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24
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Hansen BT, Bacher P, Eiz-Vesper B, Heckl SM, Klapper W, Koch K, Maecker-Kolhoff B, Baldus CD, Fransecky L. Adoptive Cell Transfer of Allogeneic Epstein–Barr Virus-Specific T Lymphocytes for Treatment of Refractory EBV-Associated Posttransplant Smooth Muscle Tumors: A Case Report. Front Immunol 2021; 12:727814. [PMID: 34925312 PMCID: PMC8677671 DOI: 10.3389/fimmu.2021.727814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Accepted: 11/01/2021] [Indexed: 11/13/2022] Open
Abstract
Posttransplant smooth muscle tumors (PTSMTs) are rare Epstein–Barr virus (EBV)-associated neoplasms, mostly occurring after solid organ transplantation. Current therapeutic strategies include surgery and reduction of immunosuppressive medication. We describe for the first time a novel treatment approach for PTSMT by adoptive cell transfer (ACT) of EBV-specific T cells to a 20-year-old patient with a medical history of cardiac transplantation, posttransplant lymphoproliferative disease, and multilocular PTSMT. During ACT, mild cytokine release syndrome occurred, while no unexpected safety signals were recorded. We observed in vivo expansion of EBV-specific T cells and reduction of EBV viremia. Best response was stable disease after 4 months with reduction of EBV viremia and normalization of lactate dehydrogenase levels. ACT with EBV-specific T cells may be a safe and efficacious therapeutic option for PTSMT that warrants further exploration.
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Affiliation(s)
- Bjoern-Thore Hansen
- Medical Department II – Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Petra Bacher
- Institute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Britta Eiz-Vesper
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Steffen M. Heckl
- Medical Department II – Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Wolfram Klapper
- Section for Hematopathology and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Karoline Koch
- Section for Hematopathology and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Britta Maecker-Kolhoff
- Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
| | - Claudia D. Baldus
- Medical Department II – Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Lars Fransecky
- Medical Department II – Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany
- *Correspondence: Lars Fransecky,
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25
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Nadeem A, Suresh K, Awais H, Waseem S. Epstein-Barr Virus Coinfection in COVID-19. J Investig Med High Impact Case Rep 2021; 9:23247096211040626. [PMID: 34428954 PMCID: PMC8392798 DOI: 10.1177/23247096211040626] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Epstein-Barr virus (EBV), a member of the herpes virus family, is a causative agent for infectious mononucleosis in young adults. It has an asymptomatic and subclinical distribution in about 90% to 95% of the world population based on seropositivity. EBV is associated with various lymphomas, nasopharyngeal carcinoma, and in immunocompromised states can give rise to aggressive lymphoproliferative disorders. Symptomatic patients mostly present with mild hepatitis, rash, oral symptoms, lymphadenopathy, and generalized malaise. Recently with the COVID-19 (coronavirus disease-2019) pandemic, hepatitis has been found to be related to acute EBV and cytomegalovirus reactivation versus acute infection in the absence of other major causes. We describe a case of EBV coinfection in a patient with resolving mild COVID-19 infection.
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Affiliation(s)
- Asim Nadeem
- Conemaugh Memorial Medical Center, Johnstown, PA, USA
| | | | - Hassan Awais
- Conemaugh Memorial Medical Center, Johnstown, PA, USA
| | - Saba Waseem
- Conemaugh Memorial Medical Center, Johnstown, PA, USA
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26
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Kamal T, Haboubi N. Epstein-Barr virus and acute liver failure: an exceedingly rare amalgamation. J R Coll Physicians Edinb 2021; 51:46-48. [PMID: 33877134 DOI: 10.4997/jrcpe.2021.111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Epstein-Barr virus (EBV) associated acute liver failure (ALF) is an exceedingly uncommon event. Despite this, EBV-associated ALF has a very high fatality rate. When looking at the number of reported cases of EBV-associated ALF requiring an emergency liver transplant, we see even fewer numbers. This presents challenges to clinicians in the diagnosis, awareness and appropriate case management. There is limited information in the medical literature about the hepatic demonstration and complications of EBV. We therefore report a case of EBV-associated ALF in a 17-year-old immunocompetent female who was treated successfully with an orthotopic liver transplantation.
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Affiliation(s)
- Tom Kamal
- Nevill Hall Hospital, Abergavenny NP7 7EG, Wales, UK,
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27
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Zaki A. Primary Epstein-Barr Virus Infection in Healthy Children in Saudi Arabia: A Single Hospital-Based Study. J Trop Pediatr 2021; 67:6044375. [PMID: 33351945 DOI: 10.1093/tropej/fmaa121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
BACKGROUND Primary Epstein-Barr virus (EBV) infection presents typically with features of infectious mononucleosis (IM) but it may present with atypical symptoms. We aim to evaluate the epidemiological, clinical and laboratory characteristics of primary EBV infection in children in western Saudi Arabia. METHODS A retrospective analysis of the electronic data of all children who were admitted to the hospital and were tested for EBV-viral capsid antigen (VCA) IgM in the period from 1 January 2018 to 31 December 2019. All data of the children with positive EBV-VCA IgM were collected. Patients were divided into two groups; IM and the non-typical presentations groups. RESULTS Fort-two patients had positive EBV-VCA IgM; 71% had IM and 29% had non-typical presentations. IM was more common in early childhood (46.7%). The non-typical presentations were more in infants below 1 year (50%). Adolescents were less affected (6.7% and 16.7%, respectively). Time to diagnose EBV in the non-typical presentations group was longer than IM group; [3.4 (3.2-4.6) vs. 4.7 (4.1-5.5), p = 0.039]. The total leucocytes count was higher in the IM syndrome group compared to the non-typical presentation group [11 (10.3-17.7) vs. 5.5 (4.5-6.4), p < 0.0001]. CONCLUSIONS Primary EBV infection in healthy children in Saudi Arabia occurs more frequently in the younger age groups. IM syndrome occurs more frequently in early childhood. The non-typical presentation occurs more frequently in infants. While adolescents are less commonly affected by primary EBV.
