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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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2
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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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3
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Da Cunha T, Wu GY. Cytomegalovirus Hepatitis in Immunocompetent and Immunocompromised Hosts. J Clin Transl Hepatol 2021; 9:106-115. [PMID: 33604261 PMCID: PMC7868697 DOI: 10.14218/jcth.2020.00088] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/22/2020] [Accepted: 12/08/2020] [Indexed: 12/25/2022] Open
Abstract
Human cytomegalovirus (HCMV) infection is common and affects between 40-100% of the worldwide population. However, the majority of cases are asymptomatic and when severe disease occurs, it is usually restricted to immunocompromised patients. Liver involvement by HCMV differs significantly, accordingly to the immune status of the host. In immunocompromised patients, particularly liver transplant patients, it often causes clinically significant hepatitis. On the other hand, in immunocompetent patients, HCMV hepatitis requiring hospitalization is extremely rare. This review aims to appraise studies regarding the pathophysiology of HCMV hepatitis, including mechanisms of latency and reactivation and its contribution to disease development, clinical presentation, diagnostic modalities and treatment, with a focus on comparing different aspects between immunocompromised and immunocompetent hosts.
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Affiliation(s)
- Teresa Da Cunha
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Teresa Da Cunha, Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA. Tel: +1-860-706-2133, Fax: +1-860-679-3159, E-mail:
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Current address: Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
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4
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Sattar SBA, Haider MA, Zia Z, Niazi M, Iqbal QZ. Cytomegalovirus Hepatitis in an Immunocompetent Patient: A Cause of Fever of Unknown Origin. Cureus 2020; 12:e10745. [PMID: 33150097 PMCID: PMC7603881 DOI: 10.7759/cureus.10745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Acute hepatitis is most often self-resolving and a benign condition that rarely requires any anti-viral drugs. In immunocompromised patients (HIV-infected patients and transplant recipients), the morbidity and mortality associated with cytomegalovirus (CMV) infection have been extensively reported in the medical literature. We are describing a rare case of acute severe cytomegalovirus hepatitis in an immunocompetent host. In immunocompetent individuals, in most cases, it causes a subclinical infection and hence doesn't require an anti-viral agent for treatment. Our patient was unique because it presented with clinically severe hepatitis and was uncharacteristically treated with the use of antiviral medications.
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5
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Lizaola-Mayo BC, Rodriguez EA. Cytomegalovirus infection after liver transplantation. World J Transplant 2020; 10:183-190. [PMID: 32844094 PMCID: PMC7416364 DOI: 10.5500/wjt.v10.i7.183] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/28/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (CMV) represents the most common opportunistic infection in liver transplant recipients. CMV infections in post liver transplant patients cause significant morbidity and mortality, directly affecting post-transplant outcomes. This review will provide the framework for the surveillance, diagnosis, prophylaxis and treatment of CMV in the liver transplant population.
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Affiliation(s)
- Blanca C Lizaola-Mayo
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ 85259, United States
| | - Eduardo A Rodriguez
- Division of Gastroenterology, Hepatology & Nutrition, University of Utah, Salt Lake City, UT 84132, United States
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6
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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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7
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McDonald GB, Sarmiento JI, Rees-Lui G, Myerson D. Cytomegalovirus hepatitis after bone marrow transplantation: An autopsy study with clinical, histologic and laboratory correlates. J Viral Hepat 2019; 26:1344-1350. [PMID: 31315152 DOI: 10.1111/jvh.13176] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 06/03/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023]
Abstract
Mortality from cytomegalovirus disease after marrow transplantation can be reduced by treatment with antiviral drugs based on the detection of viremia and organ involvement. We examined autopsy liver specimens to determine the frequency, extent and outcome of cytomegalovirus hepatitis and whether cytomegalovirus hepatitis occurred in the absence of cytomegalovirus disease elsewhere. Autopsy specimens from 50 transplant patients were evaluated for cytomegalovirus-infected cells, in five groups of 10, according to extent of CMV during life and at autopsy. Liver sections were examined by routine light microscopy, immunohistochemistry and in situ DNA hybridization. Clinical and laboratory data collected during the last 30 days of life were analysed as markers of liver cytomegalovirus infection. Cytomegalovirus-infected cells were detected in the livers of 10/10 patients with cytomegalovirus infection during life and widespread cytomegalovirus at autopsy; in 3/20 livers from patients with cytomegalovirus infection during life but negative liver cultures at autopsy; and in 1/10 livers from cytomegalovirus-seropositive patients who had been without other evidence of cytomegalovirus infection. Histology detected a lower density of cytomegalovirus-bearing cells per unit area of liver, compared to immunohistochemistry and in situ hybridization. No cytomegalovirus-infected cells were detected in livers from cytomegalovirus-seronegative controls. No distinctive clinical or laboratory findings correlated with liver cytomegalovirus detection. CMV liver disease is common in allografted patients with disseminated CMV but may rarely be isolated to the liver, best demonstrated with IHC and ISH. Massive hepatic necrosis from CMV was not seen in any autopsy liver in this study.
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Affiliation(s)
- George B McDonald
- Gastroenterology/Hepatology and Pathology Sections, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington
| | | | | | - David Myerson
- Gastroenterology/Hepatology and Pathology Sections, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington
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8
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A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology. Gastroenterol Res Pract 2019; 2019:6156581. [PMID: 30984257 PMCID: PMC6431500 DOI: 10.1155/2019/6156581] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 02/05/2019] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (CMV) is a ubiquitous Herpesviridae virus with a wide spectrum of pathology in humans. Host immunity is a major determinant of the clinical manifestation of CMV and can vary widely in the gastroenterology and hepatology practice setting. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised and inflammatory bowel disease patients. Additionally, liver allograft dysfunction is a significant consequence of CMV infection in liver transplant patients. While polymerase chain reaction and immunohistochemistry techniques allow for the reliable and accurate detection of CMV in the human host, the diagnostic value of different serologic, endoscopic, and histologic tests depends on a variety of factors. Similarly, latent CMV, CMV infection, and CMV disease carry different significance depending on the patient population, and the decision to initiate antiviral therapy can be complex and patient-specific. This review will focus on the pathophysiology, diagnosis, and management of CMV in patient populations relevant to the practice of gastroenterology and hepatology-liver transplant recipients, inflammatory bowel disease patients, and otherwise immunocompetent patients.
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9
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Leonardsson H, Hreinsson JP, Löve A, Björnsson ES. Hepatitis due to Epstein-Barr virus and cytomegalovirus: clinical features and outcomes. Scand J Gastroenterol 2017; 52:893-897. [PMID: 28446048 DOI: 10.1080/00365521.2017.1319972] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To determine the frequency of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) hepatitis among those with acute CMV and EBV infection in a population based setting and to compare these two types of hepatitis and analyze the outcomes. METHODS A retrospective search was undertaken on all patients with IgM antibodies to CMV and EBV during the period of 2006-2015 in the virological database of the University Hospital of Iceland covering the metropolitan area of Reykjavík (population 202,255). Patients with available liver tests at the University Hospital and/or admitted to this institution were included and relevant clinical data obtained from medical records. RESULT Overall, 190 patients had acute EBV infection during the study period and 118 patients were diagnosed with acute CMV. Overall, 82% of patients with acute EBV infection had hepatitis, males 43%, median age 17 years, 15% had jaundice and 26% hospitalized. Among those with acute CMV infection, 69% had elevated liver tests, 63% males, median age 33 years, 9% had jaundice and also 26% hospitalized. Overall, 17% of those with CMV hepatitis were immunosuppressed, 6% were pregnant and 4% developed Guillain-Barré syndrome following the infection. CONCLUSION A high proportion of patients with acute CMV and EBV developed hepatitis and jaundice, most of those patients have good prognosis. Patients with CMV hepatitis were more often immunosuppressed, required hospitalization or were pregnant in comparison with patients with EBV hepatitis.