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Affiliation(s)
- Ahmed Zaki
- Faculty of Medicine, Mansoura University, Mansoura, Egypt.,Department of Pediatrics, Al-Jedaani Hospital, Jeddah, Saudi Arabia
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28
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Zhang C, Cui S, Mao G, Li G. Clinical Characteristics and the Risk Factors of Hepatic Injury in 221 Children With Infectious Mononucleosis. Front Pediatr 2021; 9:809005. [PMID: 35096718 PMCID: PMC8790314 DOI: 10.3389/fped.2021.809005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 12/21/2021] [Indexed: 12/19/2022] Open
Abstract
Background: Infectious mononucleosis caused by Epstein-Barr Virus infection is a common acute infectious disease in children. About 40-80% of children with infectious mononucleosis have hepatic injury, and hepatic failure is one of the main causes of death in patients with fatal infectious mononucleosis. Identifying the demographics, presenting clinical characteristics and the risk factors of hepatic injury in infectious mononucleosis children are helpful to remind clinicians which patients are prone to have hepatic damage. Methods: A descriptive, cross-sectional study with a 31-month retrospective review was performed on all infectious mononucleosis children hospitalized in the pediatric department of Fuyang People's Hospital. Demographic data, presenting features, radiology imaging, clinical and laboratory parameters, and clinical outcomes of infectious mononucleosis children were collected. Results: Two-hundred twenty-one infectious mononucleosis inpatients were enrolled, and 43.9% (97/221) patients were considered to have a hepatic injury (defined as alanine amino transaminase > 40 U/L). Compared with patients without hepatic injury, hepatic injury patients were marked with a significantly higher percentage of hepatomegaly (31 vs. 49%), splenomegaly (58 vs. 81%) and palpebral edema (47 vs. 63%), higher age (3.05 ± 2.12 vs. 3.84 ± 2.44), hospitalization days (6.85 ± 2.64 vs. 8.08 ± 2.83), leukocyte (14.24 ± 5.32 vs. 18.53 ± 8.63), lymphocytes (9.48 ± 4.49 vs. 13.80 ± 7.47), the proportion of atypical lymphocytes (0.12 ± 0.07 vs. 0.15 ± 0.08) and aspartate aminotransferase (33.71 ± 10.94 vs. 107.82 ± 93.52). The results of correlation analysis and multiple linear regression analysis indicated that age (OR = 1.185; 95% CI = 1.035-1.357, p = 0.014), female (OR = 2.002, 95% CI: 0.261-0.955, p = 0.036) and splenomegaly (OR = 2.171, 95% CI: 1.018-4.628, p = 0.045) were independent risk factors of hepatic injury. Conclusions: In this study, the hepatic injury was associated with gender, age, and splenomegaly, which improved our understanding of risk factors about hepatic injury among infectious mononucleosis children.
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Affiliation(s)
- Chao Zhang
- Department of Pediatrics, Fuyang People's Hospital, Fuyang, China
| | - Shu Cui
- Chaohu Hospital, Anhui Medical University, Hefei, China.,School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China
| | - Guoshun Mao
- Department of Pediatrics, Fuyang People's Hospital, Fuyang, China
| | - Guitao Li
- Department of Pediatrics, Fuyang People's Hospital, Fuyang, China
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29
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Yang Y, Gao F. Clinical characteristics of primary and reactivated Epstein-Barr virus infection in children. J Med Virol 2020; 92:3709-3716. [PMID: 32558948 DOI: 10.1002/jmv.26202] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 06/10/2020] [Indexed: 11/10/2022]
Abstract
Epstein-Barr virus (EBV) infection occurs commonly in children and presents as a primary or reactivated infection, which are difficult for clinicians to distinguish. This study investigated the clinical characteristics of the two types of infections. Children with detectable plasma EBV-DNA were retrospectively enrolled and divided into primary and reactivated infection group by EBV-specific antibody. We analyzed the patients' characteristics, clinical manifestations, complications, inflammatory biomarkers, and viral load. A total of 9.3% of children with reactivation were immunocompromised over the long-term. The primary infection mostly appeared as infectious mononucleosis (99.8%), while reactivation occurred as an infectious mononucleosis-like disease (65.0%), hemophagocytic syndrome (22.6%), chronic active EBV infection (5.3%) and lymphoma (3.5%). The incidence of fevers, cervical lymphoditis, periorbital edema, pharyngotonsillitis, hepatomegaly and splenomegaly in primary infection were 93.3%, 93.0%, 51.5%, 66.0%, 76.2% and 63.9%, respectively; the incidence of those symptoms in reactivation was 84.0%, 46.9%, 15.4%, 18.5%, 18.5%, and 43.3%, respectively. The incidence of digestive, respiratory, cardiovascular, neurological, hematological, genitourinary complications and multiple serous effusion in primary infection was 68.8%, 18.1%, 8.0%, 0.8%, 2.9%, 0.0% and 2.3%; whereas the incidence of these complications in reactivation was 56.2%, 22.5%, 14.1%, 8.0%, 38.9%, 0.3% and 19.0%. Patients with reactivation were more prone to multi-systemic damage. B-cells were lower, and CD8+ T-cells were higher in primary infection. Viral load was correlated with the level of different cytokines in primary and reactivated infection. EBV primary infection often presents as infectious mononucleosis. The reactivated infection affects more immunocompromised subjects with diverse and complex manifestations. Various complications are more commonly associated with reactivation as a result of different inflammatory responses to different types of infection.