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Affiliation(s)
- Hilmar Leonardsson
- a Faculty of Medicine , University of Iceland, Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland.,b Division of Gastroenterology and Hepatology , Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland
| | - Jóhann Páll Hreinsson
- b Division of Gastroenterology and Hepatology , Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland
| | - Arthur Löve
- a Faculty of Medicine , University of Iceland, Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland.,c Department of Virology , Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland
| | - Einar S Björnsson
- a Faculty of Medicine , University of Iceland, Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland.,b Division of Gastroenterology and Hepatology , Landspitali, The National University Hospital of Iceland , Reykjavík , Iceland
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10
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Park J, Lee YH, Choi YR, Lee YJ, Kim DJ, Jheon S, Cho YJ. A Case Treated with Extracorporeal Membrane Oxygenation for Disseminated Cytomegalovirus Infection after Liver Transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2017. [DOI: 10.4285/jkstn.2017.31.2.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Jimyung Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoon Hyun Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young Rok Choi
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yeon Joo Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Dong Jung Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sanghoon Jheon
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Young-Jae Cho
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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11
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Gupta P, Suryadevara M, Das A. Cytomegalovirus-induced hepatitis in an immunocompetent patient. AMERICAN JOURNAL OF CASE REPORTS 2014; 15:447-9. [PMID: 25325934 PMCID: PMC4206484 DOI: 10.12659/ajcr.890945] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Patient: Female, 20 Final Diagnosis: Cytomegalovirus-induced hepatitis Symptoms: Chills • cough dry • decreased appetite • fever Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology
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Affiliation(s)
- Prashant Gupta
- Department of Internal Medicine, Louisiana State University Health Sciences Center - University Hospital and Clinics, Lafayette, USA
| | - Madhu Suryadevara
- Department of Internal Medicine, Louisiana State University Health Sciences Center - University Hospital and Clinics, Lafayette, USA
| | - Avash Das
- Department of Medicine, Nilratan Sircar Medical College, Kolkata, India
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12
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Cytomegalovirus infection-associated fulminant hepatitis in an immunocompetent adult requiring emergency living-donor liver transplantation: report of a case. Surg Today 2012; 43:424-8. [PMID: 22797959 DOI: 10.1007/s00595-012-0209-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2011] [Accepted: 12/15/2011] [Indexed: 02/07/2023]
Abstract
Human cytomegalovirus (CMV) infection is usually self-limiting in healthy adults, but it can lead to significant complications. This report presents the case of an immunocompetent adult with fulminant hepatitis caused by a CMV infection requiring emergency living-donor liver transplantation. A 39-year-old female with persistent fever for 6 weeks was referred for fulminant hepatitis, but the underlying etiology was not identified. Rapid deterioration of consciousness led to an emergency living-donor liver transplant using a modified right lobe graft. She showed increasing CMV antigenemia after surgery and the explant liver pathology showed massive hepatic necrosis with positive staining for CMV protein. Treatment with ganciclovir improved the graft liver function and her general condition recovered. This report presents a rare case of CMV-associated fulminant hepatitis which led to emergency liver transplantation. Although CMV is rare, it should be included in the differential diagnosis of patients with severe hepatitis, even immunocompetent patients, after other more common etiologies have been excluded.
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13
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14
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Whitington PF, Alonso EM. Fulminant hepatitis in children: evidence for an unidentified hepatitis virus. J Pediatr Gastroenterol Nutr 2001; 33:529-36. [PMID: 11740224 DOI: 10.1097/00005176-200111000-00004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- P F Whitington
- Division of Pediatric Gastroenterology, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614, U.S.A
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15
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Serna-Higuera C, González-García M, Milicua JM, Muñoz V. Acute cholestatic hepatitis by cytomegalovirus in an immunocompetent patient resolved with ganciclovir. J Clin Gastroenterol 1999; 29:276-7. [PMID: 10509956 DOI: 10.1097/00004836-199910000-00010] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We report a case of acute cholestatic hepatitis in an immunocompetent young male with cytomegalovirus (CMV) primoinfection episode. The severity of the clinical symptoms led to a high-dose treatment with parenteral ganciclovir, with an immediate response and total resolution of symptoms. Therapeutic options are discussed, particularly the use of ganciclovir, even in immunocompetent patients when the severity of the symptoms could demand it.
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Affiliation(s)
- C Serna-Higuera
- Department of Gastroenterology, Ramón y Cajal Hospital, Faculty of Medicine, Alcalá de Henares University, Madrid, Spain
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16
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Yerkovich ST, Olver SD, Lenzo JC, Peacock CD, Price P. The roles of tumour necrosis factor-alpha, interleukin-1 and interleukin-12 in murine cytomegalovirus infection. Immunology 1997; 91:45-52. [PMID: 9203964 PMCID: PMC1364033 DOI: 10.1046/j.1365-2567.1997.00226.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
The roles of the inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-12, in murine cytomegalovirus (MCMV) disease were investigated in susceptible BALB/c and resistant C57BL/6 mice. MCMV infection induced IL-1 and TNF-alpha production by peritoneal cells from BALB/c mice, as demonstrated previously in C57BL/6 mice. Overt ill-health and viral replication in the spleens of BALB/c mice were increased by in vivo treatment with soluble TNF-alpha receptors to inhibit the activity of this cytokine, whilst antibodies to IL-12 had a similar but more restricted effect C57BL/6 mice were not affected by either treatment, suggesting TNF-alpha and IL-12 are not critical for natural killer cell-mediated restriction of viral replication in the spleen. Soluble TNF-alpha receptors and antibodies to IL-12 also enhanced MCMV titres and numbers of viral antigen-positive cells in the livers of BALB/c mice and TNF-alpha receptors have similar effects in C57BL/6 livers. In contrast, IL-1 receptors improved the health of MCMV-infected BALB/c mice and reduced viral replication and hepatitis at some time-points. Mechanisms which may underlie these changes are discussed.
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Affiliation(s)
- S T Yerkovich
- Department of Microbiology, University of Western Australia, Nedlands, Australia
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17
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López-Contreras J, Ris J, Domingo P, Puig M, Rabella N, Nolla J. Disseminated cytomegalovirus infection in an immunocompetent adult successfully treated with ganciclovir. SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES 1995; 27:523-5. [PMID: 8588148 DOI: 10.3109/00365549509047059] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
We report the case of a previously healthy man who suffered a disseminated cytomegalovirus infection. He presented with prolonged fever, weight loss of 8 kg, anicteric hepatitis, upper digestive tract bleeding from gastric ulcers, acute polyneuritis and bilateral retinitis. Immunodeficiency was not detected either during admission or during a 3-year follow-up period. The patient was treated with ganciclovir (5 mg/kg BID) during 4 weeks with a favourable clinical outcome. To our knowledge, this is the first reported case with such characteristics.
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Affiliation(s)
- J López-Contreras
- Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Spain
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18
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Olver SD, Price P, Shellam GR. Cytomegalovirus hepatitis: characterization of the inflammatory infiltrate in resistant and susceptible mice. Clin Exp Immunol 1994; 98:375-81. [PMID: 7994901 PMCID: PMC1534516 DOI: 10.1111/j.1365-2249.1994.tb05500.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Mice susceptible and resistant to murine cytomegalovirus (MCMV) were infected with this virus and livers were harvested after 2-231 days. Cryostat sections were stained to visualize cells bearing CD4, CD8 or Mac-1 antigens. Mac-1+ cells were prevalent in inflammatory foci after 2 days. These cells persisted in susceptible BALB/c and A/J mice, but disappeared from livers of resistant C57Bl/6 and CBA/CaH mice by day 28. T cell inflammation peaked on days 7-11. This declined by day 56 in C57Bl/6 and CBA/CaH mice, but persisted in BALB/c and A/J mice for at least 231 days. Persistent CD8+ cells were dispersed throughout the parenchyma. More CD8+ cells were observed 7-14 days after infection in the livers of bg/bg (natural killer (NK) cell-deficient) C57Bl/6 and CBA mice, and in C57Bl/6 mice depleted of NK1.1 cells by MoAb. Thus, mice of strains susceptible to MCMV exhibit hepatitis characterized by persistence of dispersed CD8+ cells. This phenomenon may be limited by NK cells in resistant strains.