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Affiliation(s)
- Ying Yang
- Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Feng Gao
- Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
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30
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Ahmed MH, Raza M, Lucas S, Mital D. Reactivation of the Epstein-Barr Virus Leading to Acute Liver Failure in a Patient Living with HIV. J Microsc Ultrastruct 2020; 9:41-44. [PMID: 33850712 PMCID: PMC8030544 DOI: 10.4103/jmau.jmau_16_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 05/19/2020] [Indexed: 12/22/2022] Open
Abstract
We report a case of a 46-year-old female living with HIV since 2010 who was originally from Malawi and had settled in the UK in 2001. She was admitted to our hospital with confusion and quickly noted to have a decreased Glasgow Coma Scale of 10/15. Her biochemical parameters showed the presence of elevated liver function tests (LFTs), clotting abnormalities, and her ammonia were found to be >400 mmol/L with a severe metabolic acidosis (pH = 7.05). She was treated for HIV with combined antiretroviral therapy, namely tenofovir disoproxil fumarate, emtricitabine (FTC) and cobicistat boosted atazanavir 2 years previously and had normal LFTs at that time. Her HIV-1 viral load was 1400 copies/ml on admission after recently having an undetectable viral load 2 months previously, and her CD4 count was 480. Her relevant past medical history included insulin-dependent diabetes mellitus. Her other medications included insulin, ramipril, sertraline, amitriptyline, and zopiclone. Toxicology and viral hepatitis screen were negative. Epstein Barr virus (EBV) serology showed evidence of previous exposure, but she was found to have a very high EBV viral load of 55,000 copies/ml, which given her serology, was very likely to be a reactivation of EBV infection rather than a primary EBV infection. In the intensive care unit, the patient deteriorated and died very quickly. The postmortem examination showed extensive hepatic necrosis with collapse. To our knowledge, this is the first case report to show an association between EBV reactivation and fulminant hepatic failure in an individual living with HIV.
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Affiliation(s)
- Mohamed H Ahmed
- Department of Medicine and HIV Metabolic Clinic, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keyne, Buckinghamshire, London, UK
| | - Mansoor Raza
- Department of Infectious Diseases and Microbiology, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keyne, Buckinghamshire, London, UK
| | - Sebastian Lucas
- Department of Cellular Pathology, St Thomas' Hospital, London, UK
| | - Dushyant Mital
- Department of Blood Borne Viruses, Milton Keynes University Hospital NHS Foundation Trust, Eaglestone, Milton Keyne, Buckinghamshire, London, UK
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31
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Abstract
Viral hepatitis can cause a wide spectrum of clinical presentations from a benign form with minimal or no symptoms to acute liver failure or death. Hepatitis D coinfection and superinfection have distinct clinical courses, with the latter more likely leading to chronic infection. Management of chronic hepatitis D virus is individualized because of the paucity of treatment options and significant side effect profile of currently available treatments. Sporadic cases of hepatitis E caused by contaminated meats are becoming increasingly prevalent in immunocompromised hosts. Human herpesviruses are an important cause of disease also in immunocompromised individuals.
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32
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Anand AC, Nandi B, Acharya SK, Arora A, Babu S, Batra Y, Chawla YK, Chowdhury A, Chaoudhuri A, Eapen EC, Devarbhavi H, Dhiman R, Datta Gupta S, Duseja A, Jothimani D, Kapoor D, Kar P, Khuroo MS, Kumar A, Madan K, Mallick B, Maiwall R, Mohan N, Nagral A, Nath P, Panigrahi SC, Pawar A, Philips CA, Prahraj D, Puri P, Rastogi A, Saraswat VA, Saigal S, Shalimar, Shukla A, Singh SP, Verghese T, Wadhawan M. Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis. J Clin Exp Hepatol 2020; 10:339-376. [PMID: 32655238 PMCID: PMC7335721 DOI: 10.1016/j.jceh.2020.04.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/12/2020] [Indexed: 12/12/2022] Open
Abstract
Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.