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MESH Headings
- Animals
- Antibodies, Monoclonal/pharmacology
- Disease Models, Animal
- Disease Susceptibility
- Female
- Granulocytes/immunology
- Hepatitis, Viral, Animal/immunology
- Hepatitis, Viral, Animal/pathology
- Hepatitis, Viral, Animal/virology
- Herpesviridae Infections
- Immunity, Innate
- Killer Cells, Natural/immunology
- Liver/pathology
- Liver/virology
- Mice
- Mice, Inbred Strains
- Muromegalovirus
- Phenotype
- T-Lymphocytes, Cytotoxic/immunology
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Affiliation(s)
- S D Olver
- Department of Microbiology, University of Western Australia, Nedlands
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19
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Ragnaud JM, Morlat P, Gin H, Dupon M, Delafaye C, du Pasquier P, Aubertin J. [Clinical, biological and developmental aspects of cytomegalovirus infection in immunocompetent patients: apropos of 34 hospitalized patients]. Rev Med Interne 1994; 15:13-8. [PMID: 8052748 DOI: 10.1016/s0248-8663(05)82124-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
We reviewed the thirty cases of cytomegalovirus infections with occurred in previously healthy patients, hospitalised for fever from 1981 to 1992. Pregnant women, transplant recipients, HIV infected persons and all immunocompromised subjects were excluded. We observed 34 cases (18 women, 16 men) whose mean age was 34 years (17 to 79). Fever appeared progressively (73%), persisted more than 15 days (87%) and was well tolerated. The main functional symptoms were headaches, myalgia (53%), profuse sweat (50%), abdominal pain, diarrhea, recent loss of weight, dry cough (51%). Splenomegaly was present in 24% of the cases. Chest X ray was always normal. Differential blood count was always inverse and an authentic mononucleosis syndrome was present in 91%: it appeared mainly 13 days after onset of symptoms. Hepatic abnormalities were nearly constant, especially cytolytic (97%) (transaminases three or four times upper the normal limit) but also cholestatic (62%). Thrombopenia has been noticed once (48,000/mm3). Serological diagnosis was confirmed with Elisa test (anti CMV Ig M: 30 cases) or complement fixation test (seroconversion: one, significant increase of the titers: two). CMV viremia, studied in seven patients, was positive in three. Spontaneous or treated (NSAI in 30%) outcome was nearly always favourable (97%). Two patients presented severe complications: meningo encephalitis and spleen rupture. CMV infection in previously healthy patients has to be suspected, without waiting for the mononucleosis syndrome, in view of a prolonged, well tolerated febrile illness, without pharyngitis, associated with hyperlymphocytosis and mild cytolysis. A careful follow-up is needed to detect the rare but severe complications.
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Affiliation(s)
- J M Ragnaud
- Clinique médicale et des maladies infectieuses, hôpital Pellegrin, Bordeaux, France
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Dény P, Debure A, Agut H, Berche P, Degos F, Nicolas JC, Kreis H, Bréchot C. Detection of human cytomegalovirus DNA in liver biopsies from patients with cytomegalovirus-related liver disease. RESEARCH IN VIROLOGY 1989; 140:361-72. [PMID: 2549599 DOI: 10.1016/s0923-2516(89)80116-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Infection with human cytomegalovirus (HCMV) has been associated with severe diseases in immunologically impaired patients. Cytomegalovirus hepatitis has been frequently described in this population, but this diagnosis is still difficult. Molecular hybridization with the V EcoRI restriction fragment of human cytomegalovirus strain AD 169 has been tested upon DNA extracted from liver samples to assess the usefulness of this technique for cytomegalovirus hepatitis diagnosis. This probe was shown by the Southern technique not to hybridize with DNA extracted from cells infected with other herpesviruses or with DNA of non-infected normal liver. The sensitivity was estimated to be 2 x 10(5) genomes. Twenty-five renal transplant recipients under immunosuppressive therapy and three patients having the acquired immunodeficiency syndrome were studied. In 9 out of 10 renal transplant recipients with normal liver, previous exposure to cytomegalovirus, as defined by serological tests, was not sufficient to allow positive detection by the probe. Out of 11 patients with abnormal liver, cytomegalovirus DNA sequences were shown in 5. In 2 patients with histological evidence of cytomegalovirus hepatitis, a very strong signal showed the presence of viral genomes. These results show that the Southern technique with the V EcoRI probe can be useful for the diagnosis of HCMV hepatitis and might be proposed for the detection of this viral genome in human tissues.
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Affiliation(s)
- P Dény
- Unité de Recombinaison et Expression Génétique, INSERM U 163, Institut Pasteur, Paris, France
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Levy I, Shohat M, Levy Y, Alpert G, Nitzan M. Recurrent ascites in an infant with perinatally acquired cytomegalovirus infection. Eur J Pediatr 1989; 148:531-2. [PMID: 2545449 DOI: 10.1007/bf00441550] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
We describe an infant with symptomatic perinatally-acquired cytomegalovirus (CMV) infection manifested by fever, anaemia, thrombocytopenia and hepatosplenomegaly. This infant developed recurrent episodes of severe ascites during which the virus was isolated from his urine. This rare hepatic manifestation of neonatal CMV infection has, to the best of our knowledge, only been reported twice in aborted fetuses with intrauterine systemic CMV infection.
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Affiliation(s)
- I Levy
- Department of Paediatrics, Beilinson Medical Centre, Petah Tiqva, Israel
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Abstract
Cytomegalovirus (CMV) is a common infectious agent which is well adapted to its host. Following primary infection, which is almost always asymptomatic in people with normal immunity, the virus establishes latency at sites which are unknown. The virus is probably maintained in this latent state by immune surveillance mechanisms since immunosuppression frequently leads to reactivation of virus.Cytomegalovirus has been identified in most anatomical areas of the human body. The aim of this article is to define criteria for pathogenicity so that clinical and experimental data can be reviewed to determine if CMV is likely to cause disease at these various clinical sites. Thus, patients have been shown to die frequentlywithCMV but do they diefromit?
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Affiliation(s)
- P D Griffiths
- Department of Virology, Royal Free Hospital School of Medicine, London, England
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Lurie M, Elmalach I, Schuger L, Weintraub Z. Liver findings in infantile cytomegalovirus infection: similarity to extrahepatic biliary obstruction. Histopathology 1987; 11:1171-80. [PMID: 2826325 DOI: 10.1111/j.1365-2559.1987.tb01857.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The histological findings in the liver in four fatal cases of infantile cytomegalovirus (CMV) infection are presented, three occurred in premature infants, and all died at the ages of 2-4 months. Most previously reported cases showed various degrees of hepatitis with giant cell transformation. In three of our four cases, however, the main feature was cholestasis, portal fibrosis and bile duct proliferation, not unlike the findings seen in extrahepatic biliary obstruction. In one case, massive hepatic necrosis was found, a finding not previously reported in this disease. The diversity of liver findings in infantile CMV infection is stressed.