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Key Words
- ACLF, acute on chronic liver failure
- AFLP, acute fatty liver of pregnancy
- AKI, Acute kidney injury
- ALF, Acute liver failure
- ALFED, Acute Liver Failure Early Dynamic
- ALT, alanine transaminase
- ANA, antinuclear antibody
- AP, Alkaline phosphatase
- APTT, activated partial thromboplastin time
- ASM, alternative system of medicine
- ASMA, antismooth muscle antibody
- AST, aspartate transaminase
- ATN, Acute tubular necrosis
- ATP, adenosine triphosphate
- ATT, anti-TB therapy
- AUROC, Area under the receiver operating characteristics curve
- BCS, Budd-Chiari syndrome
- BMI, body mass index
- CBF, cerebral blood flow
- CBFV, cerebral blood flow volume
- CE, cerebral edema
- CHBV, chronic HBV
- CLD, chronic liver disease
- CNS, central nervous system
- CPI, clinical prognostic indicator
- CSF, cerebrospinal fluid
- DAMPs, Damage-associated molecular patterns
- DILI, drug-induced liver injury
- EBV, Epstein-Barr virus
- ETCO2, End tidal CO2
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- HAV, hepatitis A virus
- HBV, Hepatitis B virus
- HELLP, hemolysis
- HEV, hepatitis E virus
- HLH, Hemophagocytic lymphohistiocytosis
- HSV, herpes simplex virus
- HV, hepatic vein
- HVOTO, hepatic venous outflow tract obstruction
- IAHG, International Autoimmune Hepatitis Group
- ICH, intracerebral hypertension
- ICP, intracerebral pressure
- ICU, intensive care unit
- IFN, interferon
- IL, interleukin
- IND-ALF, ALF of indeterminate etiology
- INDILI, Indian Network for DILI
- KCC, King's College Criteria
- LC, liver cirrhosis
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MAP, mean arterial pressure
- MHN, massive hepatic necrosis
- MPT, mitochondrial permeability transition
- MUAC, mid-upper arm circumference
- NAPQI, n-acetyl-p-benzo-quinone-imine
- NPV, negative predictive value
- NWI, New Wilson's Index
- ONSD, optic nerve sheath diameter
- PAMPs, pathogen-associated molecular patterns
- PCR, polymerase chain reaction
- PELD, Pediatric End-Stage Liver Disease
- PPV, positive predictive value
- PT, prothrombin time
- RAAS, renin–angiotensin–aldosterone system
- SHF, subacute hepatic failure
- SIRS, systemic inflammatory response syndrome
- SNS, sympathetic nervous system
- TB, tuberculosis
- TCD, transcranial Doppler
- TGF, tumor growth factor
- TJLB, transjugular liver biopsy
- TLR, toll-like receptor
- TNF, tumor necrosis factor
- TSFT, triceps skin fold thickness
- US, ultrasound
- USALF, US Acute Liver Failure
- VZV, varicella-zoster virus
- WD, Wilson disease
- Wilson disease (WD)
- YP, yellow phosphorus
- acute liver failure
- autoimmune hepatitis (AIH)
- drug-induced liver injury
- elevated liver enzymes, low platelets
- sALI, severe acute liver injury
- viral hepatitis
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Affiliation(s)
- Anil C. Anand
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Bhaskar Nandi
- Department of Gastroenterology, Sarvodaya Hospital and Research Centre, Faridababd, Haryana, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Anil Arora
- Institute of Liver Gastroenterology &Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sethu Babu
- Department of Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad 500003, India
| | - Yogesh Batra
- Department of Gastroenterology, Indraprastha Apollo Hospital, SaritaVihar, New Delhi, 110 076, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, 700020, India
| | - Ashok Chaoudhuri
- Hepatology and Liver Transplant, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
| | - Eapen C. Eapen
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, 560034, India
| | - RadhaKrishan Dhiman
- Department of Hepatology, Post graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Ajay Duseja
- Department of Hepatology, Post graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chrompet, Chennai, 600044, India
| | | | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Mohamad S. Khuroo
- Department of Gastroenterology, Dr Khuroo’ S Medical Clinic, Srinagar, Kashmir, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology &Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Kaushal Madan
- Gastroenterology and Hepatology, Max Smart Super Specialty Hospital, Saket, New Delhi, India
| | - Bipadabhanjan Mallick
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Rakhi Maiwall
- Hepatology Incharge Liver Intensive Care, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
| | - Neelam Mohan
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta – the Medicity Hospital, Sector – 38, Gurgaon, Haryana, India
| | - Aabha Nagral
- Department of Gastroenterology, Apollo and Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Preetam Nath
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Sarat C. Panigrahi
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Ankush Pawar
- Liver & Digestive Diseases Institute, Fortis Escorts Hospital, Okhla Road, New Delhi, 110 025, India
| | - Cyriac A. Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, 682028, Kerala, India
| | - Dibyalochan Prahraj
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Pankaj Puri
- Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
| | - Amit Rastogi
- Department of Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Sanjiv Saigal
- Department of Hepatology, Department of Liver Transplantation, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 29, India
| | - Akash Shukla
- Department of Gastroenterology, LTM Medical College & Sion Hospital, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Thomas Verghese
- Department of Gastroenterology, Government Medical College, Kozikhode, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases and Head of Hepatology & Liver Transplant (Medicine), BLK Super Speciality Hospital, Delhi, India
| | - The INASL Task-Force on Acute Liver Failure
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
- Department of Gastroenterology, Sarvodaya Hospital and Research Centre, Faridababd, Haryana, India
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
- Institute of Liver Gastroenterology &Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
- Department of Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad 500003, India
- Department of Gastroenterology, Indraprastha Apollo Hospital, SaritaVihar, New Delhi, 110 076, India
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, 700020, India
- Hepatology and Liver Transplant, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
- Department of Hepatology, Christian Medical College, Vellore, India
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, 560034, India
- Department of Hepatology, Post graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chrompet, Chennai, 600044, India
- Gleneagles Global Hospitals, Hyderabad, Telangana, India
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
- Department of Gastroenterology, Dr Khuroo’ S Medical Clinic, Srinagar, Kashmir, India
- Gastroenterology and Hepatology, Max Smart Super Specialty Hospital, Saket, New Delhi, India
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751024, India
- Hepatology Incharge Liver Intensive Care, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta – the Medicity Hospital, Sector – 38, Gurgaon, Haryana, India
- Department of Gastroenterology, Apollo and Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
- Liver & Digestive Diseases Institute, Fortis Escorts Hospital, Okhla Road, New Delhi, 110 025, India
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, 682028, Kerala, India
- Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
- Department of Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh, 226 014, India
- Department of Hepatology, Department of Liver Transplantation, India
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 29, India
- Department of Gastroenterology, LTM Medical College & Sion Hospital, India
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
- Department of Gastroenterology, Government Medical College, Kozikhode, India
- Institute of Liver & Digestive Diseases and Head of Hepatology & Liver Transplant (Medicine), BLK Super Speciality Hospital, Delhi, India
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Bunchorntavakul C, Reddy KR. Epstein-Barr Virus and Cytomegalovirus Infections of the Liver. Gastroenterol Clin North Am 2020; 49:331-346. [PMID: 32389366 DOI: 10.1016/j.gtc.2020.01.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections are common and are associated with a variety of liver manifestations. EBV and CMV infections, in immunocompetent hosts, commonly manifest as acute hepatitis, with severity varying from asymptomatic, self-limited icteric hepatitis to acute liver failure. Atypical manifestations, such as cholestasis, chronic hepatitis, precipitation of acute-on-chronic liver failure, and autoimmune hepatitis, are reported with EBV infection, whereas cholestasis, portal vein thrombosis, and Budd-Chiari syndrome are reported with CMV infection. In the setting of liver transplantation, CMV is the most common infectious complication and carries significant morbidity; EBV is the major cause of post-transplant lymphoproliferative disorders.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, 2 Phayathai Road, Ratchathewi, Bangkok 10400, Thailand
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA.