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Affiliation(s)
- M Lurie
- Department of Pathology, Carmel Hospital, Haifa, Israel
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Vandelli C, Zannini A, Piaggi V, Melegari M, Battilani R, Ventura E. What is the effect of a cytomegalovirus infection when superimposed on HBsAg-positive chronic hepatitis? J Hepatol 1987; 4:343-8. [PMID: 3036939 DOI: 10.1016/s0168-8278(87)80544-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
A non-transfusion-related cytomegalovirus infection was observed in two patients with chronic HBsAg-positive liver disease. Both patients were immunodepressed and died of acute hepatic failure. A superimposed CMV infection has a high fatality rate in the case of underlying chronic type B liver disease.
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Nouasria B, Aouati A, Bernau J, Rueff B, Benhamou JP, Gaudebout C, Larouze B, Dazza MC, Saimot AG, Goudeau A. Fulminant viral hepatitis and pregnancy in Algeria and France. ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 1986; 80:623-9. [PMID: 3118829 DOI: 10.1080/00034983.1986.11812077] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The relationship between fulminant viral hepatitis (FVH) and pregnancy was compared in Algeria and France. This comparison was based on the study of 22 Algerian and 77 French pregnant and non-pregnant women, aged 15 to 49 years, consecutively admitted for FVH to the Centre Hospitalier Universitaire, Constantine, Algeria, or to Hôpital Beaujon, Clichy, France. The observed and expected (calculated from demographic data) percentage of pregnant women was significantly different among the Algerian patients with FVH (45.5% v. 24.9%, P less than 0.03), but not among the French patients (3.9% v. 5.8%). Hepatitis A was the cause of FVH in none of the Algerian patients, but in eight French patients, none of whom was pregnant. Hepatitis B was the cause of FVH in one non-pregnant Algerian patient and in 49 French patients, two of whom (4.1%) were pregnant. Hepatitis non-A, non-B was the cause of FVH in 21 Algerian patients, ten of whom (47.6%, a percentage significantly higher than expected, P less than 0.04) were pregnant, and in 19 French patients, one of whom (5.3%, a percentage similar to that expected) was pregnant. In conclusion, (1) there is a relationship between FVH and pregnancy in Algeria, but not in France, and (2) this difference is mainly or exclusively attributable to infection with a non-A, non-B virus affecting the Algerian population, but which is much less common or absent in France.
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Affiliation(s)
- B Nouasria
- Centre Hospitalier Universitaire, Constantine, Algeria
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McDonald GB, Shulman HM, Sullivan KM, Spencer GD. Intestinal and hepatic complications of human bone marrow transplantation. Part II. Gastroenterology 1986; 90:770-84. [PMID: 3510940 DOI: 10.1016/0016-5085(86)91137-6] [Citation(s) in RCA: 107] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Bianchi L. Liver biopsy interpretation in hepatitis. Part II: Histopathology and classification of acute and chronic viral hepatitis/differential diagnosis. Pathol Res Pract 1983; 178:180-213. [PMID: 6634513 DOI: 10.1016/s0344-0338(83)80032-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The morphological classification of acute and chronic viral hepatitis has been subject of considerable controversy. Main problems in nomenclature have arisen from the confusion of pathologically defined lesions with purely clinical designations. The classification used in this article is based on a number of recent reviews in which a certain measure of agreement has been reached between clinicians and histopathologists. As a general rule, in acute forms of hepatitis diffuse lobular changes predominate over portal lesions while chronic hepatitis is characterized by conspicuous alterations of portal (and periportal) areas. This report will merely summarize main diagnostic features of the different forms of viral hepatitis. For more detailed information the reader is referred to several leading articles discussing in detail morphology, and putting emphasis on pathogenesis. An exact "staging" of viral hepatitis by histologic criteria is an important tool in the evaluation of prognosis, indication and control of therapy as well as for comparison with immunologic findings.
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Bentata-Pessayre M, Krivitzky A, Stérin D, Callard P, Vésinet F, Delzant G. [Cytomegalovirus infection in healthy adults. Clinical, anatomo-pathological, hepatic and virological study of 6 cases]. Rev Med Interne 1981; 2:265-71. [PMID: 6270761 DOI: 10.1016/s0248-8663(81)80025-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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