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Mrzljak A, Tabain I, Premac H, Bogdanic M, Barbic L, Savic V, Stevanovic V, Jelic A, Mikulic D, Vilibic-Cavlek T. The Role of Emerging and Neglected Viruses in the Etiology of Hepatitis. Curr Infect Dis Rep 2019; 21:51. [PMID: 31754812 DOI: 10.1007/s11908-019-0709-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW In this review, we present the overview of emerging and neglected viruses associated with liver involvement. RECENT FINDINGS Hepatitis E virus (HEV) emerged in the last two decades, causing hepatitis in many parts of the world. Moreover, liver involvement was also described in some emerging arboviral infections. Many reports showed dengue-associated liver injury; however, chikungunya, West Nile, tick-borne encephalitis, and Zika virus are rarely associated with clinically manifest liver disease. In addition, some neglected highly prevalent viruses such as adenoviruses and parvovirus B19 are capable of causing hepatitis in specific population groups. Anelloviruses (torque teno virus/torque teno mini virus/torque teno midi virus, SEN virus), human bocavirus, pegiviruses, and lymphocytic choriomeningitis virus have shown a little potential for causing hepatitis, but their role in the etiology of liver disease remains to be determined. In addition to the well-known hepatotropic viruses, many emerging and neglected viruses have been associated with liver diseases. The number of emerging zoonotic viruses has been increasingly recognized. While zoonotic potential of HEV is well documented, the recent identification of new hepatitis-related animal viruses such as HEV strains from rabbits and camels, non-primate hepaciviruses in domestic dogs and horses, as well as equine and porcine pegivirus highlights the possible zoonotic transmission in the context of "One Health." However, zoonotic potential and hepatotropism of animal hepatitis viruses remain to be determined.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Salata 3b, 10000, Zagreb, Croatia.
- School of Medicine, University of Zagreb, Zagreb, Croatia.
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Hrvoje Premac
- Department of Medicine, Varazdin General Hospital, Varazdin, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Vladimir Savic
- Poultry Center, Laboratory for Virology and Serology, Croatian Veterinary Institute, Zagreb, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Ana Jelic
- Department of Medicine, Merkur University Hospital, Salata 3b, 10000, Zagreb, Croatia
| | - Danko Mikulic
- Department of Surgery, Merkur University Hospital, Zagreb, Croatia
| | - Tatjana Vilibic-Cavlek
- School of Medicine, University of Zagreb, Zagreb, Croatia
- Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia
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Abstract
The syndrome of infectious mononucleosis is commonly seen with Epstein-Barr virus (EBV) infection. It may cause acute hepatitis, which is usually self-limiting and characterised by mildly elevated liver enzymes, but rarely jaundice. The patient being reported showcases EBV infection with jaundice, which is an uncommon scenario.
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Affiliation(s)
- Robin G Manappallil
- Department of Internal Medicine, Baby Memorial Hospital, Calicut, Kerala, India
| | - Neena Mampilly
- Department of Pathology, Baby Memorial Hospital, Calicut, Kerala, India
| | - Blessy Josphine
- Department of Internal Medicine, Baby Memorial Hospital, Calicut, Kerala, India
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36
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Hu J, Zhang X, Yu G, Cai H, Gu J, Hu M, Xiang D, Lian J, Yu L, Jia H, Zhang Y, Yang Y. Epstein-Barr virus infection is associated with a higher Child-Pugh score and may predict poor prognoses for patients with liver cirrhosis. BMC Gastroenterol 2019; 19:94. [PMID: 31215410 PMCID: PMC6582562 DOI: 10.1186/s12876-019-1021-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 06/11/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Studies on Epstein-Barr virus (EBV) have focused mostly on neoplastic disease. Few studies have considered immunocompetent patients who are not severely immunocompromised. Liver cirrhosis is associated with various levels of immune dysfunction. In the current study, we determined EBV infection rates, the influence on liver function, and analyzed the risk factors for death in patients with liver cirrhosis. METHODS The medical records of patients diagnosed with liver cirrhosis between 1 January 2014 and 31 December 2016 were reviewed. Patients who were or were not infected with EBV were enrolled in this study. Liver functions were compared. The risk factors for 28-, 90-, and 180-day mortality rates were analyzed by univariate and multivariate logistic regression. RESULTS The medical records hospitalized patients diagnosed with liver cirrhosis were reviewed. Of these patients, 97 had assessed EBV deoxyribonucleic acid (DNA) and 36 (37.1%) patients were EBV DNA-positive. The age of the EBV-infected patients was older than patients not infected with EBV. EBV-infected patients had a lower level of albumin, and a lower albumin-to-globulin ratio (P = 0.019 and P = 0.013, respectively). EBV-infected patients had higher Child-Pugh scores (P = 0.033) and higher acute-on-chronic liver failure (ACLF) rate (P = 0.050). The Child-Pugh score and ACLF were the risk factors for the 28-, 90-, and 180-day mortality rates. CONCLUSIONS This study revealed that patients with liver cirrhosis had higher EBV infection rates, especially patients > 60 years of age, which likely reflected viral reactivation. And liver injury was aggravated in EBV-infected patients. Thus, EBV infection indirectly influenced the prognosis of EBV-infected patients by increasing the Child-Pugh score and ACLF rate.
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Affiliation(s)
- Jianhua Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Xiaoli Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Guodong Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Huan Cai
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Jueqing Gu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Menglin Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Dairong Xiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Jiangshan Lian
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Liang Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Hongyu Jia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Yimin Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China
| | - Yida Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, Zhejiang, China.
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Lv S, Li S, Wang Z, Xia J. Imbalance in the ratio of CpG and polyG contributes to impaired interferon-α expression. J Med Virol 2019; 91:1148-1157. [PMID: 30701565 DOI: 10.1002/jmv.25419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 01/03/2019] [Accepted: 01/27/2019] [Indexed: 11/07/2022]
Abstract
The secretion of interferon-α (IFN-α) is impaired during hepatitis B virus (HBV) infection. DNA sequences purified from distinct viruses, for example, HBV versus members of Herpesviridae, have been shown to differ in their IFN-α signaling properties. The present study found that DNA from HBV inhibited, while DNA from members of Herpesviridae induced, the expression of IFN-α. Furthermore, stimulatory cytosine-phosphate-guanosine (CpG) sequences derived from these DNA viruses could induce the secretion of IFN-α, while inhibitory guanosine-rich oligodeoxynucleoti (polyG) oligonucleotide sequences derived from these DNA viruses could inhibit CpG-induced IFN-α secretion. Using a computational analysis of genomic DNA sequences, the discrimination between the genomes of HBV and those of other DNA viruses that can also cause inflammation of the liver is based on different frequencies of the CpG and polyG motifs. The underrepresentation of stimulatory CpG motifs and overrepresentation of inhibitory polyG motifs were documented in HBV genomes, whereas the DNA from other viral genomes displayed the opposite trend. Moreover, it was demonstrated that HBV could suppress the activation of IFN-α via its own DNA through the high proportion of polyG motifs. To our knowledge, this is the first demonstration of a specific role for polyG motifs in the inhibition of the IFN-α response following DNA virus infection.
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Affiliation(s)
- Shujuan Lv
- Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Suping Li
- Blood Test and Identification Laboratory, Blood Transfusion Institute, Anhui Blood Center, Hefei, China
| | - Zifeng Wang
- Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Jing Xia
- Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China
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38
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[Clinical features of children with Epstein-Barr virus-related acute liver failure: an analysis of four cases]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2018. [PMID: 30572993 PMCID: PMC7389496 DOI: 10.7499/j.issn.1008-8830.2018.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
A retrospective analysis was performed for the clinical data of four children with Epstein-Barr virus (EBV)-related acute liver failure. There were two boys and two girls with a median age of 10 months (range 8.5-44 months). Of the four children, three were diagnosed with infectious mononucleosis (IM), among whom two met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH), and one was diagnosed with past EBV infection. All the children had positive EBV DNA in blood and all had pyrexia, hepatomegaly, and jaundice on admission. Three children had the symptom of splenomegaly, ascites, or vomiting. Two children had enlargement of cervical lymph nodes, skin rash, or pleural effusion. One child had gastrointestinal bleeding or stage 2 hepatic encephalopathy. All the children had an abnormal lymphocyte count of <10%, and only one child had leukocytosis and thrombocytopenia. Among the four children, alanine aminotransferase level increased by 10-100 times; total bilirubin level increased by 3-5 times; lactate dehydrogenase level increased by many 10 times; prothrombin time prolonged significantly. All the children were given antiviral therapy with intravenously injected acyclovir or ganciclovir, as well as hepatocyte growth factor to promote hepatocyte growth and hormone to alleviate inflammatory response. Two children were given plasma exchange in addition, among whom one was given the combination of continuous venovenous hemodiafiltration. Two children with HLH were given chemotherapy according to the HLH-2004 regimen. Three children survived, and one child with HLH died of multiple organ failure. It is concluded that EBV infection can cause acute liver failure and that early use of multimodality therapy including blood purification may be beneficial for prognosis in these children.
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Liu RH, Li J, Qu NY, Li ZP. [Clinical features of children with Epstein-Barr virus-related acute liver failure: an analysis of four cases]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2018; 20:1030-1033. [PMID: 30572993 PMCID: PMC7389496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 11/12/2018] [Indexed: 11/12/2023]
Abstract
A retrospective analysis was performed for the clinical data of four children with Epstein-Barr virus (EBV)-related acute liver failure. There were two boys and two girls with a median age of 10 months (range 8.5-44 months). Of the four children, three were diagnosed with infectious mononucleosis (IM), among whom two met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH), and one was diagnosed with past EBV infection. All the children had positive EBV DNA in blood and all had pyrexia, hepatomegaly, and jaundice on admission. Three children had the symptom of splenomegaly, ascites, or vomiting. Two children had enlargement of cervical lymph nodes, skin rash, or pleural effusion. One child had gastrointestinal bleeding or stage 2 hepatic encephalopathy. All the children had an abnormal lymphocyte count of <10%, and only one child had leukocytosis and thrombocytopenia. Among the four children, alanine aminotransferase level increased by 10-100 times; total bilirubin level increased by 3-5 times; lactate dehydrogenase level increased by many 10 times; prothrombin time prolonged significantly. All the children were given antiviral therapy with intravenously injected acyclovir or ganciclovir, as well as hepatocyte growth factor to promote hepatocyte growth and hormone to alleviate inflammatory response. Two children were given plasma exchange in addition, among whom one was given the combination of continuous venovenous hemodiafiltration. Two children with HLH were given chemotherapy according to the HLH-2004 regimen. Three children survived, and one child with HLH died of multiple organ failure. It is concluded that EBV infection can cause acute liver failure and that early use of multimodality therapy including blood purification may be beneficial for prognosis in these children.
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Affiliation(s)
- Rui-Hai Liu
- Department of Pediatric Intensive Care Unit, Critical Care Medicine Center of Qingdao Women and Children's Hospital, Qingdao, Shandong 266034, China.
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40
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Foong S, Pendle S, Kwok R, Kwon S, Gill R, Tomlins R, O'Toole S. Acute Epstein-Barr virus hepatitis superimposed on drug induced liver injury causing severe hepatic dysfunction. Pathology 2018; 51:104-106. [PMID: 30482400 DOI: 10.1016/j.pathol.2018.07.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/05/2018] [Accepted: 07/11/2018] [Indexed: 12/18/2022]
Affiliation(s)
- Samuel Foong
- Australian Clinical Labs, Bella Vista, NSW, Australia
| | - Stella Pendle
- Australian Clinical Labs, Bella Vista, NSW, Australia
| | - Raymond Kwok
- Australian Clinical Labs, Bella Vista, NSW, Australia
| | | | - Raghu Gill
- Australian Clinical Labs, Bella Vista, NSW, Australia
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Hu J, Zhao H, Lou D, Gao H, Yang M, Zhang X, Jia H, Li L. Human cytomegalovirus and Epstein-Barr virus infections, risk factors, and their influence on the liver function of patients with acute-on-chronic liver failure. BMC Infect Dis 2018; 18:577. [PMID: 30445927 PMCID: PMC6240234 DOI: 10.1186/s12879-018-3488-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 10/31/2018] [Indexed: 12/20/2022] Open
Abstract
Background Studies on human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have focused primarily on the immunosuppressed population. Few studies have considered immunocompetent and not severely immunocompromised patients. We determined the infection rates of HCMV and EBV, their risk factors and their influence on liver function in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods Patients infected with ACLF-based hepatitis B virus (HBV) from 1 December 2016 to 31 May 2018 were enrolled in our study and were divided into infected and uninfected groups. The risk factors for HCMV and EBV infection and their influence on liver function were analysed. Results A total of 100 hospitalized patients with ACLF due to HBV infection were enrolled in this study. Of these patients, 5% presented HCMV deoxyribonucleic acid (DNA) and 23.0% presented EBV DNA. An HBV DNA count of < 1000 IU/mL increased the occurrence of HCMV infection (P = 0.003). Age, especially older than 60 years, was a risk factor for EBV infection (P = 0.034, P = 0.033). HCMV-infected patients had lower alanine aminotransferase (ALT) levels; albumin levels and Child–Pugh scores in EBV-infected patients were higher than those in uninfected patients. Conclusions HCMV and EBV were detected in patients with ACLF caused by HBV infection. Lower replication of HBV (HBV DNA < 1000 IU/mL) may increase the probability of HCMV infection; age, especially older than 60 years of age, was a risk factor for EBV infection. HCMV infection may inhibit HBV proliferation and did not increase liver injury, while co-infection with EBV may influence liver function and may result in a poor prognosis.
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Affiliation(s)
- Jianhua Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, 310003, Zhejiang, China
| | - Hong Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, 310003, Zhejiang, China
| | - Danfeng Lou
- Shulan (Hangzhou) Hospital, 848 Dongxin Road, Hangzhou, 310004, Zhejiang, China
| | - Hainv Gao
- Shulan (Hangzhou) Hospital, 848 Dongxin Road, Hangzhou, 310004, Zhejiang, China
| | - Meifang Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, 310003, Zhejiang, China
| | - Xuan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, 310003, Zhejiang, China
| | - Hongyu Jia
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, 310003, Zhejiang, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou, 310003, Zhejiang, China.
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Schechter S, Lamps L. Epstein-Barr Virus Hepatitis: A Review of Clinicopathologic Features and Differential Diagnosis. Arch Pathol Lab Med 2018; 142:1191-1195. [DOI: 10.5858/arpa.2018-0208-ra] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Context.—
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.
Objective.—
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.
Data Sources.—
Analysis of the pertinent literature (PubMed) and clinical practice experience based on institutional materials.
Conclusions.—
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.
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Affiliation(s)
| | - Laura Lamps
- From the Department of Pathology, University of Michigan, Ann Arbor
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Butler DC, Lewin DN, Batalis NI. Differential Diagnosis of Hepatic Necrosis Encountered at Autopsy. Acad Forensic Pathol 2018; 8:256-295. [PMID: 31240042 DOI: 10.1177/1925362118782056] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 04/13/2018] [Indexed: 12/13/2022]
Abstract
The liver is subject to a variety of extrinsic and intrinsic insults that manifest with both specific and nonspecific patterns of necrosis. In the autopsy setting, these patterns are often encountered as incidental findings or even causes of death. There are several etiologies of hepatic necrosis, including toxins, drug injuries, viral infections, ischemic injuries, and metabolic disease, all of which possess overlapping gross and histologic presentations. Nonetheless, patterned necrosis in the context of clinical and demographic history allows for the forensic pathologist to develop a differential diagnosis, which may then be pruned into a specific or likely cause. The aim of the following review is to elucidate these patterns in the context of the liver diseases from which they arise with the goal developing a differential diagnosis and ultimate determination of etiology. Acad Forensic Pathol. 2018 8(2): 256-295.
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Abstract
From the standpoint of the surgical pathologist "hepatitis" is defined as the set of histologic patterns of lesions found in livers infected by hepatotropic viruses, by non-hepatotrophic viruses leading to liver inflammation in the context of systemic infection, or due to an autoimmune disease, drug, or toxin involving the liver. This article is centered on the histologic patterns of injury in acute viral hepatitis, encompassing the hepatotropic viruses A, B, C, D, and E and the "icteric hemorrhagic fevers" (dengue, hantavirus, yellow fever). A brief mention of viruses causing hepatitis in immunosuppressed patients also is presented.
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Karadeniz A, Yesilbag Z, Kaya FÖ, Akgün FS. Acute hepatitis due to Epstein-Barr virus with cross-reacting antibodies to cytomegalovirus. Indian J Med Microbiol 2018; 36:143-144. [PMID: 29735847 DOI: 10.4103/ijmm.ijmm_17_378] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Epstein-Barr virus (EBV) is the cause of systemic infection known as infectious mononucleosis with classic presentation of fever, oropharyngitis and lymphadenitis. EBV rarely causes acute hepatitis. In this report, we present a 19-year-old patient presented with nausea, fatigue and jaundice. Her physical examination and laboratory tests revealed the diagnosis as acute hepatitis due to EBV with cross-reacting antibodies to cytomegalovirus.
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Affiliation(s)
- Asli Karadeniz
- Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Maltepe University, Istanbul, Turkey
| | - Zuhal Yesilbag
- Department of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey
| | - Fatih Öner Kaya
- Department of Internal Medicine, Faculty of Medicine, Maltepe University, Istanbul, Turkey
| | - Feride Sinem Akgün
- Department of Emergency Medicine, Faculty of Medicine, Maltepe University, Istanbul, Turkey
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Tapper EB, Curry MP. Hepatitis Caused by Other Viruses. HANDBOOK OF LIVER DISEASE 2018. [PMCID: PMC7152265 DOI: 10.1016/b978-0-323-47874-8.00006-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/29/2022]
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47
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Ferreira Alves VA. Acute Viral Hepatitis. PRACTICAL HEPATIC PATHOLOGY: A DIAGNOSTIC APPROACH 2018:191-209. [DOI: 10.1016/b978-0-323-42873-6.00013-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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48
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Liver Disease Associated With Systemic Viral Infection. ZAKIM AND BOYER'S HEPATOLOGY 2018. [PMCID: PMC7099665 DOI: 10.1016/b978-0-323-37591-7.00038-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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49
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Abstract
Acute liver failure (ALF) is a life-threatening condition of heterogeneous etiology. Outcomes are better with early recognition and prompt initiation of etiology-specific therapy, intensive care protocols, and liver transplantation (LT). Prognostic scoring systems include the King's College Criteria and Model for End-stage Liver Disease score. Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality; hypertonic saline is suggested for patients with a high risk for developing intracranial hypertension, and when it does, mannitol is recommended as first-line therapy. Extracorporeal liver support system may serve as a bridge to LT and may increase LT-free survival in select cases.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Rajavithi Road, Ratchathewi, Bangkok 10400, Thailand; Division of Gastroenterology and Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA.
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Somasekar S, Lee D, Rule J, Naccache SN, Stone M, Busch MP, Sanders C, Lee WM, Chiu CY. Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By Metagenomic Next-Generation Sequencing. Clin Infect Dis 2017; 65:1477-1485. [PMID: 29020199 PMCID: PMC5848299 DOI: 10.1093/cid/cix596] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 07/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Twelve percent of all acute liver failure (ALF) cases are of unknown origin, often termed indeterminate. A previously unrecognized hepatotropic virus has been suspected as a potential etiologic agent. METHODS We compared the performance of metagenomic next-generation sequencing (mNGS) with confirmatory nucleic acid testing (NAT) to routine clinical diagnostic testing in detection of known or novel viruses associated with ALF. Serum samples from 204 adult ALF patients collected from 1998 to 2010 as part of a nationwide registry were analyzed. One hundred eighty-seven patients (92%) were classified as indeterminate, while the remaining 17 patients (8%) served as controls, with infections by either hepatitis A virus or hepatitis B virus (HBV), or a noninfectious cause for their ALF. RESULTS Eight cases of infection from previously unrecognized viral pathogens were detected by mNGS (4 cases of herpes simplex virus type 1, including 1 case of coinfection with HBV, and 1 case each of HBV, parvovirus B19, cytomegalovirus, and human herpesvirus 7). Several missed dual or triple infections were also identified, and assembled viral genomes provided additional information on genotyping and drug resistance mutations. Importantly, no sequences corresponding to novel viruses were detected. CONCLUSIONS These results suggest that ALF patients should be screened for the presence of uncommon viruses and coinfections, and that most cases of indeterminate ALF in the United States do not appear to be caused by novel viral pathogens. In the future, mNGS testing may be useful for comprehensive diagnosis of viruses associated with ALF, or to exclude infectious etiologies.
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Affiliation(s)
- Sneha Somasekar
- Department of Laboratory Medicine, University of California San Francisco (UCSF) and
| | - Deanna Lee
- Department of Laboratory Medicine, University of California San Francisco (UCSF) and
| | - Jody Rule
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas; and
| | - Samia N Naccache
- Department of Laboratory Medicine, University of California San Francisco (UCSF) and
| | - Mars Stone
- Blood Systems Research Institute, San Francisco, California
| | - Michael P Busch
- Department of Laboratory Medicine, University of California San Francisco (UCSF) and
- Blood Systems Research Institute, San Francisco, California
| | - Corron Sanders
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas; and
| | - William M Lee
- Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas; and
| | - Charles Y Chiu
- Department of Laboratory Medicine, University of California San Francisco (UCSF) and
- UCSF–Abbott Viral Diagnostics and Discovery Center and
- Department of Medicine, Division of Infectious Diseases, University of California San Francisco
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